Mycetoma, a chronic subcutaneous infection caused by bacterial or fungal species from soil and water, presents a diagnostic challenge due to its rarity and diverse clinical manifestations. Predominantly affecting male workers in endemic regions, mycetoma typically manifests as painless swelling evolving into purulent lesions with draining sinuses in the extremities. Although historically uncommon in regions like North America, rising immigration and international travel have led to an increased prevalence, necessitating heightened clinical suspicion. Early diagnosis is crucial to prevent severe complications such as limb loss and septicemia. This case report details the diagnosis and management of chronic actinomycetoma due to Nocardia spp. in a Guatemalan immigrant landscaper and emphasizes the importance of comprehensive understanding and timely intervention in mycetoma cases.

Mycetoma is a neglected invasive infection endemic in tropical and subtropical regions, presenting as a chronic subcutaneous inflammatory mass that can spread to deeper structures, leading to deformities, disabilities, and potentially mortality. The current treatment of eumycetoma, the fungal form of mycetoma, involves antifungal agents, such as itraconazole, combined with surgical intervention. However, this approach has limited success, with low cure rates and a high risk of recurrence. This study addresses to the urgent need for more effective therapeutics by designing and synthesising 47 diversely pharmacomodulated imidazo [1,2-b]pyridazine derivatives using a simple synthetic pathway with good yields and purity. Of these, 17 showed promising in vitro activity against Madurella mycetomatis, the prime causative agent of eumycetoma, with IC50 ≤ 5 μM and demonstrated significantly lower cytotoxicity compared to standard treatments in NIH-3T3 fibroblasts. Notably, compound 14d exhibited an excellent activity with an IC50 of 0.9 μM, in the same order then itraconazole (IC50 = 1.1 μM), and achieved a favourable selectivity index of 16 compared to 0.8 for itraconazole. These promising results warrant further research to evaluate the clinical potential of these novel compounds as safer, more effective treatments for eumycetoma, thus addressing a profound gap in current therapeutic strategies.

Soil-transmitted helminths (STH) are a significant public health problem in impoverished communities of tropical and subtropical areas. Improved diagnostic methods are crucial for Neglected Tropical Diseases programs, particularly for S. stercoralis, as traditional methods are inadequate. Thus, it is important to identify the most accurate and efficient methods for the diagnosis of STH. We performed a retrospective study analyzing laboratory data at the Instituto de Investigaciones de Enfermedades Tropicales from 2010 to 2019. The study included data from outpatients referred for stool analysis and public health interventions from urban and rural communities in northern Salta province, Argentina. Samples were included in this analysis if processed through sedimentation/concentration, Baermann, Harada-Mori and McMaster\'s, with a subgroup that also included Agar plate culture method (APC). Sensitivity was calculated against a composite reference standard. Of the 5625 samples collected, 944 qualified for this analysis, with a prevalence of 11.14% for A. lumbricoides, 8.16% for hookworm, 1.38% for T. trichiura, and 6.36% for S. stercoralis. The sedimentation/concentration method was the most sensitive for A. lumbricoides (96%), compared to the McMaster method, with a sensitivity of 62%. Similarly, for hookworms, sedimentation/concentration was more sensitive than McMaster\'s, Harada-Mori, and Baermann with sensitivities of 87%, 70%, 43%, and 13%, respectively. Most of these infections were of light intensity. For S. stercoralis, Baermann and sedimentation/concentration methods were the most sensitive, with 70% and 62% respectively, while Harada-Mori was the least sensitive. In a subset of 389 samples also analyzed by the APC, Baermann was more sensitive than APC for detecting S. stercoralis, and both methods were superior to Harada-Mori. Parasitological methods, mostly when used combined, offer adequate opportunities for the diagnosis of STH in clinical and public health laboratories. The incorporation of S. stercoralis into the control strategies of the World Health Organization requires rethinking the current diagnostic approach used for surveys. With sedimentation/concentration and Baermann appearing as the most sensitive methods for this species. Further studies, including implementation assessments, should help in identifying the most adequate and feasible all-STH diagnostic approach.

UNASSIGNED: Ivermectin, an effective treatment for scabies, is not licensed for children weighing <15 kg. Pharmacokinetic modelling has shown a 3 mg dose in young children (2-4 years, weighing 10-14 kg) achieves comparable drug exposure to a 200 μg/kg dose in children aged ≥5 years. This trial evaluated a 3 mg dose in young children.
UNASSIGNED: Multicentre, phase 2 trial in five health centres in Lao PDR. Children aged 2-4 years, weighing 10-14 kg with scabies received 3 mg ivermectin and had two plasma concentrations determined (Clinicaltrials.gov ID NCT05500326). On day 14, clinical outcomes and adverse effects were assessed, and a second dose given to complete treatment. The primary outcome was the mean plasma ivermectin exposure (AUC0-∞) after the first dose (compared to a historical control of Indigenous Australian children aged ≥5 years weighing ≥15 kg receiving 200 μg/kg). Secondary outcomes were clinical improvement and adverse effects.
UNASSIGNED: Overall, 100 children with a median age of 3.0 years (IQR 2.6-3.9) and weight of 11.9 kg (IQR 11.0-13.1) were enrolled. The mean observed ivermectin AUC0-∞ was comparable to the historical control group aged 5-11 years (815 μg h/L vs 953 μg h/L, p = 0.256). Complete resolution of scabies occurred in 90/99 children by day 14. Adverse effects were mild, occurring in 7/99.
UNASSIGNED: A 3 mg ivermectin dose in children aged 2-4 years and weighing 10-14 kg achieved a mean plasma AUC0-∞ comparable to older children, was highly effective in treating scabies and well tolerated. This study supports extending ivermectin treatment to younger children improving global efforts to control this neglected disease.
UNASSIGNED: Project funding provided by a Thrasher Foundation Early Career Research Award.

Human schistosomiasis is a parasitic disease caused by an infection with trematodes of the genus Schistosoma. The disease mainly affects impoverished populations. Around 800 million people are exposed to the infection, which is a public health problem in the tropical and subtropical regions of Africa, Asia, the Caribbean and South America. In Brazil, Schistosoma mansoni is the only species that causes schistosomiasis and the disease is widely distributed. Conventional diagnosis of the disease is carried out by detecting eggs using parasitological methods, such as the Kato-Katz test. Schistosomiasis has been reported in all regions of Brazil and is characterized as endemic in seven states in the Northeast Region and two states in the Southeast Region. In 2015, 78,7% of all cases reported in Brazil occurred in the Northeast Region. It is estimated that 1,5 million people is infected with this disease in Brazil and more than 25 millions live in areas with a high risk of transmission. Despite the reduction in mortality and morbidity, schistosomiasis was responsible for 8,756 deaths between 2000 and 2011 and 2,517 deaths between 2015 and 2019 in Brazil and it remains an important public health problem. In the state of Rio de Janeiro, some areas have low endemicity or isolated foci of Schistosoma mansoni and the majority of infected individuals have mild infections. The last survey of the disease in the state of Rio de Janeiro was carried out between 2010 and 2015 in students aged 7 to 17.Schistosomiasis was reported in 10 of the 21 municipalities studied. Of the 5,111 school children screened for S. mansoni infection, 46 (1,65%) were tested positive. Studies carried out in areas of low endemicity in Rio de Janeiro showed that among the 205 patients infected by S. mansoni in Sumidouro, around 84% were aged 14 or over and all, except one individual, had the intestinal form (91,2%) or hepato-intestinal (8,3%) of schistosomiasis. Another study carried out in Sumidouro showed that with tests based on patent Schistosoma egg infection determined by the Kato-Katz test, active infections were diagnosed in eight (8/108) individuals. The intensity of infection expressed by parasite loads ranged from 6 to 72 eggs per gram of feces/individual. The results showed DNA amplification in 32 of the 100 individuals tested by real-time PCR. All individuals with patent ovo infection showed positive DNA amplification. These studies showed that if we only analyzed school-age children using the Kato-Katz test, the majority of the infected population would never be diagnosed with S. mansoni infection. In situations of low endemicity, with low intensities of infection, with low severity in the population and in the most affected age groups, schistosomiasis requires a more sensitive diagnostic approach (e.g. screening by PCR rather than Kato test), otherwise many infected individuals will remain invisible to the healthcare system.
A esquistossomose humana é uma doença parasitária causada por uma infecçâo por vermes sanguíneos do gènero Schistosoma. A doença afeta principalmente populaçoes empobrecidas. Cerca de 800 milhoes de pessoas estâo expostas à infecçâo, sendo um problema de saúde pública nas regioes tropicais e subtropicais de África, Ásia, Caribe e América do Sul. No Brasil, o Schistosoma mansoni é a única espécie causadora da esquistossomose e a doença é amplamente distribuida. O diagnóstico convencional da doença é realizado pela detecçâo dos ovos através de métodos parasitológicos, como o teste de Kato-Katz. A esquistossomose foi notificada em todas as regioes do Brasil, e é caracterizada como endèmica em sete estados da Regiâo Nordeste e dois estados da Regiâo Sudeste. Em 2015, 78,7% de todos os casos notificados no Brasil ocorreram na Regiâo Nordeste. Estima-se que 1,5 milhâo de pessoas estejam infectadas com esta doença no Brasil e mais de 25 milhoes vivam em áreas com alto risco de transmissâo. Apesar da reduçâo da mortalidade e morbidade, a esquistossomose foi relatada em 8.756 mortes entre 2000 e 2011 e em 2.517 mortes entre 2015 e 2019 no Brasil e continua sendo um importante problema de saúde pública. No Estado do Rio de Janeiro, algumas áreas apresentam baixa endemicidade ou focos isolados de Schistosoma mansoni e a maioria dos individuos infectados apresenta infecçoes leves. O último levantamento da doença no Estado do Rio de Janeiro foi realizado entre 2010 e 2015 em estudantes de 7 a 17 anos. A esquistossomose foi relatada em 10 dos 21 municipios estudados. Das 5.111 crianças escolares triadas para infecçâo por S. mansoni, 46 (1,65%) testaram positivo. Estudos realizados em áreas de baixa endemicidade no Rio de Janeiro mostraram que dentre os 205 pacientes infectados por S. mansoni em Sumidouro, cerca de 84% tinham 14 anos ou mais e todos, exceto um individuo, tinham a forma intestinal (91,2%) ou hepato-intestinal (8,3%) da esquistossomose. Outro estudo realizado em Sumidouro, mostrou que testes baseados em infecçâo patente de ovo de Schistosoma determinada pelo teste de Kato-Katz, infecçoes ativas foram diagnosticadas em oito (8/108) individuos. A intensidade de infecçâo expressa pelas cargas parasitárias variou de 6 a 72 ovos por grama de fezes/individuo. Os resultados mostraram amplificaçâo do DNA em 32 dos 100 individuos testados por PCR em tempo real. Todos os indivíduos com infecçâo ovo-patente apresentaram amplificaçâo de DNA positiva. Tais estudos mostraram que se analisarmos apenas crianças em idade escolar pelo teste de Kato-Katz, a maioria da populaçâo infectada nunca seria diagnosticada com infecçâo pelo S. mansoni. Em situaçoes de baixa endemicidade, com baixas intensidades de infecçâo, com baixa gravidade na populaçâo e nas faixas etárias mais afetadas, a esquistossomose requer uma abordagem diagnóstica mais sensivel (por exemplo, triagem por PCR em vez do teste de Kato), caso contràrio, muitos individuos infectados permanecerâo invisiveis para o sistema de saúde.

UNASSIGNED: Leishmaniasis, a neglected tropical parasitic disease, is regarded as a major public health problem worldwide. The first-line drugs for leishmaniasis suffer from limitations related to toxicity and the development of resistance in certain parasitic strains. Therefore, the discovery of alternative treatments for leishmaniasis is imperative, and natural products represent a valuable source of potential therapeutic agents.
UNASSIGNED: The present study aimed at finding new potential antileishmanial agents from the aerial parts of the medicinal plant Momordica charantia. This study was based on bioassay-guided fractionation of the M. charantia extract against promastigotes and amastigotes of Leishmania (Leishmania) amazonensis. The cytotoxicity of the extract, fractions, and isolated compounds were evaluated against peritoneal murine macrophages by employing the MTT assay for assessing cell metabolic activity.
UNASSIGNED: Antileishmanial assay-guided fractionation of the M. charantia extract led to the bioactive cucurbitacin-enriched fraction and the isolation of four bioactive cucurbitacin-type triterpenoids, which exhibited significant antileishmanial activity, with IC50 values between 2.11 and 3.25 μg.mL-1 against promastigote and amastigote forms, low toxicity and selectivity indexes ranging from 8.5 to 17.2.
UNASSIGNED: Our findings demonstrate that the fractions and cucurbitacin-type triterpenoids obtained from the aerial parts of M. charantia are promising natural leishmanicidal candidates.

UNASSIGNED: This paper explores the role of Brazilian research institutions in the global and national context of study of medicinal plants. Most of these plants have ethnopharmacological use and herbal medicines related to the Amazon. It highlights Brazil\'s position in scientific production and the importance of Amazonian resources in developing phytomedicines. The study aims to provide an overview of the technical-scientific production of medicinal plants and herbal medicines related to the Amazon, focusing on scientific impact, collaboration, Technology Readiness Level (TRL) of scientific production, and innovation system maturity.
UNASSIGNED: The study employs a comprehensive methodological approach, including data collection from Scopus covering the period from 2002 to 2022. The data was cleaned and analyzed using bibliometric and network analysis techniques. Advanced natural language processing techniques, such as Latent Dirichlet Allocation and Jaccard distance measure, were used for TRL classification.
UNASSIGNED: The findings reveal a predominant contribution from Brazilian institutions and authors, with 1,850 publications analyzed. Key areas identified include Pharmacology, Toxicology, Pharmaceuticals, Medicine, and Biochemistry. The study also uncovers various collaborative networks and technological maturity levels, with a significant focus on early-stage development phases.
UNASSIGNED: The research concludes that Brazilian institutions, particularly those in the Amazon region, play a significant role in the scientific exploration and development of medicinal plants and herbal medicines. Despite this, countries like the USA were proportionally more productive in clinical trial research. The study underscores the potential of Brazil\'s rich biodiversity and traditional knowledge in the pharmaceutical industry, particularly for neglected diseases. It suggests the need for stronger research systems and international collaboration to leverage these resources for global health benefits.

暂无摘要。

UNASSIGNED: Rabies and snakebite envenoming are two zoonotic neglected tropical diseases (NTDs) transmitted to humans by animal bites, causing each year around 179,000 deaths and are most prevalent in Asia and Africa. Improving geographical accessibility to treatment is crucial in reducing the time from bite to treatment. This mini review aims to identify and synthesize recent studies on the consequences of distance and travel time on the victims of these diseases in African countries, in order to discuss potential joint approaches for health system strengthening targeting both diseases.
UNASSIGNED: A literature review was conducted separately for each disease using Pubmed, Google Scholar, and snowball searching. Eligible studies, published between 2017 and 2022, had to discuss any aspect linked to geographical accessibility to treatments for either disease in Africa.
UNASSIGNED: Twenty-two articles (8 on snakebite and 14 on rabies) were eligible for data extraction. No study targeted both diseases. Identified consequences of low accessibility to treatment were classified into 6 categories: (1) Delay to treatment; (2) Outcome; (3) Financial impacts; (4) Under-reporting; (5) Compliance to treatment, and (6) Visits to traditional healers.
UNASSIGNED: Geographical access to treatment significantly influences the burden of rabies and snakebite in Africa. In line with WHO\'s call for integrating approaches among NTDs, there are opportunities to model disease hotspots, assess population coverage, and optimize geographic access to care for both diseases, possibly jointly. This could enhance the management of these NTDs and contribute to achieving the global snakebite and rabies roadmaps by 2030.

The WHO aims to eliminate schistosomiasis as a public health problem by 2030. However, standard morbidity measures poorly correlate to infection intensities, hindering disease monitoring and evaluation. This is exacerbated by insufficient evidence on Schistosoma\'s impact on health-related quality of life (HRQoL). We conducted community-based cross-sectional surveys and parasitological examinations in moderate-to-high Schistosoma mansoni endemic communities in Uganda. We calculated parasitic infections and used EQ-5D instruments to estimate and compare HRQoL utilities in these populations. We further employed Tobit/linear regression models to predict HRQoL determinants. Two-thirds of the 560 participants were diagnosed with parasitic infection(s), 49% having S. mansoni. No significant negative association was observed between HRQoL and S. mansoni infection status/intensity. However, severity of pain urinating (β = -0.106; s.e. = 0.043) and body swelling (β = -0.326; s.e. = 0.005), increasing age (β = -0.016; s.e. = 0.033), reduced socio-economic status (β = 0.128; s.e. = 0.032), and being unemployed predicted lower HRQoL. Symptom severity and socio-economic status were better predictors of short-term HRQoL than current S. mansoni infection status/intensity. This is key to disentangling the link between infection(s) and short-term health outcomes, and highlights the complexity of correlating current infection(s) with long-term morbidity. Further evidence is needed on long-term schistosomiasis-associated HRQoL, health and economic outcomes to inform the case for upfront investments in schistosomiasis interventions.