Miltefosine 10mg capsules

BackgroundVisceral leishmaniasis (VL), also known as kala-azar, is a life-threatening neglected tropical disease primarily caused by Leishmania donovani and transmitted by infected sandflies. Despite notable advancements in public health, VL continues to pose significant challenges, especially in South Asia, East Africa, and South America.MethodsA systematic review was conducted in accordance with PRISMA guidelines. Peer-reviewed literature published from 2000 to 2024 was retrieved from PubMed, Scopus, and Web of Science to assess epidemiological patterns, diagnostic advancements, therapeutic options, and vector control strategies.ResultsThe analysis revealed progress in diagnostic tools such as rK39-based rapid tests and molecular diagnostics. Therapeutic improvements, notably liposomal amphotericin B and miltefosine, have emerged, although drug resistance and limited accessibility remain problematic. Vector control through residual spraying and community programs shows promise but is hindered by insecticide resistance. Furthermore, HIV co-infection and climate-driven spread exacerbate control efforts.ConclusionsComprehensive management of VL requires integrative approaches that combine novel diagnostics, targeted treatment, innovative vector control, and robust public health systems. Emphasis on vaccine development, digital health solutions, and community participation is crucial for sustainable control and eventual elimination.

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Background/objectivesPrimary amoebic meningoencephalitis (PAM) is a rare, fulminant, and often fatal central nervous system infection caused by the opportunistic free-living amoeba Naegleria fowleri. Although Naegleria species are widely present in freshwater and soil worldwide, human disease is associated specifically with pathogenic N. fowleri rather than the many nonpathogenic environmental species, and virulence may vary across N. fowleri isolates. This systematic review aimed to synthesize contemporary global data from 2000 to 2024 to identify recent trends in epidemiology, clinical presentation, diagnosis, treatment, and outcomes.MethodsA systematic literature search was conducted across PubMed, Scopus, and the Cochrane Library, identifying 58 eligible publications encompassing 66 individual cases.ResultsMost reports originated from the United States, India, and China. The median patient age was 14 years, with 78% of cases occurring in males. Annual case reports increased from one per year (2000-2005) to over four per year (2020-2024), reflecting either a true rise in incidence or improved detection. Common presenting symptoms included fever, headache, and altered mental status. Diagnosis was confirmed via polymerase chain reaction (PCR) testing or post-mortem biopsy in nearly one-third of cases. Treatment regimens varied, with amphotericin B and miltefosine being the most frequently used agents. Overall mortality was 83%, with survival strongly associated with early initiation of combination therapy. Pediatric patients had a higher survival rate (22%) compared to adults (7.1%).ConclusionsThe findings highlight the need for heightened clinical awareness, especially in the context of climate-driven ecological changes that may expand N. fowleri's geographic range. This review underscores critical gaps in surveillance and diagnostics and emphasizes the importance of a One Health approach to addressing emerging threats like PAM. Further research into novel therapeutics, rapid diagnostics, and global case reporting systems is urgently needed.

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BackgroundAntileishmanial drug resistance in Leishmania infantum is a major challenge for visceral leishmaniasis control, yet the genetic evidence remains fragmented across functional, genomic, structural and expression-based studies. This systematic review mapped parasite genes and loci associated with resistance, altered drug susceptibility, therapeutic failure or relapse.MethodsA PRISMA 2020-compliant systematic review was conducted using PubMed, SciELO and VHL/LILACS, with searches updated before manuscript finalization. Eligible studies evaluated Leishmania infantum genetic or locus-level evidence linked to antileishmanial susceptibility or clinically anchored outcomes. Gene-drug associations were synthesized without meta-analysis and stratified into three evidence layers: functional validation with phenotype, genomic or structural association, and expression-based association.ResultsTwenty-nine studies were included. Evidence was concentrated in a limited number of therapeutic axes, mainly antimonials, miltefosine, amphotericin B and allopurinol. The most consistently supported evidence axes included the MT/ROS3 miltefosine transport axis, MRPA-associated antimony resistance, NUC1/NUC2 within the miltefosine sensitivity locus, and loci linked to redox, sequestration, sterol and lipid remodeling. Structural evidence highlighted MSL deletion as a clinically anchored structural association with miltefosine treatment failure or relapse and reduced METK copy number as an allopurinol-associated signal in canine isolates. Expression-based studies showed heterogeneous profiles, especially for antimony-related uptake and thiol/redox pathways.ConclusionsAltered drug susceptibility in L. infantum is best explained by layered, stage-dependent and context-sensitive genetic modules rather than a single universal resistance marker. This evidence-graded synthesis supports cautious prioritization of candidate loci for prospective validation and informs the design of molecular surveillance studies within a One Health framework.

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