BACKGROUND Triatoma vitticeps (Stål, 1859), a primarily sylvatic vector of Trypanosoma cruzi (Chagas, 1909), has been reported invading dwellings and peridomiciliary ecotopes in several regions of Brazil. OBJECTIVES and METHODS Here, we report for the first time, the colonisation of a brick house by T. vitticeps in the municipality of São José do Vale do Rio Preto, Rio de Janeiro State. FINDINGS Inside the house, indicators of colonisation were recorded, including 15 eggs, 11 nymphs, two exuviae, and 19 adult specimens. T. cruzi infection was detected in 13 specimens and the blood meal source identification, through amplification of DNA fragments indicated the presence of human blood as one of the feeding sources in seven specimens. MAIN CONCLUSIONS The infested dwelling was treated with insecticide to control the infestation, and residents were appropriately instructed to remain vigilant for the presence of triatomines and to contact health authorities if new specimens were detected.
BACKGROUND Respiratory viral infections in children are characterised by the co-circulation of multiple viral pathogens, but the relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-detection with other respiratory viruses remains unclear. OBJECTIVES To evaluate the clinical and epidemiological implications of respiratory viral co-detection and the impact of viral diversity in paediatric SARS-CoV-2 infection. METHODS We conducted a retrospective-prospective molecular epidemiology study including children (0-11 years) with reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection in Natal, northeast Brazil, between 2021 and 2024. Samples were analysed by multiplex RT-PCR for ten respiratory viruses. Associations between co-detection, the number of co-detected viruses, and clinical manifestations were assessed using multivariable logistic regression. FINDINGS Among 545 cases, 13.2% showed viral co-detection. Co-detection was associated with dyspnoea, respiratory distress, low oxygen saturation, and diarrhoea, and inversely associated with cough. An increasing number of co-detected viruses was linked to more severe manifestations. Distinct viral combinations were associated with different clinical profiles. SARS-CoV-2 viral load and variants were not associated with co-detection. MAIN CONCLUSIONS Respiratory viral co-detection is associated with distinct clinical and epidemiological profiles influenced by the number of co-detected viruses and viral combinations. These findings highlight the role of viral co-circulation and suggest interactions among respiratory viruses in the clinical expression of disease in children.
Chikungunya virus (CHIKV) can cause acute arboviral illness, usually accompanied by severe polyarthralgia. In 2025, live-attenuated CHIKV vaccine Ixchiq® (Valneva, Saint-Herblain, France) was authorised for use in Brazil, where CHIKV often co-circulates with other arboviruses. A central public health question emerges: how should this vaccine be optimally deployed in a country characterised by hyperendemic transmission, frequent underdiagnosis, and marked regional disparities? We conducted an epidemiological analysis using notified CHIKV cases from the Notifiable Diseases Information System (SINAN) and socioeconomic indicators from the Brazilian Human Development Atlas. This framework enabled the identification of municipal clusters with shared epidemiological and socioeconomic profiles, allowing exploration of the relationship between disease notification rate and social health determinants. Our results showed that CHIKV transmission exhibited a cyclic pattern with geographic expansion toward the Southeast/South - Brazil's most densely populated regions characterised by low population immunity. Cluster analyses showed that the greatest disease burden is concentrated in socioeconomically disadvantaged municipalities, particularly in the Northeast, where healthcare disparities may further impact diagnostic capacity. Based on the obtained results, we believe in a hybrid immunisation strategy starting from high-incidence municipalities in the northeast and reaching major urban centres in the southeast in order to prevent larger outbreaks. Implementation must account also for current vaccine contraindications in high-risk groups and be guided by real-time epidemiological and entomological surveillance.
BACKGROUND:Candida auris is an emerging fungal pathogen associated with invasive infections, notable for nosocomial spread and multidrug resistance. Despite its public health importance, genetic data from Peruvian isolates remain limited. OBJECTIVES:To perform a multi-isolate genomic analysis of Peruvian C. auris isolates, including epidemiological analysis, clade assignment, phylogenetic reconstruction, and characterisation of antifungal resistance-associated mutations. METHODS:Twenty clinical samples from hospitals in Lima and Callao were identified using MALDI-TOF and subjected to antifungal susceptibility testing. Genomic DNA was sequenced, and genomes meeting quality criteria (n = 19) were included in the analysis. Phylogenomic and ERG11 phylogenetic analyses were performed, and protein modelling combined with molecular docking was used to assess interactions with lanosterol 14-α-demethylase. FINDINGS:All analysed isolates belonged to clade IV and exhibited resistance to fluconazole. The ERG11 gene harboured four relevant mutations; notably, K143R was located within the hemi-binding region of lanosterol 14-α-demethylase and was predicted, based on molecular docking, to potentially alter fluconazole binding. These findings highlight the circulation of a resistant clade and underscore the need for strengthened genomic surveillance and antifungal stewardship strategies. MAIN CONCLUSIONS:This study expands the genomic data available for C. auris and reinforces the urgent need for sustained genomic surveillance to monitor and contain antifungal resistance.
Chromoblastomycosis (CBM) is a chronic, debilitating subcutaneous mycosis that remains a major therapeutic challenge due to its limited responsiveness to conventional antifungal agents. Our research group investigated key cellular mechanisms underlying fungal virulence, persistence, and resistance, revealing that CBM-associated fungi can exhibit ectophosphatase and calcineurin activities, secrete aspartic and metallo-type peptidases, and form highly structured biofilms that reinforce their chronic behaviour and tolerance to treatment. Targeted inhibition of these enzymatic systems using classical inhibitors of peptidases [e.g., human immunodeficiency virus (HIV) aspartic peptidase inhibitors], acid phosphatases (e.g., sodium orthovanadate), and calcineurin (e.g., tacrolimus and cyclosporine A) markedly impaired fungal growth, morphogenesis, biofilm development, and/or host-cell interactions, underscoring their potential roles in key fungal biological processes and infection establishment. Furthermore, coordination compounds incorporating transition metals (e.g., silver) and 1,10-phenanthroline-derived ligands demonstrated potent antifungal efficacy against CBM-associated fungi and may interfere with key physiological and virulence-associated pathways. Collectively, these findings advance the understanding of CBM fungal pathophysiology, unveiling novel molecular targets and highlighting opportunities for alternative therapeutic strategies and antifungal drug development.
BACKGROUND The Leishmania (Viannia) subgenus contains important pathogens that cause a variety of different clinical forms of cutaneous leishmaniasis in the Americas. Their response to antimonial chemotherapy differs according to species. Having high-quality genomic resources of these species is a significant step towards investigating and understanding these factors. OBJECTIVES This study aims to characterise the main genomic features of L. (V.) guyanensis strain MHOM/BR/75/M4147 and L. (V.) shawi strain MCEB/BR/84/M8408. METHODS Genomes were sequenced combining short- and long-read sequencing platforms and assembled, scaffolded, and polished using Flye2, Ragtag, and Pilon, respectively. Annotations were performed using mainly similarity and profile search methods, and phylogenetic analyses were performed using the maximum likelihood (ML) and Bayesian inference approaches, using IQ-TREE and MrBayes, respectively. FINDINGS De novo assembly produced genome sizes of 32.27 Mb for L. guyanensis and 32.41 Mb for L. shawi, and predicted 8,505 and 8,592 protein-coding genes, respectively. Phylogenetic analysis based on these assemblies confidently places L. guyanensis and L. shawi as the closest known relatives to L. panamensis within the Viannia clade. MAIN CONCLUSIONS These genomes will increase the knowledge about the subgenus L. (Viannia) in the Americas and also represent valuable information for future comparative studies with other human pathogenic Leishmania spp.
BACKGROUND Research on Leishmania pathogenesis, as well as drug and vaccine discovery, primarily relies on complex mammalian models that raise ethical concerns. To overcome these limitations, we tested a simpler and more accessible experimental system. In this study, we examined the interaction between Leishmania amazonensis and Acanthamoeba, a widespread free-living protozoan that interacts with various microorganisms. OBJECTIVES To provide a deeper morphological and kinetic characterisation of the interaction between L. amazonensis and Acanthamoeba. METHODS The parasite interaction was characterised using light microscopy, fluorescence microscopy, scanning electron microscopy (SEM), confocal microscopy, and live-cell imaging. FINDINGS Co-culture was most optimal in RPMI medium at 26 degrees C. L. amazonensis promastigotes invaded Acanthamoeba trophozoites via their flagellum; trophozoites phagocytosed parasites through acanthopodia. Inside the amoeba, L. amazonensis became rounded and shortened, with no visible flagellum. These forms, isolated after 3 h of co-culture, differentiated back into promastigotes and were viable. The percentage of amoebas with L. amazonensis decreased over time. MAIN CONCLUSIONS Acanthamoeba trophozoites can interact and clear out L. amazonensis. This model is unsuited for sustained infection studies necessary for drug screening. However, it could be an effective model for exploring cellular leishmanicidal mechanisms.
BACKGROUND Dengue, the disease caused by dengue virus (DENV), is responsible for over 300 million cases worldwide. Although DENV-4 usually presents with milder symptoms, some cases can result in death. OBJECTIVES The present study aims to characterise the immunohistopathological profile of hepatic, pulmonary, cardiac and renal involvement in fatal cases of DENV-4 that occurred between 2011 and 2013 in Brazil. METHODS To this end, tissue samples from the patients were subjected to histopathological analysis using bright-field microscopy and cytokine detection by immunohistochemistry. FINDINGS Cells stained for tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were observed in the liver, lungs and kidneys. In the liver, the most common finding was periportal necrosis, along with steatosis and mononuclear cell infiltration. In the lungs, pneumocyte necrosis was only observed in areas of alveolar oedema. Septal and alveolar haemorrhage were present, along with thickening of the alveolar walls. In the kidneys, glomerular capillary congestion was observed in most of the analysed cases. Inflammatory cell infiltration was observed in the cortical region, along with proximal and distal tubule necrosis. Finally, in the heart, despite limited local cytokine expression, the cardiac tissue remained morphologically preserved. MAIN CONCLUSIONS Although the findings reported in this study are consistent with those described in fatal dengue cases, the absence of cardiac alterations indicates that DENV-4 may cause a milder infection in this organ.
BACKGROUND Single-nucleotide polymorphisms (SNPs) can influence the hepatitis C virus (HCV) infection and progression. ABCB1-gene SNPs - c.1236C>T, c.2677G>T and c.3435C>T - are associated with drug efficacy, hepatotoxicity, and liver injury. ABCB11 c.1331T>C is associated with cholestasis and altered bilirubin levels, potentially worsening liver disease. OBJECTIVE To investigate the impact of ABCB1 and ABCB11 SNPs on disease progression in chronic HCV patients. METHODS A total of 232 HCV patients unresponsive to conventional therapy were analysed. Serum samples were genotyped by quantitative polymerase chain reaction (qPCR), and the genotype and allele-based analysis was performed using RStudio. FINDINGS Cirrhosis was present in 59.1% of patients, along with diabetes (28.4%) and hepatic steatosis (46.1%). The most frequent ABCB1 variant allele was c.3435C>T (36.8%), followed by c.1236C>T (30.8%) and c.2677G>T (26.7%). The ABCB11 c.1331CC genotype was observed in 31.3% of the cohort. Genotypes 1236TT and 2677TT and their alleles were associated with lower total cholesterol. 2677TT genotype and 2677T allele were associated with lower high-density lipoprotein. Patients with 1331CC genotype had higher aspartate aminotransferase levels, and the 1331CC genotype was a risk factor for cirrhosis. A fully variant combined allele (1236T and 2677T and 3435T and 1331C) was associated with higher alpha-fetoprotein and lower cholesterol. MAIN CONCLUSIONS ABCB1 and ABCB11 SNPs are associated with worse clinical outcomes in HCV, underscoring their relevance in disease monitoring.
BACKGROUND:Triatoma infestans complex comprises 39 species of South American triatomines, organised into different subcomplexes. These species act as vectors of the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. However, the evolutionary relationships among the subcomplexes remain unresolved. OBJECTIVES:In this study, we present the most comprehensive morphological cladistic analysis of these species to date. METHODS:Phylogenetic relationships were examined in a new analysis based on morphological data. We analysed a data matrix comprising 48 terminal taxa and 72 morphological characters, coded under implicit parsimony weights, with a range of concavities (k1-80). FINDINGS:Our results indicate that the T. infestans and Triatoma rubrovaria subcomplexes constitute monophyletic groups, while Triatoma brasiliensis, Triatoma matogrossensis and Triatoma sordida subcomplexes are merophyletic. We also confirm that Triatoma maculata does not belong to the homonymous subcomplex. MAIN CONCLUSIONS:The study presents the first cladistic analysis and provides a solid foundation for understanding phylogenetic relationships within of the T. infestans complex.
Klebsiella pneumoniae (Kp) is currently a top priority for the development of alternative therapeutic strategies, according to the World Health Organisation, due to serious concerns regarding infections caused by multiple drug resistant (MDR) bacteria. The convergence of hypervirulence and MDR represents a major threat to public health worldwide. Kp displays an extensive genomic diversity, reflecting a variable repertoire of resistance and virulence factors. Despite this heterogeneity, the type VI secretion system (T6SS) is encoded in most Kp-genomes and plays important roles in competition and pathogenesis. The T6SS is a large macromolecular complex assembled in the cytoplasm that spans the inner and outer membranes. Upon activation, it undergoes conformational changes allowing the delivery of effectors into the extracellular milieu or target cells. Herein, we summarise the current knowledge on the Kp-T6SS, presenting a chronological overview of published studies, discussing the mechanisms, signals, and regulators involved in T6SS expression. Next, we detail both predicted and characterised effector proteins, including Tle1, Pld1 and VgrG4. Finally, we discuss the presence of Kp-T6SS in mobile genetic elements or in clinical samples, highlighting the importance of genomic vigilance and Kp-T6SS detection in high-risk cases. This review integrates available evidence, identifies knowledge gaps, and outlines future directions.
BACKGROUND:Chagas disease (CD) is caused by Trypanosoma cruzi. Treatment is based on benznidazole (Bz), although it has significant limitations, such as low efficacy in the chronic phase. Therefore, the search for new therapies with greater selectivity and antiparasitic activity is necessary. In this context, 1,2,4-oxadiazole stands out for its biological properties, including antiparasitic activities. OBJECTIVE:To evaluate the in vitro activity of N-cyclohexyl 3-(3-methylphenyl)-1,2,4-oxadiazol-5-amine derivatives against the Y strain of T. cruzi and an in vivo toxicity study. METHODS:Cytotoxicity was evaluated in LLC-MK2 cells by the MTT assay, while the antiparasitic effect on the three T. cruzi life forms was determined by counting. Flow cytometry analyses were then conducted to investigate possible death pathway mechanisms and antioxidant and antiacetylcholinesterase activities. Scanning electron microscopy (SEM) was also performed to observe morphological changes caused by the compounds. Finally, in vivo acute toxicity tests were performed on ZebraFish embryos. RESULTS:The results presented show distinct cellular toxicity profiles in LLC-MK2 cells, in addition to demonstrating antiparasitic activity at different concentrations. In amastigotes, cytotoxic effects were stimulated. The molecules also induced an increase in reactive oxygen species and membrane damage, in addition to loss of integrity and morphological changes. The antioxidant activity revealed a high capacity for scavenging free radicals, suggesting an alteration of the redox balance of the parasite, in addition to showing inhibition of acetylcholinesterase, an important enzyme present in the formation of parasites, which choline is a constituent. In the ZebraFish model, molecule 2a showed dose-dependent embryonic toxicity, with an LC50 of 14-15 µM. MAIN CONCLUSIONS:The calculated conclusions appear to indicate an antiparasitic effect associated with cell death mechanisms. However, further studies are needed to reduce toxicity in the animal model and increase delivery to the site of action.
BACKGROUND:Benznidazole (BZN) has been used for more than fifty years in the treatment of Chagas disease (CD). It is produced by only three pharmaceutical companies worldwide: Lafepe (Brazil); Elea (Argentina) and Liconsa (Spain). The therapeutic interchangeability among these products has never been evaluated. OBJECTIVES:To assess bioequivalence between three 100 mg BZN formulations. METHODS:Pharmaceutical equivalence, with dissolution testing, was assessed prior to the bioequivalence study. For bioequivalence, healthy adult participants received 100 mg of BZN formulations after meal, in a randomised clinical trial. Blood BZN concentrations were measured. Pharmacokinetic parameters were determined by non-compartmental analysis. FINDINGS:The BZN Liconsa demonstrated faster in vitro dissolution. However, bioavailability was not different between formulations. The mean area under the curve (AUC)84h values were 49431.22 h*ng/mL (SD = 9938.53) to Lafepe, 48974.38 h*ng/mL (SD = 10304.67) to Elea and 48204.17 h*ng/mL (SD = 9342.18) to Liconsa. The mean Cmax values were 2339.23 ng/mL (SD = 445.53) for Lafepe, 2209.04 ng/mL (SD = 448.02) for Elea and 2303.90 ng/mL (SD = 431.41) for Liconsa. The mean tmax was not different between formulations. AUC were higher in women for Elea (20%) and Lafepe (27%). The adverse events did not differ between sexes. MAIN CONCLUSIONS:The 100 mg BZN formulations demonstrated bioequivalence.
BACKGROUND:Children experience Coronavirus disease 2019 (COVID-19) often with milder symptoms but severe outcomes. OBJECTIVES:To compare clinical, epidemiological and viral load profiles of hospitalised paediatric COVID-19 cases before and after the emergence of the Omicron variant in Espírito Santo, Brazil, and to explore factors associated with hospitalisation duration. METHODS:This cross-sectional observational study included 54 hospitalised children with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, grouped according to epidemiological period: G1 (2020-2021) and G2 (2022). Viral load was quantified by reverse transcription real-time polymerase chain reaction (RT-qPCR), and whole-genome sequencing was performed using Nanopore technology. Group comparisons used chi-square/Fisher's exact tests and Mann-Whitney U tests. Cox regression was applied in an exploratory manner to identify factors associated with hospitalisation duration. FINDINGS:The median age was 19.5 months and 68.5% were male. Comorbidities were present in 65% of the cohort, with no significant differences between groups. Children in G1 were more often hospitalised for respiratory syndromes, while G2 had a longer intensive care unit (ICU) stay. More than half of the patients required oxygen support, and those needing oxygen at admission were younger. Viral load was higher in G1 than in G2. In the multivariable Cox model, comorbidities [aHR = 0.47; 95% confidence interval (CI): 0.26-0.86] and male sex (aHR = 0.47; 95% CI: 0.25-0.89) were associated with prolonged hospitalisation. Sequencing identified five SARS-CoV-2 lineages (P.1., B.1.1., BA.1*, BQ.1.1, and BE.9), reflecting the transition from pre-Omicron to Omicron periods. MAIN CONCLUSIONS:The pre-Omicron period was marked by higher viral loads and distinct clinical patterns compared with the Omicron period. Comorbidities and male sex were associated with prolonged hospitalisation. These findings should be interpreted as exploratory and hypothesis-generating given the limited cohort size.
The treatment of Chagas disease (CD) has relied for more than five decades on two drugs, benznidazole (BZ) and nifurtimox (NTX), both with significant limitations and severe adverse effects. Their limited efficacy during the chronic phase underscores the urgent need for new chemotherapeutic strategies. The pursuit of new therapeutic agents for CD is focused on identifying molecular targets essential for Trypanosoma cruzi survival that are either absent or highly divergent in human, thereby enhancing selectivity and minimising off-target toxicity. These targets exploit the parasite's unique biology at multiple levels. Key metabolic vulnerabilities include: ergosterol biosynthesis, a sterol pathway distinct from human cholesterol metabolism; glycosomal metabolism, reflecting parasite´s unique compartmentalisation of glycolysis; and redox homeostasis, which depends on trypanothione rather than glutathione. Additional promising avenues involve the parasite's genetic and epigenetic regulation, mRNA processing and translational control. Furthermore, virulence-associated factors, and specific enzymes such as type I nitroreductase (NTR-1) can be exploited for selective prodrug activation. The complex genomic organisation and pronounced plasticity of T. cruzi complicate the identification of novel therapeutic targets. The abundance of proteins annotated as hypothetical or of unknown function further obscure critical metabolic pathways that could serve as druggable targets. In this context, the discovery of new drugs for CD strategically integrates phenotypic, target-based, and computational approaches, all of which require rigorous validation through preclinical in vitro and in vivo studies. Although modern approaches have yielded several promising lead compounds, successfully controlling CD will also depend on overcoming socioeconomic and access-related barriers to ensure that new therapies reach the populations most affected by this neglected tropical disease.
BACKGROUND Tuberculosis/human immunodeficiency virus (TB/HIV) coinfection is associated with advanced HIV disease and variable responses to antiretroviral therapy (ART). OBJECTIVES We examined whether baseline HIV severity markers, ART regimes, or human genetic variants influenced HIV-1 virologic suppression in HIV-associated TB. METHODS We included TB/HIV participants from Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil study, who received standard TB therapy and antiretroviral treatment. The primary endpoint was HIV-1 virologic suppression (≤ 1,000 copies/mL); Baseline characteristics, viral load (VL), CD4 cell count, timing of ART initiation, and ART regimens were included. We genotyped UGT1A1 (rs887829; integrase strand transfer inhibitor-related) and CYP2B6 [rs3745274, rs28399499, rs4803419; efavirenz (EFZ)-related]; all have defined normal, intermediate, and slow genotypes. Genotyping was performed by MassARRAY iPLEX Gold; Kaplan-Meier curves compared time-to-suppression with log-rank tests; Cox proportional hazards models estimated hazard ratios. FINDINGS Among 194 participants, 68% (n = 132) achieved virologic suppression (≤ 1,000 copies/mL). Median time-to-suppression: 84 days [95% confidence interval (CI): 42-125]. Participants with higher baseline viral load (BVL) (≥ 5 log10 copies/mL) had delayed suppression compared with those with lower VL (< 5 log10; log-rank χ² = 75.9; p < 0.001). Individuals with CD4 ≤ 200 cells/µL suppressed more slowly than those with CD4 > 200 cells/µL (log-rank χ² = 29.6; p < 0.001). Participants starting ART before TB treatment achieved suppression faster than ART-naïve individuals (32 vs. 147 days; log-rank χ² = 48.5; p < 0.001). Higher BVL was associated with reduced hazard of suppression [adjusted hazard ratio (aHR) = 0.67; 95% CI: 0.61-0.75], while higher baseline CD4 count increased the hazard of suppression (per 100 cells/µL: aHR = 1.11; 95% CI: 1.01-1.21). ART-naïve status was associated with lower hazard of suppression in univariate analysis (Hazard Ratio = 0.51; 95% CI: 0.36-0.72) but not after adjustment. ART regimen class and pharmacogenetic metabolizer profiles were not significantly associated with virologic suppression. MAIN CONCLUSIONS BVL and CD4 count were the strongest determinants of virologic suppression in TB/HIV patients. Suppression rates were low, and neither ART regimen nor pharmacogenetic profiles significantly influenced the likelihood of suppression.
BACKGROUND:Dengue outbreaks pose a significant public health risk in Suriname, with challenges in mosquito surveillance and limited data on insecticide resistance hampering control efforts. OBJECTIVES:To investigate the resistance status and involved mechanisms of Aedes aegypti mosquitoes for malathion and λ-cyhalothrin insecticides. METHODS:The Centres for Disease Control and Prevention (CDC) bottle bioassay was used to test the resistance phenotypic status of Ae. aegypti while the occurrence and frequency of knockdown resistance (kdr) mutations were accessed by TaqMan genotype assays for the sites 410L (Valine/Leucine), 1016I (Valine/Isoleucine), and 1534C (Phenylalanine/Cysteine). FINDINGS:Results showed resistance to malathion in the Blauwgrond population, with other regions exhibiting reduced susceptibility based on mortality rates between 89% and 94%. Very low mortality rates indicate resistance to λ-cyhalothrin in all tested areas. Knockdown resistance (kdr) mutations were detected at high frequencies. The triple homozygous kdr genotype leucine/leucine, isoleucine/isoleucine, cysteine/cysteine (LL/II/CC) predominated (84.2%), while the wild-type genotype was found only in 1.8% of the samples. MAIN CONCLUSION:This study reports the first detection of malathion resistance in Ae. aegypti from Suriname and confirms high levels of resistance to λ-cyhalothrin, possibly driven by kdr gene mutations. The results emphasise the importance of sustained surveillance and continued research on resistance mechanisms to guide effective and evidence-based vector control strategies.
BACKGROUND:Chagas disease (CD) and Leishmaniasis, caused by Trypanosoma cruzi and Leishmania species, are treated with outdated drugs that are toxic and have limited efficacy. New therapeutic alternatives are therefore needed. Natural products are valuable scaffolds for drug discovery, and Asteraceae species exhibit microbicidal activity. OBJECTIVES:This study evaluated the antiparasitic activity and selectivity of two Asteraceae species, Chromolaena hookeriana and Campuloclinium macrocephalum, against trypanosomatids. METHODS:C. hookeriana and C. macrocephalum extracts were profiled by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), and their cytotoxicity and antiparasitic activity were evaluated against multiple forms and strains of T. cruzi and Leishmania amazonensis (L. amazonensis) in 2D and 3D cultures. FINDINGS:UHPLC-MS/MS revealed predominantly pentacyclic triterpenoids in C. macrocephalum, including ursolic and oleanolic acids (negative mode) and lupeol derivatives (positive mode). C. macrocephalum was more effective than Benznidazole (Bz) (EC50 = 1.17 vs 4.47 µg/mL) against epimastigotes and nine times more potent against trypomastigotes (EC50 = 0.38 vs 3.5 µg/mL). Both extracts matched Bz activity on intracellular T. cruzi but exhibited time-dependent cytotoxicity. They also showed similar effectiveness to miltefosine (Mt) against L. amazonensis amastigotes (EC50 = 0.36-0.70 µg/mL). MAIN CONCLUSIONS:The chemical profile supports the stronger antiparasitic activity of C. macrocephalum, likely linked to triterpenoids, and highlights Asteraceae extracts as promising candidates for drug discovery against neglected tropical diseases (NTDs).
BACKGROUND Dengue has long been considered a neglected disease since its emergence. However, in recent years, the number of cases has increased significantly, particularly in tropical countries across Latin America. OBJECTIVE This study aims to describe the evolution of dengue during the 2023 outbreak in Peru. METHODS Here, we describe the analysis of 245 positive samples for dengue carried out by the National Institute of Health (INS) of Peru through genomic surveillance protocols, and analyse the evolution of serotypes and genotypes during the outbreak. FINDINGS We analysed 245 dengue-positive samples sequenced by the INS of Peru during the 2023 outbreak to describe the evolutionary dynamics of circulating serotypes. We identified dengue virus (DENV)-1 genotype V (lineages D.1 and D.2), DENV-2 genotype II (Cosmopolitan, lineage F.1.2), and DENV-3 genotype III (lineage B.3). Phylogenetic and population-structure analyses revealed multiple introductions, rapid diversification, and wide dispersal of DENV-1 and DENV-2 across Peru, while DENV-3III showed a localised introduction in Lima with phylogenetic links to the Caribbean. Our findings provide the most comprehensive genomic characterisation to date of dengue circulation in Peru in 2023 year, and highlight the need for sustained genomic surveillance. MAIN CONCLUSION To summarise, the three serotypes of dengue in Peru show a dynamic diversity that becomes necessary to understand, to improve public health decisions by authorities.
Wolbachia-based vector control has emerged as one of the most innovative biological interventions in contemporary dengue prevention, offering an ecologically grounded alternative to insecticide-dependent strategies. By exploiting cytoplasmic mosquitoes can suppress or replace competent vector populations, thereby reducing dengue virus (DENV) transmission potential. Large-scale field deployments in Australia, Indonesia and Brazil have reported substantial reductions in dengue incidence approaching 70-80% in selected settings, demonstrating proof of principle. However, the long-term sustainability of this approach remains uncertain. Accumulating field evidence indicates that Wolbachia persistence and epidemiological impact are highly context-dependent, shaped by mosquito fitness, strain-host compatibility, climatic sensitivity, urban ecology and operational continuity. Experiences from Vietnam, Thailand and parts of Brazil illustrate that stable introgression cannot be assumed and may decline when releases are interrupted or ecological conditions are unfavourable. Operational constraints - including mass-rearing quality, dispersal limitations, surveillance intensity and financial costs - pose additional scalability challenges. This perspective critically evaluates whether Wolbachia can function as a sustainable dengue control strategy across diverse endemic settings. We argue that Wolbachia should not be framed as a self-sustaining or stand-alone solution, but rather as a maintenance-dependent, context-sensitive intervention whose effectiveness relies on ecological tailoring, thermotolerant strains, robust post-release surveillance and integration within adaptive integrated vector management (IVM) frameworks. When deployed judiciously alongside complementary control measures, Wolbachia has the potential to become an important - though not exclusive - pillar of long-term dengue control.
