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Memorias Do Instituto Oswaldo Cruz[JOURNAL]

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The impact of probiotic administration in vivo on peritoneal mouse macrophages infected by Leishmania amazonensis ex vivo.

Broeck LVD, de Azevedo RS, Fiuza LFA … +6 more , Batista MM, Cascabulho CM, Van de Velde E, Van Calenbergh S, Caljon G, Soeiro MNC

Mem Inst Oswaldo Cruz · 2025 · PMID 40990794 · Full text

BACKGROUND: The microbiome is fundamental in the host's immunobiology and dysbiosis leads to pathological conditions, potentially affecting parasitic diseases. OBJECTIVES: To investigate how oral probiotics affect infect... BACKGROUND: The microbiome is fundamental in the host's immunobiology and dysbiosis leads to pathological conditions, potentially affecting parasitic diseases. OBJECTIVES: To investigate how oral probiotics affect infection and antiparasitic treatment of Leishmania in macrophages. METHODS: Swiss mice were orally treated with 109 colony forming units (CFU) multi- or single-strain probiotic formulations (PB8, Bifilac), their peritoneal mouse macrophages (PMMs) were obtained and infected ex vivo with L. amazonensis amastigotes. The effects of prior probiotic administration on ex vivo infection and treatment responses to 1 µM miltefosine and N 6-methyltubercidin were evaluated. Flow cytometry measured the inflammatory mediator release in the supernatant of the PMMs. FINDINGS AND MAIN CONCLUSIONS: PB8 or Bifilac administration significantly reduced (p < 0.05) ex vivo infection of PMMs from male mice by 27% and 12%, respectively. No gender-dependent effect of probiotics was observed. No improved antiparasitic activity of 1 µM miltefosine or N 6-methyltubercidin was observed in probiotic-treated PMMs. Ex vivo Leishmania infection stimulated tumour necrosis factor (TNF), MCP-1, and interleukin-6 (IL-6) production by PMMs (p < 0.05). A trend of increase was recorded with elevated levels of TNF and IL-6 in PB8-treated male groups (around 43 and 52%, respectively) but were not statistically significant. Collectively, probiotic treatment of mice influences Leishmania infection in PMMs. Clinical applications in leishmaniasis warrant further studies.

Phospholipids and phospholipase A1 as antigens during the course of experimental Trypanosoma cruzi infection.

Bott E, López SA, Gimenez G … +2 more , Solana ME, Belaunzarán ML

Mem Inst Oswaldo Cruz · 2025 · PMID 40960771 · Full text

BACKGROUND: Trypanosoma cruzi, causative agent of Chagas disease (CD), remains a public health problem in Latin America and is emerging in non-endemic areas. Phospholipids (PL) are essential components of biomembranes an... BACKGROUND: Trypanosoma cruzi, causative agent of Chagas disease (CD), remains a public health problem in Latin America and is emerging in non-endemic areas. Phospholipids (PL) are essential components of biomembranes and their enzymatic modification by phospholipases yields bioactive lipids that modulate immune responses. Anti-PL antibodies have been associated with autoimmune diseases and inflammation, potentially influencing CD pathology by recognising PL and PL-binding proteins. T. cruzi Phospholipase A1 (TcPLA1) hydrolyses membrane PL and participates in parasite-host cell interactions. OBJECTIVES: This study evaluated IgM and IgG antibody responses against phosphatidylcholine, phosphatidylethanolamine, and their derived lysophospholipids (LPL), as well as recombinant TcPLA1, during experimental T. cruzi infection with two strains: RA (high virulence) and K98 (low virulence). It also aimed to predict the recognition capacity of TcPLA1 by CD patients using in silico analysis. METHODS: Antibody responses were analysed by enzyme-linked immunosorbent assay (ELISA) using different PL and recombinant TcPLA1 as antigens. Lytic activity assays were performed to evaluate the functional impact of anti-PL antibodies. The CHAGASTOPE resource was used to predict TcPLA1 antigenicity. FINDINGS: This study identified IgM and IgG antibodies against PL, LPL and TcPLA1 during experimental T. cruzi infection. Different amino acid sequences of TcPLA1 showed stronger antigenic recognition by CD patient's sera. MAIN CONCLUSIONS: The presence of these antibodies suggests their involvement in the pathogenesis of CD and their potential as markers for disease monitoring and prognosis.

Concomitant use of anti-leishmanial therapy and antibacterial prophylaxis reduces plasma LPS levels and improves several aspects of experimental Leishmania infantum infection in golden hamsters.

Santos-Oliveira JR, Silva-Freitas ML, Cappato MDS … +10 more , Marques-Paulo E, Paiva MB, Soares SR, de Oliveira DA, Lopes-Torres EJ, Pelajo-Machado M, Pinto EF, Lindoso JAL, Goto H, Da-Cruz AM

Mem Inst Oswaldo Cruz · 2025 · PMID 40929455 · Full text

BACKGROUND: Parasite antigens and plasma lipopolysaccharide (LPS) levels from luminal origin in visceral leishmaniasis (VL) patients are correlated with cellular activation and low CD4+T cell counts. OBJECTIVES: Our aim... BACKGROUND: Parasite antigens and plasma lipopolysaccharide (LPS) levels from luminal origin in visceral leishmaniasis (VL) patients are correlated with cellular activation and low CD4+T cell counts. OBJECTIVES: Our aim was to verify whether Leishmania infantum infection damages the intestinal barrier and whether combination antimonial/antibiotic contributes to the reduction of LPS levels and immune activation. METHODS: Golden hamsters were grouped in: G1-uninfected; G2-infected with L. infantum; and G3/G4 and G5-infected, treated with antimonial, antibiotic or both drugs, respectively. The treatment initiated 45 days post infection (dpi), daily by 10 days. FINDINGS: G2, G3, and G4 animals showed a significant increase in spleen weight compared to G1. An elevated parasite load was observed in G2, unlike the G3, G4, and especially, G5, whose decrease was significant at 120 dpi. Intestinal mucosal alterations and elevated LPS levels were observed in G2 group. However, G3, G4 and G5 animals showed lower LPS levels than G2. Moreover, G4 and G5 presented higher CD4+T-cell percentages and lower activation levels than G2 and G3, either at 60 or 101-120 dpi. MAIN CONCLUSIONS: Our results showed evidence of bacterial translocation in experimental VL and that the concomitant use of antimonial and antibiotic may reduce LPS levels, along with an improvement of the immunosuppression and reduction of lymphocyte activation.

Opening the conversation in peer review, finally.

Brandão AA, Vicente ACP

Mem Inst Oswaldo Cruz · 2025 · PMID 40929382 · Full text

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Beyond the first case of Chagas disease: the Berenice strain as a model for understanding long-term Trypanosoma cruzi infection.

Bahia D, Costa-Martins AGD, Pereira WB … +3 more , Marchiano FS, Yonamine CM, da Silveira JF

Mem Inst Oswaldo Cruz · 2025 · PMID 40699059 · Full text

Here, we review the key findings on the genetic characterisation of Berenice strains of Trypanosoma cruzi isolated from a 2-year-old child, Berenice, the first patient with Chagas disease described in the literature in 1... Here, we review the key findings on the genetic characterisation of Berenice strains of Trypanosoma cruzi isolated from a 2-year-old child, Berenice, the first patient with Chagas disease described in the literature in 1909. Be-62 and Be-78 strains were isolated from Berenice when she was 55 and 71 years old, respectively. They were comparatively studied, revealing several important genetic differences that indicated the presence of heterogeneous T. cruzi populations within the infection of patient Berenice. Recently, a high-quality whole-genome assembly was generated using the strain Be-62, which was isolated in 1962. Even after decades-long persistence in the patient, there is a high level of conservation in synteny between Be-62 and different T. cruzi lineages. It has been suggested that T. cruzi diversity is driven by the evolution of multigene families encoding target antigens of anti-parasite immune responses, located in disruptive regions of the genome. Most studies of Berenice have been conducted on genomic bulk samples, resulting in a biased analysis that favours the dominant genotype. Single-cell omics technologies enable us to study the genetic diversity within an infection caused by protozoan parasites in detail. Sequencing individual genomes of Berenice strains will be the key to elucidating the population structure of individual infections, the dynamics of parasite populations, and adaptive mechanisms.

Population structure of Anopheles (Kerteszia) bellator in the Brazilian Atlantic Forest.

Pinheiro IC, Voges K, Yoshikawa AAG … +4 more , Cardoso SF, Carvalho AB, Pitaluga AN, Rona LDP

Mem Inst Oswaldo Cruz · 2025 · PMID 40699058 · Full text

BACKGROUND: Malaria, caused by protozoa of the genus Plasmodium and transmitted by Anopheles mosquitoes, remains a significant global health concern. In 2022, approximately 249 million malaria cases were reported worldwi... BACKGROUND: Malaria, caused by protozoa of the genus Plasmodium and transmitted by Anopheles mosquitoes, remains a significant global health concern. In 2022, approximately 249 million malaria cases were reported worldwide, including 163,000 in Brazil. In the Atlantic Forest, An. bellator and An. cruzii are the primary vectors of malaria transmission. OBJECTIVES: This study used a cytochrome C oxidase I (COI) gene fragment to investigate the genetic population structure of An. bellator in the Brazilian Atlantic Forest. METHODS: Mosquitoes were collected from Itaparica (BA), Camacan (BA), Ilha Grande (RJ), Antonina (PR), Ilha do Mel (PR), and Florianópolis (SC). They were morphologically identified and individually photographed. DNA was extracted, and a COI gene fragment was amplified using polymerase chain reaction (PCR), purified, and sequenced. Additionally, sequences from Trinidad, Colombia, and São Paulo State, obtained from GenBank, were included in the analysis. These sequences were used for molecular identification, genetic variation analysis within and between populations, and phylogenetic assessment. FINDINGS: The analysis revealed that the An. bellator population from Trinidad is genetically distinct from all analysed populations. Furthermore, the Camacan population forms a distinct group separate from the Itaparica population, with both differing from the southern Brazilian populations and that of Colombia. Additionally, the data suggest that the southern Brazilian populations may represent distinct incipient species, particularly the Ilha Grande sample. This divergence is strongly supported by fixed genetic differences, high F ST values, and genealogical analysis. MAIN CONCLUSION: The findings provide strong evidence of cryptic species within An. bellator, which appears to consist of at least three sibling groups: one from Trinidad and Tobago; An. bellator B, which includes sequences from Camacan; and An. bellator A, which contains sequences from Colombia, Itaparica, Ilha Grande, São Paulo, Florianópolis, Ilha do Mel, and Antonina. Despite its geographical proximity to Camacan (280 km), the Itaparica population clusters with southern populations ~2,000 km away, while remaining genetically distinct from them. Additionally, the study identified higher F ST values between the Ilha Grande population and other southern Brazilian samples, highlighting further genetic divergence.

Chagas disease in Brazil: new challenges and perspectives for old problems.

Santos FLN, Costa VMD, Silva RAE

Mem Inst Oswaldo Cruz · 2025 · PMID 40699036 · Full text

Mandatory notification of chronic Chagas disease (CD) is vital for improving public health responses in Brazil, where millions are affected. Implemented nationally in 2020 and supported by the "e-SUS Notifica" platform i... Mandatory notification of chronic Chagas disease (CD) is vital for improving public health responses in Brazil, where millions are affected. Implemented nationally in 2020 and supported by the "e-SUS Notifica" platform in 2023, this system enables accurate disease burden assessment, early diagnosis, and treatment planning. It facilitates resource allocation and targeted interventions, addressing gaps in surveillance and care. Expanding these efforts and ensuring access to treatment is essential for Brazil's goal of eliminating CD by 2030.

A 20-month longitudinal study to evaluate humoral and cellular immunity after COVID-19 vaccines.

Sobrinho WBS, Salgado BB, Barbosa ARC … +6 more , Passos VA, Vieira LP, do Nascimento LD, Lalwani JDB, Lalwani PJ, Nogueira PA

Mem Inst Oswaldo Cruz · 2025 · PMID 40699035 · Full text

BACKGROUND: The effectiveness of coronavirus disease 2019 (COVID-19) vaccines is well established; however, the long-term durability of vaccine-induced immunity remains to be fully elucidated. OBJECTIVES: This study long... BACKGROUND: The effectiveness of coronavirus disease 2019 (COVID-19) vaccines is well established; however, the long-term durability of vaccine-induced immunity remains to be fully elucidated. OBJECTIVES: This study longitudinally compared humoral and cellular immune responses in two groups: G1, who received two doses of Sinovac-CoronaVac, and G2, who received two doses of AstraZeneca-Oxford, both subsequently boosted with Pfizer. METHODS: Immune responses were assessed at five time points: P1 (prior to the second dose), P2 (90-180 days after the second dose), P3 (pre-booster, six-eight months post-second dose), P4 (90-180 days post-booster), and P5 (180-270 days post-booster). Anti-Spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), while IFNγ-producing cells in response to Spike peptides were quantified using enzyme-linked immune absorbent spot (ELISPOT). IgG subclasses were analysed in a subset of samples. RESULTS: Following the first dose, Sinovac-CoronaVac induced lower anti-Spike IgG levels than AstraZeneca-Oxford, though levels equalised after the second dose. After the Pfizer booster, anti-Spike IgG levels remained elevated for up to six months in both groups. IgG1 was predominant in both groups, with occasional expression of IgG2 and IgG4. The mean frequency of IFNγ-producing cells was lower in the Sinovac-CoronaVac group before and up to six months after the second dose, compared to AstraZeneca-Oxford. However, post-Pfizer booster, both means became comparable. Between 90-180 days post-booster, the Sinovac-CoronaVac + Pfizer group exhibited a statistically significant decline in IFNγ-producing cells relative to the AstraZeneca-Oxford + Pfizer group. By P5, over half of individuals in the Sinovac-CoronaVac + Pfizer group demonstrated no detectable cellular response. MAIN CONCLUSIONS: High antibody levels were maintained for up to six months following both homologous and heterologous vaccination. However, cellular immunity declined more markedly in the Sinovac-CoronaVac + Pfizer group, resulting in a higher proportion of non-responders. These findings underscore the importance of tailored booster strategies to sustain protective immunity against COVID-19.

Susceptibility of Aedes aegypti to spinosad larvicide and space spray adulticides in Brazil.

Dias LDS, Martins AJ, Rodovalho CM … +7 more , Bellinato DF, de Ázara TMF, do Nascimento AMR, Corbel V, Macoris MLDG, Andrighetti MTM, Lima JBP

Mem Inst Oswaldo Cruz · 2025 · PMID 40667965 · Full text

BACKGROUND: Insecticides play a critical role in controlling insect vectors, particularly during epidemics. Effective chemical control relies on the robust monitoring of insecticide resistance to guide evidence-based dec... BACKGROUND: Insecticides play a critical role in controlling insect vectors, particularly during epidemics. Effective chemical control relies on the robust monitoring of insecticide resistance to guide evidence-based decision-making in vector control strategies. OBJECTIVES: This study assessed the susceptibility of Aedes aegypti, the primary vector of dengue, Zika, and Chikungunya viruses, to various larvicides and adulticides deployed during Brazil's national campaigns from 2020 to 2023. METHODS: Mosquito collection was performed in 46 Brazilian municipalities using ovitraps. Eggs were transported to FIOCRUZ to establish the F1 and F2 generations. The Rockefeller strain was employed to determine the discriminating concentrations (DC) for the larvicide Natular™ 20EC (spinosad) and the adulticides Cielo™ (imidacloprid and prallethrin) and Fludora® Fusion (clothianidin and deltamethrin) using a modified World Health Organization (WHO) bottle bioassay. These DCs were then used to estimate the resistance status of Ae. aegypti populations in the tested formulations. Resistance intensity was assessed by exposing mosquitoes to five, 10, or 20 times the DC concentrations. FINDINGS: All Ae. aegypti populations were fully susceptible to larvicide spinosad. However, resistance to both adulticide formulations was detected based on WHO criteria (mortality rates < 90%). Intensity assays revealed high to very high resistance to combined adulticide products. MAIN CONCLUSIONS: Our findings indicate the full susceptibility of Ae. aegypti populations in Brazil to spinosad, but substantial resistance to adulticides used in space spraying and residual applications, likely due to pre-existing pyrethroid resistance. However, the specific contributions of each active ingredient remain unclear, owing to the evaluation of the combined formulations. The efficacy of both traditional and alternative vector control strategies must be continuously evaluated and closely monitored to ensure the real-time assessment of their performance. For chemical control, future studies should prioritise the assessment of combination products in field trials, refining laboratory assays, and sustaining insecticide resistance surveillance to optimise control efforts in Brazil.

Expanded range of Haemagogus leucocelaenus in yellow fever hotspots: new findings from Santa Catarina State, southern Brazil.

Cardoso SF, Pinheiro IC, Kikuti LAO … +3 more , Yoshikawa AAG, Pitaluga AN, Rona LDP

Mem Inst Oswaldo Cruz · 2025 · PMID 40638508 · Full text

BACKGROUND: The Haemagogus genus includes nine mosquito species reported in Brazil, each with distinct distribution patterns. Haemagogus leucocelaenus, a major yellow fever vector, is widely distributed throughout the co... BACKGROUND: The Haemagogus genus includes nine mosquito species reported in Brazil, each with distinct distribution patterns. Haemagogus leucocelaenus, a major yellow fever vector, is widely distributed throughout the country, while Haemagogus leucophoebus, a morphologically similar species, has only been identified in Acre State. OBJECTIVES: This study evaluated the presence of Haemagogus species in southern Brazil by comparing their morphological and molecular characteristics. METHODS: Mosquitoes were collected from five municipalities in southern Santa Catarina State, Brazil. Each specimen was identified morphologically and photographed. Genomic DNA was extracted, and a Cytochrome C Oxidase Subunit I (COI) gene fragment was amplified using polymerase chain reaction (PCR). The positive amplicons were sequenced for molecular identification. FINDINGS: New records of Hg. leucocelaenus were found in Santa Rosa de Lima, Rio Fortuna, Braço do Norte, São Martinho, and Pedras Grandes, located at the southern edge of the Atlantic Forest. This study expands the known distribution of Hg. leucocelaenus, the only Haemagogus species identified in the area, with 91 specimens collected. Although some specimens exhibited morphological variations that might lead to misidentification as Hg. leucophoebus, molecular identification confirmed that all were Hg. leucocelaenus. MAIN CONCLUSIONS: This study is the first to report Hg. leucocelaenus in Santa Catarina, Brazil, and provides DNA barcoding sequences from southern Brazil. This method offers a reliable alternative for species identification, especially when combined with morphological analysis. Further molecular studies are needed to determine whether the morphological variations observed indicate intraspecific differences.

Orthoflavivirus nilense surveillance in the State of Piauí, northeastern Brazil.

Lobato OL, Nogueira TDS, Lima TET … +20 more , Andrade FJDC, de Macedo MGG, Pereira RS, Xavier J, Amorim MR, Barbosa PP, da Rocha AS, Silva SDC, Alcantara LCJ, de Souza WM, Proenca-Modena JL, Costa ÉA, Lima Neto AS, Feitosa LCS, Pires E Cruz MDS, Silva SMMS, Baêta SAF, Vieira MADCES, Deem SL, Catenacci LS

Mem Inst Oswaldo Cruz · 2025 · PMID 40638500 · Full text

BACKGROUND: The cycle of the Orthoflavivirus nilense (West Nile virus - WNV) involves birds and mosquitoes, while humans and equids serve as terminal hosts. In 2014, the first human case in Brazil was confirmed in Piauí... BACKGROUND: The cycle of the Orthoflavivirus nilense (West Nile virus - WNV) involves birds and mosquitoes, while humans and equids serve as terminal hosts. In 2014, the first human case in Brazil was confirmed in Piauí State. OBJECTIVES: To investigate the presence of WNV in birds, mosquitoes, and equids in municipalities of Piauí. METHODS: Collections were carried out following recommendations from the Ministry of Health of Brazil, in 11 municipalities (all with human cases or bird mortality), where biological samples were collected from birds, mosquitoes, and equids. The Viral RNA extraction was performed using a commercial kit, following the manufacturers' recommendations; samples were subjected to reverse transcription and polymerase chain reaction, with specific primers for WNV. FINDINGS: 2,706 samples were collected (636 birds, belonging to 99 species; 420 equids, and 1,650 mosquitoes, grouped into 346 pools, totaling 18 species. No collected sample yielded a positive result, corroborating with other studies showing the difficulty of molecular detection of WNV in healthy animals, which may explain the non-detection, in addition to the delayed diagnosis in humans. MAIN CONCLUSIONS: A local investigation involving suspected cases is still recommended in animals; however, in locations with late diagnosis in humans we suggest a serological survey of asymptomatic birds and equids.

Neurobasal medium enhances titan cell formation in Cryptococcus spp.

Godoy J, Avellar-Moura I, Soares J … +2 more , Pontes B, Frases S

Mem Inst Oswaldo Cruz · 2025 · PMID 40608595 · Full text

BACKGROUND: Titan cells in Cryptococcus species play a critical role in fungal virulence by resisting oxidative stress, phagocytosis, and antifungal treatments. Developing reliable methods to induce titan cells is crucia... BACKGROUND: Titan cells in Cryptococcus species play a critical role in fungal virulence by resisting oxidative stress, phagocytosis, and antifungal treatments. Developing reliable methods to induce titan cells is crucial for understanding the mechanisms of Cryptococcus pathogenesis. OBJECTIVES: In this study we report an unexpected discovery of a simple in vitro induction of titan cells in Cryptococcus neoformans and Cryptococcus gattii using Neurobasal™ (NB) medium. METHODS AND FINDINGS: By employing established in vitro culture methods, we demonstrate a significantly higher capacity for titan cell formation in Cryptococcus spp. Cells grown in complete NB medium exhibited larger cell bodies, increased capsule sizes, and a higher percentage of titan cells compared to those grown in minimal medium (MM). NB medium without the B27 supplement significantly impacted titan cell formation. MAIN CONCLUSIONS: Our findings indicate that NB medium, originally developed for neuronal cell cultures, is a useful tool for studying titan cell biology. This is particularly relevant given the association between titan cells and the central nervous system, highlighting their potential role in Cryptococcus pathogenesis.

Identification of polymorphisms associated with attenuation of Vif and Vpr in HIV-1 Elite Controllers.

de Azevedo SSD, Côrtes FH, Morgado MG … +5 more , Hoagland B, Villela LM, Grinsztejn B, Veloso VG, Bello G

Mem Inst Oswaldo Cruz · 2025 · PMID 40608594 · Full text

BACKGROUND: Elite controllers (ECs) are a rare subset of individuals who naturally suppress human immunodeficiency virus type 1 (HIV-1) replication in the absence of antiretroviral therapy. Specific polymorphisms in the... BACKGROUND: Elite controllers (ECs) are a rare subset of individuals who naturally suppress human immunodeficiency virus type 1 (HIV-1) replication in the absence of antiretroviral therapy. Specific polymorphisms in the accessory proteins Vif and Vpr have been associated with diminished viral fitness in vitro and are more frequently detected in ECs compared to other individuals infected with HIV-1. OBJECTIVE: To assess the frequency of gross genetic defects or polymorphisms that may attenuate the function of the HIV-1 accessory proteins Vif and Vpr within the proviral quasispecies of ECs. METHODS: We performed single-genome amplification (SGA) and sequence analysis of the proviral quasispecies of the accessory genes vif and vpr in samples obtained from eight ECs with over 10 years of suppressive viral control and no evidence of disease progression. FINDINGS: In subjects EC11, EC38 and EC52, most proviral clones encode full-length, intact vif and vpr open reading frames without known attenuating polymorphisms. Subject EC35 displayed stop codons in a substantial fraction of vif (33%) and vpr (67%) proviral clones. Subject EC36 exhibited the attenuating polymorphisms Vpr-Q3R + R77Q combined in all proviral clones. Subject EC17 showed stop codons in 20-30% of vif-vpr proviral clones, hypermutated sequences in 20% of vif proviral clones, and the attenuating polymorphism Vpr-R77Q in all proviral clones. Subject EC19 presented stop codons in 8-17% of vif-vpr proviral sequences, hypermutated sequences in 25% of vif-vpr proviral clones, and the polymorphisms Vif-R132S+Ins61(EDK) and Vpr-R77Q in all clones analysed. Finally, subject EC42 displayed stop codons in 25-38% of vif-vpr proviral sequences, hypermutated sequences in 25% of vif proviral clones, and the polymorphisms Vif-T20A+R132S and Vpr-R77Q in most (> 80%) proviral clones. MAIN CONCLUSIONS: Mutations associated with attenuation of HIV-1 Vif and/or Vpr functions may contribute to the long-term control of viral replication and disease progression in certain ECs.

Genome characterisation of the first isolate of human enterovirus c99 from an acute flaccid paralysis case in Brazil.

Sauthier JT, Dias JB, Ferreira CS … +14 more , Gomes BON, Fraga KA, Pereira EC, da Silva BM, Lima LF, Gonçalves IMDS, de Souza AAA, de Melo MAF, Dos Santos AAC, Müller BLA, Moreira ADS, Resende PC, Volotão EM, da Silva EE

Mem Inst Oswaldo Cruz · 2025 · PMID 40608593 · Full text

BACKGROUND: Human enterovirus C99 (HEV-C99) is a member of the species Enterovirus C. Currently, three complete genomes of HEV-C99 were reported in Brazil, all obtained from children with gastroenteritis symptoms. Notwit... BACKGROUND: Human enterovirus C99 (HEV-C99) is a member of the species Enterovirus C. Currently, three complete genomes of HEV-C99 were reported in Brazil, all obtained from children with gastroenteritis symptoms. Notwithstanding, no HEV-C99 complete genome associated with AFP cases in Brazil have been analysed so far. OBJECTIVES: In light of this, molecular characterisation of an HEV-C99 isolated from a case of acute flaccid paralysis (AFP) in Brazil was carried out. METHODS: In 2005, an HEV-C99 strain was isolated from a 2-year-old female child in Santa Catarina State, Brazil, showing classic symptoms of AFP. Stool sample was inoculated into specific cell cultures. Viral RNA was extracted, and polymerase chain reaction (PCR) were performed to amplify the VP1 gene; the sequence was analysed for molecular identification. Subsequently, the complete genome was sequenced and analysed, including a phylogenetic analysis of the VP1 gene. FINDINGS: The isolate, denominated HEV-C99/33322/BRA/2005 presented 85.85% identity to other HEV-C99 strains also described in Brazil, subsequently. Besides, the isolate grouped together with HEV-C99 cluster C strains. To our knowledge, this was the first described HEV-C99 isolated from an AFP case in Brazil. MAIN CONCLUSIONS: The data generated in this study bolster the role of HEV-C99 as an etiologic agent of AFP. Furthermore, this research enhances our knowledge regarding the HEV-C99 genetic diversity.

Trichophyton rubrum inhibits Candida albicans filamentation and its gene expression when grown in biofilms in vitro.

Bila NM, Vaso CO, Belizário JA … +5 more , Biasioli MMS, Fusco-Almeida AM, Martinez LR, Costa-Orlandi CB, Mendes-Giannini MJS

Mem Inst Oswaldo Cruz · 2025 · PMID 40608592 · Full text

BACKGROUND: Dermatomycoses are caused by various fungi, including dermatophytes and Candida species, which are the most prevalent in isolated or associated forms. A great number of virulence factors expressed by these fu... BACKGROUND: Dermatomycoses are caused by various fungi, including dermatophytes and Candida species, which are the most prevalent in isolated or associated forms. A great number of virulence factors expressed by these fungi are important for infection, and biofilm formation leads to the persistence of these infections. OBJECTIVES: This work aimed to evaluate the dynamics of Candida albicans filamentation genes in biofilms formed by Candida albicans and Trichophyton rubrum. METHODS: The effect of the supernatants on the biofilms was assessed by XTT reduction assay, confocal microscopy, and gene expression profile analysis by real-time polymerase chain reaction (RT-PCR). FINDINGS: The supernatants did not reduce the metabolic activities or damage the topography of the monospecies biofilms but caused a reduction in their thickness. The filamentation of C. albicans was inhibited when both fungi were cultivated directly. The filamentation genes studied (CPH1, HWP1, and EFG1) were negatively modulated in C. albicans. MAIN CONCLUSIONS: Our findings suggest that the antagonistic relationship shown by T. rubrum against C. albicans may be attributed to alterations of C. albicans filamentous genes.

A multicentre comparative study of serological methods for diagnosing Chagas disease in Brazil.

Ostermayer AL, Medeiros FAC, Iturra JAD … +8 more , de Souza Filho JA, Leony LM, Vasconcelos LCM, Siriano LDR, Tavares SBDN, Belo VS, de Sousa AS, Santos FLN

Mem Inst Oswaldo Cruz · 2025 · PMID 40531673 · Full text

BACKGROUND: Chagas disease (CD), a neglected tropical disease caused by Trypanosoma cruzi, remains a significant often underdiagnosed public health challenge in endemic regions, affecting millions globally. Accurate and... BACKGROUND: Chagas disease (CD), a neglected tropical disease caused by Trypanosoma cruzi, remains a significant often underdiagnosed public health challenge in endemic regions, affecting millions globally. Accurate and timely diagnosis is critical, but the performance of existing diagnostic methods varies widely in sensitivity and specificity. OBJECTIVES: This multicentre study assessed the diagnostic performance of 17 serological assays for detecting anti-T. cruzi antibodies. METHODS: Commercial enzyme immunoassays (EIA), indirect haemagglutination assays (IHA), indirect immunofluorescence assays (IIF), rapid diagnostic tests (RDT), and a chemiluminescent microparticle immunoassay (CMIA) were included in this study. FINDINGS: Some EIA-based tests achieved 100% sensitivity, while IHAs and IIFs demonstrated reduced specificity. CMIA exhibited 100% sensitivity, highlighting its potential as a robust screening tool. Combining EIAs with IHAs or IIFs improved overall sensitivity, often surpassing 99%, although specificity remained variable. Cross-reactivity with other parasitic diseases posed challenges to specificity, particularly in assays employing crude antigens. MAIN CONCLUSIONS: These findings emphasise the importance of tailoring diagnostic tool selection to regional epidemiological contexts and advancing antigen refinement to enhance diagnostic accuracy and accessibility, particularly in resource-limited settings.

Assessing the spatial influence of deforestation on malaria incidence in Pará State, Amazon region, Brazil, 2008-2019.

Garcia CGR, Ribeiro BC, Souza Júnior AS … +4 more , Lima LJP, Póvoa MM, Laporta GZ, Cunha MG

Mem Inst Oswaldo Cruz · 2025 · PMID 40531672 · Full text

BACKGROUND: Malaria transmission is prevalent in tropical regions and is heavily influenced by environmental factors such as deforestation, which is particularly significant in the Brazilian Amazon, especially in Pará St... BACKGROUND: Malaria transmission is prevalent in tropical regions and is heavily influenced by environmental factors such as deforestation, which is particularly significant in the Brazilian Amazon, especially in Pará State. OBJECTIVE: This study aimed to assess the relationship between deforestation indicators and malaria incidence across all 144 municipalities in Pará. METHODS: Using municipal-level data from 2008 to 2019, the study applied geographically weighted regression (GWR) to analyse spatial relationships between malaria incidence and deforestation metrics. These metrics included forest cover loss from the previous year, pastureland, forest cover, fragmentation, urbanisation, and water levels, analysed over three distinct 4-year periods. The study also incorporated poverty levels to examine their influence on municipalities with high malaria risk. FINDINGS: During the study period, the total deforested area in Pará was 30,000 km2, with 679,846 malaria cases reported. Malaria incidence rates varied across municipalities, with stable rates in high-risk areas, and were linked to pastureland, forest loss, fragmentation, and forest cover. The GWR models effectively captured spatial heterogeneity in these interactions. MAIN CONCLUSIONS: Malaria incidence was associated with areas of Pará State experiencing significant forest loss and fragmentation, indicating that changes in forest composition and configuration influence malaria risk.

Prevalence of pfhrp2/pfhrp3 gene deletions among patients with Plasmodium falciparum malaria with false-negative in the HRP2-based rapid diagnostic test in Colombia.

Olivera MJ, Guerra AP, Cortés LJ … +3 more , Suárez-Jurado AG, Ade MP, Cárdenas IM

Mem Inst Oswaldo Cruz · 2025 · PMID 40531671 · Full text

BACKGROUND: In malaria-endemic regions, rapid diagnostic tests (RDTs) play a crucial role in promptly identifying infections, especially in remote areas with limited microscopy services. OBJECTIVES: Conduct a cross-secti... BACKGROUND: In malaria-endemic regions, rapid diagnostic tests (RDTs) play a crucial role in promptly identifying infections, especially in remote areas with limited microscopy services. OBJECTIVES: Conduct a cross-sectional, multi-site study to determine whether the local prevalence of mutations in the Plasmodium falciparum hrp2/3 genes in false-negative RDTs has reached a threshold that might require a local or national change in diagnostic strategy in accordance with the WHO guidelines (2018). METHODS: Individuals were screened for P. falciparum with microscopy and HRP2-based RDT at health facilities. Discordant results between these two tests triggered diagnostic confirmation by polymerase chain reaction (PCR) and detection of the pfhrp2/pfhrp3 genes. FINDINGS: Among the 347 patients included, false negatives constituted 4.61% (16/347). Molecular analysis revealed all 16 false negatives were P. falciparum positive with hrp2 gene present, displaying high polymorphism. However, hrp3 gene deletion was observed in 93.8% (15/16) of these cases. MAIN CONCLUSIONS: The prevalence of false-negative RDTs is low, and these results were not linked to deletions in the hrp2 gene. This suggests that there is no immediate need to modify the RDTs used along the Colombian Pacific Coast. However, molecular surveillance for hrp2 deletions remains crucial to detect any potential increase in prevalence.

X-linked polymorphisms in TLR7 and TLR8 genes are associated with protection against Chikungunya fever.

Gotay WJP, Maciel MSC, Rodrigues RO … +4 more , Cardoso CC, Oliveira CN, Montenegro AFL, Yaochite JNU

Mem Inst Oswaldo Cruz · 2025 · PMID 40531670 · Full text

BACKGROUND: Chikungunya virus (CHIKV) causes an infection that leads to the activation of the innate immune response, triggering receptor pathways such as toll-like receptors (TLRs). OBJECTIVE: The present study aimed to... BACKGROUND: Chikungunya virus (CHIKV) causes an infection that leads to the activation of the innate immune response, triggering receptor pathways such as toll-like receptors (TLRs). OBJECTIVE: The present study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in genes encoding toll-like receptors 3, 7, and 8 and IRF5 in susceptibility to CHIKV infection and persistent joint pain. METHODS: A case-control study was carried out. The study included 121 symptomatic cases, 29 asymptomatic cases, and 182 healthy controls matched for age and sex. Polymorphisms were identified by TaqMan® SNP Genotyping assays. FINDINGS: The G allele of the TLR7 variant (rs3853839 G/C) and the G allele of TLR8 (rs3764879 G/C) were associated with protection against CHIKV infection [adjusted odd ratio (OR) = 0.64; p = 0.02 and adjusted OR = 0.54; p = 0.001, respectively]. Moreover, individuals who presented the G allele in the rs3764879 variant have a greater chance of developing the asymptomatic form (adjusted OR =2.88; p =0.004). The development of persistent joint pain was not associated with any investigated SNPs in positive anti-CHIKV IgG individuals. MAIN CONCLUSIONS: This study identified TLR7 and TLR8 gene polymorphisms as protective factors for Chikungunya infection.

Challenges in developing new tuberculosis vaccines.

Sadigurschi G, Kuschnir MCC, Dos Santos EAP … +9 more , da Silva BRA, Marques CMC, de Andrade RC, Vianna CM, de Barros DG, Mazzi MT, Lago EA, Dos Santos EM, Maia MLS

Mem Inst Oswaldo Cruz · 2025 · PMID 40498907 · Full text

Tuberculosis (TB) is a preventable and curable disease caused by the bacillus Mycobacterium tuberculosis. In 2022, according to the World Health Organisation (WHO), TB was the second leading cause of death worldwide caus... Tuberculosis (TB) is a preventable and curable disease caused by the bacillus Mycobacterium tuberculosis. In 2022, according to the World Health Organisation (WHO), TB was the second leading cause of death worldwide caused by a single infectious agent, after coronavirus disease (COVID-19). Brazil is ranked among the 30 countries with the highest TB burden. Currently, the neonatal Bacillus Calmette-Guérin (BCG) is the only vaccine against TB and offers significant efficacy against disseminated and meningeal disease in children. However, BCG has a limited efficacy in preventing adult-type cavitary TB, reinforcing the need for a new effective vaccine against pulmonary TB. There are currently over 22 TB vaccines under evaluation in clinical trials worldwide. Despite significant advancements, several challenges persist in developing and producing an effective TB vaccine. These include understanding the immune mechanisms that confer protection against M. tuberculosis, identifying immune correlates of protection, defining immune responses in BCG-vaccinated individuals, establishing efficacy endpoints for TB vaccine trials, and ensuring vaccine safety and effectiveness in individuals with human immunodeficiency virus (HIV), among other obstacles. Therefore, this study aims to explore the key obstacles in developing new TB vaccines and potential strategies to overcome them.
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