Performance of Three Commercial Rapid Diagnostic Tests for Detection of IgM and IgG Antibodies Against SARS-CoV-2 Moyra Machado Portilho, Stephane Fraga de Oliveira Tosta, Maysa Pellizzaro, Rosângela Oliveira dos Anjos, Elaine Carvalho de Oliveira, et al. Immunity Inflammation and Disease, 2026 Background Despite widespread vaccination, SARS‐CoV‐2 transmission continues, and serological testing remains relevant for selected diagnostic scenarios and population‐based assessments of antibody responses. Rapid diagnostic tests (RDTs) for SARS‐CoV‐2 antibodies are attractive for field use and decentralized settings, but their diagnostic performance varies and requires independent evaluation. We assessed the performance of three commercially available lateral flow RDTs (PANBIO™ COVID‐19 IgG/IgM Rapid Test Device, Bio‐Manguinhos‐Fiocruz TR COVID‐19 (IgM‐IgG), and Bio‐Manguinhos‐Fiocruz TR DPP® COVID‐19 IgM/IgG) in Salvador, Brazil. Methods Using blind analyses, we evaluated 257 serum samples from RT‐PCR‐confirmed cases and 199 control samples from individuals with other febrile illnesses or healthy donors collected before and during the pandemic. Results Overall sensitivity for IgM or IgG detection was limited across all tests (52%–58%), while specificity was high for two assays (97%–98%) and lower for one (80%). Sensitivity peaked between 11 and 20 days after symptom onset (80%–91%) and declined thereafter. Among 75 vaccinated individuals without prior COVID‐19, antibody positivity ranged from 39% to 55%. Conclusion These findings indicate that the evaluated RDTs had high specificity but insufficient sensitivity for reliable clinical diagnosis or for assessing vaccination status in serological surveys. Our results support cautious use of these assays and highlight the need for more accurate and robust antibody‐based rapid tests to strengthen immunological surveillance and public health preparedness in the post‐pandemic period.
Oral Treatment With Heat Shock Protein 65-Producing Lactococcus lactis Induces Regulatory T Cells, Modulating Inflammatory Response in Leishmania braziliensis Infection Camila Mattos Andrade, Ítalo da Silva Gonçalves, Maria Luiza das Neves Nascimento, Washington Luís Conrado Santos, Vasco Ariston Azevedo, et al. Immunology, 2026 Cutaneous leishmaniasis (CL), a neglected tropical disease prevalent in Brazil, is caused by Leishmania braziliensis (L. braziliensis) and is marked by ulcerative skin lesions and an exacerbated Th1‐driven inflammatory response. This study investigates the therapeutic potential of oral tolerance (OT) induced by a genetically modified strain of Lactococcus lactis (L. lactis) producing heat shock protein 65 (HSP65) from Mycobacterium leprae in a murine model of CL. BALB/c mice were infected with L. braziliensis and treated orally with HSP65‐producing L. lactis or control L. lactis (empty vector) for four consecutive days, starting at 4 weeks post‐infection. Mice receiving HSP65‐producing L. lactis showed reduced lesion size and parasite burden. Cytokine analysis in draining lymph nodes revealed a shift from a pro‐inflammatory IFN‐γ response to an increased IL‐10 production, correlating with milder inflammation and less tissue damage. Additionally, the treatment promoted an increase in regulatory T cells (Tregs), including CD4+CD25+FOXP3+ and CD4+LAP+ (membrane‐associated TGF‐β) cells in the draining lymph nodes. This therapeutic effect was not observed in a more severe model of CL using Leishmania major. This study underscores the potential of oral tolerance induction using HSP65‐producing L. lactis as a promising immunoregulatory therapeutic approach for some chronic inflammatory infections, mainly those that display a primed balance in immune response.
Pharmacological inhibition of key metabolic pathways attenuates Leishmania spp infection in macrophages Elaine Carvalho de Oliveira, Rafael Tibúrcio, Gabriela Duarte, Amanda Lago, Léon de Melo, et al. Plos Neglected Tropical Diseases, 2025 Macrophages represent a fundamental component of the innate immune system that play a critical role in detecting and responding to pathogens as well as danger signals. Leishmania spp. infections lead to a notable alteration in macrophage metabolism, whereby infected cells display heightened energy metabolism that is linked to the integrity of host mitochondria. However, little is known about how different species of Leishmania manipulate host metabolism. Here, we demonstrate that despite differences in their mechanisms for evading host immune responses, L. amazonensis and L. braziliensis induce comparable disruptions in key metabolic pathways. We found that infected macrophages exhibited an overall elevation in energy metabolism regardless of the parasite strain, evidenced by the elevation in glycolysis and oxygen consumption rates, along with increased proton leak and decreased ATP production. We also analyzed the effects of both Leishmania spp. strain infection on mitochondria function, further revealing that infected cells display heightened mitochondrial mass and membrane potential. To investigate the metabolic pathways required for Leishmania amastigotes to persist in BMDMs, we pre-treated cells with small molecule drugs that target major metabolic pathways, revealing that perturbations in several metabolic processes affected parasite survival in a strain-independent manner. Treatments with inhibitors of the oxidative phosphorylation and glycolysis substantially reduced parasite loads. Collectively, our findings suggest that L.amazonensis and L.braziliensis exploit host cell metabolic pathways similarly to survive in macrophages.
Intraperitoneal Administration of 17-DMAG as an Effective Treatment against Leishmania braziliensis Infection in BALB/c Mice: A Preclinical Study Kercia P. Cruz, Antonio L. O. A. Petersen, Marina F. Amorim, Alan G. S. F. Pinho, Luana C. Palma, et al. Pathogens, 2024 Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutaneous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG’s cytotoxic effect on bone marrow-derived macrophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound’s efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction in lesion size and the decrease in parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index = 432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and resulted in parasite clearance from ears and lymph nodes. It also diminished inflammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-γ, TNF) and the regulatory cytokine IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusions: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.
Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis Marcos Ferrante, Bruna Martins Macedo Leite, Lívia Brito Coelho Fontes, Alice Santos Moreira, Élder Muller Nascimento de Almeida, et al. Pharmaceuticals, 2024 In the New World, dogs are considered the main reservoir of visceral leishmaniasis (VL). Due to inefficacies in existing treatments and the lack of an efficient vaccine, dog culling is one of the main strategies used to control disease, making the development of new therapeutic interventions mandatory. We previously showed that Tanespimycin (17-AAG), a Hsp90 inhibitor, demonstrated potential for use in leishmaniasis treatment. The present study aimed to test the safety of 17-AAG in dogs by evaluating plasma pharmacokinetics, dose-proportionality, and the tolerability of 17-AAG in response to a dose-escalation protocol and multiple administrations at a single dose in healthy dogs. Two protocols were used: Study A: four dogs received variable intravenous (IV) doses (50, 100, 150, 200, or 250 mg/m2) of 17-AAG or a placebo (n = 4/dose level), using a cross-over design with a 7-day “wash-out” period; Study B: nine dogs received three IV doses of 150 mg/m2 of 17-AAG administered at 48 h intervals. 17-AAG concentrations were determined by a validated high-performance liquid chromatographic (HPLC) method: linearity (R2 = 0.9964), intra-day precision with a coefficient of variation (CV) ≤ 8%, inter-day precision (CV ≤ 20%), and detection and quantification limits of 12.5 and 25 ng/mL, respectively. In Study A, 17-AAG was generally well tolerated. However, increased levels of liver enzymes–alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT)–and bloody diarrhea were observed in all four dogs receiving the highest dosage of 250 mg/m2. After single doses of 17-AAG (50–250 mg/m2), maximum plasma concentrations (Cmax) ranged between 1405 ± 686 and 9439 ± 991 ng/mL, and the area under the curve (AUC) plotting plasma concentration against time ranged between 1483 ± 694 and 11,902 ± 1962 AUC 0–8 h μg/mL × h, respectively. Cmax and AUC parameters were dose-proportionate between the 50 and 200 mg/m2 doses. Regarding Study B, 17-AAG was found to be well tolerated at multiple doses of 150 mg/m2. Increased levels of liver enzymes–ALT (28.57 ± 4.29 to 173.33 ± 49.56 U/L), AST (27.85 ± 3.80 to 248.20 ± 85.80 U/L), and GGT (1.60 ± 0.06 to 12.70 ± 0.50 U/L)–and bloody diarrhea were observed in only 3/9 of these dogs. After the administration of multiple doses, Cmax and AUC 0–48 h were 5254 ± 2784 μg/mL and 6850 ± 469 μg/mL × h in plasma and 736 ± 294 μg/mL and 7382 ± 1357 μg/mL × h in tissue transudate, respectively. In conclusion, our results demonstrate the potential of 17-AAG in the treatment of CVL, using a regimen of three doses at 150 mg/m2, since it presents the maintenance of high concentrations in subcutaneous interstitial fluid, low toxicity, and reversible hepatotoxicity.
A new experimental model to study shrimp allergy Ivanéia Valeriano Nunes, Camila Mattos Andrade, Priscila Valera Guerra, Mariana Ivo Khouri, Maria Poliana Leite Galantini, et al. Immunology Letters, 2023
