Revista do Instituto de Medicina Tropical de São Paulo
To publish articles dealing with research on tropical diseases and related sciences.
Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
Safety of two-dose schedule of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan) and heterologous additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised and immunocompetent individuals”,
Immunocompromised individuals were considered high-risk for severe disease due to SARS COV-2 infection. This study aimed to describe the safety of two doses of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan), followed by additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised (IC) adults, compared to immunocompetent/healthy (H) individuals. This phase 4, multicenter, open label study included solid organ transplant and hematopoietic stem cell transplant recipients, cancer patients and people with inborn errors of immunity with defects in antibody production, rheumatic, end-stage chronic kidney or liver disease, who were enrolled in the IC group. Participants received two doses of CoronaVac and additional doses of mRNA BNT162b2. Adverse reactions (AR) data were collected within seven days after each vaccination. Serious adverse events and of special interest (AESI) were monitored throughout the study. We included 241 immunocompromised and 100 immunocompetent subjects. Arthralgia, fatigue, myalgia, and nausea were more frequent in the IC group after CoronaVac. Following the first additional dose of mRNA BNT162, pain, induration, and tenderness at injection site, fatigue and myalgia were more frequent in the H group. A heart transplant recipient had a graft rejection temporally associated with the second CoronaVac dose, but there was no literature evidence of causal association. Four cases of AESI were considered related to the vaccine: three erythema multiforme after CoronaVac, all in IC participants, and one paresthesia after mRNA, in a H participant. Our findings were comparable to other studies that evaluated the safety of COVID-19 vaccines in different immunocompromised populations. Both vaccines were safe for immunocompromised participants.
Copyright (c) 2025 Karina Takesaki Miyaji https://creativecommons.org/licenses/by-nc/4.0
Spatiotemporal patterns of acute paracoccidioidomycosis hospitalizations in Brazil, 2014-2023
Paracoccidioidomycosis (PCM) is a neglected fungal disease with a rising incidence in Brazil, including increasing hospitalizations in previously non-endemic regions outside the Amazon. This study analyzed the spatiotemporal patterns of acute PCM hospitalizations and their relationship with deforestation. We carried out a retrospective ecological analysis of all PCM-related hospitalizations that were registered in the Brazilian Hospital Information System from 2014 to 2023. Acute and subacute cases were defined using ICD-10 codes (B40.0, B40.7, B40.8, B40.9, B41.0, B41.7, B41.8, and B41.9), whereas chronic forms were excluded. Rates were calculated with census population data and stabilized by Spatial Empirical Bayes smoothing. Space-time cube analysis was applied to detect clusters, which were then compared with deforestation alerts from the DETER-B satellite monitoring system. This study found 4,232 acute PCM hospitalizations, predominantly in men (80%), with a median age of 49 years. Cases were reported in 1,292 municipalities (23%), of which 78% were outside the Amazon. This study also found four significant hotspot clusters, including a newly emergent area in the Cerrado region along the Tocantins–Goias border near Brasilia. Hotspot municipalities showed the largest deforested areas (1,178 km2) when compared to coldspots (24 km2), suggesting a strong spatial association. The spatiotemporal dynamics of acute PCM indicate expansion into deforested areas of the Cerrado, highlighting the role of environmental disruption in shaping disease risk. Mitigating PCM spread in Brazil urgently requires strengthened surveillance and integrated health–environmental policies.
Copyright (c) 2025 Marina Cristina Gadêlha, Gustavo Cezar Wagner Leandro, Deisiany Gomes Ferreira, Amanda de Carvalho Dutra, Rosane Christine Hahn, Luciano de Andrade, Melyssa Negri https://creativecommons.org/licenses/by-nc/4.0
Impact of HIV co-infection on liver fibrosis regression after HCV treatment
Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma, which may lead to liver transplantation. Co-infection with HIV may accelerate liver disease and impact treatment response. Monitoring liver fibrosis involves non-invasive methods such as transient hepatic elastography (THE), AST to Platelet Ratio Index (APRI), and Fibrosis-4 (FIB-4). This study compared changes in THE, APRI, and FIB-4 among patients with HCV alone and those with HIV-HCV co-infection before and after direct-acting antiviral (DAA) therapy. We conducted a retrospective cohort study using medical records from patients treated at a reference clinic in Sao Paulo, Brazil, between January 2015 and February 2019. Fibrosis assessments (THE, APRI, FIB-4) were performed pre-treatment and six months post-treatment. APRI and FIB-4 were also evaluated at 12 months. Among 148 participants, 105 (70%) had HCV mono-infection and 43 (30%) had HIV-HCV co-infection. Genotype 1 was most prevalent (86%). At six months post-treatment, greater reductions in THE, APRI, and FIB-4 were observed in the HCV mono-infection group. Pre-treatment THE values positively correlated with subsequent reductions. However, multivariable analysis showed no significant differences between groups in THE reductions, and no significant group differences in APRI or FIB-4 at six and 12 months. DAA treatment led to fibrosis regression in most participants. HIV co-infection did not significantly alter fibrosis outcomes following successful HCV treatment.
Copyright (c) 2025 Ferdinando Lima de Menezes, Vivian Iida Avelino-Silva, Paulo Roberto Abrão Ferreira https://creativecommons.org/licenses/by-nc/4.0
Retrospective evaluation of the epidemiological importance of Triatoma infestans and Panstrongylus megistus in the transmission of Trypansoma cruzi in a region of southeastern Brazil
Panstrongylus megistus is the most important autochthonous vector of Trypanosom cruzi, the etiological agent of Chagas disease, in the midwest region of the Minas Gerais State, Brazil. This study investigates the vectorial roles of Triatoma infestans and P. megistus in Chagas disease in this geographical area during the late 1970s. A retrospective analysis of entomological and serological surveys from 1975–1983 was conducted, comparing the presence of T. infestans and P. megistus with the seroprevalence of T. cruzi infection in the human population within the Divinopolis Regional Health Superintendency. Panstrongylus megistus was recorded in all surveyed municipalities (52/52), whereas T. infestans co-occurrence with P. megistus was recorded in only 19.2% (10/52) of them. In the 41 municipalities where only P. megistus was found and relevant data were available, the mean seroprevalence of human T. cruzi infection was 17.8% ranging from 1.0% to 41.9%. In the municipalities where T. infestans occurred, the mean seroprevalence was higher, at 25.8%, ranging from 9.8% to 40.8%. Among the municipalities where only P. megistus was present, 19.5% had a low, 29.3% an intermediate, and 51.2% a high seroprevalence of human T. cruzi infection. In the ten municipalities where both T. infestans and P. megitus were found, 80% showed high seroprevalence, whereas only one municipality each showed low or intermediate levels. The findings highlight the significant role of P. megistus in T. cruzi transmission, even in the absence of T. infestans. The wide distribution of P. megistus increased the risk of transmission. P. megistus was the main household vector in the region in the 1970s. Nowadays, continuous surveillance remains essential for monitoring triatomine infestations and evaluating the current risk of T. cruzi transmission.
Copyright (c) 2025 Nilvanei Aparecido da Silva Neves, Rita de Cássia Moreira de Souza, David Eladio Gorla, Lileia Gonçalves Diotaiuti https://creativecommons.org/licenses/by-nc/4.0
Unusual cutaneous manifestations of disseminated Cryptococcus gattii infection in an immunocompetent host
We report a rare case of disseminated Cryptococcus gattii species complex (CGSC) infection in a 51-year-old immunocompetent man who initially had extensive ulcerated skin nodules, an uncommon cutaneous manifestation of cryptococcosis. Positron emission tomography/computed tomography (PET/CT) revealed hypermetabolic lesions in the skin and lungs, while brain magnetic resonance imaging (MRI) demonstrated multiple cryptococcomas with mass effect. The diagnosis was confirmed by skin and lung biopsies and a positive serum cryptococcal antigen test. Induction therapy with lipid complex amphotericin B, flucytosine, and corticosteroids was initiated. This case highlights the importance of recognizing atypical cutaneous lesions as potential indicators of disseminated CGSC infection in immunocompetent individuals, and underscores the need for early antifungal management.
Stephanie Victoria Camargo Leão Edelmuth
Copyright (c) 2025 Carolina Andrade Lopes, Stephanie Victoria Camargo Leão Edelmuth, Alessandra Luna-Muschi, Mariane Taborda, Vítor Falcão de Oliveira, Adriana Satie Gonçalves Kono Magri, Afonso Rafael da Silva Junior, Ana Catharina de Seixas Santos Nastri, Marcello Mihailenko Chaves Magri https://creativecommons.org/licenses/by-nc/4.0
Secondary syphilis sparing palms and soles, with pulmonary involvement
Secondary syphilis can compromise many organs and is widely known for manifesting with classic signs, such as a rash that involves palms and soles along with mucosal lesions. The absence of these manifestations, along with false negative serological tests, as seen with the prozone phenomenon, poses a difficult challenge for the clinician. When skin lesions are visible, a biopsy for pathological description and immunohistochemistry for Treponema pallidum may help aid in the confirmation and certainty of the diagnosis. Here, we report a case of secondary syphilis with atypical manifestations.
Copyright (c) 2025 María Pineda‑Muñoz, Ayleen Rivera‑Tenorio, Cindy Alejandra Bonilla‑Sánchez, Mariana Botero, Javier Hernández‑Moreno, Miguel C. Duarte‑Villalba, Álvaro A. Faccini‑Martínez https://creativecommons.org/licenses/by-nc/4.0
Atypical dengue fever in a partially vaccinated patient: a case report
Dengue fever is an acute, systemic, and debilitating febrile illness that poses a significant global public health threat. Vaccination is important in combating the virus in highly prevalent countries, as it reduces the risk of symptomatic infection, hospitalizations, morbidity, and mortality. We report a unique case of atypical dengue fever in a previously healthy 42-year-old Brazilian woman. She developed dengue without the characteristic fever or elevated inflammatory markers 15 days after her initial TAK-003 (Q-denga) vaccine dose, setting her case apart from typical manifestations. ’Whether the mildness of the case was due to the vaccine’s protective effect or if it was caused by the vaccine virus itself, as genetic sequencing of DENV-2 was not possible, is unclear. In regions where the vaccine is being introduced, atypical cases, particularly those without fever, require thorough investigation, so dengue can be excluded.
Copyright (c) 2025 Vasco João Mendes, Ezequias Batista Martins, Otilia Lupi, Anielle de Pina-Costa, Guilherme Amaral Calvet, Clarisse da Silveira Bressan, Ana Beatriz T. B. C. Ferreira, Fernanda de Bruycker-Nogueira, Ana Maria Bispo Filippis, Patrícia Brasil https://creativecommons.org/licenses/by-nc/4.0
Sarocladium implicatum: an unusual agent of opportunistic infection in a COVID-19 patient
Sarocladium spp. are filamentous fungi commonly associated with plant diseases and only rarely cause hyalohyphomycosis in humans. Immunosuppressed patients are at risk for this infection, which typically presents with skin and subcutaneous lesions that may eventually disseminate to internal organs. This study reports a case of a man in intensive care following SARS-CoV-2 infection. During hospitalization, he developed neutropenia, persistent fever, and a cavitary lung lesion. Sarocladium spp. was isolated from blood cultures, and the patient was treated with voriconazole, leading to a successful cure. To our knowledge, this is the first reported case of Sarocladium implicatum infection in a COVID-19 patient, underscoring the importance of monitoring opportunistic fungal infections in immunocompromised individuals, particularly during epidemics and pandemics.
Copyright (c) 2025 Gilberto Gambero Gaspar, Ludmilla Tonani, Patrícia Helena Grizante Barião, Otávio Guilherme Gonçalves de Almeida, Roberto Martinez, Marcia Regina von Zeska Kress https://creativecommons.org/licenses/by-nc/4.0
Leprosy in the 21st century: a comprehensive review of immunological mechanisms, diagnosis, and treatment
Leprosy remains a significant public health challenge, with approximately 182,815 new cases annually. This review synthesizes current knowledge on pathogenesis, diagnosis, and treatment, emphasizing recent advances. We discuss the immunological spectrum, ranging from Th1-dominant tuberculoid forms to Th2/regulatory-dominant lepromatous forms, and highlight the roles of B-lymphocyte, inflammasome activation, and Schwann cell antigen presentation in granuloma formation and neural damage. Leprosy reactions—type 1 and 2—arise from distinct immunopathological mechanisms triggered by various factors, with emerging evidence pointing to the involvement of Th17 and regulatory B cells. Diagnostic advances include molecular techniques, nerve ultrasonography, monofilament testing, and serological assays that complement traditional approaches. Treatment is based on multidrug therapy, with country-specific adaptations such as Brazil’s PQT-U, although challenges with adherence and resistance persist. Alternative regimens may include minocycline, clarithromycin, and fluoroquinolones, with bedaquiline showing promising results. Prophylactic strategies include BCG vaccination and the debated use of single-dose rifampicin for contacts. Management of reactional states employs corticosteroids, thalidomide, with biologics and JAK inhibitors reserved for refractory cases. Genetic and epigenetic factors, including TLR polymorphisms and HLA variants, influence susceptibility and outcomes. Despite recent progress, delayed detection, stigma, and inadequate follow-up remain barriers. Comprehensive approaches integrating early diagnosis, active case finding, chemoprophylaxis, stigma reduction, and rehabilitation are essential. The elimination of leprosy requires sustained commitment, improved resource access, and ongoing research into host-pathogen interactions. This review offers clinicians and researchers an updated understanding to support global control strategies.
Copyright (c) 2025 Luis Alberto Ribeiro Froes Junior, Mirian Nacagami Sotto, Maria Angela Bianconcini Trindade https://creativecommons.org/licenses/by-nc/4.0
Necrosis as a reaction to a wasp sting: a case report
A 62-year-old Brazilian woman with type 2 diabetes mellitus developed necrosis in her right arm following a single wasp sting. Severe reactions such as hers are typically associated with multiple stings and often manifest as anaphylactic shock rather than necrosis.
Copyright (c) 2025 Abraão Aires Urquiza Carvalho, João Vitor Parente Mendes, Cristine Hirsch, Marcelo Dantas Tavares de Melo https://creativecommons.org/licenses/by-nc/4.0
Transmission risk of Trypanosoma cruzi through blood donors in a third-level care hospital
Blood transfusion is a major way of Trypanosoma cruzi transmission, a neglected parasite infection that produces Chagas disease (CD). CD has high morbidity and is potentially fatal in the chronic phase due to the parasite’s ability to invade the myocardium, colon, and esophagus. CD prevalence focuses on Latin America; however, its presence in non-endemic areas has been increasing in the last decade, particularly in North America and Europe, due to high migration rates of infected people. This study established the CD seroprevalence in a blood bank located in Mexico City. A total of 851 donor samples were analyzed by ELISAn and Western blotn (ELISA and WB using native antigens obtained from Mexican strains). Positive samples were analyzed by a commercial ELISA kit, named Chagatest (non-native antigens). Average donor age was 36.5 years, and most were men. Seroprevalence by ELISAn and WBn was 3.9% (33/851); whereas by Chagatest only six samples (0.7%) were reactive. Mexico City is not considered an endemic CD area; however, the high mobility of infected people increases the transmission risk in all receptor areas, particularly in blood banks, as seen in this study. Our findings showed a difference between native and non-native serological tests, and the need to maximize the identification of infected people to curb CD spread.
Copyright (c) 2025 Viridiana Gonzalez-Lopez, Carlos Alberto Zuñiga-Cruz, Sahara Vázquez-Ramírez, Emilio Rendon-Franco, Guiehdani Villalobos, Lucia Rangel-Gamboa, Fernando Martinez-Hernandez https://creativecommons.org/licenses/by-nc/4.0
Detection of Plasmodium in Anopheles spp (Diptera: Nematocera: Culicidae) using molecular biology techniques: a systematic review
This study aims to find evidence of the effectiveness of molecular biology techniques in detecting Plasmodium in Anopheles spp mosquitoes. This systematic review was based on the PRISMA 2020 protocol. It was carried out in five electronic databases (LILACS, PubMed, SciELO, Scopus, and Web of Science, with published studies in health and interdisciplinary areas) in addition to complementary research on Google Scholar. Studies that used molecular biology techniques to detect and evaluate Plasmodium in anopheles (the results of which determined the type of Plasmodium in the samples) were included in this review. In total, 484 recent studies were retrieved from the electronic databases. According to the inclusion/exclusion criteria, only 12 studies met the objectives of this systematic review. Molecular biology was used in mosquitoes to determine parasitic species in all studies. Despite the difficulties and challenges in using molecular biology in mosquitoes, the obtained scientific advances show the accuracy and reliability of the results, contributing to an effective epidemiological response and monitoring of the spread of Plasmodium in endemic areas.
Copyright (c) 2025 Erique da Costa Fonseca, Everson dos Santos David, Karen Carmo dos Santos, Franciane Pereira de Oliveira, Ledayane Mayana Costa Barbosa, Shirley Vasconcelos Komninakis, Raimundo Nonato Picanço Souto https://creativecommons.org/licenses/by-nc/4.0
Changes in the malaria transmission profile in a low-endemic area of the Brazilian Amazon: a cause for concern
Since 2015, there has been a renewed global commitment to malaria elimination. Understanding the dynamics of the disease in regions with declining cases is essential to prevent reintroduction. This study aims to analyze the epidemiological indicators of malaria in Maranhao, a Brazilian state with a significant decline in cases. This is a descriptive, retrospective, and ecological study, with data from the malaria surveillance system, from 2003 to 2022. Demographic, spatial, temporal, and parasitological variables were analyzed. During this period, 83,517 malaria cases were reported, of which 67.8% were autochthonous, and among these, 83.1% occurred in rural areas. The Annual Parasitic Incidence (API) has recently been considered low risk in most municipalities. The analysis of seasonality was important at the beginning of the series, but with the reduction of cases, it lost relevance. The epidemiological profile has shifted, with an increase in imported cases initially from abroad and more recently from other Brazilian states. There was also a significant reduction in the proportion of P. falciparum, from 17.7% in 2003 to 6.01% in 2022. Most infected individuals were male, predominantly aged 15 to 45 years, of which increased from 59.1% to 70.5%. Although the overall trend is downward, recent changes in the disease profile are concerning, as they could reverse progress and cause a new rise in cases in a state close to elimination. Surveillance must be strengthened and adapted to prevent the reintroduction and resurgence of endemic transmission.
Copyright (c) 2025 Francisco Marques de Oliveira-Neto, Hermano Gomes Albuquerque, Antonio Rafael da Silva, Eloisa da Graça do Rosario Gonçalves, Martha Cecilia Suárez-Mutis https://creativecommons.org/licenses/by-nc/4.0
Pathological characterization of hepatic and mesenteric neotropical Echinococcosis in Brazilian Amazonian patients using light and scanning electron microscopy
Neotropical Echinococcosis (NE) is an emerging parasitic zoonosis of significant public health concern. The disease is caused by the larval stage (metacestodes) of Echinococcus vogeli and affects humans in tropical forests of Central and South America. While clinical presentation, radiological imaging, and surgical procedures have been investigated, the pathological features of NE remain partially understood. We performed a comparative study of hepatic and mesenteric metacestodes obtained from Brazilian patients in Acre and Amazonas States during surgical procedures, using both light and scanning electron microscopy for detailed analysis. Liver metacestodes showed three characteristic layers: adventitious, laminated, and germinal. In contrast, mesenteric cysts lacked a consistent layer organization, as the adventitious layer was absent, and the laminated layer was the most prominent membrane within the cyst. Compression exerted by the metacestodes led to hepatic and mesenteric hypertension, characterized by passive hyperemia. Other features induced by hypertension included an expanded sinusoidal bed and extensive areas of hemorrhage resulting from vascular rupture and subsequent blood leakage. In conclusion, the development of mesenteric and hepatic cysts follows distinct patterns, and scanning electron microscopy proves to be a valuable investigative tool for evaluating the pathology of Neotropical Echinococcosis.
Copyright (c) 2025 Fernanda Barbosa de Almeida, Alba Cristina Miranda de Barros Alencar, Christiane Leal Corrêa, Eduardo José Lopes Torres, Fernanda Bittencourt de Oliveira, Rosângela Rodrigues-Silva, Nilton Ghiotti Siqueira, Tuan Pedro Dias Correia, José Roberto Machado-Silva https://creativecommons.org/licenses/by-nc/4.0
High azole MICs in Fusarium spp.: a key factor in treatment decisions for cancer patients?
Invasive fusariosis (IF) is an exceptionally severe disease, particularly affecting patients with prolonged neutropenia. Even with antifungal therapy, mortality rates remain high, emphasizing the need for stringent control over hospital environment and further research to enhance patient outcomes. This study aims to assess the antifungal susceptibility of clinical and environmental Fusarium isolates and their clinical relevance in a cancer hospital. Sixteen environmental and 21 clinical isolates were identified, with the Fusarium solani species complex being the most common. Amphotericin B demonstrated in vitro activity, but most isolates exhibited elevated minimum inhibitory concentrations (MICs) for azoles. A total of 80% of patients had IF, primarily those with hematological malignancies, and the 30-day mortality rate was 43.8%. Isolates with elevated MICs were often managed with combination therapy. In conclusion, elevated azole MICs may lead to increased use of combination therapy in real-world clinical settings. Our findings emphasize the importance of careful interpretation of antifungal susceptibility testing results in IF management.
Evangelina da Motta Pacheco Alves de Araujo
Copyright (c) 2025 Raquel Keiko de Luca Ito, Marcia de Souza Carvalho Melhem, Lucas Xavier Bonfietti, Milena Dropa, Juliana Possatto Fernandes Takahashi, Rogério Antonio de Oliveira, Dulcilena de Matos Castro e Silva, Maria Emília Batista de Sousa, Patrícia Rodrigues Bonazzi Pontes, Vítor Falcão de Oliveira, Afonso Rafael da Silva Junior, João Nóbrega de Almeida Junior, Evangelina da Motta Pacheco Alves de Araujo, Marcello Mihailenko Chaves Magri, Edson Abdala https://creativecommons.org/licenses/by-nc/4.0
Screening for anti-Leishmania antibodies and Leishmania infections in kidney transplant recipients and donors from Brazil
This study examines the prevalence of anti-Leishmania IgG antibodies and Leishmania spp. infections among Brazilian kidney transplant recipients and their living donors before and after transplantation. A total of 48 donor-recipient pairs were recruited from July 14, 2022, to December 18, 2023. ELISA was used to test donors and recipients with a crude antigen of Leishmania major-like (Lm-ELISA), along with recombinant Lb6H (rLb6H-ELISA) and K39 (rK39-ELISA). Additionally, PCR was used to test recipients. Of the 48 donors, 25 (52.1%, 95%CI: 38.3–65.5) tested positive with Lm-ELISA, 4 (8.3%, 95%CI: 2.8–20.1) with rLb6H-ELISA, and 2 (4.2%, 95%CI: 0.4–14.8) with rK39-ELISA. Before transplantation, 31 recipients (64.6%, 95%CI: 50.4–76.6) were positive with Lm-ELISA, 5 (10.4%, 95%CI: 4.1–22.6) with rLb6H-ELISA, 1 (2.1%, 95%CI: <0.01–11.9) with rK39-ELISA, and 2 (4.2%, 95%CI: 0.4–14.8) with PCR. At 365 days post-transplant, 35 recipients underwent serological and molecular testing. Of these, 14 (40.0%, 95%CI: 25.5–56.5) tested positive with Lm-ELISA, 4 (11.4%, 95%CI: 3.9–26.5) with rLb6H-ELISA, 0 (0.0%, 95%CI: 0.0–11.8) with rK39-ELISA, and 2 (5.7%, 95%CI: 0.6–19.6) with PCR. Combining serological and molecular methods showed promising potential for early detection and ongoing monitoring of leishmaniasis in kidney transplant recipients and their donors. These findings highlight the urgent need for regulatory measures to implement Leishmania-specific donor screening and recipient monitoring using PCR and targeted serological tests, as well as close observation of signs and symptoms of leishmaniasis.
Copyright (c) 2025 Gustavo Henrique Johanson, Maria Carmen Arroyo Sanchez, Regina Maia de Souza, Beatriz Julieta Celeste, Ruth Tamara V alencia-Portillo, Elias David Neto, Ligia Camera Pierrotti, Valdir Sabbaga Amato https://creativecommons.org/licenses/by-nc/4.0
Plasmodium vivax circumsporozoite surface protein (PvCSP) as a vaccine candidate: a brief review
For decades, research and development toward malaria vaccine has prioritized infections caused by Plasmodium falciparum, since it is the species responsible for the most severe cases of malaria, which results in a comparatively smaller number of studies devoted to Plasmodium vivax. This disparity is due to complexities inherent in the biology of P. vivax, including the formation of hypnozoites in the pre-erythrocytic phase, difficulties in establishing robust in vitro culture systems, and the absence of fully representative experimental models. Among the antigens investigated for vaccine formulations, the Plasmodium vivax circumsporozoite surface protein (PvCSP) stands out for its immunogenic potential and the partial protection observed in preclinical studies. However, clinical trials with PvCSP-based vaccines have not yet demonstrated a consistent protective response. This review aims to show a historical overview of the studies that have evaluated the potential of vaccines based on the PvCSP protein, as well as to explore the innovative approaches that have been investigated in the last decade to overcome the challenges and advance the development of an effective vaccine against malaria caused by P. vivax.
Copyright (c) 2025 Kessia Caroline Souza Alves, Victor Calebe Alves da Costa, Emmily Myrella Vasconcelos Mourão, Joyce Marinho Melo, Maria Edilene Martins Almeida, Juliana Gomes de Souza Oliveira, Luís André Morais Mariúba https://creativecommons.org/licenses/by-nc/4.0
Role of the Notch ligand DLL4 in the immune response of children with Mycoplasma pneumoniae pneumonia
Mycoplasma pneumoniae pneumonia (MPP) is a common pediatric respiratory infection linked to excessive immune-inflammatory responses. This study investigated the role of the Notch ligand DLL4 in the immunopathogenesis of MPP by assessing its expression in peripheral blood mononuclear cells of affected children. A total of 128 children with MPP and 35 controls were recruited. PBMCs were analyzed for the expression of Notch ligands (Jagged1, Jagged2, DLL1, DLL4) using real-time PCR. Lymphocyte subsets were assessed via flow cytometry, and cytokine levels were measured using ELISA. Clinical data were compared between severe and mild MPP cases, and correlations between DLL4 expression and immune indicators were evaluated. DLL4 expression was significantly higher in the MPP and severe MPP groups than in controls (P < 0.01). MPP patients showed lower CD3+ and CD3+CD4+ lymphocyte levels, and higher CD3+CD8+ and CD3-CD19+ levels compared with controls (P < 0.001). Plasma levels of IFN-γ, IL-17, and IL-36α were elevated in MPP patients (P < 0.001), whereas IL-4 and IL-10 levels were reduced (P < 0.01). Severe cases had higher IFN-γ, IL-17, and IL-36α levels than mild cases (P < 0.05). DLL4 expression positively correlated with plasma IFN-γ and IL-17 levels in MPP patients (P < 0.05). Elevated DLL4 expression in MPP patients, particularly in severe cases, suggests its role in enhancing Th1/Th17-mediated immune responses while suppressing Th2 pathways. Such findings implicate the Notch signaling pathway, via DLL4, in the immunopathogenesis of MPP and highlight its potential as a therapeutic target for modulating immune responses in severe MPP.
Copyright (c) 2025 Heting Dong, Zhiao Du, Yaru Liao, Jiying Sun, Huiming Sun, Peng Mo, Ge Dai, Li Huang, Feng Huang, Chuangli Hao, Zhengrong Chen, Yongdong Yan https://creativecommons.org/licenses/by-nc/4.0
Comparative performance of BD-BACTEC® Mycosis IC/F versus standard aerobic and anaerobic bottles in simulated fungemia and mixed bloodstream infections
Candidemia is a leading cause of bloodstream infection–associated morbidity and mortality, particularly among critically ill patients. Time to detection (TTD) is crucial, but standard blood culture systems often fail to recover yeasts, filamentous fungi, or identify fungi in polymicrobial infections. The BD BACTEC™ Mycosis IC/F bottle was designed to improve fungal detection, yet comparative performance data are limited. This study aimed to compare the detection rate and TTD of BD BACTEC™ Mycosis IC/F with those of standard BD BACTEC™ Plus Aerobic/F and BD BACTEC™ Plus Anaerobic/F bottles using simulated models of fungemia and mixed fungal–bacterial bloodstream infections. This in vitro study included 333 blood culture bottles inoculated with Candida spp., Cryptococcus neoformans, Trichosporon asahii, Fusarium spp., and Aspergillus terreus, as well as bottles simulating coinfections with multidrug-resistant Gram-negative bacteria. All bottles were incubated in the BD BACTEC™ FX system for up to 14 days. BD BACTEC™ Mycosis IC/F achieved 100% detection for Candida spp., outperforming BD BACTEC™ Plus Anaerobic/F (58.5%) and matching BD BACTEC™ Plus Aerobic/F. It showed shorter TTDs for Nakaseomyces glabratus, Candidozyma haemuli, Meyerozyma guilliermondii, and molds. In mixed infections, BD BACTEC™ Mycosis IC/F provided better fungal recovery, especially at low inocula, although recovery was impaired when coinoculated with carbapenemase-producing bacteria. In conclusion, BD BACTEC™ Mycosis IC/F improved fungal detection and recovery compared with standard bottles, including in polymicrobial settings. Its use may enhance diagnostic yield in suspected fungemia, though cost and limited availability may limit widespread adoption.
Copyright (c) 2025 Juliene Carla Endo Borges, Lumena Pereira Machado Siqueira, Vera Lucia Teixeira de Freitas, Vítor Falcão de Oliveira, Adriana Satie Gonçalves Kono Magri, Afonso Rafael da Silva Junior, Evangelina da Motta Pacheco Alves de Araujo, Marcello Mihailenko Chaves Magri https://creativecommons.org/licenses/by-nc/4.0
Nanobodies as antivirals against rabies in experimentally infected mice
Despite its 100% lethality and approximately 59,000 human deaths every year, rabies still lacks an effective treatment. Numerous trials have aimed to impair the life cycle of Lyssavirus rabies (RABV), the primary worldwide lyssavirus causing rabies, but with limited success. Treatments targeting host factors and attempting to mitigate the damage caused by RABV have also been unsatisfactory. This article describes the effects of intracerebral transfection of anti-RABV recombinant monoclonal nanobodies as antivirals against rabies in vivo, in a post-exposure protocol. Mice were intranasally inoculated with the RABV CVS strain and, 72 h later, were injected via the intracerebral route with two different anti-RABV llama-derived VHH nanobodies complexed with a transfection agent. One of the VHHs was able to reduce the viral load in mice, but no significant effect on survival was detected. Though not completely effective, nanobody therapy could be attempted in association with other antivirals to improve therapies against rabies.
Copyright (c) 2025 Washington Carlos Agostinho, Viviana Parreño, Celina Guadalupe Vega, Matias Aduriz, Carolina Moura de Oliveira, Sheila Olivera de Sousa Silva, Joana Aguiar, Sueli Akemi Taniwaki, Paulo Eduardo Brandão https://creativecommons.org/licenses/by-nc/4.0
Characterization of aminoglycoside resistance in multidrug-resistant Klebsiella pneumoniae isolates
Multidrug-resistant (MDR) Klebsiella pneumoniae, particularly the lineages resistant to carbapenems and aminoglycosides, is an escalating global public health threat across human, animal, and environmental reservoirs. We examined phenotypic and genetic features of MDR K. pneumoniae isolates. A total of 70 K. pneumoniae strains were collected from clinical (n=55), environmental (n=7), and animal (n=8) sources. To better understand the evolutionary relationship between these isolates, a phylogenetic analysis was performed alongside 35 publicly available K. pneumoniae genomes from NCBI and Pathogenwatch. Whole-genome sequencing (WGS) revealed that 43 isolates carried the blaKPC gene, including blaKPC-2 and blaKPC-3 variants, with different susceptibility profiles to aminoglycosides. Among all isolates, 84% (n = 59/70) were resistant to amikacin and 53% (n = 37/70) were resistant to gentamicin. Aminoglycoside resistance was primarily associated with aminoglycoside-modifying enzymes, including aph(3’)-Ia (52%), aac(3)-IIa/aadA2 (49%), and aac(6’)-Ib-cr (37%). Additionally, 16S rRNA methyltransferases rmtB and rmtG were detected in 14% of isolates and were associated with high-level amikacin MICs. Overall, 81% of strains were non-susceptible to at least one aminoglycoside, underscoring the clinical importance of these determinants. Phylogenetic analysis based on WGS data showed two main clusters (A and B), and the multilocus sequence type ST11 predominated among Brazilian isolates. Our findings showed a heterogeneous distribution of sequence type profiles across the two clusters and a close relationship between K. pneumoniae strains from human, animal, and environmental sources, highlighting the need for integrated One Health surveillance.
Copyright (c) 2025 Saidy Vásconez Noguera, Ana Paula Marchi, Marina Farrel Côrtes, Nazareno Scaccia, Roberta Cristina Ruedas Martins, Maura Salaroli de Oliveira, Flavia Rossi, Anna Sara Levin, Silvia Figueiredo Costa, Lauro Vieira Perdigão Neto https://creativecommons.org/licenses/by-nc/4.0
Effective interventions to prevent catheter-associated urinary tract infections: a systematic review
Catheter-associated urinary tract infections (CAUTIs) are a prevalent and preventable healthcare-associated infection that significantly impacts healthcare systems, contributing to increased patient morbidity, length of stay, and costs. This systematic review aims to evaluate the effectiveness of various interventions in reducing CAUTI incidence in healthcare settings. Following the PRISMA guidelines, we conducted a thorough literature search across multiple databases—Web of Science, Scopus, PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar—up to August 8, 2024. Eligible studies included randomized controlled trials, case-control studies, and experimental designs that met inclusion criteria, namely CAUTIs prevention among hospitalized adult patients. After screening 9,476 titles and abstracts, we reviewed 163 texts in full. Of these, 12 studies were included in this review. Results showed that antiseptic solutions like chlorhexidine, specialized catheters (e.g., BIP Foley and silver alloy-coated types) and educational sessions all significantly reduced CAUTI rates, with some interventions achieving reductions as high as 94%. Reminder systems promoting timely catheter removal and amikacin bladder washing also showed notable effectiveness. Adverse effects were minimal. This review underscores the importance of evidence-based CAUTI prevention strategies and the need for consistent implementation across healthcare facilities. Enhanced catheter maintenance practices and judicious catheter use can significantly reduce CAUTI rates, thereby improving patient outcomes and reducing healthcare-associated costs. Future research should continue exploring diverse, context-specific interventions to address barriers to CAUTI prevention.
Copyright (c) 2025 Na Li, Rongjie Shi, Yan Sun, Qingli Chen https://creativecommons.org/licenses/by-nc/4.0
Acute myocardial infarction in a young patient with Chikungunya: a case report
Chikungunya virus (CHIKV) is globally distributed and transmitted by Aedes mosquitoes, with a mortality rate of 0.8/1,000 cases. The heart is the second most affected organ, with the osteoarticular system being the first. Cardiac involvement ranges from acute symptoms like myocarditis and exacerbation of pre-existing conditions to long-term complications such as dilated cardiomyopathy. While a direct association between CHIKV and acute myocardial infarction (AMI) is rare, systemic inflammation associated with chronic post-Chikungunya arthritis may destabilize atherosclerotic plaques, increasing AMI risk. This case report describes an AMI with non-obstructive coronary arteries in a previously healthy 24-year-old male infected with CHIKV. He presented low back pain, nausea, sweating, dyspnea, progressive leg edema, fever, and polyarticular pain in the knees and ankles. He was in critical condition upon admission, with decreased consciousness and hemodynamic instability, requiring transfer to the intensive care unit. He died 24 h later. Autopsy revealed a significantly enlarged heart, no visible atherosclerosis in the coronary arteries, and an extensive infarction in the interventricular septum. Histology showed coagulation necrosis, alveolar hemorrhage, and hepatic congestion. RT-PCR for CHIKV was detected in the lungs and heart tissues, while tests for other infectious diseases were negative. Studies highlight the role of mitochondrial antiviral signaling protein (MAVS) in protecting cardiac tissue from chronic CHIKV-related effects. Impaired MAVS signaling may enable continued viral replication, leading to myocarditis and vascular inflammation. Co-infection with dengue fever further increases the risk of cardiac complications. Postmortem analysis is essential to confirm CHIKV-related cardiac deaths and improve understanding and management of severe manifestations.
Copyright (c) 2025 João Gabriel Costa, Pedro Manuel Barros de Sousa, Marina Medeiros Orsi, Marcos Adriano Garcia Campos, Romullo José Costa Ataides, Joyce Santos Lages, Gyl Eanes Barros Silva https://creativecommons.org/licenses/by-nc/4.0
Findings and outcomes of hospitalized unvaccinated patients during the COVID-19 pandemic: impact of comorbidities on clinical, laboratory, and immunological parameters
The COVID-19 pandemic continues to highlight the significant impact of pre-existing comorbidities on disease progression and patient outcomes due to the risk factors for severe disease in unvaccinated patients. We evaluated the association between several clinical/laboratory findings and comorbidities in a cohort of unvaccinated patients hospitalized in the intensive care unit in Recife, Pernambuco State, Brazil. We enrolled 36 unvaccinated volunteers, and performed clinical, biochemical, hematological, and microbiological analyses. Cellular immunity, cytokine measurement, and gene expression were also analyzed. Additionally, serum samples were submitted to serological and neutralization assays by using SARS‐CoV‐2 B.1 Lineage, Gamma (P.1), Delta (B.1.617.2-like), and Omicron (BA.1) variants. Hypertension was the most common comorbidity in patients requiring oxygen supplementation, followed by diabetes and metabolic syndrome. Such conditions were linked to increased disease severity, with elevated levels of inflammatory biomarkers (D-dimer, C-reactive protein), neutrophilia, and lymphopenia. Chronic inflammation, which is often seen in diabetes and metabolic syndrome, worsens the inflammatory response triggered by COVID-19, which exacerbates endothelial injury and leads to a hypercoagulable state. Additionally, patients with comorbidities had impaired humoral immunity, and showed reduced seroconversion and neutralizing activity, which hindered their ability to combat the virus effectively. Furthermore, this study revealed that patients with diabetes and metabolic syndrome had an exaggerated Th17-driven immune response, which contributed to severe outcomes and multi-organ failure. These findings underscore the importance of personalized care and targeted interventions for patients with comorbidities, thus highlighting the need for further research on metabolic disorders, immune dysfunction, and COVID-19.
Copyright (c) 2025 Georon Ferreira de Sousa, Jéssica Pires Farias, Bárbara Rafaela da Silva Barros, Danilo Bancalero Mendonça Lucchi, Simone Ravena Maia Alves, Guilherme Antonio da Souza Silva, Leonardo Carvalho de Oliveira Cruz, Rodrigo Cesar Abreu de Aquino, Edson Barbosa de Souza, Evonio de Barros Campelo Junior, Antonio Carlos de Freitas, Luís Carlos de Souza Ferreira, Carla Torres Braconi, Cristiane Moutinho-Melo https://creativecommons.org/licenses/by-nc/4.0
Spatiotemporal distribution of leptospirosis in the Espirito Santo State, Brazil
Leptospirosis, a neglected zoonotic disease of global relevance, particularly affects populations in socio-environmentally vulnerable regions. In tropical countries such as Brazil, the prevalence of leptospirosis increases significantly during floods, increasing human exposure to contaminated environments. This study aims to investigate the spatiotemporal distribution and prevalence of confirmed leptospirosis cases in Espirito Santo State, Brazil, from 2020 to 2024. This ecological study used secondary data from the Espirito Santo State Health Department and population estimates from the Brazilian Institute of Geography and Statistics. Prevalence rates were calculated by municipality. Kernel density estimation was used to assess spatial clustering. A total of 344 confirmed cases were reported during the study period, with the highest prevalence in the Southern and Metropolitan mesoregions. Most cases occurred in urban areas and predominantly affected economically active men aged 20-59 years. These findings highlight the influence of socio-environmental determinants on leptospirosis distribution and reinforce the importance of geospatial tools in finding high-risk areas and supporting targeted public health strategies.
Copyright (c) 2025 Nicolas Brune-Gonçalves, Gustavo Brune Gonçalves, Lucas Prata Vicente, Fernando Maffioletti Ferrari, Leone Salomão Vieiras Dalla Bernardina, Bernardo Santos Roza, Luis Augusto Pereira, Cecília Schettino de Araújo, Joamyr Victor Rossoni Junior, Clairton Marcolongo-Pereira https://creativecommons.org/licenses/by-nc/4.0
Comparison between chimeric Trypanosoma cruzi antigens (ABBOTT PRISM Chagas assay) and local antigenic extracts in blood bank screening for Chagas disease in an endemic area for the Triatoma dimidiata vector
Trypanosoma cruzi can be transmitted by blood transfusion in non-endemic areas, and in endemic areas the risks may be higher. We investigated the seroprevalence of anti-T. cruzi antibodies in 1,500 blood donors from a blood bank in an endemic area where Triatoma dimidiata constitutes the main vector and in 2,800 healthy young subjects. Choosing antigens is crucial in diagnostic tests as it directly influences performance across regions. We screened 1,500 blood donors in parallel for chimeric Trypanosoma cruzi antigens with the ABBOTT PRISM Chagas assay at the State Blood Transfusion Center and with an in-house ELISA assay using local T. cruzi antigenic extracts at a Biomedical Research Center laboratory. Overall, 13 T. cruzi isolates from the Yucatan Peninsula, Mexico, were characterized for their antigenic profiles before being used in an in-house ELISAs. All T. cruzi isolates shared immunodominant antigens among themselves and with South American strains (particularly those below 100 kDa). Seroprevalence of anti-T. cruzi antibodies in blood donors totaled 0.2% (3/1500) in the ABBOTT PRISM Chagas assay and 0.26% (4/1500) in the in-house ELISA. We found low sensitivity (33%; 95%CI 0.01710 to 0.8815), high specificity (99.8%; 95%CI 0.9941 to 0.9995), and a low kappa index (0.2). Seroprevalence in young subjects totaled 0.14 %. We found comparable seroprevalence to blood banks in large Mexican municipalities free of vector transmission. Thus, optimal public immunodominant antigens are needed to cover the broad immune spectrum induced by T. cruzi infection.
Copyright (c) 2025 Floribeth León Pérez, Gloria Miss-Vivas, Virginia Peña Hernández, Victor Monteon https://creativecommons.org/licenses/by-nc/4.0
In vitro susceptibility pattern of Rhodococcus equi isolated from patients to antimicrobials recommended exclusively to humans, to domestic animals and to both
Rhodococcus equi is an opportunistic soil-borne bacterium that is eliminated in feces of multi-host animals. An increase in multidrug-resistant R. equi isolates has been reported in humans and domestic animals, and it has been hypothesized that the treatment of R. equi in foals could increase the selective pressure on multidrug-resistant isolates and favor human infections by resistant isolates. We investigated the in vitro antimicrobial susceptibility/resistance of 41 R. equi strains from humans, which were isolated from patients with pulmonary signs, using 19 antimicrobials from 10 distinct classes, recommended exclusively to humans, recommended exclusively to domestic animals and used in both. All isolates were subjected to mass spectrometry and identified as R. equi. Among the antimicrobials used exclusively in humans, tigecycline and vancomycin showed 100% efficacy. Amikacin, amoxicillin/clavulanic acid, imipenem, levofloxacin, clarithromycin, rifampin, ciprofloxacin, and gentamicin, used in both humans and animals, revealed high efficacy (97–100%). Conversely, a higher frequency of isolates was resistant to penicillin (87.8%) and trimethoprim/sulfamethoxazole (43.9%), which are used in both humans and animals. Among the antimicrobials used only in animals, isolates were resistant to florfenicol (46.4%), ceftiofur (17.1%), and enrofloxacin (2.5%). Multidrug resistance was observed in 34% of isolates. The identification of drug-resistant R. equi isolated from humans used exclusively in animals is circumstantial evidence of the pathogen transmission from domestic animals to humans. This study contributes to the molecular identification of Rhodococcus species from humans and to the epidemiological vigilance of the multidrug-resistant isolates.
Copyright (c) 2025 Nícolas Garcia Ribeiro, Paulo da Silva, Patrik Júnior de Lima Paz, Marcelo Fagali Arabe Filho, Fernando Paganini Listoni, Evandro Paganini Listoni, Letícia Colin Panegossi, Márcio Garcia Ribeiro https://creativecommons.org/licenses/by-nc/4.0
Nipah virus infection: preparedness for the pathological diagnosis of an emerging Paramyxoviridae disease with epidemic potential
Copyright (c) 2025 Cinthya dos Santos Cirqueira Borges, Ana Maria Gonçalves, Fernanda Alencar Rodrigues, Thais de Souza Lima, Ana Catharina Seixas Nastri, Venâncio Avancini Ferreira Alves, Mirian Nacagami Sotto, Thais Mauad, Soon Hao Tan, Paulo Hilário Nascimento Saldiva, Luiz Fernando Ferraz Silva, Kum Thong Wong, Marisa Dolhnikoff, Amaro Nunes Duarte-Neto https://creativecommons.org/licenses/by-nc/4.0
Intrauterine fetal death due to Brucella melitensis infection: a case report and literature review
Brucellosis is a zoonotic disease caused by Brucella species In pregnant women, this disease may lead to adverse obstetric outcomes, such as abortion, preterm delivery, intrauterine fetal death (IUFD), and congenital brucellosis. However, only a few studies have reported IUFD due to Brucella. In our case, one woman residing in Guangxi Province, China—a non-endemic region—developed symptoms 11 months after exposure. The disease manifested during her pregnancy—Brucella melitensis was identified via blood culture and confirmed by MALDI-TOF mass spectrometry. Despite receiving antibiotic treatment for brucellosis, she subsequently experienced IUFD. Additionally, we reviewed cases of IUFD secondary to brucellosis in the literature published until December 2024. Only three cases from the literature were enrolled in this study, which demonstrates that Brucella-related IUFD can occur in non-endemic zones, underscoring the need for increased clinical awareness.
Copyright (c) 2025 Minxue Liu, Lina Zhou, Jiahui Liang, Linlin Li, Liying Huang, Huan Zhang https://creativecommons.org/licenses/by-nc/4.0
Evaluation of strategies for the diagnosis of Chagas disease in an endemic area: SaMi-Trop study
This study aims to evaluate strategies for diagnosing Chagas disease (CD) using rapid tests and risk questions in an endemic area. This is an analytical cross-sectional study conducted with 751 individuals from two municipalities in an endemic region for CD in the North of Minas Gerais State, Brazil. Participants answered a questionnaire with personal information and the risk criteria for CD infection recommended by the Clinical Protocol and Therapeutic Guidelines for Chagas disease (PCDT). Subsequently, they underwent capillary blood collection for the rapid diagnostic test (RDT). Individuals with a positive RDT result, along with negative controls, underwent venipuncture for serological testing. The mean age of participants was 51.4 (±18.2) years, most were female (n=434/57.8%). In the RDT, 699 (93.1%) individuals tested negative; of these, 109 (15.6%) underwent serology and 4 (3.7%) tested positive. Among the 52 (6.9%) individuals with a positive RDT result, 48 (94.1%) had their result confirmed by the serological tests. RDT result, age, and risk factors—except for blood transfusion before 1992—were statistically associated with positive serology for CD. The RDT demonstrated high sensitivity (0.92; 95% CI: 0.81–0.92) and specificity (0.97; 95%CI: 0.92–0.99).
Copyright (c) 2025 Ingredy Carolline de Jesus Santos, Cesar Augusto Taconeli, Ester Cerdeira Sabino, Antonio Luiz Pinho Ribeiro, Andréia Brito de Souza, Ana Beatriz Cardoso Sena, Dardiane Santos Cruz, Sâmara Fernandes Leite, Ana Clara de Jesus Santos, Amanda Mota Lacerda, Luciano de Freitas Fernandes, Desirée Sant’Ana Haikal, Israel Molina Romero, Diego Dias de Araújo, Ariela Mota Ferreira https://creativecommons.org/licenses/by-nc/4.0