Dengue is a global health emergency, with annually increasing case numbers that overwhelm healthcare systems, an ever-expanding range of the mosquito vector, and no antiviral or host-directed treatments proven to alter the course of disease. This article reports on a meeting of the Dengue Therapeutics Consortium, which included attendees from 19 countries with backgrounds in basic science, clinical research, drug development, industry, clinical trial methodology and policy. We summarise the current state of dengue therapeutics research and highlight the necessary steps to ensure that patients have equitable access to affordable and effective treatments. We review the antiviral pipeline, including novel and repurposed antiviral candidates, and we propose both human challenge and rate of viral clearance studies as methods to rapidly screen for antiviral activity prior to larger phase 3 clinical trials. We review ongoing phase 2 and phase 3 clinical trials to evaluate repurposed host-directed therapies for patients with moderate and severe disease, and we suggest considerations for future trial design, such as factorial randomisation and the use of a core outcome set to maximise efficiency and enable evidence synthesis by meta-analysis. We consider that multisectoral collaboration will be essential to achieve our aim of effective treatments for dengue. This will include drug development aligned to target product profiles, conduct of clinical trials with endpoints acceptable to both patients and regulators and sustained commitment from the pharmaceutical industry, non-profit initiatives and policymakers to ensure that effective treatments reach those who need them the most.
Introduction: Meningitis is a communicable infectious disease with a significant disease burden and possible unfavorable outcomes. In this context, the World Health Organization (WHO) and the Pan American Health Organization (PAHO) developed the roadmap “Defeating Meningitis by 2030: A Global Roadmap”, which sets the following objectives by 2030: eliminate bacterial meningitis epidemics; reduce cases and deaths from vaccine-preventable bacterial meningitis; and reduce sequelae and improve quality of life after meningitis of any etiology. In line with this, the Brazilian Ministry of Health published the “Guidelines for Addressing Meningitis by 2030” in 2024. Furthermore, in 2025, Technical Note No. 77/2025 was released, replacing the booster dose of meningococcal C vaccine with the meningococcal ACWY vaccine. Method: This was a descriptive, quantitative epidemiological study, using secondary data from meningitis epidemiological investigation forms (FIE) in Sinan and the National Immunization Program Information System (SI-PNI), from 2019 to 2025, for reported and confirmed cases of meningococcal disease, as well as data on vaccine coverage. Results: A total of 748 cases were reported and confirmed. The annual incidence per 100,000 inhabitants was approximately 1.65 (2019), 0.63 (2020), 0.40 (2021), 0.84 (2022), 1.22 (2023), and 1.22 (2024). Regarding serogroups, most were group B (38.37%), followed by group C (26.60%), group Y (4.15%), group W (2.67%), and group X (0.8%). As for outcomes, 72.33% were discharged cured and 19.25% died from meningitis. Meningococcal C vaccine coverage in São Paulo was 86.15% in 2019, then 76.25% (2020), 67.23% (2021), 68.11% (2022), 85.5% (2023), and 88.51% (2024). Conclusion: There was a downward trend in disease incidence until 2021, with a subsequent increase through 2023, stabilizing at 1.22 cases per 100,000 inhabitants by 2024. There is still a considerable proportion of serogroup C cases (26.60%), even with increased meningococcal C vaccine coverage. Serogroup B accounts for the largest proportion of reported and confirmed cases (38.37%), and there is no vaccine for this serogroup available in the Brazilian Unified Health System (SUS). Considering the high lethality, it is essential to reinforce training of healthcare professionals for the management of meningococcal disease.
Introduction Sporotrichosis is an endemic mycosis with global distribution, caused by Sporothrix spp., ubiquitous fungi found in vegetation, organic matter, and soil. In immunocompetent individuals, it usually results in localized disease, presenting as cutaneous or lymphocutaneous forms. However, in immunosuppressed patients, such as people living with HIV/AIDS, or depending on inoculum size, it may lead to disseminated disease. Objective To report a case of disseminated sporotrichosis in a patient living with HIV/AIDS with probable cross-reactivity of the histoplasmosis antigen test. Case report A 43-year-old male patient, diagnosed with HIV two months earlier (initial CD4 count of 32 cells/mm³), pulmonary tuberculosis also diagnosed two months earlier, and clinical-epidemiological diagnosis of disseminated sporotrichosis four months prior (the patient reported being scratched by his cat, which later died of sporotrichosis). He was already receiving itraconazole 200 mg/day, tenofovir + lamivudine + dolutegravir, with a most recent viral load of 856 copies/mL and CD4 count of 120 cells/mm³, and was on rifampicin. He was admitted to an infectious diseases ward due to worsening ulcerative-crusted lesions on the upper limbs, generalized lymphadenopathy, and a new pulmonary infiltrate. Skin lesion biopsies were performed, and histopathology revealed numerous yeasts with a report suggestive of histoplasmosis; therefore, a urinary histoplasma antigen test was requested and resulted weakly positive. However, other histoplasmosis investigations (serum PCR and antibodies) were negative, and culture of skin lesion fragments showed growth of a filamentous fungus identified as Sporothrix spp. Disseminated sporotrichosis was therefore confirmed, and liposomal amphotericin B at 300 mg/day was initiated, with marked clinical improvement of the lesions. Discussion Cross-reactivity of the urinary histoplasmosis antigen is described in package inserts but is rarely reported in the literature, with few documented cases. In the present case, cross-reactivity with Sporothrix spp. was observed, which should be considered, as both mycoses may cause cutaneous lesions and disseminated disease in patients with severe immunosuppression.
Opportunistic infections result from infections caused by bacteria, mycobacteria, viruses, fungi, protozoa, or helminths, potentially leading to severe disease and death. These infections are a significant cause of morbidity and mortality among individuals with profound immunosuppression, such as people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) and solid organ transplant recipients. Mycobacterial infections, including those caused by Mycobacterium tuberculosis and nontuberculous mycobacteria (NTM), particularly the Mycobacterium avium complex (MAC), are responsible for potentially severe and disseminated disease. In this article, we report three cases from a public teaching hospital in the state of São Paulo, Brazil, involving the evaluation of PLWHA presenting with nonspecific gastrointestinal symptoms and the diagnostic workup for gastrointestinal tract (GIT) mycobacterial infection, with a focus on endoscopic imaging findings and their different patterns of involvement.
Walruses are classified into nine extant and two extirpated populations across their circumpolar distribution. While there are hints that these differ morphologically, thus far there has been no in-depth comparison of their morphology and ecology, limiting insights into their conservation and evolutionary status. Here, we investigate regional differences in walrus morphology and ecology during the 17th-21st centuries ce by integrating morphometric analysis of crania (N = 188) and mandibles (N = 193), multi-isotope analysis of bone collagen (delta 13C, delta 15N, and delta 34S; N = 142), and genetic analysis (N = 115). The Pacific and Atlantic subspecies show morphological and isotopic distinctions. Distinct regional selection pressures on males and females can be inferred. This was most visible in the extirpated Maritimes walrus, where females had a unique cranium shape. Regional isotopic and genetic differences were also observed; we found regional differences in delta 13C, delta 15N, and delta 34S, and identified multiple genetic clades coinciding with geographic populations. Overall, the comparative insight into the morphological, ecological, and genetic characteristics of different walrus populations sets a frame of reference for conservation management and from which to understand how each has been impacted by human exploitation and environmental changes in the past.
