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BackgroundVisceral leishmaniasis (VL) remains a major public health challenge in East Africa, particularly in Ethiopia. Clinical trials on VL often exclude patients with severe comorbidities or laboratory abnormalities, limiting the generalizability of evidence used to guide real-world management. We comprehensively characterised the clinical profile, treatment outcomes, and mortality of VL patients treated in a referral centre.Methodology and principal findingsThis prospective cohort study enrolled patients at the Leishmaniasis Research and Treatment Center (LRTC), University of Gondar (02/2023-06/2024). All VL cases fulfilling eligibility criteria underwent detailed clinical, laboratory, and radiological assessments. VL treatment followed WHO guidelines. Outcomes, adverse events, and supportive care measures were recorded during treatment and over a 12-month follow-up period. Patients meeting at least one exclusion criterion (e.g., comorbidities, clinical signs of severe VL) of standard phase III VL treatment trials were defined as trial-ineligible patients and compared with trial-eligible patients. A total of 314 VL patients, mostly young adult males (median age 22 years), were enrolled. Of these, 21 (6.7%) had HIV co-infection; 204 (65%) met ≥ 1 key exclusion criterion typically used in VL clinical trials. Trial-ineligible patients had high parasitemia, more concurrent infections, more pronounced clinical and laboratory abnormalities and a higher need of supportive care measures including systemic antibiotics and blood transfusion. Overall cure rate was 90.1%. Mortality after the first VL treatment course was 6.4%, ranging from 1.8% in trial-eligible patients to 8.8% in trial-ineligible patients. Leading causes of death included severe bacterial infections, acute liver failure and haemorrhagic complications.ConclusionsThese findings underscore the severity and complexity of VL in routine care in our study population, and highlight the limitations of current trial populations to inform broader clinical practice. Strengthening supportive care and expanding research inclusivity designed to respond to the needs of this patient population are critical to achieve VL elimination targets.
Introduction: Dengue persists as a public health challenge in Brazil and is highly influenced by sociodemographic, environmental, and climatic conditions. The objective of this study is to describe the evolution of dengue cases, hospitalizations, and deaths in Brazil from 2014 to 2024, characterizing the clinical–epidemiological profiles and regional differences, with an emphasis on age gradients of severity. Methods: This is a real–world retrospective cohort study, with spatial and temporal ecological components. We utilized confirmed Dengue cases from Brazil’s Ministry of Health (MoH). Definitions for Dengue with Warning Signs and Severe Dengue followed MoH standards. Rates per 100,000 inhabitants (incidence, hospitalization, and mortality) were estimated by age group and region. Additionally, signs/symptoms, comorbidities, and available viral serotyping were assessed. Results: Between 2014 and 2024, a total of 14,215,369 cases were confirmed. Dengue with Warning Signs accounted for 1.5% (217,619) and Severe Dengue for 0.1% (18,331). There were 12,760 deaths (case–fatality rate: 0.1%), of which 80.1% had laboratory confirmation. There were 464,413 hospitalizations (3.3%); among those hospitalized, 10,436 progressed to death (2.25%). Women accounted for 54.1% of the cases; hypertension and diabetes mellitus were the most frequent comorbidities and were concentrated among Severe Dengue and deaths. The Southeast Region accounted for 58.6% of the cases; growth was observed in the Southern Region. Adjusted rates evidenced an age gradient: dengue incidence was highest in the 10–39 age group, but hospitalizations, Severe Dengue, and mortality increased sharply after the age of 60; this pattern was more intense in the South and Southeast regions. The most described warning sign was intense and continuous abdominal pain, present in 49.6% of cases in the 5–to–9 age group. Among those over 70 years old, postural hypotension/lipothymia was a clinical sign described as frequently as abdominal pain. Conclusions: A decade of data indicates the territorial expansion of dengue with worsening outcomes in the elderly, possibly leading to growing pressure on healthcare networks, mainly in the country’s historically naive areas. These findings support the prioritization of clinical triage based on age–related risk and comorbidities, and the need to strengthen integrated surveillance in high–risk and naïve populations.
Lymphatic filariasis (LF) remains a significant public health concern, with India contributing nearly 55
Infections with the protozoan parasite Trypanosoma cruzi are widespread in the Americas and can lead to severe cardiac and/or gastrointestinal pathology. Current treatments are limited to monotherapies characterised by prolonged dosing regimens, disputed efficacy and toxic side-effects. Here, we demonstrate that short duration co-administration of well-tolerated sub-efficacious oral doses of the parasite-selective proteasome inhibitor GNF6702 and the pro-drug benznidazole produce parasitological cure in an experimental model of chronic Chagas disease. ### Competing Interest Statement The authors have declared no competing interest. Medical Research Council, https://ror.org/03x94j517, MR/T015969/1 Drugs for Neglected Diseases Initiative, https://ror.org/022mz6y25, NA University of Granada, PP2023.PRI.I.14
Introduction:Chagas disease is one of the main endemic diseases in Latin America, affecting between 6 and 7 million people and causing approximately 12,000 deaths annually. Although antiparasitic treatment is effective in acute and chronic stages, only 10% of patients are diagnosed and only 1% receive timely treatment. In Argentina, an estimated 1.5 million people are affected by the infection, and progress has been made in reducing cases thanks to different public health interventions. Methods:In Robles, Santiago del Estero, a diagnostic algorithm was implemented using rapid tests (RT) in the field, venous extraction of positive samples and approximately 10% of negative samples, and processing using conventional serology (CS) to improve access to diagnosis in at-risk populations. Results:This algorithm enabled serological diagnosis of CD for 1,380 people between November 2021 and June 2022 in the department of Robles, confirming 48 infected individuals through SC, with an estimated loss of 4 or 5 seropositive individuals. Conclusions:The strategy proved effective, with a low patient loss rate and improved access to diagnosis, especially for women of childbearing age. Implementing PR can facilitate diagnosis in resource-limited and difficult-to-reach areas, contributing to the control of this endemic disease.
