BACKGROUND:Acute respiratory viral diseases are a major public health challenge in the Brazilian Amazon, where ecological, logistical, and social factors shape patterns of transmission and response. METHODS:This study aimed to analyze the epidemiological patterns and temporal-spatial distribution of Influenza-like illness (ILI) and severe acute respiratory syndrome (SARS) in the state of Amazonas, Brazil, between 2015 and 2025, distinguishing SARS-CoV-2 and non-SARS-CoV-2 etiologies using data from OpenDataSUS. RESULTS:Incidence peaks occurred in early 2021 and 2022, with pronounced regional disparities. The highest burdens were concentrated in specific municipalities, with Manaus exhibiting an intermediate incidence and playing a central role in case notifications and healthcare provision. DISCUSSION:We describe the integration of surveillance systems, laboratory networks, and healthcare infrastructure, which enabled improvements in diagnosis, monitoring, and care. The region's response model, centered in Manaus, includes primary-to-tertiary care coordination, molecular diagnostics, telemedicine, and mobile health units for Indigenous and remote areas. Research efforts during the COVID-19 pandemic provided critical insights into therapeutic strategies, immunopathology, and long-term sequelae, while also highlighting persistent inequities and diagnostic gaps. Our findings underscore the co-circulation of multiple respiratory pathogens and the need for continued genomic and syndromic surveillance. Future strategies must address regional disparities, support decentralized diagnostics, and expand clinical research. Strengthening integrated health systems in the Brazilian Amazon is essential for timely, equitable responses to emerging respiratory threats.
ABSTRACT Neglected tropical diseases (NTDs) affect more than 1.6 billion people worldwide and remain major contributors to morbidity, disability, stigma, and poverty. Metabolomics has emerged as a promising approach for investigating disease-associated biochemical alterations and identifying biomarkers for diagnosis, prognosis, and treatment monitoring. This systematic review evaluated the available evidence on metabolomic profiles in WHO-defined NTDs and their potential clinical applications. MEDLINE/PubMed, Web of Science, and Scopus were searched through March 2026. Observational studies investigating metabolomic profiles in human subjects with NTDs were included, and methodological quality was assessed using a modified QUADOMICS tool. Seventy-four studies met the inclusion criteria. Most were conducted in China and Brazil and focused on dengue, onchocerciasis, schistosomiasis, leprosy, and Chagas disease. Across diseases, metabolomic alterations were predominantly observed in amino acid, lipid, carbohydrate, and energy metabolism pathways. Several candidate biomarkers were identified, including N-acetyltyramine-O-β-glucuronide for onchocerciasis, bile acid derivatives for schistosomiasis, amino acids and peptides for Chagas disease, lipid mediators for leprosy, and lipid- and serotonin-related metabolites for dengue. However, most studies remained exploratory, and only two validated biomarkers in independent populations. Risk-of-bias assessment revealed frequent methodological limitations, including inadequate reporting of pre-analytical procedures, insufficient characterization of study populations, and lack of strategies to address overfitting. Human metabolomics studies were absent for several WHO-defined NTDs, highlighting major research gaps. Future research should prioritize standardized methodologies, multicenter validation studies, and greater inclusion of underrepresented diseases and endemic populations to translate metabolomic discoveries into clinically useful tools for NTD diagnosis, monitoring, and control.
ABSTRACT In the Amazon, Chagas disease (CD) transmission is associated with the consumption of contaminated foods -most notably açaí-and constitutes an important public health concern. In Brazil, the state of Amazonas ranks third in acute-phase notifications among states in the region, with 25% of municipalities having already reported acute CD cases, predominantly in outbreaks in rural areas. This study describes the current overview of knowledge on CD in Amazonas, bringing together research findings from the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), developed in partnership with the graduate program in Tropical Medicine at the Universidade do Estado do Amazonas (UEA). The findings show that, in addition to oral transmission, accidental contact with the traditional vector (Triatominae) has been reported. The predominant transmission pattern represents an important shift in the dynamics of the disease and reinforces the need for surveillance strategies focused on controlling foodborne transmission. Among the main challenges are logistical difficulties for post-treatment clinical follow-up, especially in remote areas, and the absence of a structured and specialized network for continuous case monitoring and detection of new outbreaks. Added to this is the lack of systematic CD screening in women of childbearing age during prenatal care, which hinders surveillance of vertical transmission. These issues highlight the urgency of strengthening surveillance and preventing new incidences.
ABSTRACT Thrombocytopenia is a known and potentially severe manifestation of dengue hemorrhagic fever, raising concerns regarding the risk of hemorrhage. To prevent such complications, prophylactic platelet transfusion (PT) has been suggested as a possible intervention. We aimed to evaluate the efficacy and safety of PT in dengue-associated thrombocytopenia. We conducted a systematic literature search for randomized controlled trials and cohorts across PubMed, Cochrane Library, Web of Science, Scopus, and Embase from inception to November 2025. Primary outcomes were time to platelet count ≥ 50 × 10³ platelets/µL and mortality. Secondary outcomes were bleeding events and length of hospital stay. Risk of bias was assessed using the RoB 2 and ROBINS-I tools. Of 1,900 articles screened, 9 studies were included (6 retrospective cohorts, 2 RCTs, and 1 prospective cohort), comprising 3,377 patients. The PT group included 2,383 patients, whereas the standard supportive care group included 994 patients. PT was not associated with significant reductions in time to platelet recovery (mean difference, 0.73 days; 95% CI: -0.01 to 1.47; I² = 95.9%) or length of hospital stay (mean difference, 0.53 days; 95% CI: -0.15 to 1.22; I² = 96.7%) but was associated with significantly higher risks of mortality (risk ratio, 3.61; 95% CI: 1.12-11.66) and bleeding events (risk ratio, 1. 37; 95% CI: 1.03-1.82). Prophylactic platelet transfusion demonstrated no measurable benefit and was associated with increased mortality and bleeding risk, arguing against its routine use in dengue-associated thrombocytopenia. Evidence was primarily derived from retrospective studies, limiting interpretability and warranting randomized studies.
ABSTRACT Trypanosoma cruzi exhibits substantial genetic diversity, classified into discrete typing units (DTUs) that may differ in geographical distribution, host associations, and epidemiological relevance. Although several DTUs have been reported in Mexico, evidence on their national distribution across vectors, reservoirs, and humans remains fragmented. A systematic review was conducted following PRISMA guidelines to synthesize available information on the geographical distribution, host associations, and epidemiological cycles of Trypanosoma cruzi DTUs in Mexico. Seven scientific databases were searched for studies published between January 2006 and July 2025. Inclusion criteria focused on studies reporting molecular identification of T. cruzi DTUs in vectors, reservoirs, and humans within Mexican territory. Forty-seven studies were analyzed, providing a total of 1,337 individual records. The analysis confirmed the circulation of six DTUs (TcI-TcVI) in 22 states, with TcBat being absent from the records. TcI was identified as the most frequent and widely distributed lineage, present in 20 of the 22 states. Veracruz documented the highest genetic diversity, with all six DTUs reported. The genus Triatoma and domestic dogs exhibited the highest diversity of reported DTUs, acting as key epidemiological bridges between transmission cycles. TcI is the predominant lineage in Mexico, demonstrating high connectivity across all transmission cycles. This systematic review highlights significant information gaps in northern Mexico and underscores the need for strengthened surveillance to better understand the impact of T. cruzi genetic diversity on public health.
ABSTRACT Chagas cardiomyopathy is associated with a higher risk of severe cardiovascular events and increased mortality. Among the factors associated with Chagas cardiomyopathy, impairment in functional capacity-commonly assessed using the New York Heart Association (NYHA) functional classification-is notable and may contribute to risk stratification. In this review, we assessed the prognostic value of the NYHA classification on cardiovascular events and mortality in patients with Chagas cardiomyopathy. The search was performed across EMBASE, LILACS, MEDLINE, and Web of Science databases. Prospective and retrospective cohort studies in which the prognostic value of the NYHA classification was assessed were eligible. Risk of bias was assessed using the Quality in Prognostic Studies tool. Evidence was classified using the adapted GRADE system. Eighteen studies were included in the systematic review. The meta-analysis results indicate that the NYHA classification is an important prognostic factor for mortality. Patients with NYHA class III and IV showed a higher risk of death than those with class I and II (hazard ratio, 2.63; 95% confidence interval: 2.00-3.45; moderate GRADE evidence). Patients with NYHA class IV had a higher risk of death than those with class I, II, and III (hazard ratio, 2.80; 95% confidence interval: 1.06-7.43; low GRADE evidence). Very low evidence suggests that the NYHA classification does not predict heart transplantation or stroke, but may predict cardiac pacemaker implantation. Overall, the NYHA classification is a key prognostic indicator of mortality in Chagas cardiomyopathy, although its ability to predict stroke, heart transplantation, and pacemaker implantation is inconsistent.
ABSTRACT Background: Schistosoma mansoni infection remains a major public health concern in Brazil. Accurate diagnostic methods are essential for monitoring transmission and guiding control and elimination strategies. This systematic review and meta-analysis aimed to assess the performance of diagnostic tests used for S. mansoni infection in Brazil. Methods: Studies conducted in endemic areas of Brazil that used parasitological methods as the reference standard, reported sensitivity and specificity, and were published through October 2024, were included in the analysis. Diagnostic performance was synthesized using univariate and multivariate meta-analyses, and risk of bias was assessed with QUADAS-2. Results: Thirty-three studies were included; most were conducted in Minas Gerais (63%). The main reference standard was Kato-Katz alone (48%) or combined with other parasitological methods (42.4%). Enzyme-linked immunosorbent (ELISA)-SEA results showed higher accuracy than ELISA-SWAP (81% vs 68%), although both exhibited heterogeneity above 80%. Point-of-care circulating cathodic antigen with trace results interpreted as positive (POC-CCA+) or negative (POC-CCA-) showed similar accuracy (70% vs 73%, respectively), with heterogeneity exceeding 80%. For conventional PCR, PCR-ELISA, real-time PCR, and loop-mediated isothermal amplification (LAMP), accuracy ranged from 67% to 82% (heterogeneity: > 90%. In multivariate analysis, conventional PCR had the highest diagnostic odds ratio (DOR: 99.4), followed by PCR-ELISA (DOR: 12.4), whereas the two POC-CCA reading criteria resulted in lower values (trace-positive: 8.5, trace-negative: 6.1). Conclusions: Overall, these observations support the use of combined diagnostic strategies and underscore the need for multicenter, methodologically rigorous studies to strengthen surveillance, control, and elimination efforts for Schistosoma mansoni infection in Brazil.
ABSTRACT American tegumentary leishmaniasis (ATL) remains a significant public health problem in the Americas, with the Amazon region standing out in Brazil for its high number of cases. This article aimed to present advances in the understanding of epidemiology, diagnosis, treatment and control of ATL in the state of Amazonas over the past decades. This study is a narrative review of scientific studies published in the literature between 2011 and 2025, retrieved from databases such as PubMed and SciELO, as well as public data from the Notifiable Diseases Information System (SINAN), official reports from the Ministry of Health and technical notes from the Amazonas Health Surveillance Foundation. The evolution of disease incidence is reported, highlighting the predominance of Leishmania (Viannia) guyanensis and the environmental factors associated with the increase in cases, such as deforestation and unplanned urbanization. Advances in diagnostic strategies include the expanded use of molecular techniques and the strengthening of the primary healthcare network. Regarding therapy, clinical trials with drugs such as pentamidine, miltefosine, tamoxifen and itraconazole have demonstrated their efficacy in treatment. The review also includes socio-environmental, genetic and experimental studies that have contributed to a better understanding of the disease. It emphasizes the need to establish a priority agenda that includes the use of telemedicine and the institutionalization of collaborative research for therapeutic innovation, integration between research and healthcare services and strategies adapted to the Amazonian context. Regional scientific advances can support more effective control policies and reduce the burden of ATL in this highly endemic setting.
BACKGROUND:Infectious and parasitic diseases remain a significant cause of mortality in the state of Amazonas, and are shaped by structural, environmental, and social vulnerabilities. METHODS:This descriptive, population-based study examines the temporal evolution and spatial distribution of mortality caused by infectious disease in Amazonas between 2013 and 2024. We analyzed monthly mortality rates using data from the Mortality Information System (SIM), focusing on International Classification of Diseases, 10th Revision (ICD-10) Chapter I (A00-B99) and selected codes from Chapter X (J09-J18). RESULTS:Despite initial stability (2013-2018), mortality rates increased markedly from 2019 to 2021, associated with the direct and indirect impacts of the Coronavirus Disease (Covid-19) pandemic. After 2022, rates stabilized but remained elevated, indicating a shift toward a new endemic level. Spatial analysis revealed a persistent concentration of deaths in metropolitan areas and riverine municipalities, with recent expansion into medium-sized towns of the interior. Pneumonia, human immunodeficiency virus / acquired immunodeficiency syndrome (HIV/AIDS), septicemia, and tuberculosis accounted for most deaths, with a predominance of older adults and people identified as mixed race or Indigenous. High proportions of ill-defined causes and non-specific diagnoses, particularly in pneumonia and sepsis, highlight diagnostic limitations and the urgent need to strengthen death investigation services and expand etiological investigation. CONCLUSIONS:Our findings highlight persistent inequalities in health access and call for integrated public health strategies, including improved surveillance systems, expanded diagnostic capacity, and intersectoral approaches adapted to the Amazonian context.
ABSTRACT During the COVID-19 pandemic, an unprecedented outbreak of mucormycosis affected tens of thousands of patients, mainly in India. This study reviewed the available published cases up to 2022 and updated the epidemiological curve up to November 2025. PRISMA-guided systematic review of PubMed, Embase, and SciELO (Dec. 2019-Dec. 2022), supplemented by official reports and cohort studies published until 2025. We analyzed 1,482 cases from 39 studies (90.8% conducted in India; 69.7% male individuals; mean age 52 years). Diabetes mellitus was present in >78% of patients, and 64.3% received corticosteroids. Rhino-orbital (40.7%) and rhino-orbito-cerebral (33.9%) were the dominant forms of mucormycosis. Amphotericin B was used in 49.5% of cases, and surgical debridement in 55.5%. The mortality rate was 25%. After 2022, the incidence collapsed globally: India dropped from >47,000 cases in 2021 to <100 cases/year; Europe, the Middle East, and Latin America reported zero outbreaks in 2024-2025. COVID-19-associated mucormycosis represented a major opportunistic infection during the acute phase of the pandemic. Although its incidence declined markedly after widespread vaccination implementation, improved corticosteroid use, and better glycemic control, it remains a serious and life-threatening condition in vulnerable populations. The findings highlight important risk factors, clinical challenges, and management considerations that remain relevant to inform current clinical practice and future post-pandemic scenarios.
ABSTRACT Background: Arboviral infections continue to be a significant public health challenge in the Brazilian Amazon. Overlapping symptoms, limited laboratory access, and the circulation of multiple arboviruses hamper clinical diagnosis. This study aimed to characterize the epidemiological, clinical, laboratory and genomic profiles of arboviral infections in febrile patients in Manaus, Brazil, and explore additional viral agents using metagenomic sequencing. Methods: A cross-sectional study was conducted between February 2021 and February 2023 at a tertiary reference center in Manaus, Brazil. Patients aged ≥ 5 years of age presenting with a rash and either a fever or a history of fever lasting <7 days and a negative thick blood smear for malaria were enrolled. Serum samples were tested for dengue virus (DENV), Zika virus (ZIKV), Chikungunya virus (CHIKV), yellow fever virus (YF), Oropouche virus (OROV), and Mayaro virus (MAYV) using ELISA and RT-qPCR. Positive samples were subjected to amplicon-based genome sequencing for phylogenetic analysis. A subset of RT-qPCR negative samples was analyzed using de novo shotgun metagenomic sequencing. Results: Among the 708 enrolled participants, 243 (34.3%) had a laboratory-confirmed arboviral infection: 92 (37.9%) DENV, 64 (26.3%) CHIKV, and 4 (1.6%) ZIKV, while 83 (34.2%) laboratory profiles were compatible with coinfection, predominantly DENV+CHIKV (55/83; 66.3%). Circulation of DENV-1 genotype V and DENV-2 genotypes III (Asian American) and II (Cosmopolitan) was identified. Metagenomic analysis of 35 samples detected Pegivirus hominis and Erythroparvovirus primate 1. Conclusions: These findings demonstrate complex arbovirus co-circulation in Manaus and support integrated surveillance strategies combining molecular, serological, and genomic approaches.
BACKGROUND:Tuberculosis (TB) remains a major public health challenge in Brazil, particularly in the state of Amazonas, where geographic, socioeconomic, and health system barriers hinder the implementation of TB preventive treatment (TPT). This study describes the scale-up of TPT, supported by integrated actions across surveillance, health services, and academia in this high-burden setting. METHODS:We conducted a retrospective implementation analysis of TPT in Amazonas, Brazil (2016-2024), using data from the IL-TB system, SINAN-TB, and HIV/AIDS Clinical Monitoring Panel. A structured set of indicators was used to assess TPT delivery, decentralization, diagnostic practices, regimen uptake, and treatment outcomes. Proportions and rates were estimated with 95% confidence intervals (95% CI). RESULTS:A total of 8,120 individuals initiated TPT, including 5,001 TB contacts, whereas more than 70,000 contacts were recorded in the SINAN-TB. Following the IL-TB implementation in 2019, the indicators showed a sustained expansion of TPT delivery. By 2024, TPT initiation among contacts reached 18.4% (95% CI: 17.6-19.3), and 959 PLHIV initiated TPT, corresponding to 441.33 per 1,000 antiretroviral therapy. The proportion of TPT initiation in primary health care increased from 19.3% (95% CI: 13.8-26.4) in 2018 to 55.2% (95% CI: 53.3-57.1) in 2024. Use of 3HP (weekly rifapentine plus isoniazid for three months) rose from 12.7% (95% CI: 10.6-15.1) in 2021 to 93.3% (95% CI: 92.3-94.2) in 2024. Completion reached 84.8% (95% CI: 82.9-86.6) and remained above 80% thereafter. CONCLUSIONS:TPT scale-up in Amazonas was accompanied by expanded access, greater decentralization, and rapid adoption of shortened regimens, although important coverage gaps among priority populations remain.
Malaria continues to be a major public health issue in the Brazilian Amazon, with the state of Amazonas accounting for approximately 40% of all national cases. The region presents diverse epidemiological scenarios and different infrastructure conditions, which hinder the implementation of diagnostic, treatment, management, and control strategies. Through dedicated control, surveillance and research initiatives, considerable progress has been made in reducing the incidence of cases, hospitalizations and deaths attributed to the two endemic protozoan species, Plasmodium falciparum and Plasmodium vivax. This article provides an overview of the key research and surveillance endeavors undertaken in the state of Amazonas. These efforts aim to achieve the objectives outlined in the national malaria elimination plan, enhance the understanding of the disease's pathophysiology and associated comorbidities, and leverage the advances and contributions of research groups within the state, which are focused on comprehending vector behavior and developing effective control strategies, creating more efficient diagnostic tools and researching and developing safe and effective drugs for treatment, relapse prevention and the elimination of transmission reservoirs.
ABSTRACT Background: Dengue remains a public health challenge, driven by Aedes aegypti proliferation within complex socio-environmental conditions. Methods: This study investigated the spatiotemporal distribution of dengue in Manaus from 2016 to 2022. Temporal analysis used negative binomial regression adjusted for seasonality. Seasonal and spatial clusters were identified using scan statistics (p < 0.05, 95% CI). A Bayesian spatial model assessed sociodemographic and environmental determinants. Results: Lagged temperature and wind speed showed protective effects. The Bayesian model identified significant associations with population density, vegetation indices (NDVI), sewage infrastructure, and housing types. Conclusions: Integrating climatic and socioeconomic data is essential for intersectoral dengue control strategies.
This case report describes a 43-year-old man admitted in November 2024 with recurrent deep anterior chest wall and thoracoabdominal soft-tissue infection caused by Klebsiella pneumoniae. Multidrug-resistant K. pneumoniae was isolated in December 2024. From January to April 2025, the patient required prolonged hospitalization, repeated debridements, and skin grafting, complicated by flap infection, acute kidney injury, and ICU admission. After initial improvement with polymyxin B and tigecycline, a severe recurrent infection caused by pan-resistant K. pneumoniae occurred in June 2025. Given the limited therapeutic options, treatment was changed to cefotaxime plus polymyxin B, leading to complete clinical recovery, which was later confirmed by in vitro synergy results.
This narrative review examines how interdisciplinary and participatory research has advanced the understanding and control of socially determined diseases in the Brazilian Amazon. The integration of social sciences into the Tropical Medicine Foundation Dr. Heitor Vieira Dourado marks a shift from purely biomedical approaches toward those recognizing the cultural, environmental and territorial dimensions of health. Qualitative studies on snakebite envenoming among Indigenous populations revealed that treatment integrates biomedical and spiritual practices, highlighting the need for intercultural dialogue. In malaria elimination, research emphasized evaluating the acceptability and feasibility of new tools such as point-of-care G6PD testing and single-dose tafenoquine, demonstrating that understanding perceptions of innovations is indispensable for effective implementation. Studies on human immunodeficiency virus (HIV) prevention and trachoma among Indigenous and urban populations illustrated how stigma, gender relations and structural inequalities shape health outcomes. Extreme climate events, such as the 2023 Amazon drought, exacerbate vulnerabilities by disrupting livelihoods and healthcare access. The article concludes by proposing an interdisciplinary research agenda aligned with Brazil's Healthy Brazil Program, emphasizing community engagement, intersectional analysis, One Health integration and implementation science as key strategies for equitable disease elimination in the Amazon.
Leprosy remains a major public health challenge in the state of Amazonas, Brazil, despite a remarkable 95.7% reduction in detection rates between 1981 and 2024. In 2024, 326 cases were reported, 80.4% of which were new diagnoses, predominantly multibacillary forms, with 9.3% presenting grade 2 disability on diagnosis. The continued occurrence of cases among children under 15 years of age (3.4%) indicates active transmission, particularly in geographically isolated municipalities. The Fundação Hospitalar Alfredo da Matta (FUHAM) serves as the main regional reference center, coordinating surveillance, diagnosis, rehabilitation and research activities. The decentralization of primary care and the integration of telehealth strategies have strengthened diagnostic capacity and improved the management of leprosy reactions. Historically, Amazonas has played a pivotal role in advancing scientific knowledge on leprosy, from early reports of dapsone resistance to participation in key clinical trials such as U-MDT/CT-BR, and studies on leprosy/HIV coinfection, immunopathogenesis and host genetic susceptibility (NOD2, IFNG, PKLR). More recently, genomic surveillance in the region has identified both classical and novel antimicrobial resistance mutations, consolidating Amazonas as a sentinel site for molecular monitoring. Persistent challenges include limited professional training, delayed diagnosis and ongoing social stigma. Research priorities for the next decade include strengthening active case detection, validating simplified diagnostic algorithms, expanding antimicrobial resistance monitoring, exploring genetic determinants of susceptibility and adopting One Health approaches to understand environmental and zoonotic transmission. These integrated strategies are crucial to sustain progress toward the elimination of leprosy as a public health problem in the Amazonian context.
ABSTRACT Snakebite envenomations have a disproportionate burden in the Brazilian Amazon compared to other regions of Brazil. Studies conducted in the state of Amazonas show that Bothrops atrox snakebites are the most common, occurring in every municipality of the state. All the 62 municipalities in the state have at least one urban health unit that offers antivenom treatment. The most affected populations in terms of incidence and fatality rate are riverine communities and indigenous people, who have limited access to antivenom treatment. A significant proportion of cases are not reported to the official surveillance system, and many deaths occur due to lack of medical care. In the last decade, important advances have been made in research into snakebites in the state of Amazonas, in a collaborative network led by the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, a referral institution for patient care, teaching and research in tropical medicine. Findings on the burden of disease in vulnerable populations; clinical, therapeutic and pathophysiological aspects; long-term disabilities; barriers to antivenom treatment; and cultural aspects of snakebites, are presented in this paper. We highlight the findings of the SAVING Program, which aimed to implement a culturally tailored antivenom decentralization program in indigenous community-health centers. We conclude by presenting a priority research agenda for snakebites for the coming years in the Amazon region.
