Medicine and Pharmacology

Abstract: Dengue is the most prevalent arthropod-borne viral disease, caused by infection with dengue virus (DENV). Severe dengue is characterized by significant vasculopathy involving a proinflammatory and procoagulant state associated with increased vascular permeability. However, the host–virus interactions driving this process remain incompletely elucidate. Monocytes are primary target cells during DENV infection and actively release extracellular vesicles, like microparticles (MPs), mediating intercellular communication contributing to dengue pathogenesis. Here, we evaluated whether MPs released by DENV-infected monocytes represent a previously underappreciated mechanism contributing to dengue-associated vascular dysfunction. The vascular endothelium plays a determining role in the response to injury because it functions as a regulatory interface during hemostasis (coagulation–fibrinolysis–inflammation) and by preserving endothelial barrier. We found that these vesicles transport viral components capable of mediating DENV endothelial vascular cells (EVC) infection, while simultaneously exhibiting a procoagulant profile promoting thrombin generation and cell activation. DENV-infected Mø MPs interaction induces a shift toward a procoagulant, proinflammatory, and proadherent phenotype, characterized by increased expression of PAR-1, TF, ICAM-1, and VCAM-1, reflecting the establishment of a sustained EVC activation that compromises vascular barrier integrity, leading to increased permeability, a hallmark of DENV-associated vasculopathy and a central event in the progression to severe dengue.

Abstract: Objective: The objective was to determine whether individuals who received doxycycline had a shorter hospitalization time. Methods: A retrospective, observational, and comparative study was conducted with 64 patients diagnosed with dengue. One group received standard symptomatic treatment, while the other also received doxycycline (initial dose of 200 mg, followed by 100 mg every 12 hours until discharge). Clinical and laboratory variables were compared. Results: Compared to patients who received only the standard treatment, patients treated with doxycycline had a shorter hospitalization time (26.30 ± 13.72 vs 93.18 ± 25.29 h, p<0.0001), hours of fever (13.79 ± 16.18 vs 127.08 ± 51.22, p<0.0001), headache (16.30 ± 19.27 vs 94.59 ± 26.11, p<0.0001), and myalgia (23.94 ± 10.90 vs 120.24 ± 25.20, p<0.0001). Furthermore, the doxycycline group exhibited a higher platelet recovery rate (0.54 ± 0.49 vs 0.23 ± 0.29, p=0.003) than the other group. No adverse effects were reported. Despite limitations (sample size and lack of randomization), the findings suggest that doxycycline would be a promising and useful therapeutic alternative in the management of dengue. Conclusion: The use of doxycycline in dengue treatment was associated with a reduction in hospitalization time, duration of symptoms, and a higher platelet recovery rate.

Abstract: A decade has elapsed since the first recognized cluster of congenital anomalies associated with Zika virus (ZIKV) was reported in Brazil in 2015, culminating in the formal delineation of Congenital Zika Syndrome (CZS) as a specific pattern of birth defects. This narrative review examines the ten-year trajectory of CZS as a tropical infectious disease, from its initial emergence and public health emergency declaration by the World Health Organization (WHO) in February 2016, through evolving epidemiological, clinical, and scientific understanding. CZS is characterized by a spectrum of severe neurological manifestations—including microcephaly, subcortical calcifications, malformations of cortical development, ventriculomegaly, and corpus callosum abnormalities—alongside ophthalmic, auditory, and musculoskeletal complications. Transmitted primarily by Aedes aegypti mosquitoes in tropical and subtropical regions, ZIKV disproportionately affects low- and middle-income countries in Latin America, Africa, and Southeast Asia, underscoring its nature as a quintessential tropical disease linked to poverty, inadequate vector control, and health inequity. Over ten years, substantial advances have been made in understanding ZIKV pathogenesis, neurodevelopmental outcomes, diagnostic criteria, and multidisciplinary clinical management of affected children. In the therapeutic and preventive domain, over 45 vaccine candidates have been identified, with 16 reaching Phase 1 or 2 clinical trials by late 2025, though no licensed vaccine or specific antiviral therapy yet exists. This review contextualizes CZS within the broader framework of neglected tropical diseases, evaluates its global and family-level burden, and critically appraises progress and remaining gaps in clinical care, vaccination, and vector control over the past ten years.

Abstract: AbstractBruceine A is a major quassinoid isolated from the seeds of Brucea javanica and has been reported to exhibit significant anticancer and antiplasmodial activities. Structural modification of Bruceine-A through semisynthesis is a rational approach to improve its biological potential. This study aimed to design and evaluate semisynthesized pathways for Bruceine-A derivatives and to elucidate the reaction mechanism. Two semisynthesis routes were evaluated: (i) a protection–deprotection strategy involving tert-butyldimethylsilyl chloride (TBDMS-Cl), and (ii) a direct acylation approach. Due to limitations in material availability and reaction complexity, the second pathway was selected. Direct acylation of Bruceine A in N,N-dimethylformamide (DMF) using imidazole as a base catalyst successfully yielded 3-O-chlorobenzoylbruceine (P1). Structural elucidation was performed using UV, IR, ^1H-NMR, ^13C-NMR, and LC–MS. The results demonstrate that direct acylation at the C-3 hydroxyl group is an efficient and selective strategy for the semisynthesis of Bruceine A derivatives.Keywords: Bruceine A, quassinoid, semisynthesis, acylation, Brucea javanica, 3-O-chlorobenzoylbruceine

Abstract: Our study explored the scientific rationale behind the traditional use of medicinal plants as a foundation for evidence-based strategies for the management of sickle cell disease (SCD) in developing countries. Firstly, we conducted a survey among people living at Kisangani city in DR Congo to identify the plants used alone or in combination for the SCD management considering the following criteria: used parts, preparation methods, administration routes and common combinations with other substances. This step allowed to select the most used plants which were harvested from two different soil types and prepared according to local practices. Secondly, different preparations were tested at laboratory focusing on the antioxidant and anti-inflammatory biological activities which are mainly observed with people suffering from SCD. Out of 384 surveyed people, 201 reported the use of 45 medicinal plants whereas the additives comprised sugar, caramel, ash and lemon juice. Alchornea cordifolia Müll. Arg and Hibiscus tiliaceus L. were selected for laboratory analyses. Their leaves were collected from both dry and marshy soils and prepared following local methods with additive. A. cordifolia showed significantly higher antioxidant (p = 0.001) and anti-inflammatory activity (p = 0.01) than H. tiliaceus. Soil type influenced activity in H. tiliaceus, favoring marshy soil. However, sugar and caramel significantly reduced bioactivity, ash and lemon juice enhanced antioxidant effects without significantly altering anti-inflammatory properties.

Abstract: Background: Leptospirosis is a globally prevalent zoonosis with significant morbidity and mortality, especially in tropical regions like South Asia. In its severe form, the disease often leads to multiorgan dysfunction, with pulmonary haemorrhage being a significant cause of death. Evidence supporting specific treatments for severe leptospirosis with pulmonary involvement remains limited. Recent studies suggest that immunomodulatory therapies, such as therapeutic plasma exchange (TPE), may offer survival benefits. This case series examines the application and outcomes of TPE in patients with severe leptospirosis at a tertiary-care hospital in Sri Lanka. Methods: We studied a case series involving 10 patients with confirmed severe leptospirosis and multiorgan involvement, from September 2021 to October 2022. All patients received intravenous antibiotics and methylprednisolone. TPE was initiated in nine patients based on clinical severity, particularly in the presence of pulmonary haemorrhage. Clinical, laboratory, and radiological data were collected from patient records and follow-up. ELISA IgM confirmed Leptospirosis. A multidisciplinary team made TPE decisions. Results: Of the nine patients who received TPE, seven survived (77.8%). Pulmonary haemorrhage was the primary indication for TPE in all the cases. All patients had multiorgan involvement: renal failure (90%), hepatic dysfunction (60%), and myocarditis (70%). Mortality was associated with inotropic-dependent myocarditis and mechanical ventilation at TPE initiation. Patients requiring intubation had a 50% mortality rate, compared to 14.3% in those who were not intubated. Non-survivors also had elevated lactate levels (>4 mmol/L) and worsening acid-base status. Four patients required dialysis: three survived. Clinical severity scores increased from admission (mean 3.78) to TPE initiation (mean 4.44), and no patient showed improvement before TPE. Conclusion: Early initiation of TPE may be beneficial in severe leptospirosis, particularly when performed before irreversible cardiopulmonary failure. The combined use of TPE and corticosteroids may provide additional benefit by mitigating immune-mediated tissue injury. These findings support further investigation into the timing and patient selection criteria for TPE in severe leptospirosis, particularly in resource-limited settings.

Abstract:

Kenya’s recent achievement of eliminating Human African Trypanosomiasis (HAT) as a public health problem, as validated by the World Health Organization, provides a critical model for the systematic defeat of complex zoonotic diseases. This success, marking the end of indigenous transmission since 2018, emerged from a century-long struggle against the disease in historically endemic foci like the Lambwe Valley, where it severely constrained socio-economic development. The elimination architecture rested on three synergistic pillars: a decentralized, community-based surveillance system that transformed health workers into frontline epidemiological sensors; the operationalization of a One Health framework through the Kenya Tsetse and Trypanosomiasis Eradication Council (KENTTEC), enabling integrated vector control and livestock treatment; and a robust post-elimination vigilance system integrated into national surveillance. Key innovations included the deployment of rapid diagnostic tests, targeted use of insecticide-treated targets, and the adoption of oral therapeutics like fexinidazole. Kenya’s experience demonstrates that sustained elimination of a zoonosis requires transitioning from isolated interventions to a coordinated, cross-sectoral system. The model offers technically replicable and economically justifiable lessons for global efforts targeting the 2030 roadmap goals for neglected tropical diseases. This case proves that with strategic integration, political commitment, and sustained vigilance, the eradication of long-standing zoonotic threats is an achievable goal.

Abstract: Respiratory syncytial virus (RSV) resurged in many regions after the relaxation of stringent non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic. Here, we characterized the epidemiological patterns and molecular evolution of RSV among pediatric inpatients with acute respiratory tract infections (ARTIs) on tropical Hainan Island, China. We retrospectively analyzed 32,329 children (≤18 years) hospitalized at Hainan Women and Children’s Medical Center from January 2021 to December 2024. RSV positivity was determined using targeted next-generation sequencing. In total, 4483/32,329 (13.86%) patients were RSV-positive, with a high positivity in 2021 (20.27%, 957/4721), marked suppression in 2022 (2.03%, 106/5227) during intensive NPIs, and a rebound in 2023–2024 (15.31%, 1490/9732; 15.26%, 1930/12,649). RSV positivity was higher in boys than girls (14.42% vs. 13.00%). Seasonality shifted from a summer–autumn peak in 2021 to a spring–summer predominance in 2023–2024. Among 56 sequenced RSV-positive specimens (29 RSV-A; 27 RSV-B), all RSV-A strains belonged to genotype ON1 (lineages A.D.3 and A.D.5.2), and all RSV-B strains belonged to genotype BA9 (lineages B.D.4.1.1, B.D.E.1, and B.D.E.2). Subtype dominance transitioned from RSV-A (2021–2023; mainly A.D.3) to RSV-B in 2024 (all B.D.E.1). Lineage-specific amino-acid and predicted N-glycosylation changes were observed, including loss of the N179 site in A.D.5.2 and acquisition of N258 in B.D.E.1. These findings indicate that RSV circulation on tropical Hainan was strongly suppressed during intensive NPIs and re-established after policy relaxation, accompanied by earlier seasonal activity and clear lineage replacement, underscoring the need for sustained genomic surveillance to inform locally tailored clinical preparedness and immunization strategies.

Abstract: Objective: The aim of this retrospective study was to evaluate clinical and laboratory characteristics in adult patients with neuroinvasive West Nile virus (WNV) infections. We also studied the phylogeny and molecular characteristics of some of the WNV strains. Methods: A retrospective analysis was conducted at “Annunziata” Hub Hospital, a secondary referral facility in Calabria region in Southern Italy. Patients with confirmed WNV infection were included in the study. Biochemical and serological analysis of blood and cerebrospinal fluid (CSF), as well as radiological imaging were done. Sample pre-processing, sequencing and bioinformatic analyses were carried out at IRCCS Sacro Cuore Don Calabria Hospital in Negrar di Valpolicella, Verona, Veneto region in North-East Italy. All the analyses were performed on the same whole blood samples used for the laboratory diagnosis. Results: 9 cases of West Nile encephalitis (WNE) were analyzed, involving 8 males and 1 female, with a mean age of 70.33 years (Range, 60 – 85). Encephalitis was confirmed by the demonstration of specific IgM and IgG antibodies in serum using routine serological screening tests. All the patients had specific IgM antibodies at admission and IgG antibodies were present in 90%. The overall average hospital stay was 20.6 days (range, 6 – 46). Six patients made a full recovery with no neurological sequelae after a meanof 35.3days of acute care.30-day mortality rate was 23%. A 63-year-old man developed a fulminat Guillain-Barré syndrome (GBS) and he died after approximately two months because of severe respiratory complications. Two male patients died after 21 and 13 days, respectively, due to intraparenchimal cerebral hemorrage (ICH) as clinical presentation of WNV encephalitis. A third male patient presented with encephalitis and cauda equina syndrome, complicated by diffuse ICH and a concomitant extensive epidural hematoma. This patient was transferred to a rehabilitation long-term care facility and is still alive after a three-month ‘ follow-up, although he is no longer able to walk. Finally, a 66-year-old male patient presented a severe right Bell’s palsy regressing very gradually in about two months. Phylogenetic analysis shows that our sequences are closely related to other southern-Italian and cluster with Central-Southern-Eastern European sequences, while being evidently separated from northern-Italian and Central-Western European ones, belonging to the sub-lineage 2a of the WNV-2, clustering with sequences from the Central-South-Eastern clade, mainly to Hungary. Conclusions: Cerebrovascular complications of WNE may be an important clinical manifestation of WNV neuroinvasive infection. Preliminary data do not allow us to determine whether our strains, closely related to other southern-Italian and cluster with Central-Southern-Eastern European sequences, really presented an increased neurovirulence.

Abstract:

Background/Objectives: Periprosthetic joint infections (PJIs) remain one of the most challenging complications after arthroplasties due to the ability of pathogens to form biofilms on implant surfaces. Although staphylococci predominate, Gram-negative bacilli, have increasingly been associated with more aggressive clinical courses and diagnostic failure. This study aimed to evaluate the structural characteristics and maturation of E. coli and P. aeruginosa biofilms and to assess the effectiveness of a standardized sonication protocol in disrupting these biofilms and releasing viable cells. Methods: Biofilms of E. coli (ATCC 25922) and P. aeruginosa (ATCC 53278) were grown on polyethylene catheter segments for 24, 48, and 72 hours. Morphological and structural features were assessed by scanning electron microscopy. A standardized sonication protocol was then applied to evaluate its ability to disrupt the extracellular polymeric matrix. Viability of released cells was confirmed by culturing aliquots of the sonication fluid on BHI agar. Biofilms were produced in triplicate for each time point. Results: Both species formed increasingly dense and structured biofilms over time. Mature biofilms exhibited markedly thicker EPS layers compared to 24-h biofilms. P. aeruginosa developed highly complex, multilayered matrices, while E. coli produced characteristic but less elaborate biofilm structures. Sonication consistently disrupted immature and mature biofilms of both organisms, fragmenting the matrix and releasing individual or small clusters of bacterial cells. Cultures from the sonication fluid demonstrated that bacterial cells remained viable following the procedure. Conclusions: The standardized sonication protocol effectively disrupted Gram-negative biofilms at different maturation stages and released viable microorganisms, reinforcing its value as a complementary diagnostic tool for PJIs, especially in chronic or low-grade infections where conventional culture methods show reduced sensitivity.

Abstract:

Concurrent evaluation of the antiparasitic efficacy of synthetic and natural compounds can provide novel insights into the development of anti-Toxoplasma drugs. We assessed 16 synthetic compounds and fractions derived from the leaves of two Tabebuia tree species for their in vitro activity against live parasites, employing strains that express green fluorescent protein and specific identification of bradyzoites with an anti-BAG1 monoclonal antibody. This study successfully identified several promising synthetic compounds with potent anti-Toxoplasma activity and favorable in vitro selectivity profiles, notably pyrazoline 2 and thiazolidinone 9. One thiazolidinone compound exhibited significant activity against extracellular tachyzoites, whereas one tree fraction demonstrated excellent activity against both tachyzoites and bradyzoites. Additionally, their in silico ADMET properties suggest their potential for good in vivo performance and CNS penetration. Although the natural extracts showed less potency in their crude form, they provide a basis for future purification efforts. The simultaneous evaluation of compounds sourced from diverse discovery pipelines can offer valuable insights into the development of drugs that target various biological pathways.

Abstract: This scoping review of original literature published before 1 March 2025 examined the de-mographic, clinical and simple laboratory findings associated with the development of severe leptospirosis. The definition of severe leptospirosis varied in different studies, but for the purposes of this review it included death or patients with a more complicated clinical course. There were 35 articles that satisfied the review’s inclusion criteria. Increasing age was asso-ciated with severe disease in 7 studies. Abnormal respiratory examination findings (18 stud-ies), hypotension (11 studies), oliguria (8 studies), jaundice (7 studies) and altered mental status (4 studies) also helped identify high-risk patients. Abnormal laboratory tests – specifi-cally the complete blood count (17 studies), measures of renal function (16 studies) and liver function (14 studies) – were also associated with severe disease. There was geographical heterogeneity in the clinical phenotype of severe disease, but the presence of hypotension, respiratory or renal involvement had prognostic utility in all regions. Simple bedside findings and basic laboratory tests can provide valuable clinical information in patients with lepto-spirosis. Integration of these indices into early risk stratification tools may facilitate recogni-tion of the high-risk patient and expedite escalation of care in resource-limited settings where most cases of life-threatening leptospirosis are seen.

Abstract: Lung involvement in patients with leptospirosis is associated with a more complicated disease course. However, the demographic and clinical associations of lung involvement are incompletely defined, and its optimal management is uncertain. This retrospective study examined consecutive patients admitted to a referral hospital in tropical Australia, with laboratory-confirmed leptospirosis between January 2015, and June 2024. Lung involvement was defined as new lung parenchymal changes on chest imaging at any point during the patients’ hospitalisation. The demographics, clinical findings and clinical course of the patients with – and without – lung involvement were compared. The median (interquartile range (IQR)) age of the 109 patients was 39 (24-56) years; 93/109 (85%) were male. Lung involvement was present in 62/109 (57%), 55 (89%) of whom had no documented comorbidities. Patients with lung involvement re-ceived antibiotics later in their disease course than those without lung involvement (median (IQR): 5 (4-6) versus 3 (2-5) days of symptoms, p=0.001). Lung involvement was frequently just one component associated with multi-organ failure: patients with lung involvement were more likely to require inten-sive care unit admission than patients without lung involvement (41/62 (66%) versus 15/47 (32%), p< 0.001). Overall, 30/109 (28%) satisfied criteria for acute respiratory distress syndrome (ARDS) and 26/109 (24%) developed pulmonary haemorrhage. Patients with lung involvement received cautious fluid resuscitation, vasopressor support and prompt initiation of additional supportive care – including me-chanical ventilation, renal replacement therapy and extracorporeal membranous oxygenation – guided by the patients’ physiological parameters and clinical trajectory. All 109 patients in the cohort were alive 90 days after discharge. Life-threatening lung involvement can complicate leptospirosis in young and otherwise well individuals. However, in Australia’s well-resourced health system excellent outcomes can be achieved using a standard contemporary approach to the management of a patient with undif-ferentiated infection while a confirmed diagnosis of leptospirosis is awaited.

Abstract: Background: The global incidence of dengue has markedly increased over the last decades. Consequently, the risk for infection has increased significantly. This resulted in record numbers of imported cases in various European countries and elsewhere in 2024 and large numbers of travellers with dengue are treated in the endemic destination countries. Methods: In early 2023, TAK003, a novel, live attenuated vaccine against dengue became available in Germany. At the Berlin Centre for Travel & Tropical Medicine, we delivered 56,459 doses during the first 24 months from February 2023 until February 2025. In order to gain data on the tolerability of the vaccine in travellers, an active follow-up survey was initiated. Results: 30,306 (53.7%) vaccinees agreed to being contacted. Out of those 11,827 (39.0%) completed the anonymous questionnaire ≥4 weeks after the vaccination. Overall, 6,856 (58.0%) were female, 565 subjects (4.8%) reported to have had a prior dengue infection. The average age was 42.1 years (median 35 years, range 4-86 years). The journey to an endemic area had been completed by 6,309 subjects before answering the questionnaire and among those, 46 (0.7%) reported a dengue infection while abroad. All cases were mild, no complications were reported. TAK003 was applied with other vaccines in 7,363 (62.3%) travellers. Local adverse reactions were reported by 5,263 (47.5%) of subjects, mostly local pain. Systemic reactions were reported by 4,891 subjects (41.4%), most frequently fatigue, myalgia, and flu-like symptoms. The majority of adverse events manifested in the second week after vaccination (average 9.3 days, median 8 days) and were mostly limited to a duration of 1-3 days. A macular exanthema was described by 1,844 subjects (15.6%), typically during the second week after the vaccination. Conclusions: Side effects were frequently reported but generally well tolerated. Age groups above 50 years showed a decline of reactogenicity. Co-vaccination was frequent and led to an increase of systemic adverse events. Denominator data of the study population suggest a strong reporting bias towards adverse events. This survey adds evidence on the chronology and characteristics of adverse events associated with TAK003 and may support decision making when vaccinating dengue naïve travellers.

Abstract: Cystic echinococcosis (CE) is an endemic zoonotic disease caused by Echinococcus granulosus, which forms cysts in ungulates’ intermediate hosts. Humans are accidental hosts, and CE affects more than one million people worldwide. Imaging remains the diagnostic gold standard, outperforming serological methods. This study presents an in silico analysis of two glyceraldehyde-3-phosphate dehydrogenase (GAPDH) isoenzymes from E. granulosus (EgGAPDH), isolated from a parasite cell line (EGPE). EgGAPDHs were recognized by sera from CE patients, identified through LC-MS/MS and PCR from metacestodes’ cattle liver. One isoenzyme is intracellular (IC) (UniProt: W6UJ19), and the other is extracellular (EC) (UniProt: W6V1T8). GAPDH is involved in host-parasite interactions and metabolic processes. We characterized the physicochemical properties, linear epitopes, and amino acid domains of EgGAPDH, its hosts and other parasites. W6UJ19 emerged as the most promising isoenzyme as a marker of infection. Molecular dynamics simulations of isoenzymes, performed in the presence or absence of two bisphosphonates (BPs), revealed how drug binding alters conformational epitopes and suggest that enzymatic activity is more likely associated with W6UJ19. Binding affinity analysis using the MMPBSA method revealed that etidronate (EHDP) binds EgGAPDH with greater affinity than phosphate (Pi) and alendronate (AL), in the order: EHDP > Pi > AL.

Abstract: Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the Leptospira genus. Genome editing in Leptospira has been difficult to perform. Currently, the functionality of the CRISPR-Cas system has been demonstrated in species such as Leptospira interrogans. However, the different CRISPR-Cas systems present in most of the 77 species are unknown. Therefore, the objective of this study was to identify the CRISPR-Cas systems present in the genomes of the Leptospira genus using bioinformatics tools. Methods: bioinformatics workflow was followed: the genomes were downloaded from the NCBI database, Cas proteins detection was carried out using the CRISPR-CasFinder and RAST web servers, functional analysis of Cas proteins (InterProScan, ProtParam, Swiss Model, Alphafold3, Swiss PDB Viewer, and Pymol), conservation pattern detection (MEGA12, and Seqlogos), spacer identification (Actinobacteriophages db and BLAST), and bacteriophage detection (Phaster, and Phastest). Results: Cas proteins were detected in 36/77 species of the Leptospira genus, these proteins were (Cas1-Cas9, and Cas12). The proteins were classified into class 1 and class 2 systems, and types I, II, and V. Direct repeats and spacers were detected in 19 species. The direct repeats presented two nucleotide conservation motifs. With the spacer sequences, 270 different bacteriophages were identified. Three intact bacteriophages were detected in the genome of four Leptospira species. Two saprophytic species have complete CRISPR-Cas systems. Conclusions: The presence of Cas proteins, direct repeats, and spacer sequences homologous to bacteriophage genomes suggests a functional CRISPR-Cas system in at least 19 species.

Abstract: HTLV-1/2 coinfection in people with HIV (PWH) has been little studied in the Peruvian Amazon, an endemic area for both viruses. We aimed to estimate its prevalence and describe the main clinical and epidemiological features of co-infected individuals. We conducted a prospective, cross-sectional study (October–December 2023) at the Divi-sion of Infectious Diseases and Tropical Medicine from the Regional Hospital of Loreto, in Iquitos. We performed a screening test (recombinant HTLV I+II ELISA) and confirm the results with INNO-LIA. Among 293 PWH analyzed, 14 (4.1%) were HTLV positive: 1 was HTLV-1 (0.3%; 95% CI: 0.06-0.9), 11 were HTLV-2 (3.8%; 95% CI: 2.1-6.8) and 2 were non-typeable (0.7%; 95% CI: 0.1-2.7). Compared with HIV-monoinfected indi-viduals, coinfected patients were older (55 vs. 39 years; p=0.001) and more often had low education (35.7% vs. 15.4%; p=0.05). In conclusion, HIV–HTLV-2 coinfection is relatively common (~4%) in the Peruvian Amazon, particularly among older, ru-ral-born individuals, underscoring the need for targeted screening and prevention strategies in endemic areas.

Abstract: Kala-azar is associated with lethality rates of up to 10%, even with timely treatment. Early identification of mortality biomarkers can significantly reduce this risk. This study, strengthened by a relatively high number of kala-azar-related deaths, aimed to identify serum cytokines as predictive biomarkers of fatal kala-azar. We compared 48 deceased patients with kala-azar to 42 survivors. The concentrations of IL-1β, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α (TNF-α) were measured by flow cytometry. Cytokine levels, were compared between groups using the Wilcoxon rank-sum test. Receiver-operating-characteristic (ROC) analysis, coupled with Youden's index, defined the optimal diagnostic threshold. Upon admission, IL-8 concentrations were substantially higher in deceased kala-azar patients (median 76.5 pg/mL [IQR 35.2–242.4 pg/mL]) than in survivors (median 26.4 pg/mL [IQR 15.1–47.7 pg/mL]; p &lt; 0.0001). ROC analysis identified 49.3 pg/mL as the optimal cutoff. When rounded to the clinically convenient value of 50 pg/mL, IL-8 predicted a fatal outcome with an area under the curve of 0.75, sensitivity of 70.8%, and specificity of 76.2%. In contrast, IL-1β, IL-6, IL-10, IL-12, and TNF-α showed no significant prognostic utility. Our findings suggest that IL-8 levels equal to or greater than 50 pg/mL are a reliable predictor of fatal kala-azar.

Abstract: Background: Chikungunya virus (CHIKV) has historically been regarded as a low-fatality infection; however, growing evidence from diverse study designs demonstrates a substantial mortality burden during large-scale epidemics. In 2025, Réunion Island experienced a major CHIKV outbreak, raising renewed concerns about its fatal impact. Methods: We conducted an ecological time-series analysis of all-cause mortality in Réunion Island from March to May 2025, focusing on individuals aged ≥65 years. Excess deaths were estimated using a log-linear model adjusted for long-term trends and seasonality, with a baseline derived from the preceding five years. Observed deaths were compared to officially reported CHIKV fatalities and contextualized with data from previous epidemics worldwide. Results: An estimated 208 excess deaths occurred among older adults during the three-month epidemic, corresponding to a mortality rate ratio of 1.34 (95% CI: 1.22–1.47; p < 0.000001) in April 2025. Officially, only 27 deaths were attributed to CHIKV during this period (17 direct, 10 indirect), highlighting a substantial discrepancy between excess and reported mortality. Similar patterns have been repeatedly documented across different regions, including India (2006), the French Caribbean (2014), Puerto Rico (2014), Brazil (2015–2023), Jamaica (2014), and Mauritius (2006), where thousands of excess deaths far exceeded confirmed counts. Conclusions: Chikungunya epidemics are consistently associated with substantial underrecognized mortality worldwide. Routine surveillance relying solely on laboratory confirmation underestimates the true burden of disease. Integrating excess mortality analysis, strengthening diagnostic and postmortem investigations, and implementing timely mitigation measures are essential to accurately assess and reduce preventable deaths during future CHIKV outbreaks.

Abstract: The increasing incidence of Streptococcus suis (S. suis)-associated meningitis, which is significantly associated with sudden deafness, necessitates further investigation into its clinical characteristics and outcomes. To evaluate the clinical features and outcomes of S. suis-associated meningitis in a tertiary hospital in Bali, Indonesia, this cross-sectional study reviewed the medical records of patients diagnosed with suspected S. suis-associated meningitis from 2022 to 2024. The diagnosis of meningitis was based on the presence of fever, headache, neck stiffness, and altered mental status. Blood cultures were performed to confirm S. suis-associated meningitis. The diagnosis was confirmed when a blood culture was positive for S. suis and was probable based on a history of consuming raw pork. Both cases were categorized as S. suis-associated meningitis. Out of 67 patients, 34 (50.7%) presented with deafness. Common symptoms of meningitis include fever (100%), neck stiffness (100%), and severe headache (28.4%). Blood cultures revealed S. suis in 10.5% of cases. The total number of S. suis-associated meningitis cases was 31 out of 67 (46.3%), comprising probable cases (30, 44.8%) and confirmed cases (7, 10.4%). S. suis bacteremia caused deafness in 85.7% of cases. This study found no significant association between raw pork consumption and deafness (p = 0.151; odds ratio = 1.538, 95% CI = 0.584-4.055). The overall case fatality rate was 4.5%, with a 1.5% mortality rate among patients with confirmed S. suis-associated meningitis. The most common complications noted in this study were septic shock and sudden deafness. Increased awareness and preventive measures regarding pig-related exposure are crucial for managing this emerging public health threat.