Medicine and Pharmacology

Abstract: Background: Intravenous meropenem and ceftazidime are the preferred antibiotics for the intensive phase treatment of melioidosis. Most patients receive intravenous ceftazidime via elastomeric infusers to complete treatment as outpatient parenteral antimicrobial therapy (OPAT). Concerns regarding meropenem’s stability in continuous infusion limit options when ceftazidime cannot be used. Methods: We reviewed all cases of melioidosis managed at Cairns Hospital from 2016 to 2026 and documented the rationale for patients receiving intravenous meropenem as a continuous infusion as OPAT. We recorded each Burkholderia pseudomallei isolate’s MIC for meropenem and the patients’ creatinine clearance, continuous infusion dose, serum meropenem concentrations, treatment duration and clinical course. Results: In 560 cases of melioidosis, 9 (2%) received meropenem as a continuous infusion as OPAT. This was due to an adverse drug reaction (ADR) to ceftazidime in 6/9 patients. The isolates’ median (range) MIC for meropenem was 1 (0.5-1) mg/L. All patients received twice daily elastomeric infusers; initial dosing was 1.5g 12-hourly in 5 patients and 3g 12-hourly in 4 patients. The initial median (range) meropenem random concentration was 6.5 (2.3-18.1) mg/L. The meropenem dose was increased in 2 patients following therapeutic drug monitoring (TDM). One patient was changed from meropenem to ceftazidime due to eosinophilia without end-organ sequelae; there were no other ADRs. All patients achieved clinical cure. Conclusion: Twice daily continuous meropenem infusions administered as OPAT are an alternative treatment option for select patients with melioidosis where ceftazidime cannot be used. The use of TDM can overcome concerns regarding stability and degradation in extended infusions.

Abstract: Background: Lyssaviruses remain a global public health threat, requiring broad-spectrum, high-potency neutralizing antibodies as part of recommended human rabies post-exposure prophylaxis (PEP). A humanized monoclonal antibody cocktail, SYN023, is approved for PEP in China and is under global regulatory review. Its epitope mapping data are promising. However, the neutralization breadth across diverse lyssaviruses and the reliability of pseudovirus-based neutralization assays still require comprehensive validation to support worldwide regulatory approval and clinical use. Methods: First, the correlation between authentic lyssaviruses virus and pseudotyped viruses neutralization was established experimentally to verify the reliability of the pseudovirus-based neutralization assay. Second, epitope mapping was performed using a highly virulent rabies virus (RABV) variant (New York City strain: NYC) provided by the U.S. Department of Agriculture, followed by in vivo PEP efficacy studies in a standardized canine model to functionally validate the mapped epitopes. Third, the neutralizing activity of SYN023 was evaluated against a phylogenetically diverse panel of non-RABV lyssaviruses and directly benchmarked against clinically validated comparator monoclonal antibodies, thereby providing robust, quantitative empirical evidence supporting its broad-spectrum neutralization capability. Results: A strong positive correlation was observed between neutralization titers elicited by authentic lyssaviruses and pseudotyped viruses (Pearson R2 = 0.83, P < 0.0001), validating the pseudovirus-based assay as a robust surrogate for authentic virus neutralization. Specifically, SYN023 recognized and potently neutralized the epitope mapped on the prototypic NYC RABV strain. The in vivo PEP studies conducted in a standardized canine challenge model, using the NYC strain as the challenge virus, demonstrated high protective efficacy at SYN023 doses ranging from 0.1 to 0.5 mg/kg. Furthermore, SYN023 exhibited broad, potent, and reproducible neutralizing activity against a phylogenetically diverse panel of non-RABV lyssaviruses, including European bat lyssavirus 1 (EBLV1), European bat lyssavirus 2 (EBLV2), Australian bat lyssavirus (ABLV), Bokeloh bat lyssavirus (BBLV), Taiwan bat lyssavirus 1 (TWBLV1), Taiwan bat lyssavirus 2 (TWBLV2), Kotalahti bat lyssavirus (KBLV), Divača bat lyssavirus (DBLV), Gannoruwa bat lyssavirus (GBLV), Duvenhage virus (DUVV), Khujand virus (KHUV), Aravan virus (ARAV), Mokola virus (MOKV), Lagos bat virus (LBV) and Shimoni bat virus (SHIBV). Notably, SYN023 achieved robust neutralization of MOKV (EC50 = 14.74 µg/mL), whereas clinically referenced monoclonal antibodies—Rabishield, Ormutivimab and GR1801—exhibited no detectable neutralizing activity against MOKV even at concentrations up to 1,000 µg/mL. This pan-lyssavirus neutralizing capacity was attributable mechanistically to SYN023’s targeting of a highly conserved conformational epitope within the viral glycoprotein, which is structurally preserved across all major lyssavirus phylogroups. Conclusion: This study demonstrated that the pseudovirus-based neutralization assay is a reliable surrogate platform. In addition, it confirmed the functional accuracy of the epitope mapping strategy, showed the protective efficacy against a virulent RABV challenge in dogs, and demonstrated the broad neutralization spectrum of the SYN023 antibody cocktail against both RABV and a phylogenetically diverse panel of non-RABV lyssaviruses.

Abstract: Paederus dermatitis is an acute irritant contact dermatitis caused by inadvertent contact with rove beetles of the genus Paederus (Coleoptera: Staphylinidae). The condition may be difficult to recognize in individuals and healthcare professionals from non‑endemic regions because the characteristic skin lesions can mimic other inflammatory, infectious, or vesiculobullous dermatoses. The causative toxin, pederin, is associated predominantly with female beetles and is produced by endosymbiotic bacteria of the genus Pseudomonas. We present a series of cases of Paederus dermatitis observed in Russian physicians working in Nicaragua. Several hours after presumed contact with Paederus beetles, the patients developed burning and mild pruritus followed by erythematous macules and streak‑like lesions. Over the following days, grouped vesicles and non‑tense bullae developed, with subsequent erosions, crusting, and post‑inflammatory hyperpigmentation and hypopigmentation. The diagnoses were established clinically on the basis of the characteristic morphology, exposure history, and epidemiological setting. Conservative treatment resulted in gradual resolution of the inflammatory lesions within approximately 2–3 weeks, with residual post‑inflammatory hyperpigmentation. This case series highlights the diagnostic value of recognizing the characteristic linear and bizarrely configured lesions of Paederus dermatitis, particularly in healthcare professionals working in endemic regions.

Abstract: Background: The zoonotic epidemic of sporotrichosis caused by Sporothrix brasiliensis has expanded throughout Brazil and other countries, with a rise in deep forms of disease. Detailed comparative data on presentation, treatment and outcome of cutaneous and deep disease are needed to follow how Brazilian cohorts are evolving. Methods: Retrospective observational cohort of patients with sporotrichosis treated at a quaternary university hospital in Belo Horizonte between 2011 and 2026, restricted to culture-positive cases. Localized cutaneous disease was compared with deep infection using logistic regression adjusted for age and sex. Results: Of 313 patients, 213 had a positive culture. Median age was 41 years and 54.0% were women. Lymphocutaneous disease predominated (54.0%) and contact with cats was reported by 53.1%. Median treatment duration was 150 days. Among the 101 patients with a defined outcome, 97 were cured (96.0%), with no documented treatment failure. All four sporotrichosis-related deaths occurred in the deep infection group, which was independently associated with comorbidity (OR 9.69; 95% CI 2.52 to 37.23) and with an immunosuppressive condition (OR 6.61; 95% CI 1.89 to 23.09). Conclusions: Localized cutaneous sporotrichosis was cured in nearly all patients with documented follow-up, whereas mortality was confined to deep infection associated with comorbidity and immunosuppression.

Abstract: Leishmaniasis is a widely distributed vector-borne neglected tropical disease for which current therapeutic options remain suboptimal because of toxicity, emerging drug resistance, and limited induction of long-term protective immunity. Immunotherapeutic approaches that enhance host protective immune responses therefore represent an attractive alternative strategy. In this study, we evaluated the immunotherapeutic efficacy of recombinant Leishmania (L.) infantum eukaryotic initiation factor (LieIF) in BALB/c murine models of cutaneous (Leishmania (L.) major) and visceral (Leishmania (L.) infantum) leishmaniasis. Mice received recombinant LieIF after infection, and disease progression, parasite burden, humoral and cellular immune responses and immune-related gene expression were assessed. LieIF treatment significantly attenuated lesion progression in cutaneous leishmaniasis and reduced parasite burden in visceral disease model. Therapeutic efficacy was associated with enhanced Th1-associated immune responses, including increased frequencies of IFN-γ-producing CD4⁺ lymphocytes, increased IL-12-producing cells, and elevated expression of the Th1-associated genes (transcription factor Tbx21 and IFN-γ). In the cutaneous model, treatment also reduced Leishmania-specific IgG1 responses, whereas antibody isotype responses were largely unchanged in visceral leishmaniasis, indicating that protection was primarily associated with cellular rather than humoral immune modulation. The demonstration of therapeutic efficacy in two distinct experimental models highlights the broad immunomodulatory capacity of LieIF. Collectively, these findings identify LieIF as a promising host-directed immunotherapeutic candidate for leishmaniasis and provide a strong rationale for further studies to optimize treatment regimens, elucidate its mechanisms of action, and evaluate its efficacy in combination with conventional antileishmanial chemotherapy.

Abstract: Bundibugyo virus disease, caused by Bundibugyo virus (Orthoebolavirus bundibugyoense), is a severe human ebolavirus disease with substantial mortality, unresolved reservoir ecology, limited diagnostic implementation, and no licensed vaccines or therapeutics specifically approved for this ebolavirus species. The May 2026 public health emergency in the Democratic Republic of the Congo and Uganda renewed the need for a focused synthesis of Bundibugyo virus-specific diagnostics and medical countermeasures. This review synthesizes peer-reviewed literature, preprints, and official public-health documents on diagnostics, antivirals, therapeutics, vaccines, and post-exposure prophylaxis. Comparative evidence from Ebola virus, Sudan virus, Marburg virus, and pan-filovirus platforms is included only where it clarifies Bundibugyo virus-specific evidence, exposes unsupported extrapolation, or defines preparedness gaps. The 2007–2008 outbreak showed that assays optimized for known filoviruses can miss divergent ebolaviruses; the 2026 outbreak underscored the importance of diagnostic breadth, sequencing-based confirmation, decentralized laboratory capacity, and regional coordination. Clinical and immunological data indicate that Bundibugyo virus cannot be reduced to an Ebola virus-like model. Countermeasure evidence remains largely preclinical: recombinant vesicular stomatitis virus vaccines expressing Bundibugyo virus glycoprotein provide the strongest direct animal protection data, whereas antiviral and antibody-based evidence varies widely and requires careful separation of direct Bundibugyo virus data from platform-based extrapolation.

Abstract: Whole-genome sequencing (WGS) is central to outbreak response for high-consequence ribonucleic acid (RNA) viruses, but useful genomes depend on workflow design, sample quality, biosafety, diagnostic breadth, infrastructure, and bioinformatics as much as sequencing platform. The 2026 Bundibugyo virus disease outbreak in the Democratic Republic of the Congo and Uganda provides a case example. Bundibugyo virus (BDBV) was already known from the 2007–2008 Uganda and 2012 Democratic Republic of the Congo outbreaks, but sparse historical genome sampling, Ebola virus-centered diagnostic assumptions, non-specific febrile and viral hemorrhagic fever presentations, and difficult field conditions created a need for broad differential diagnosis, rapid species assignment, and representative genome generation. This Review compares outbreak WGS strategies by the degree of prior viral sequence knowledge required, distinguishing direct RNA sequencing, random-primed complementary DNA (cDNA) sequencing, sequence-independent amplified cDNA sequencing, background-depleted or particle-enriched cDNA sequencing, probe-based hybrid capture, tiled amplicon sequencing, portable field sequencing, culture-derived sequencing, and associated bioinformatics workflows. For BDBV-like outbreaks, the most defensible strategy is staged and adaptive: broad viral hemorrhagic fever and febrile-illness differential testing at recognition; Filoviridae-wide testing when filovirus disease remains plausible; divergence-tolerant first-genome recovery; quantification-cycle-informed sequencing prioritization without BDBV-only diagnostic narrowing; validated amplicon scale-up; and representative sequencing across locations and time.

Abstract: The “doxycycline deficiency syndrome” is a colloquial term used in tropical Australia to describe the overlapping, non-specific findings seen in leptospirosis, Q fever, and the rickettsial diseases scrub typhus and Queensland tick typhus (QTT). A laboratory confirmed diagnosis is frequently delayed, however, early differentiation of these potentially life-threatening infections has important implications for clinical management. We examined consecutive laboratory-confirmed cases of leptospirosis, Q fever, and rickettsial diseases managed at a referral centre in tropical Australia. The patients’ symptoms, clinical signs and simple laboratory and radiology investigations at presentation were compared. There were 111 cases of leptospirosis, 59 cases of Q fever, and 34 cases of rickettsial disease (17 cases of QTT and 17 of scrub typhus). Patients with leptospirosis had a shorter duration of symptoms and were more likely to have gastrointestinal symptoms, arthralgia, haemoptysis, hypotension, conjunctival suffusion and abnormal chest auscultation at presentation than patients with the other infections. They were more likely to have renal impairment and an elevated creatine kinase but less likely to have an elevated serum ferritin and serum lactate dehydrogenase. Patients with leptospirosis were more likely to have alveolar and multilobar changes on chest imaging. Patients with Q fever were more likely to have abnormal liver function tests at presentation but were more likely to have preserved renal function and normal chest imaging. Patients with rickettsial disease were more likely to have a rash, an eschar, lymphadenopathy and splenomegaly. Overall, 76/204 (37%) required ICU admission, of whom 56 (74%) had leptospirosis, but all 204 patients survived to hospital discharge. Leptospirosis, Q fever, and rickettsial diseases can have a similar presentation but simple clinical, laboratory and imaging findings can help distinguish these infections and expedite their optimal management.

Abstract: (1) Background: Indonesia faces the dual challenge of a high tuberculosis (TB) burden and increasing drug resistance. Conventional molecular diagnostics frequently fail to detect isoniazid resistance and nontuberculous mycobacteria (NTM). This study evaluates a domestic multiplex Open PCR system in Medan, Indonesia. (2) Methods: From July to November 2025, 1,569 sputum specimens from suspected TB pa-tients were analysed using the Indigen MTB/NTM/DR-TB Real-time PCR Kit Gen 2. (3) Results: Mycobacterial DNA was detected in 421 specimens (26.8%). Among these, 396 (94.1%) were drug-susceptible TB, while 16 (3.8%) showed resistance, predominantly INH mono-resistance (n=14; 0.89% of total). Additionally, 9 cases (2.1%) involved NTM or TB-NTM co-infections. Tertiary hospitals showed significantly higher positivity rates (33.5%) than primary care (18.9%; p < 0.001). TB status was significantly associated with male (p = 0.0052) and older age (p = 0.006), whereas resistance profiles and NTM distribu-tion were consistent across all demographic groups (p > 0.80). (4) Conclusions: The Open PCR system effectively identified INH resistance and NTM cases overlooked by standard rifampicin-only assays. By bridging diagnostic gaps across a decentralized referral network, this facilitates rapid and targeted therapy. Integrating multiplex domestic innovations into national diagnostic algorithms is essential for achieving Indonesia’s TB elimination targets.

Abstract: Background Pre-travel health consultations require individualised risk assessment across itinerary, destination epidemiology, traveller characteristics, vaccine history, comorbidities, medication profile, pregnancy status, immune status, activities, timing, and access to care [8,10,11]. Artificial intelligence (AI), particularly large language models (LLMs), may support pre-consultation education, structured history collection, guideline retrieval, multilingual communication, and post-consultation reinforcement, but unsafe use may introduce hallucinated, outdated, or insufficiently personalised recommendations [5,6,14,15]. Objectives This scoping review maps the current evidence on AI tools relevant to pre-travel health consultations, characterises implementation gaps, identifies patient-safety risks, and proposes a supervised implementation model for travel medicine clinics [1,28-30]. Methods The review was conducted as a scoping review using the Arksey and O'Malley framework as advanced by Levac and colleagues and operationalised through the JBI scoping review guidance, with reporting aligned to the PRISMA Extension for Scoping Reviews (PRISMA-ScR) [1,28-30]. The review was not prospectively registered. Eligibility was defined by a Population–Concept–Context (PCC) framework. Targeted retrieval was conducted in May 2026 through PubMed/MEDLINE (one direct search string), academic and web-indexed search tools, citation chasing from Journal of Travel Medicine and Travel Medicine and Infectious Disease, and authoritative guideline and regulator websites. The search date range was January 2017 to May 2026. Sources were eligible if they addressed AI or digital decision support in pre-travel health, travel medicine, travel-related clinical decision support, clinical LLM safety, or guidance defining the standard pre-travel consultation. Screening and data charting were conducted by a single reviewer using a structured eligibility checklist (Supplement S2). Results Seventy records were identified, one duplicate was removed, 69 records were screened, 12 reports were sought for retrieval, one record could not be retrieved within the search window, and 11 reports were assessed in full text and included in the synthesis. Included sources comprised four direct pre-travel AI sources, one travel-related decision-support study, four guideline and context sources, and two clinical LLM safety sources. Direct evidence is thin: the only patient-level implementation report involved 26 travellers using a GPT-4 Travel Clinic Assistant in a Singapore tertiary travel clinic, where physicians and travellers reported acceptability and workflow benefit but objective effectiveness outcomes were not measured [3]. A ChatGPT pre-travel advice evaluation found generally readable and comprehensive answers to common questions, but responses lacked sufficient personalisation to itinerary, comorbidity, vaccine history, and cost considerations [2]. Broader clinical LLM evidence indicates that evaluation methods remain heterogeneous and that LLMs may repeat or elaborate false clinical details and hallucinate clinical guidelines in simulated decision-support tasks [13,14,16]. Conclusions Current evidence supports supervised AI augmentation of pre-travel consultations but does not support autonomous AI-led vaccine selection, malaria prophylaxis, contraindication screening, or individualised travel-risk clearance [2-6,14,15,48,50]. Near-term deployment should be restricted to clinician-supervised education, structured intake, source-grounded guideline retrieval, after-visit reinforcement, and escalation-triggered workflow support [4,5,34,49]. Travel medicine specialists, clinic leaders, regulators, and digital health developers should prioritise domain-specific hallucination audits, equity testing across visiting friends and relatives, migrant, older-adult, First Nations Australian, and Pacific Islander travellers, and prospective trials reported under CONSORT-AI, SPIRIT-AI, and TRIPOD+AI standards [31-33,37,38,41-44].

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.