Tropical biomedicine最新文献

The primary pharmaceutical treatments for the cutaneous leishmaniasis (CL) are linked to a range of negative complications. The development of innovative pharmacological agents aimed at enhancing cellular immune responses could denote a promising therapeutic approach for CL therapy. Here, the present study investigated the impact of phellandrene (PR), a cyclic monoterpene found in various plant species, on Leishmania tropica, focusing on its antileishmanial properties, immunomodulatory effects, antioxidant activity, and capacity to induce apoptosis. The antileishmaial and synergistic properties effects of PR alone and in conjunction with glucantime (GCT) on L. tropica promastigote and amastigote forms were investigated. As well, the influence of PR on the immunomodulatory-associated genes, antioxidant-associated genes, plasma membrane integrity, ROS generation, apoptosis induction, and nitric oxide (NO) production was assessed. We found that PR principally in conjunction with GCT notably reduced by the number of promastigote and amastigote forms within macrophages a dose-dependent reduction (p%lt;0.001). We found a significant upregulation in the expression of the iNOS, interferon gamma (IFN-g), and tumor necrosis factor (TNF-a) genes in infected macrophages subsequent to treatment with RP, particularly in conjunction with GCT. Conversely, there was a notable downregulation in the expression of interleukin 10 (IL-10), superoxide dismutase (SOD), and catalase (CAT) genes; whereas, results in a substantial rise in NO release in macrophage cells (p<0.001). PR, GCT, PR+GCT resulted in a dose-dependent enhancement of caspase-3 activity, increase in plasma membrane integrity, and reactive oxygen species (ROS) production (p<0.001). The findings indicate that the PR mainly along with GCT has a substantial effect on the inhibition and elimination of Leishmania parasites in controlled laboratory environments. Although certain cellular mechanisms of action have been recognized, including immune modulation cellular immunity response, the induction of apoptosis, ROS and NO production, reducing the antioxidant activity, and affecting membrane integrity in response to Leishmania, additional research is required to interpret its effectiveness in both animal models and human participants.

Leptospirosis is an infectious and zoonotic disease caused by pathogenic spirochetes of Leptospira. It affects global health issues, especially endemic in tropical and subtropical regions. This meta-analysis assessed the prevalence of leptospirosis in Malaysia and explored factors contributing to variability studies. A systematic review was conducted, which identified 301 records from six key databases. After eliminating duplicates and applying the inclusion criteria, 24 studies were selected for qualitative and quantitative analysis. Pooled prevalence and heterogeneity were calculated using a random-effects model. The pooled prevalence of leptospirosis was 26.7% (95% CI: 20.5-34.0%) with high heterogeneity (I² = 97.43%, p < 0.001). Thus, the reported prevalence decreased from 29.7% (2001-2010) to 18.1% (2011-2020). Additionally, cross-sectional studies reported a 27.4% prevalence, while prospective studies showed a higher rate (53.0%). Diagnostic methods affected the results, with MAT reporting 29.8% and combined PCR-MAT showing the highest prevalence at 31.9%. Leptospirosis remains common in Malaysia, demonstrating the need for better public health interventions, especially in flood-prone areas. Diagnostic techniques and surveillance must be improved and essential for better detecting and managing the disease.

Cat scratch disease (CSD) is a worldwide preventable zoonotic disease caused by a Gram-negative bacteria, Bartonella henselae (B. henselae). A retrospective study was performed to determine the seroprevalence of B. henselae and to identify its associated factors among cat scratch disease suspected patients in Malaysia from 2015-2019. A total of 3525 serum samples from Malaysian government and private hospitals were tested using an indirect immunofluorescence antibody (IFA) test kit. The IgM seropositivity of B. henselae was 41.8% and this rate showed an increasing trend each year. Among the states, Selangor had the highest B. henselae infection rate (23%), while Perlis had the lowest (1%). Further analysis revealed a significant association between B. henselae infection and female gender, as well as the younger age group between 10-19 years old (AOR 1.20, 95% CI: 1.04, 1.38; AOR 2.84, 95% CI: 2.13, 3.79). Patients presenting with fever, axillary and inguinal lymphadenopathy were found to be at a higher risk of B. henselae infection with AOR 1.73, 95% CI: 1.43, 2.09; AOR 3.71, 95% CI: 2.01, 6.84; AOR 1.91, 95% CI: 1.05, 3.48 respectively. In conclusion, our study demonstrates that B. henselae infection is not uncommon among at-risk patients in Malaysia. Clinicians should have a high level of suspicion when encountering patients with significant clinical presentations and risk factors of CSD.

Oral opportunistic pathogens resulting from poor oral health can lead to serious issues in elderly and immunocompromised individuals, including lower respiratory tract infections and aspiration pneumonia (AP). The main objective of this study is to evaluate the antibacterial effect 1'S-1'-acetoxychavicol acetate (ACA) isolated from Alpinia conchigera rhizome extract against selected oral opportunistic pathogens which are Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa. In this study, a total of 13 respondents were recruited to obtain the clinical isolates of selected oral opportunistic pathogens. From these samples, 3 strains of S. aureus, 1 strain of S. pneumoniae, 3 strains of K. pneumoniae and 1 strain of P. aeruginosa were obtained and further tested. To achieve the objective, disc diffusion assay (DDA), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time kill assay were carried out to determine the antibacterial properties. Based on DDA results, ACA displayed good antibacterial activity against clinical isolates and ATCC strains of S. aureus, S. pneumoniae and P. aeruginosa with the zone of inhibition recorded at 25.07 ± 0.09 mm, 36.83 ± 0.85 mm and 14.00 ± 0.82 mm respectively while clinical isolates and ATCC strains of K. pneumoniae did not show any inhibition diameter. The range of MIC and MBC values for ACA recorded were between 0.39 mg/mL until 12.50 mg/mL. ACA exhibited both bacteriostatic and bactericidal properties mostly when treated with concentration of 2 × MIC and MIC at different time intervals. In conclusion, ACA possesses antibacterial effect against clinical isolates and ATCC strains of S. aureus, S. pneumoniae, K. pneumoniae and P. aeruginosa.

Rodent-borne zoonotic diseases, including hantavirus pulmonary syndrome, leptospirosis, and rickettsiosis, significantly impact public health. However, there is a limited understanding of these diseases in Southeast Asia, a region emerging as a hotspot for zoonotic diseases. To address this, the authors reviewed the recent developments in prevalent rodent-borne diseases in Southeast Asia from 2000 to 2024. A comprehensive literature search was conducted in databases such as PubMed, Scopus, Web of Science, Google, and Google Scholar, using keywords like "rodent-borne diseases," "prevalence," "epidemiology," "humans," and "Southeast Asia.". Leptospirosis is widespread in several Southeast Asian countries. Malaysia and Thailand have established effective national surveillance systems, tracking annual cases and fatalities. For viral diseases, such as haemorrhagic fever with renal syndrome, most countries lack a structured reporting system. Vector-borne rodent diseases deal with similar underreporting, with diseases like bartonellosis and borreliosis noted only anecdotally, even in relatively-resourced countries like Thailand and Malaysia. This underreporting is concerning, as the causative pathogens are often detected in rodent reservoirs and their arthropod vectors around these regions during biosurveillance studies. Invasive rodents have long infiltrated into human environments and thrive as successful commensal species, facilitating the transmission of zoonotic pathogens to humans. Therefore, robust surveillance systems, often essential in disease control are urgently needed across the Southeast Asian region. Further scientific research and biosurveillance studies are crucial in understanding the impact of these diseases on human health, rodent populations, and the environment.

Soil-transmitted helminths (STH) are among the most common parasitic infections associated with neglected tropical diseases (NTDs), particularly in regions with poor sanitation and hygiene. The prevalence of STH is disproportionately high in middle- to low-income countries due to inadequate infrastructure and hygiene practices. This study aimed to identify risk factors associated with STH infections among native communities in the rural Simalungun District, North Sumatra, Indonesia. A cross-sectional study was conducted among 592 native Simalungun Bataknese individuals living and working in 14 villages across the district. Participants were interviewed regarding sanitation, hygiene practices, and demographic factors, while fecal samples were collected for parasitological examination using the direct smear and Kato-Katz methods. All laboratory analyses were conducted at the Parasitology Laboratory, Faculty of Medicine, Universitas Sumatera Utara, and interpreted by a parasitologist. Statistical analysis was performed using chi-square tests and multivariate logistic regression to identify significant risk factors for STH infection. The overall STH prevalence was 14.5% (86/592 participants), with identified species including Trichuris trichiura (33.7%), hookworm (31.4%), Ascaris lumbricoides (11.6%), and mixed infections (23.3%). Multivariate analysis revealed two significant risk factors for STH infection: consumption of uncooked drinking water (AOR 2.05, 95% CI 1.10-3.81, p=0.000) and not using a toilet with a septic tank (AOR 2.38, 95% CI 1.46-3.87). These findings highlight the critical role of sanitation and water safety in reducing STH transmission. Improving access to safe drinking water and proper sanitation facilities is essential for controlling STH infections in rural communities.

Assessing the efficacy and safety of potential therapeutics for multidrug-resistant (MDR) Acinetobacter baumannii infections necessitates the use of in vivo models, typically involving mice and highly virulent isolates of the bacterium. In this study, we investigated the clinical isolate Ab35 of MDR Acinetobacter baumannii to determine its ability to infect and induce pneumonia in a mouse infection model. Immunocompetent BALB/c mice were infected through the oropharyngeal aspiration route. Enlarged spleen germinal center, reduced lung air space, and infiltration of immune cells within the lungs of infected mice were observed. Notably, there were no significant changes in body weight among the infected mice. Clinical scores were elevated from days 5 to 10 post-infection in groups administered with 1×10⁸ CFU/ml Ab35 (score: 3) and 1×10¹⁰ CFU/ml Ab35 (score: 6). In contrast, immunosuppressed mice exhibited clinical scores as early as 5 minutes after inoculation with 1×10¹⁰ CFU/ml Ab35, with observations beginning on day 2. Furthermore, a lung burden of 1.32 log10 CFU/ml (21 CFU/ml) was recorded in immunocompetent mice inoculated with 1×10¹⁰ CFU/ml Ab35. These findings suggest that infection with clinical isolates of A. baumannii in BALB/c mice through oropharyngeal aspiration can lead to symptomatic infections, including pneumonia. Thus, this study supports the feasibility of utilizing an in vivo mouse infection model with immunocompetent mice and clinical isolates of A. baumannii for future therapeutic evaluations.

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, releases extracellular vesicles (EVs) that impair macrophage functions and circulate bacterial components to modulate the host immune response. While EVs are increasingly investigated as new vaccines and biomarkers, studying MTB EVs is challenging due to the slow growth rate and pathogenic properties of MTB. Mycolicibacterium smegmatis (MSMEG), a non-pathogenic surrogate with a faster growth rate, offers a safer and more convenient option for laboratory studies due to its similarities to MTB. In this study, we explore the antigenic properties of MSMEG EVs to assess their potential use in developing safer tuberculosis vaccine strategies. Through an immunoproteomics approach that combines comprehensive protein separation by OFFGELTM fractionation, Western blot analysis and mass spectrometry, we identified alcohol dehydrogenase (ADH) - a 46 kDa protein involved in mycobacterial cell wall synthesis - as an antigenic protein from MSMEG EVs. Our findings suggest that MSMEG EVs-derived ADH could improve tuberculosis vaccine formulations and potentially be used for coimmunization with the BCG vaccine, offering new and safer strategies to combat tuberculosis.

Enterovirus A71 (EV-A71) is a common pathogen of hand, foot, and mouth disease (HFMD) frequently contracted by young children. The virus commonly transmits by faecal contamination, and possibly through direct or indirect contact via fomite and respiratory routes. Transmission via fomites and the respiratory route via airborne or droplets is not clearly understood. Mouse-adapted EV-A71 (MP4 EV-A71) was used to study the effect of EV-A71 fomite-induced and respiratory transmission in one-week-old hamsters. For fomite transmission, the hamsters were exposed to coins contaminated with 10⁴ 50% tissue culture infectious dose (TCID₅₀) of EV-A71. All hamsters survived, showing self-limiting progression, and no significant loss of weight, but low viral RNA loads were detected in the oral washes and the mother of the exposed hamsters developed low neutralization titers. Despite the low fomite doses, transmission likely occurred in these hamsters. In respiratory transmission using an aerosol test chamber which was placed within the biological safety cabinet, self-limiting progression were seen in contact hamsters exposed to index hamsters orally infected with 10⁴ TCID₅₀ of EV-A71. Index hamsters showed infection and died, but all contact hamsters survived. Computational fluid dynamics analysis showed that the transmission risk of the virus was heavily dependent on the cabinet airflow. Due to the strong convection flow, the exhaled air from the index-infected hamsters were defected, reducing the risk of infection to the contact hamsters. Taken together, our findings suggest that compared to control oral infections, fomites and respiratory transmission is less effective, but could still occur. This first animal model transmission study can be further refined with different virus dosages, exposure time and air flow to study fomite and respiratory transmission of EV-A71 in hamsters.

Garcinia mangostana is a tropical tree native to India, Sri Lanka, and Southeast Asia. In Traditional Medicinal Systems (TMS), decoctions and infusions prepared from mangosteen fruits have effectively treated skin lesions and various inflammatory conditions. Researchers have also reported its extensive biological activities, viz. antimicrobial, antioxidant, anticancer, antidiabetic, neuroprotective, and cardioprotective effects. This literature review comprehensively describes the biological potential of G. mangostana over the last twenty-five years. It includes a discussion of the bioactive compounds of G. mangostana and their extraction, purification, and characterization processes. Antimicrobial, anticancer, antitumorigenic, antidiabetic, anti-inflammatory, neuroprotective, and antiparasitic activities are discussed in detail. Furthermore, the paper addresses the main obstacles associated with using mangosteen extracts and suggests ways to overcome these challenges. The medicinal properties of G. mangostana are primarily attributed to a-mangostin and other bioactive xanthones. However, other bioactive compounds with potential therapeutic activities remain not fully characterized. Therefore, developing effective extraction methods for these bioactive compounds, along with their characterization, possible bioactivities (pharmacodynamics), and any synergistic effects, is essential. Additionally, pharmacokinetic studies, including absorption, distribution, metabolism, excretion, and toxicity (ADMET), are necessary. It is also worth considering plant parts other than the pericarp.