Coinfection of Pseudomonas and Aspergillus has not been previously reported in patients with chronic obstructive pulmonary disease (COPD). A middle-aged, thinly built woman (Body Mass Index: 18.1 kg/m²) who smokes bidi (a type of tobacco) and has a history of exposure to open log fires for cooking, has been suffering from COPD for the last 4 years. She has been taking inhaled betamethasone and tiotropium. Additionally, she had uncontrolled diabetes for a few months. She presented with fever, productive cough, shortness of breath and chest pain for 5 days. She required non-invasive ventilation support for type-2 respiratory failure. Chest X-ray and CT confirmed pneumonia, cavities and abscesses in both lungs. Repeated sputum and bronchoalveolar lavage confirmed coinfections with Pseudomonas aeruginosa and Aspergillus fumigatus, respectively. Along with supportive therapy, she was treated with tablet levofloxacin and injection amikacin for 6 weeks based on culture sensitivity reports, and capsule itraconazole for 6 months. She recovered completely to her baseline COPD and diabetes status. This case study confirms that coinfections can occur in COPD and diabetes, highlighting the need for clinicians to be vigilant for the possibility of such symbiotic coinfections.

BACKGROUND: Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting.
METHODS: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity.
BACKGROUND: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial.
BACKGROUND: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.

UNASSIGNED: This review aims to elucidate the etiologies of brain abscesses in the tropics. Despite the similarities in causes of brain abscesses across global regions, tropical settings manifest distinguishing characteristics, prominently observed on computed tomography or magnetic resonance imaging.
UNASSIGNED: In tropical climates, the leading conditions predisposing individuals to brain abscesses are polymicrobial bacterial infections originating from paranasal sinuses, dental sources, and otitis media. However, the tropics present unique etiologies to be aware of, including Trypanosoma cruzi (Chagas disease), free-living amoebas like Balamuthia mandrillaris, infections from Burkholderia pseudomallei (melioidosis), fungi such as Talaromyces marneffei, and Mycobacterium tuberculosis. Given the differential diagnoses, which include neoplastic, inflammatory, and demyelinating diseases, a stereotactic biopsy coupled with a microbiological assessment remains valuable for accurate diagnosis.
UNASSIGNED: In tropical regions, brain abscesses are a concern when confronted with mass-occupying or other types of brain lesions. Successful clinical management of brain abscesses typically combines surgical intervention and extended anti-microbial treatment. However, specific parasitic invasions like Chagas disease, free-living amoebas, and Entamoeba histolytica necessitate targeted anti-parasitic therapies. Furthermore, international policy efforts should focus on prevention measures in resource limited regions with heightened risks and disease burden.

BACKGROUND: The implementation of digital disease surveillance systems at national levels in Africa have been challenged by many factors. These include user applicability, utility of IT features but also stable financial support. Funding closely intertwines with implementations in terms of geographical reach, disease focus, and sustainability. However, the practice of evidence sharing on geographical and disease coverage, costs, and funding sources for improving the implementation of these systems on the continent is unclear.
OBJECTIVE: To analyse the key characteristics and availability of evidence for implementing digital infectious disease surveillance systems in Africa namely their disease focus, geographical reach, cost reporting, and external funding support.
METHODS: We conducted a systematic review of peer-reviewed and grey literature for the period 2003 to 2022 (PROSPERO registration number: CRD42022300849). We searched five databases (PubMed, MEDLINE over Ovid, EMBASE, Web of Science, and Google Scholar) and websites of WHO, Africa CDC, and public health institutes of African countries. We mapped the distribution of projects by country; identified reported implementation cost components; categorised the availability of data on cost components; and identified supporting funding institutions outside Africa.
RESULTS: A total of 29 reports from 2,033 search results were eligible for analysis. We identified 27 projects implemented in 13 countries, across 32 sites. Of these, 24 (75%) were pilot projects with a median duration of 16 months, (IQR: 5-40). Of the 27 projects, 5 (19%) were implemented for HIV/AIDs and tuberculosis, 4 (15%) for malaria, 4 (15%) for all notifiable diseases, and 4 (15%) for One Health. We identified 17 cost components across the 29 reports. Of these, 11 (38%) reported quantified costs for start-up capital, 10 (34%) for health personnel compensation, 9 (31%) for training and capacity building, 8 (28%) for software maintenance, and 7(24%) for surveillance data transmission. Of 65 counts of external funding sources, 35 (54%) were governmental agencies, 15 (23%) foundations, and 7 (11%) UN agencies.
CONCLUSIONS: The evidence on costing data for the digitalisation of surveillance and outbreak response in the published literature is sparse in quantity, limited in detail, and without a standardised reporting format. Most initial direct project costs are substantially donor dependent, short lived, and thus unsustainable.

Postweaning diarrhea (PWD) is a multifactorial disease caused by different aetiological agents, like viruses or bacteria and where the role of the microbiota remains unclear. The aim of this study was to assess differences between healthy and diarrheic weaned pigs concerning the prevalence of pathogens and changes in the intestinal microbiota. Eighteen farms with PWD were selected and 277 fecal samples were collected (152 diarrheic vs 125 healthy). Presence of Rotavirus A (RVA), B (RVB), C (RVC) and Porcine Epidemic Diarrhea Virus (PEDV), virulence factors of Escherichia coli and Clostridioides difficile were analyzed by PCR. Finally, the microbiota composition was also study by 16 S rRNA sequencing on 148 samples (102 diarrheic vs 46 healthy). RVA (53.95 % vs 36 %, p=0.04) and RVB (49.67 % vs 28.8 %, p<0.001) were more frequent in diarrheic animals. Furthermore, RVA viral load was higher in diseased animals. VT2 toxin was significantly associated with diarrhea, whereas other virulence factors were not. Presence of C. difficile and PEDV was almost negligible. Regarding microbiota changes, Fusobacteriota phylum was more frequent in diarrheic samples and Ruminococcaceae family in healthy penmates. During the first week postweaning, Enterobacteriace and Campylobacteria were enriched in animals presenting diarrhea. Furthermore, Lactobacillus was detected in those individuals with no RVA infection. In conclusion, RVA seems to play a primary role in PWD. Classic E. coli virulence factors were not associated with diarrhea, indicating the need for revising their implication in disease. Moreover, Lactobacillus was found frequently in animals negative for RVA, suggesting some protective effect.

Cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity globally. Studies have shown that infections especially bacteraemia and sepsis are associated with increased risks for endothelial dysfunction and related CVDs including atherosclerosis. Extracellular vesicles (EVs) are small, sealed membrane-derived structures that are released into body fluids and blood from cells and/or microbes and are critically involved in a variety of important cell functions and disease development, including intercellular communications, immune responses and inflammation. It is known that EVs-mediated mechanism(s) is important in the development of endothelial dysfunction in infections with a diverse spectrum of microorganisms including Escherichia coli, Candida albicans, SARS-CoV-2 (the virus for COVID-19) and Helicobacter pylori. H. pylori infection is one of the most common infections globally. During H. pylori infection, EVs can carry H. pylori components, such as lipopolysaccharide, cytotoxin-associated gene A, or vacuolating cytotoxin A, and transfer these substances into endothelial cells, triggering inflammatory responses and endothelial dysfunction. This review is to illustrate the important role of EVs in the pathogenesis of infectious diseases, and the development of endothelial dysfunction in infectious diseases especially H. pylori infection, and to discuss the potential mechanisms and clinical implications.

BACKGROUND: The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of differences in sepsis pathophysiology between women and men, sex is currently not being considered in the SOFA score. We aimed to investigate potential sex-specific differences in organ dysfunction, as measured by the SOFA score, in patients with sepsis or septic shock and explore outcome associations.
METHODS: Retrospective analysis of sex-specific differences in the SOFA score of prospectively enrolled ICU patients with sepsis or septic shock admitted to one of 85 certified Swiss ICUs between 01/2021 and 12/2022.
RESULTS: Of 125,782 patients, 5947 (5%) were admitted with a clinical diagnosis of sepsis (2244, 38%) or septic shock (3703, 62%). Of these, 5078 (37% women) were eligible for analysis. A statistically significant difference of the total SOFA score on admission was found between women (mean 7.5 ± SD 3.6 points) and men (7.8 ± 3.6 points, Wilcoxon rank-sum p < 0.001). This was driven by differences in the coagulation (p = 0.008), liver (p < 0.001) and renal (p < 0.001) SOFA components. Differences between sexes were more prominent in younger patients < 52 years of age (women 7.1 ± 4.0 points vs men 8.1 ± 4.2 points, p = 0.004). No sex-specific differences were found in ICU length of stay (women median 2.6 days (IQR 1.3-5.3) vs men 2.7 days (IQR 1.2-6.0), p = 0.13) and ICU mortality (women 14% vs men 15%, p = 0.17).
CONCLUSIONS: Sex-specific differences exist in the SOFA score of patients admitted to a Swiss ICU with sepsis or septic shock, particularly in laboratory-based components. Although the clinical meaningfulness of these differences is unclear, a reevaluation of sex-specific thresholds for SOFA score components is warranted in an attempt to make more accurate and individualised classifications.

Cutaneous leishmaniasis (CL), a neglected tropical disease, is a major public health concern in Yemen, with Leishmania tropica identified as the main causative agent. This study aims to investigate the occurrence and distribution of Leishmania parasites in domestic and wild animals in CL endemic areas in the western highlands of Yemen. A cross-sectional study was conducted in the Utmah District of western Yemen. Blood and skin scraping specimens were collected from 122 domestic and wild animals and tested for the Leishmania DNA using internal transcribed spacer 1 (ITS1) nested polymerase chain reaction. Phylogenetic analyses were performed on 20 L. tropica sequences obtained from animals in this study and 34 sequences from human isolates (collected concurrently from the same study area) retrieved from the GenBank. Overall, L. tropica was detected in 16.4% (20/122) of the examined animals, including 11 goats, two dogs, two bulls, one cow, one donkey, one rabbit, one rat and one bat. None of the examined cats and sheep was positive. The animal sequences were segregated into four different L. tropica haplotypes, with the majority of the animal (15/20) and human (32/34) sequences composed of one dominant haplotype/genotype. These findings represent the first confirmed evidence of natural L. tropica infections in different kinds of domestic and wild animals in western Yemen, suggesting these animals potentially have a role in the transmission of CL in Yemen. Therefore, a One Health approach is required for the effective prevention and control of this devastating disease among endemic populations.

UNASSIGNED: Human immunodeficiency virus (HIV) infection is highly prevalent and often coexists with other infectious diseases, especially Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Men who have sex with men (MSM) represent a vulnerable population in terms of HIV infection. We aimed to determine the prevalence of HCV, HBV among HIV-infected MSM.
UNASSIGNED: This systematic review and meta-analysis searched PubMed, Cochrane, Scopus, Web of Science, and ProQuest up-to 2023/04/22. All studies reporting the prevalence of HBV or HCV infection in MSM PLHIV were included. Meta-analysis used random effect model for synthesis and I 2 along with prediction interval for heterogeneity. Subgroup analysis based on continent and meta-regression for study size, average age and year of publication were used to explore heterogeneity. Modified Newcastle-Ottawa Scale was used to evaluate the quality of studies according to the protocol (PROSPERO: CRD42023428764).
UNASSIGNED: Fifty-six of 5948 studies are included. In 53 studies with 3,07,589 participants, a pooled prevalence of 7% (95% confidence interval [CI]: 5-10) was found for HCV among MSM PLHIV, while a 9% (95% CI: 4-18) prevalence was found for HBV infection from five studies which included 5641 MSM PLHIV. Asia reported the lowest pooled prevalence at 5.84% (95% CI: 2.98-11.13) for HCV while Europe reported the highest pooled prevalence at 7.76% (95% CI: 4.35-13.45). Baujat plot and influence diagnostic identified contributors to influence and between-study heterogeneity. Sensitivity analyses omitting these studies result in considerably more precise estimates. Another sensitivity analysis as leave-one-out meta-analysis did not change any pooled estimate significantly.
UNASSIGNED: There is a significant burden of HCV and HBV among MSM PLHIV worldwide, with varying prevalence rates. Future studies should focus on these multimorbidity clusters and investigate factors influencing disease burden, long-term outcomes, optimal testing strategies, and tailored interventions.

Public transportation is an important mode of transportation in developing countries like Pakistan since it is accessible and convenient. But there are also serious health hazards associated with it, especially when it comes to the transmission of infectious diseases including COVID-19, TB, and Haemophilus influenzae. Worldwide transportation systems are vulnerable, as the COVID-19 pandemic has shown, underscoring the necessity for study and mitigating measures. The danger of disease transmission is increased in Pakistan by crowded metropolitan areas, inadequate sanitation, and low health awareness. In addition, congested public transportation and inadequate ventilation lead to reduced air quality and elevated stress levels among commuters. Comprehensive actions are needed to address these health hazards, such as promoting physical distance, improving cleanliness, enforcing traffic safety laws, and implementing policy changes that support sustainable transportation. Community involvement and advocacy are critical in campaigning for safer and more sustainable transportation networks. Pakistan can enhance public health outcomes and reduce the health hazards linked to public transportation by giving priority to these measures.