Systematic review of the evidence for treatment and management of common skin conditions in resource-limited settings: An update.

INTRODUCTION: The skin is the largest and most visible organ of the human body. As such, skin infections can have a significant impact on overall health, social wellbeing and self-image. In 2019, we published a systematic review of the treatment, prevention and public health control of skin infections including impetigo, scabies, crusted scabies and tinea in resource-limited settings where skin infections are endemic. This current review serves as an update to assess the evidence for treatment of these conditions as well as atopic dermatitis, molluscum contagiosum and head lice in endemic settings. The data from this systematic review have supported an update to the Australian National Healthy Skin guidelines. METHODS: A systematic review was conducted using two separate searches in MEDLINE, PubMed, Embase, CINAHL, Cochrane and Web of Science. The first search was an update of the 2018 systematic review using the same search strategy for the same skin conditions to identify emerging literature from 2018 to 2022. The second search strategy used the same key terms but with the addition of atopic dermatitis, head lice and molluscum contagiosum from 1960 to 2022. Eligible studies included Indigenous peoples and populations in resource-limited settings with a diagnosis of impetigo, scabies, crusted scabies, tinea capitis, atopic dermatitis, molluscum contagiosum or who presented with head lice. Studies conducted in high-income countries were excluded. Articles were screened for inclusion independently by one author with a second group of reviewers independently double screening. Data extraction and an in-depth quality assessment conducted by one author and checked by two others. RESULTS: Of 1466 original articles identified, 68 studies were included and key findings outlined for impetigo, scabies, crusted scabies, atopic dermatitis, head lice and molluscum contagiosum. Recommendations for each condition based on the available evidence are provided. CONCLUSION: The importance of assessing literature relevant to the populations with heavy burden of skin infections is outlined in this systematic review. We have summarised updates to this literature, which may benefit in developing guidelines for skin infection management similar to the National Healthy Skin Guidelines for Australia.

Scabies.

Scabies is one of the most common and highest-burden skin diseases globally. Estimates suggest that >200 million people worldwide have scabies at any one time, with an annual prevalence of 455 million people, with children in impoverished and overcrowded settings being the most affected. Scabies infection is highly contagious and leads to considerable morbidity. Secondary bacterial infections are common and can cause severe health complications, including sepsis or necrotizing soft-tissue infection, renal damage and rheumatic heart disease. There is no vaccine or preventive treatment against scabies and, for the past 30 years, only few broad-spectrum antiparasitic drugs (mainly topical permethrin and oral ivermectin) have been widely available. Treatment failure is common because drugs have short half-lives and do not kill all developmental stages of the scabies parasite. At least two consecutive treatments are needed, which is difficult to achieve in resource-poor and itinerant populations. Another key issue is the lack of a practical, rapid, cheap and accurate diagnostic tool for the timely detection of scabies, which could prevent the cycle of exacerbation and disease persistence in communities. Scabies control will require a multifaceted approach, aided by improved diagnostics and surveillance, new treatments, and increased public awareness.

NEARER SCAN (LENO BESIK) evaluation of a task-sharing echocardiographic active case finding programme for rheumatic heart disease in Australia and Timor-Leste: protocol for a hybrid type II effectiveness-implementation study.

INTRODUCTION: Rheumatic heart disease (RHD) is underdiagnosed globally resulting in missed treatment opportunities and adverse clinical outcomes. We describe the protocol for a study which aims to co-design, implement and conduct an evaluation of a task-sharing approach to echocardiographic active case finding for early detection and management of RHD in high-risk settings in Australia and Timor-Leste. METHODS AND ANALYSIS: Echocardiograms will be obtained by trained local staff using hand-held echocardiographic devices employing the 'Single Parasternal Long Axis view with a Sweep of the Heart' (SPLASH) technique and interpreted by experts remote from the site of acquisition. Approximately 1500 children and pregnant women will be screened across high-risk communities in Australia and Timor-Leste over an 18-month period. The study will use a type II effectiveness-implementation hybrid design. A tailored package of implementation strategies will be co-designed with communities and health services and mapped onto a Theory of Change framework. The clinical effectiveness will be assessed as the change in the proportion of the target population that are prescribed secondary prophylaxis for RHD by the end of the study compared with baseline. The implementation will be assessed as the adoption, penetration, sustainability, fidelity and cost of the programme with a mixed-methods theory-based and economic evaluation. Data will include numbers of normal, abnormal and uninterpretable SPLASH echocardiograms obtained, numbers of participants progressing through the cascade of care, interviews with staff and programme costs. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Research Ethics Committee of the NT Department of Health and Menzies School of Health Research, Darwin (HREC-2022-4479), the Western Australian Aboriginal Health Ethics Committee (HREC-1237) and the Instituto Nasional Saude Publika Timor-Leste Ethics and Technical Committee (03-UEPD/INSP-TL/V/2023). Informed consent is required to be enrolled. Study findings will be disseminated in the communities involved and submitted for publication. TRIAL REGISTRATION NUMBER: NCT06002243.

Performance of MALDI-TOF MS, real-time PCR, antigen detection, and automated biochemical testing for the identification of Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of melioidosis, a disease highly endemic to Southeast Asia and northern Australia, though the area of endemicity is expanding. Cases may occur in returning travelers or, rarely, from imported contaminated products. Identification of B. pseudomallei is challenging for laboratories that do not see this organism frequently, and misidentifications by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and automated biochemical testing have been reported. The in vitro diagnostic database for use with the Vitek MS has recently been updated to include B. pseudomallei and we aimed to validate the performance for identification in comparison to automated biochemical testing with the Vitek 2 GN card, quantitative real-time polymerase chain reaction (qPCR) targeting the type III secretion system, and capsular polysaccharide antigen detection using a lateral flow immunoassay (LFA). We tested a "derivation" cohort including geographically diverse B. pseudomallei and a range of closely related Burkholderia species, and a prospective "validation" cohort of B. pseudomallei and B. cepacia complex clinical isolates. MALDI-TOF MS had a sensitivity of 1.0 and specificity of 1.0 for the identification and differentiation of B. pseudomallei from related Burkholderia species when a certainty cutoff of 99.9% was used. In contrast, automated biochemical testing for B. pseudomallei identification had a sensitivity of 0.83 and specificity of 0.88. Both qPCR and LFA correctly identified all B. pseudomallei isolates with no false positives. Due to the high level of accuracy, we have now incorporated MALDI-TOF MS into our laboratory's B. pseudomallei identification workflow.IMPORTANCEBurkholderia pseudomallei causes melioidosis, a disease associated with high morbidity and mortality that disproportionately affects rural areas in Southeast Asia and northern Australia. The known area of endemicity is expanding and now includes the continental United States. Laboratory identification can be challenging which may result in missed or delayed diagnoses and poor patient outcomes. In this study, we compared mass spectrometry using an updated spectral database with multiple other methods for B. pseudomallei identification and found mass spectrometry highly accurate. We have therefore incorporated this fast and cost-effective method into our laboratory's workflow for B. pseudomallei identification.

Use of Comparative Genomics To Resolve an Unusual Case of Aminoglycoside Susceptibility in the Melioidosis Pathogen Burkholderia pseudomallei in Bangladesh.

Melioidosis is an emerging tropical infectious disease with a rising global burden caused by the environmental bacterium Burkholderia pseudomallei. It is endemic in Southeast and South Asia, including Bangladesh. A rare aminoglycoside-susceptible B. pseudomallei isolate (Y2019) has recently been reported from a melioidosis patient in Dhaka, Bangladesh. To understand the geographical origins of Y2019, we subjected it and 10 other isolates from Bangladesh to whole-genome sequencing. In a phylogenetic tree with a global set of B. pseudomallei genomes, most Bangladeshi genomes clustered tightly within the Asian clade. In contrast, Y2019 was closely related to ST881 isolates from Sarawak, Malaysian Borneo, a gentamicin-sensitive sequence type, suggesting infection in Borneo. Y2019 also contained the same gentamicin sensitivity conferring nonsynonymous mutation in the drug efflux pump encoding the amrB gene. In the absence of a full travel history, whole-genome sequencing and bioinformatics tools have revealed the likely origin of this rare isolate.

Lower Rates of Staphylococcus aureus Bloodstream Infection in Patients on Hemodialysis Receiving Trimethoprim-Sulfamethoxazole Melioidosis Prophylaxis.

Hemodialysis is a risk factor for Staphylococcus aureus bloodstream infection (SAB). In this single-center study, SAB rates were 56% lower during the monsoonal wet season when patients on hemodialysis receive supervised melioidosis prophylaxis with trimethoprim-sulfamethoxazole. This intervention may reduce SAB rates in high-risk patients; however, further targeted studies are required.

Clinical Presentation and Outcomes Following Infection With Vibrio spp, Aeromonas spp, Chromobacterium violaceum, and Shewanella spp Water-Associated Organisms in Tropical Australia, 2015-2022.

Background: Water-associated bacterial infections cause a wide spectrum of disease. Although many of these infections are typically due to human host commensal Staphylococcal or Streptococcal spp, water exposure can result in infections with environmental gram negatives such as Vibrio spp, Aeromonas spp, Chromobacterium violaceum, and Shewanella spp (collectively VACS). Methods: We performed a retrospective analysis of the epidemiology, clinical presentation, and outcomes of deep and superficial infections associated with VACS organisms in our health service between 1 January 2015 and 31 December 2023. Results: We identified 317 patient episodes of infection with VACS organisms over this period. Of these, Aeromonas spp (63%) was the most common, followed by Vibrio spp (19%), Shewanella spp (13%), and C violaceum (5%). The majority were isolated from males (74.4%) and involved the lower limb (67.5%). Mild infections were more common than severe presentations, with only 15 (4.7%) admissions to the intensive care unit and 8 (2.5%) deaths. Colonization occurred in 6.9% of patients, in contrast to the perceived severity of some of these bacteria. Copathogens were common and included Staphylococcus aureus (48%) and enteric bacteria (57%). The majority of patients (60%) had no documented water exposure. Initial empiric antimicrobial therapy presumptively covered the susceptibilities of the isolated organisms in 47.3% of patients; however, a lack of VACS-covering empirical therapy was not associated with readmission. Conclusions: The isolation of a VACS organism in our setting was often not associated with documented water exposure, which has implications for empiric antimicrobial therapy. Severe disease and death were uncommon.

Population sequencing for diversity and transmission analyses.

Genomic diversity in a pathogen population is the foundation for evolution and adaptations in virulence, drug resistance, pathogenesis, and immune evasion. Characterizing, analyzing, and understanding population-level diversity is also essential for epidemiological and forensic tracking of sources and revealing detailed pathways of transmission and spread. For bacteria, culturing, isolating, and sequencing the large number of individual colonies required to adequately sample diversity can be prohibitively time-consuming and expensive. While sequencing directly from a mixed population will show variants among reads, they cannot be linked to reveal allele combinations associated with particular traits or phylogenetic inheritance patterns. Here, we describe the theory and method of how population sequencing directly from a mixed sample can be used in conjunction with sequencing a very small number of colonies to describe the phylogenetic diversity of a population without haplotype reconstruction. To demonstrate the utility of population sequencing in capturing phylogenetic diversity, we compared isogenic clones to population sequences of Burkholderia pseudomallei from the sputum of a single patient. We also analyzed population sequences of Staphylococcus aureus derived from different people and different body sites. Sequencing results confirm our ability to capture and characterize phylogenetic diversity in our samples. Our analyses of B. pseudomallei populations led to the surprising discovery that the pathogen population is highly structured in sputum, suggesting that for some pathogens, sputum sampling may preserve structuring in the lungs and thus present a non-invasive alternative to understanding colonization, movement, and pathogen/host interactions. Our analyses of S. aureus samples show how comparing phylogenetic diversity across populations can reveal directionality of transmission between hosts and across body sites, demonstrating the power and utility for characterizing the spread of disease and identification of reservoirs at the finest levels. We anticipate that population sequencing and analysis can be broadly applied to accelerate research in a broad range of fields reliant on a foundational understanding of population diversity.

Melioidosis and Activation from Latency: The "Time Bomb" Has Not Occurred.

Burkholderia pseudomallei, the causative agent of melioidosis has long been considered able to exist in a latent form. Seropositivity among U.S. soldiers returning from the Vietnam conflict led to melioidosis being dubbed "the Vietnamese time bomb." Cases assigned to "(re)activation from latency" over 30 years of the Darwin Prospective Melioidosis Study (DPMS) were reviewed and reassessed and additional cases from DPMS years 31-34 were added. Historical reports of melioidosis attributed to activation from latency were reviewed. Some earlier DPMS cases and most historical cases described as activation from latency more accurately reflect undiagnosed chronic melioidosis, often with relapsing-remitting courses, rather than truly latent, asymptomatic infection. Such protracted disease should now be diagnosable much earlier, provided melioidosis is considered and laboratory facilities are available. The longest plausible duration of asymptomatic latency remains 29 years. In conclusion, activation from latency is a rare event in melioidosis, accounting in our analysis for under 3% of DPMS cases, consistent with why the Vietnamese time bomb never eventuated.

Epidemiology and genetic diversity of Burkholderia pseudomallei from Riau Province, Indonesia.

Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, that is common in tropical and subtropical countries including Southeast Asia and Northern Australia. The magnitude of undiagnosed and untreated melioidosis across the country remains unclear. Given its proximity to regions with high infection rates, Riau Province on Sumatera Island is anticipated to have endemic melioidosis. This study reports retrospectively collected data on 68 culture-confirmed melioidosis cases from two hospitals in Riau Province between January 1, 2009, and December 31, 2021, with full clinical data available on 41 cases. We also describe whole genome sequencing and genotypic analysis of six isolates of B. pseudomallei. The mean age of the melioidosis patients was 49.1 (SD 11.5) years, 85% were male and the most common risk factor was diabetes mellitus (78%). Pulmonary infection was the most common presentation (39%), and overall mortality was 41%. Lung as a focal infection (aOR: 6.43; 95% CI: 1.13-36.59, p = 0.036) and bacteremia (aOR: 15.21; 95% CI: 2.59-89.31, p = 0.003) were significantly associated with death. Multilocus sequence typing analysis conducted on six B.pseudomallei genomes identified three sequence types (STs), namely novel ST1794 (n = 3), ST46 (n = 2), and ST289 (n = 1). A phylogenetic tree of Riau B. pseudomallei whole genome sequences with a global dataset of genomes clearly distinguished the genomes of B. pseudomallei in Indonesia from the ancestral Australian clade and classified them within the Asian clade. This study expands the known presence of B. pseudomallei within Indonesia and confirms that Indonesian B. pseudomallei are genetically linked to those in the rest of Southeast Asia. It is anticipated that melioidosis will be found in other locations across Indonesia as laboratory capacities improve and standardized protocols for detecting and confirming suspected cases of melioidosis are more widely implemented.

Melioidosis Knowledge Awareness in Three Distinct Groups in the Tropical Northern Territory of Australia.

Melioidosis is a potentially life-threatening infection. This study aimed to assess the melioidosis knowledge among distinct participant groups in the tropical Top End of the Northern Territory (NT) of Australia. Participants were categorised into three groups: NT medical students and health research staff (Group 1: Hi-Ed), Aboriginal Rangers and Aboriginal Healthcare Workers (Group 2: Rangers/AHWs), and patients with a history of melioidosis infection (Group 3: Patients). A questionnaire was developed to collect data on demographics, risk and protective factor awareness, and knowledge acquisition sources. We used responses to calculate indices for risk knowledge (RKI), protective knowledge (PKI), overall melioidosis knowledge (MKI), and information sources (ISI). We found that 93.6% of participants in Group 1 (Hi-Ed) said that they had heard of melioidosis, followed by 81.5% in Group 3 (Patients), and 72.0% in Group 2 (Rangers/AHWs). Group 1 (Hi-Ed) participants demonstrated greater knowledge of risk-increasing behaviours but had gaps in knowledge of clinical risks like diabetes. Multiple regression revealed that the number of resources used was the only significant predictor of MKI. There are varying melioidosis knowledge levels across different NT participant groups. Targeted educational interventions are needed to enhance melioidosis awareness. A weblink with an interactive summary of our analysis can be found under Results part.

Overlapping Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis household transmission and mobile genetic element exchange.

Streptococcus dysgalactiae subspecies equisimilis (SDSE) and Streptococcus pyogenes share skin and throat niches with extensive genomic homology and horizontal gene transfer (HGT) possibly underlying shared disease phenotypes. It is unknown if cross-species transmission interaction occurs. Here, we conduct a genomic analysis of a longitudinal household survey in remote Australian First Nations communities for patterns of cross-species transmission interaction and HGT. Collected from 4547 person-consultations, we analyse 294 SDSE and 315 S. pyogenes genomes. We find SDSE and S. pyogenes transmission intersects extensively among households and show that patterns of co-occurrence and transmission links are consistent with independent transmission without inter-species interference. We identify at least one of three near-identical cross-species mobile genetic elements (MGEs) carrying antimicrobial resistance or streptodornase virulence genes in 55 (19%) SDSE and 23 (7%) S. pyogenes isolates. These findings demonstrate co-circulation of both pathogens and HGT in communities with a high burden of streptococcal disease, supporting a need to integrate SDSE and S. pyogenes surveillance and control efforts.

A systematic review of immunosuppressive risk factors and comorbidities associated with the development of crusted scabies.

OBJECTIVES: Crusted scabies (CS, Norwegian scabies) is a severe form of scabies, characterized by hyper-infestation of Sarcoptes scabiei mites. CS is commonly associated with immunosuppression but is also reported in overtly immunocompetent individuals. We reviewed immunosuppressive risk factors and comorbidities associated with CS. METHODS: The National Library of Medicine (PubMed) database was reviewed for patient case reports of CS from January 1998 to July 2023. Two authors screened records for eligibility, extracted data, and one critically appraised the quality of the studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023466126. RESULTS: A total of 436 records were identified, of which 204 were included for systematic review. From these, 683 CS patients were included. CS impacted both genders equally. Adults (21-59 years) were more commonly affected (45.5%) compared to children (0-20 years, 21%). Corticosteroid use was the most prevalent immunosuppressive risk factor identified (27.7% of all cases). About 10.2% of reports were associated with HIV/AIDS, and 8.5% with HTLV-1 infection. 10.5% of patients were overtly immunocompetent with no known risk factors. Overall, 41 (6.0%) died, many subsequent to secondary bacteremia. CONCLUSION: This study represents the first systematic review undertaken on immunosuppressive risk factors associated with CS. This provides insights into trends of immunosuppression and mechanisms of CS development.

Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention.

Burkholderia pseudomallei and melioidosis.

Burkholderia pseudomallei, the causative agent of melioidosis, is found in soil and water of tropical and subtropical regions globally. Modelled estimates of the global burden predict that melioidosis remains vastly under-reported, and a call has been made for it to be recognized as a neglected tropical disease by the World Health Organization. Severe weather events and environmental disturbance are associated with increased case numbers, and it is anticipated that, in some regions, cases will increase in association with climate change. Genomic epidemiological investigations have confirmed B. pseudomallei endemicity in newly recognized regions, including the southern United States. Melioidosis follows environmental exposure to B. pseudomallei and is associated with comorbidities that affect the immune response, such as diabetes, and with socioeconomic disadvantage. Several vaccine candidates are ready for phase I clinical trials. In this Review, we explore the global burden, epidemiology and pathophysiology of B. pseudomallei as well as current diagnostics, treatment recommendations and preventive measures, highlighting research needs and priorities.

Socio-environmental and clinical features of invasive group A streptococcal disease in the Northern Territory of Australia.

Objective: To describe the socio-environmental profile and clinical features of invasive group A streptococcal (iGAS) infections in the Northern Territory (NT) of Australia over 10 years. Methods: Cases of iGAS disease diagnosed between 1 May 2011 and 30 April 2021 were retrospectively identified from the NT Notifiable Diseases System and electronic health records accessed. Remoteness of residence, socio-economic index, seasonality and clinical characteristics were recorded. Results: There were 692 cases of iGAS disease identified in the NT during the period 1 May 2011 - 30 April 2021. The age-standardised incidence of iGAS disease was significantly higher in people living in very remote (57.1 cases per 100,000 population, 95% confidence interval [95% CI]: 48.6-65.5) and remote areas (40.9 cases per 100,000 population, 95% CI: 34.7-47.2) than in outer regional areas of the NT (15.7 cases per 100,000 population, 95% CI: 13.4-17.9). People with socio-economic disadvantage were also disproportionately affected, with an incidence of 52.6 cases per 100,000 population (95% CI: 46.2-58.9) in decile 1-3 populations, compared to 8.9 cases per 100,000 population (95% CI: 6.9-10.9) for decile 7-10. For cases with recorded severity data, 135 of 378 (36%) met locally-defined criteria for severe iGAS disease. Recurrent iGAS disease was commonly observed in the dialysis cohort, affecting 17 of the 106 patients during the study period (16% recurrence rate) and causing two deaths. Five molecularly-confirmed clusters of iGAS disease were identified from the study period. Conclusions: iGAS disease is unevenly affecting people in the NT. Those living in areas of socio-economic disadvantage, those in remote and very remote communities, and those receiving dialysis were most affected. It is important that primordial, primary and secondary prevention measures be directed towards supporting these disadvantaged population groups.

Cutaneous melioidosis: An updated review and primer for the dermatologist.

Melioidosis is an emerging infection with increasing endemic foci and global distribution. It is underrecognized and underdiagnosed because of factors including limited awareness of the disease, nonspecific clinical presentation, lack of diagnostic facilities in some locations, misidentification in laboratories inexperienced with culture, and identification of Burkholderia pseudomallei. Cutaneous findings are reported in approximately 10% to 20% of melioidosis cases and dermatologists may play a significant role in its recognition and management. The most dynamic situation of melioidosis recognition and/or expansion currently is in the United States. Global modeling had predicted that B. pseudomallei were potentially endemic in the southern United States and endemicity with local cases of melioidosis was confirmed in 2022. With the distribution and prevalence of melioidosis increasing globally and with this recent recognition that melioidosis is now endemic in the southern United States, it is important for dermatologists to maintain high clinical suspicion in appropriate patients and be familiar with its diagnosis and treatment. Here we review the available literature on cutaneous melioidosis to evaluate its epidemiology, etiology, pathophysiology and clinical presentation and provide guidance for diagnosis and management in dermatology practice.

A Graphical Overview of the Histopathology of Human Melioidosis: A Case Series.

Background: Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, has a major global health impact and a wide range of different disease manifestations. Histopathological descriptions of melioidosis remain limited. Granulomatous inflammation with multinucleated giant cells are considered classic features. We aim to present a graphical overview of histopathological manifestations of melioidosis, serving as an aid in diagnosing this disease. Methods: We performed a retrospective international multicenter laboratory-based analysis of formalin-fixed paraffin-embedded (FFPE) tissue from culture-confirmed melioidosis autopsy and biopsy cases. Available FFPE tissue was stained with hematoxylin and eosin and immunostainings including a monoclonal antibody targeting the capsular polysaccharide (CPS) of B pseudomallei. Tissue with site-specific cultures and/or positive CPS staining were included in the graphical histopathological overview. Results: We identified tissue of 8 autopsy and 5 biopsy cases. Pneumonia and soft tissue abscesses were the leading foci of disease displaying mainly necrosis and suppuration. Infrequent disease manifestations included involvement of bone marrow and adrenal glands in an autopsy case and biopsied mediastinal tissue, the latter being the only case in which we identified multinucleated giant cells. Using the CPS staining, we demonstrated granulomata as part of rare gastric tissue involvement. Conclusions: We found fatal melioidosis to be a necrotizing and suppurative inflammation, usually without multinucleated giant cell formation. Gastric and mediastinal involvement points to ingestion and inhalation as possible routes of infection. The CPS staining proved beneficial as an aid to establish a histopathological diagnosis. Our graphical overview can be used by infectious diseases specialists, microbiologists, and pathologists.

Melioidosis in Timor-Leste: First Case Description and Phylogenetic Analysis.

Burkholderia pseudomallei, the causative agent of melioidosis, has not yet been reported in Timor-Leste, a sovereign state northwest of Australia. In the context of improved access to diagnostic resources and expanding clinical networks in the Australasian region, we report the first 3 cases of culture-confirmed melioidosis in Timor-Leste. These cases describe a broad range of typical presentations, including sepsis, pneumonia, multifocal abscesses, and cutaneous infection. Phylogenetic analysis revealed that the Timor-Leste isolates belong to the Australasian clade of B. pseudomallei, rather than the Asian clade, consistent with the phylogeographic separation across the Wallace Line. This study underscores an urgent need to increase awareness of this pathogen in Timor-Leste and establish diagnostic laboratories with improved culture capacity in regional hospitals. Clinical suspicion should prompt appropriate sampling and communication with laboratory staff to target diagnostic testing. Local antimicrobial guidelines have recently been revised to include recommendations for empiric treatment of severe sepsis.