Melioidosis masquerading as malignancy in tropical Australia; lessons for clinicians and implications for clinical management.

Melioidosis is a life-threatening, emerging infectious disease caused by the environmental bacterium Burkholderia pseudomallei. Melioidosis is hyperendemic in tropical Australia and southeast Asia, however the disease is increasingly encountered beyond these regions. Early diagnosis is essential as the infection has a case-fatality rate of up to 50%. Melioidosis most commonly involves the lungs, although almost any organ can be affected. Most patients present acutely but an insidious presentation over weeks to months is also well described. We present a case series of 7 patients from tropical Australia whom local clinicians initially believed to have cancer ‒ most commonly lung cancer ‒ only for further investigation to establish a diagnosis of melioidosis. All 7 patients had comorbidities that predisposed them to developing melioidosis and all survived, but their delayed diagnosis resulted in 3 receiving anti-cancer therapies that resulted in significant morbidity. The study emphasises the importance of thorough diagnostic evaluation and repeated collection of microbiological samples. It is hoped that our experience will encourage other clinicians ‒ in the appropriate clinical context ‒ to consider melioidosis as a potential explanation for a patient's presentation, expediting its diagnosis and the initiation of potentially life-saving therapy.

Disseminated Mycobacterium abscessus with endocarditis.

We present an uncommon case of endocarditis caused by Mycobacterium abscessus in an immunocompetent patient following a caesarean section. We discuss her turbulent admission course leading to her diagnosis following persistent M. abscessus bacteraemia, medical and surgical management, including a splenectomy and valve resection and repair, and subsequent prolonged course of combination antimicrobials for 24 months post valve surgery. The patient is alive 9 months after completing her treatment and 36 months after her valve surgery. We emphasise the importance of a multidisciplinary team approach in the management of such a complex case.

Recurrent leishmaniasis infection isolated in the pleural fluid.

We present a rare case of recurrent leishmaniasis infection in a female in her 80s who re-presented with a pleural effusion. The patient was initially investigated as an outpatient for cytopenia and underwent a bone marrow biopsy which subsequently diagnosed visceral leishmaniasis. Following full treatment, and apparent recovery, she re-presented with pleural effusion, hypoalbuminaemia and cytopenia. Leishmania was eventually isolated in a pleural fluid sample obtained on therapeutic drainage, and she was treated for a recurrence at a tertiary infectious disease unit. This interesting and challenging case demonstrates the importance of suspecting leishmaniasis recurrence in previously treated cases and the diagnostic benefit of pleural fluid analysis in the context of suspected leishmaniasis.

Tuberculous pyomyositis presenting as septic arthritis and multiple site pyomyositis.

Primary tropical pyomyositis, commonly caused by Staphylococcus aureus, is characterised by suppuration in skeletal muscles, which manifests as single or multiple abscesses. Another rare causative organism is Mycobacterium tuberculosis in endemic areas. Here, we report a case of primary tuberculous pyomyositis presenting as septic arthritis of the right knee and multiple site pyomyositis of the right thigh and chest wall. A tuberculous aetiology was overlooked at first, which resulted in a diagnostic delay. The patient was initially diagnosed, using ultrasonography, MRI and an absence of systemic symptoms of tuberculosis, with bacterial pyomyositis and treated with broad-spectrum antibiotics. However, further investigations performed on knee joint aspirate yielded negative cultures and a positive cartridge-based nucleic acid amplification test, which, along with a non-resolution of his symptoms, suggested a primary tuberculous pyomyositis. He was successfully managed with incision and drainage of the lesions and completion of anti-tubercular therapy.

Dengue-associated longitudinally extensive transverse myelitis.

We diagnosed a patient with dengue fever who developed acute onset of sensorimotor quadriparesis with bladder involvement, and facial nerve involvement. Despite initial negative results in routine investigations and cerebrospinal fluid analysis, spinal MRI confirmed longitudinally extensive transverse myelitis. The aetiological workup was negative, prompting an investigation into the presence of dengue in the cerebrospinal fluid, which returned positive. This case underscores the importance of considering rare neurological complications in dengue, the value of advanced diagnostic techniques and the potential effectiveness of tailored interventions in challenging cases.

Does the Era of Globalization Dictate a change in the Definition of Public Health?

Globalization has a major impact on public health in all countries of the world. Unfortunately, there are attempts to treat global challenges in the field of public health separately from national ones, following the model of tropical medicine, where the focus of action was in fact primarily on the identification and control of tropical diseases. This was especially in the interest of countries that colonized certain areas in the tropical part of the world. Global health, which is to some extent the successor of tropical medicine, cannot be a separate entity. The lines between global health and public health are blurring. In essence, global health is just another aspect of public health, important both in terms of recognizing the situation and taking action to improve the situation. The problems are mostly no longer local or national, and, to a greater or lesser extent, already affect the entire population or threaten the health of future generations. Such a view of global health also requires different approaches. Of course, due to cultural and socio-economic characteristics, the field and method of work must be adapted to the specific local environment, but nevertheless, these are challenges that are present everywhere. Therefore, it is vital that we act decisively, with a united approach - regardless of where we live and at what stage of social development we are. The world has become one, so the division into public health and global public health has become meaningless.

Isolated laryngeal tuberculosis complex infection: expect the unexpected.

Laryngeal tuberculosis (LT), a rare but possible manifestation of extrapulmonary tuberculosis (TBC) and the most frequent granulomatous disease of the larynx, is slowly resurfacing due to the worldwide recrudescence of TBC. We present the case of a 59 y-o Caucasian woman, non-smoker, with no history of recent travels in endemic areas, affected by pulmonary sarcoidosis, that presented with a symptomatic vegetating lesion involving the left free margin of the epiglottic and a small, ulcerated lesion over the right arytenoid mucosa. While the patient's profile would not lead to a primary suspect of laryngeal TBC, the diagnostic workup and histological examination confirmed the unusual finding, and the patient was started on standard antitubercular therapy, with a complete laryngeal response. Although isolated laryngeal tuberculosis is still a rare finding, it should be kept into consideration also in non-endemic areas, especially in patients with chronic disease requiring immunosuppressive drugs.

Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial.

INTRODUCTION: Seasonal malaria chemoprevention (SMC) involves repeated administrations of sulfadoxine-pyrimethamine plus amodiaquine to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. While highly impactful in reducing Plasmodium falciparum malaria burden in controlled research settings, the impact of SMC on infection prevalence is moderate in real-life settings. It remains unclear what drives this efficacy decay. Recently, the WHO widened the scope for SMC to target all vulnerable populations. The Ministry of Health (MoH) in Burkina Faso is considering extending SMC to children below 10 years old. We aim to assess the impact of SMC on clinical incidence and parasite prevalence and quantify the human infectious reservoir for malaria in this population. METHODS AND ANALYSIS: We will perform a cluster randomised trial in Saponé Health District, Burkina Faso, with three study arms comprising 62 clusters of three compounds: arm 1 (control): SMC in under 5-year-old children, implemented by the MoH without directly observed treatment (DOT) for the full course of SMC; arm 2 (intervention): SMC in under 5-year-old children, with DOT for the full course of SMC; arm 3 (intervention): SMC in under 10-year-old children, with DOT for the full course of SMC. The primary endpoint is parasite prevalence at the end of the malaria transmission season. Secondary endpoints include the impact of SMC on clinical incidence. Factors affecting SMC uptake, treatment adherence, drug concentrations, parasite resistance markers and transmission of parasites will be determined. ETHICS AND DISSEMINATION: The London School of Hygiene & Tropical Medicine's Ethics Committee (29193) and the Burkina Faso National Medical Ethics Committee (Deliberation No 2023-05-104) approved this study. The findings will be presented to the community; disease occurrence data and study outcomes will also be shared with the Burkina Faso MoH. Findings will be published irrespective of their results. TRIAL REGISTRATION NUMBER: NCT05878366.

Nodular lesions of the buttock for 20 years: the challenge of chromoblastomycosis in non-endemic settings.

Chromoblastomycosis is an implantation mycosis of the skin caused by certain species of melanised fungi. A man in his 50s, born in Kerala but living in England for 14 years, presented with a nodular lesion on his left buttock, which had been present for 20 years. Biopsy revealed muriform cells and fungal culture isolated Fonsecaea spp, consistent with a diagnosis of chromoblastomycosis. Treatment with oral terbinafine was initiated and changed to itraconazole based on results of antifungal susceptibility. Drug intolerance and low drug levels of itraconazole necessitated change to voriconazole and topical terbinafine. Despite long-term combined therapy, the lesions worsened, and the patient opted for surgical excision abroad. Recurrence was evident at surgical sites and combined therapy continues. Chromoblastomycosis is an insidious and burdensome neglected tropical disease. Within non-endemic countries, diagnosis remains challenging. A travel history and appropriate fungal investigations are vital.

Subcutaneous pythiosis in human treated successfully with antimicrobial treatment, debridement and immunotherapy.

Pythiosis is caused due to a filamentous eukaryotic micro-organism called Pythium insidiosum and the disease occurs commonly in horses and cattle. Subcutaneous pythiosis infection in humans is rare with no clear clinical guidelines for treatment. We present a case of a man in his 20s with non-resolving ulcers noted over lower extremity after exposure to swamp water draining animal remains. The patient received several courses of oral antibiotics with no improvement in symptoms before getting admitted to our institution. A diagnosis of subcutaneous pythiosis was made after deep wound culture following debridement detected P. insidiosum by use of PCR. Due to the rare incidence of such infection in humans and no clear guidelines available for treatment, the case was discussed with infectious disease specialists outside our institution and with veterinary physicians. An emergent approval for use of immunotherapy in conjunction with surgical debridement and antimicrobials was obtained from Food and Drug administration. The patient underwent successful treatment of infection and skin graft following treatment.

Fusarium falciforme eumycetoma: a diagnostic challenge of a neglected tropical disease.

Eumycetoma, a subcutaneous infection caused by various fungi with pathognomonic discharging grain, is rarely reported in Malaysia. This case concerns a eumycetoma infection in an immunocompetent man who presented with progressive left foot swelling complicated with pustules, sinuses and pale grain discharge for the past year after recurrent thorn pricks. Histological findings of the grain and tissue showed foci of septate fungal hyphae. Tissue culture yielded no growth. Amplification and sequencing of the rDNA internal transcribed spacer 1 (ITS1), ITS4 and large subunit regions of the tissue identified the causative agent as Fusarium falciforme, highlighting the role of molecular diagnostic method in identifying fungal species in eumycetoma. The patient was treated with surgical excision and oral itraconazole with excellent improvement. However, he presented again with recurrence after defaulting therapy. F. falciforme has been implicated in causing diseases in crops and sea turtles. Therefore, the One Health approach should be adopted to manage this emerging species.

Impairment of health-related quality of life and its determinants among patients with podoconiosis in East Wollega Zone, Oromia Regional State, Ethiopia: institutional-based cross-sectional study.

OBJECTIVE: This study aimed to assess the impairment of health-related quality of life (HRQoL) and its determinants among patients diagnosed with podoconiosis in East Wollega Zone, Oromia Regional State, Ethiopia. METHODS: An institutional-based cross-sectional study design was used in the setting of primary healthcare facilities to assess impaired HRQoL among patients with podoconiosis in the East Wollega Zone from 1 March 2023 to 30 April 2023, using the Dermatologic Life Quality Index (DLQI). Data was collected from 494 patients with podoconiosis, and a multistage sampling technique was employed. The data was entered into EpiData V.4.6 and exported to SPSS V.27 for analysis. A linear regression model with a 95% cofidence interval (CI) was used to estimate level of HRQoL and to identify its determinants estimating beta (ß) coefficient declaring the significance level at p<0.05. RESULTS: The quality of life among patients was impaired on average by 9.6±6.1 with the lowest DLQI Score in the domain of treatment (0.8±0.97) and the highest in the domain of daily activity (2.3±1.72). The identified significant determinants of impairment of HRQoL associated with DLQI scores were duration of disease (95% CI, ß=0.11 (0.08 to 0.15)), acute dermato-lymphangio-adenitis (ADLA) (95% CI, ß=0.08 (0.01 to 0.16)), comorbidity (95% CI, ß=1.26 (0.37 to 2.16)), consistently wearing shoes (95% CI, ß=-0.06 (-0.09 to -0.03)), feeling of stigmatised (95% CI, ß=0.21 (0.16 to 0.25)) and psychological distress (95% CI, ß=0.17 (0.14 to 0.21)) and being female (95% CI, ß=1.16 (0.19 to 2.12)). CONCLUSION: Overall, HRQoL among patients with podoconiosis was moderately impaired. The duration of disease, ADLA, comorbidity, stigma, psychological distress and being female in sex significantly impaired HRQoL, whereas consistently wearing shoes significantly improved HRQoL among the patients with podoconiosis. Therefore, healthcare providers and public health experts should work on educating communities and counselling patients to avoid stigma and psychological distress, wearing shoes consistently and treating podoconiosis and other comorbidities among these patients.

Scoring systems for prediction of malaria and dengue fever in non-endemic areas among travellers arriving from tropical and subtropical areas.

BACKGROUND: Fever is a common symptom among travellers returning from tropical/subtropical areas to Europe, and promptly distinguishing severe illnesses from self-limiting febrile syndromes is important but can be challenging due to non-specific clinical presentation. METHODS: A cross-sectional study enrolled adults and children who sought care during 2015-2020 at Karolinska University Hospital, Stockholm, Sweden with fever within 2 months after returning from travel to a tropical/subtropical area. Data on symptoms and laboratory parameters were prospectively and retrospectively collected. Two separate scoring systems for malaria and dengue were developed based on backward elimination regressions. RESULTS: In total, 2113 adults (18-94 years) and 202 children (1-17 years) were included, with 112 (4.8%) confirmed malaria by blood thick smear and 90 (3.9%) PCR/serology dengue-positive cases. Malaria was more likely in a patient who had visited sub-Saharan Africa and presented with combination of thrombocytopenia, anaemia and fever ≥39.5°C. Leucopenia, muscle pain and rash after travelling to Asia or South/Latin America indicated high probability of dengue. Two scoring systems with points between 0 and 7 for prediction of malaria or dengue were created based on the above predictors. Scores ≥3 indicated >80% sensitivity and specificity for malaria and >90% specificity for dengue in children and adults (area under the curve (AUC) for dengue: 0.92 in adults (95% CI 0.90 to 0.95) and 0.95 in children (95% CI 0.88 to 1.0); AUC for malaria: 0.93 in adults (95% CI 0.91 to 0.96) and 0.88 in children (95% CI 0.78 to 0.99)). Internal validation of optimism and overfitting was managed with bootstrap. CONCLUSION: The presented scoring systems provide novel tools for structured assessment of patients with tropical fever in a non-endemic area and highlight clinical signs associated with a potential severe aetiology to direct the need for microbial investigation.

Original algorithms for the detection of cardiovascular involvement of neglected tropical diseases.

INTRODUCTION: Neglected tropical diseases (NTDs) introduce considerable morbidity and mortality on a global scale, directly impacting over 1 billion individuals as well as their families and communities. Afflicted individuals may have limited access to resources and care in these regions, contributing to a high proportion of chronic, progressive, and systemic disease. The cardiovascular system is at particular risk of demise for several NTDs, yet remains largely unstudied due in part to the lack of robust data collection mechanisms in the most impacted regions. AREAS COVERED: The present review is a part of the Neglected Tropical Diseases and other Infectious Diseases affecting the Heart (NET-Heart) Project, aiming at summarizing the current knowledge on cardiovascular implications of NTDs and providing diagnostic as well as management recommendations which can be tailored to low-resource settings. The diagnostic and management algorithms of 13 unique NTDs are presented and summarized. EXPERT OPINION: Recognizing cardiac manifestations of NTDs can significantly alter disease trajectory and all physicians benefit from improved knowledge about NTDs. Great potential exists to advance patient care by improving data collection, communication, and international collaboration.

The Defence General Practitioner: an Updated Definition and Model.

The geopolitical setting has changed significantly since the definition of UK Armed Forces General Practice was published in 2012. New operating models require medical services to provide smaller teams operating at greater reach from secondary care and logistical support. The Defence Medical Services have reorganised to meet these changing needs. Defence general practices (DGPs) are key enablers of the Defence strategic effort, both integral to deployed units, in preparing forces for deployment and managing their rehabilitation back to fitness. A formal role performance statement (RPS) has been created to guide the training and development of DGPs to meet these changing requirements. The RPS details the additional scope of practice, beyond the national GP licensing standard, in which DGPs work. In this article, we compare and contrast the RPS with the previous definition of a DGP. The resultant updated model recharacterises the extended roles into five themes of DGP built on the foundation of the Royal College of General Practitioners curriculum. This new model provides the platform on which to develop the clinical specialty over the next decade and highlights avenues for educational interventions to develop future generations of DGPs.

Overlapping between squamous cell carcinoma and mucocutaneous leishmaniasis in a diabetic patient.

Mucocutaneous leishmaniasis (MCL) is a leishmania infection; that usually affects the oral and nasal mucosa. The coexistence of leishmania and malignancy is rarely reported and mainly in immunocompromised patients. We report a case of an overlapping between leishmania and squamous cell carcinoma (SCC) in a 60-year-old immunocompetent Syrian female. The patient presented with a one-year crusty nodule on the lower lip. Since she lives in an endemic region, leishmaniasis was suggested, and confirmed with a Giemsa-stained smear. After 20 days of meglumine antimoniate treatment, the patient revealed no signs of recovery, thus, the treatment was prolonged with the addition of sodium stibogluconate injections. Later, she presented with increased symptoms. A biopsy was performed due to SCC suspicion, and it was verified. The patient underwent complete surgical removal of the lesion. After a one-year follow-up, no recurrence was observed. We illustrated the importance of considering SCC in cases of refractory leishmaniasis.

Protocol for the challenge non-typhoidal Salmonella (CHANTS) study: a first-in-human, in-patient, double-blind, randomised, safety and dose-escalation controlled human infection model in the UK.

INTRODUCTION: Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, Salmonella enterica serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%-20%. Several iNTS vaccine candidates are in early-stage assessment which-if found effective-would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-human Salmonella Typhimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis. METHODS AND ANALYSIS: This double-blind, safety and dose-escalation study will randomise 40-80 healthy UK participants aged 18-50 to receive oral challenge with one of two strains of S. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%-75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host-pathogen interactions in response to infection. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the NHS Health Research Authority (London-Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants. TRIAL REGISTRATION NUMBER: NCT05870150.

Infections diagnosed in children and young people screened for malaria in UK emergency departments: a retrospective multi-centre study.

BACKGROUND: Data on imported infections in children and young people (CYP) are sparse. AIMS: To describe imported infections in CYP arriving from malaria-endemic areas and presenting to UK emergency departments (ED) who were screened for malaria. METHODS: This is a retrospective, multi-centre, observational study nested in a diagnostic accuracy study for malaria rapid diagnostic tests. Any CYP < 16 years presenting to a participating ED with a history of fever and travel to a malaria-endemic area between 1 January 2016 and 31 December 2017 and who had a malaria screen as a part of standard care were included. Geographical risk was calculated for the most common tropical infections. RESULTS: Of the 1414 CYP screened for malaria, 44.0% (n = 622) arrived from South Asia and 33.3% (n = 471) from sub-Saharan Africa. Half (50.0%) had infections common in both tropical and non-tropical settings such as viral upper respiratory tract infection (URTI); 21.0% of infections were coded as tropical if gastro-enteritis is included, with a total of 4.2% (60) cases of malaria. CYP diagnosed with malaria were 7.44 times more likely to have arrived from sub-Saharan Africa than from South Asia (OR 7.44, 3.78-16.41). CONCLUSION: A fifth of CYP presenting to participating UK EDs with fever and a history of travel to a malaria-endemic area and who were screened for malaria had a tropical infection if diarrhoea is included. A third of CYP had no diagnosis. CYP arriving from sub-Saharan Africa had the greatest risk of malaria.Abbreviations: CYP: children and young people; ED: emergency department; PERUKI: Paediatric Emergency Research in the UK and Ireland; RDT: rapid diagnostic test; VFR: visiting friends and relatives.