Study protocol: diagnostic accuracy study comparing Cy-Tb and STANDARD F TB-Feron FIA tests for tuberculosis infection diagnosis in Vietnam.

INTRODUCTION: The large reservoir of tuberculosis (TB) infections is one of the main reasons for the persistent incidence of TB. Accurate diagnostic tests are crucial to correctly identify and treat people with TB infection, which is vital to eliminate TB globally. The rdESAT-6 and rCFP-10 (Cy-Tb) injection ('Cy-Tb'), a TB-specific antigen skin test and STANDARD F TB-Feron FIA ('Standard F TB') measuring interferon-gamma by fluorescence immunoassay assay are two novel tools for the diagnosis of TB infection which offer advantages compared with current tests in low-resource settings and reduced costs to both health systems and TB-affected people. The proposed study aims to evaluate the diagnostic accuracy of these two new tests for TB infection diagnosis. METHODS AND ANALYSIS: This cross-sectional study aims to assess the diagnostic accuracy for TB infection of the Cy-Tb skin test and Standard F TB assay (investigational tests) compared with the QuantiFERON-TB Gold Plus (QFT-Plus) assay as the immunological reference standard. Three different cohorts of study participants will be recruited at the Vietnam National Lung Hospital: adults with bacteriologically confirmed pulmonary TB (n=100), household contacts of people with TB (n=200) and people without TB infection (n=50). All consenting participants will undergo simultaneous testing with Cy-Tb, Standard F TB and QFT-Plus. The primary endpoint is the diagnostic accuracy of the Cy-Tb skin test and Standard F TB assay, expressed as sensitivity and specificity against the reference standard. ETHICS AND DISSEMINATION: Ethical approval was granted by the Vietnam National Lung Hospital Institutional Review Board (65/23/CN-HDDD-BVPTU) and the Swedish Ethical Review Authority (Dnr 2023-04271-01). Study results will be disseminated to the scientific community and policymakers through scientific publications. TRIAL REGISTRATION NUMBER: NCT06221735.

Septic cardioembolic stroke secondary to infective endocarditis in a young patient with rheumatic heart disease: a case report.

The risk of stroke due to infective endocarditis is particularly high during the first week. Moreover, in low-resource settings where imaging access is limited, and diagnostic pathways are inaccurate the risk further increases. In addition to antibiotic therapy, treatment may include intravenous thrombolysis, with high risk of hemorrhagic complications in patients with infective endocarditis or mechanical thrombectomy. We report here a case of a 24-year-old male with rheumatic heart disease presenting a septic cardioembolic stroke secondary to infective endocarditis that was successfully treated in a low-resource setting.

Leptospirosis transmitted from a pet dog.

Leptospirosis is a widespread zoonosis in tropical regions and it is not frequently recognised in developed countries. We report a case of leptospirosis transmitted from a pet dog. A middle-aged woman was referred to our emergency department with a 7-day history of fever and diarrhoea. She presented with hypotension, tachycardia, grasping pain in the entire muscle and petechiae. A detailed medical interview revealed that her pet dog had been to the veterinarian 1 month earlier with similar symptoms. We treated her with intravenous antibiotics. The patient's diagnosis of leptospirosis was confirmed by serological testing and the detection of DNA in her urine. We contacted the veterinarian and shared the information. We found that the dog had suffered from leptospirosis based on serological testing. We emphasise the possibility of leptospirosis being transmitted from pet dogs. Persistent suspicion of leptospirosis will contribute to its diagnosis and improved public health.

Acute intravascular haemolysis associated with scrub typhus.

Scrub typhus, a prevalent tropical infection, may sometimes manifest with unusual complications. Here, we present the case of a young man who was admitted to our facility with a fever for the past 3 days and passage of dark-coloured urine since that morning. On investigation, we identified intravascular haemolytic anaemia. Through meticulous examination, a black necrotic lesion (eschar) was discovered on his right buttock, a pathognomonic sign of scrub typhus infection. Treatment was initiated with oral doxycycline 100 mg two times a day. Subsequently, diagnosis of scrub typhus was confirmed through positive results from scrub typhus IgM via ELISA and PCR analysis from the eschar tissue. The patient responded well to oral doxycycline and his symptoms resolved within the next few days. This case highlights severe intravascular haemolysis associated with scrub typhus infection.

Establishment of a multisite umbrella cohort study protocol to describe the epidemiology and aetiologies of acute undifferentiated febrile illness in Latin America.

INTRODUCTION: Acute undifferentiated febrile illnesses (AUFIs) impose a large burden in the tropics. Understanding of AUFI's epidemiology is limited. Insufficient diagnostic capacity hinders the detection of outbreaks. The lack of interconnection in healthcare systems hinders timely response. We describe a protocol to study the epidemiology and aetiologies of AUFI and pathogen discovery in strategic areas of Latin America (LA). METHODS AND ANALYSIS: Global Infectious Diseases Network investigators comprising institutions in Colombia, Dominican Republic, México, Perú and the USA, developed a common cohort study protocol. The primary objective is to determine the aetiologies of AUFI at healthcare facilities in high-risk areas. Data collection and laboratory testing for viral, bacterial and parasitic agents are performed in rural and urban healthcare facilities and partner laboratories. Centralised laboratory and data management cores deploy diagnostic tests and data management tools. Subjects >6 years with fever for <8 days without localised infection are included in the cohort. They are evaluated during the acute and convalescent phases of illness. Study personnel collect clinical and epidemiological information. Blood, urine, nasal or pharyngeal swabs and saliva are collected in the acute phase and blood in convalescent phase. Specimens are banked at -80°C. Malaria, dengue and COVID-19 are tested onsite in the acute phase. The acute-phase serum is PCR tested for dengue, chikungunya, Venezuelan equine encephalitis, Mayaro, Oropouche, Zika, and yellow fever viruses. Paired convalescent and acute serum antibody titters are tested for arbovirus, Leptospira spp, and Rickettsia spp. Serum is used for viral cultures and next-generation sequencing for pathogen discovery. Analysis includes variable distributions, risk factors and regression models. Laboratory results are shared with health authorities and network members. ETHICS AND DISSEMINATION: The protocol was approved by local ethics committees and health authorities. The results will be published in peer-reviewed journals. All study results are shared with local and regional health authorities.

How can oral second-line anti-tuberculosis medications be administered to an extremely preterm neonate?

Congenital pre-extensively drug-resistant tuberculosis is rare, and administration of second-line anti-tuberculosis medications to neonates is challenging due to the small doses required and limited availability of suitable formulations. Paediatric formulations have increasingly become available but may not be readily accessible in all countries. For the extremely preterm and low birth weight neonate, doses equivalent to a fraction of a tablet or capsule are required, with frequent dose adjustment for increasing age and weight during the course of treatment. The pharmaceutical formulation must be suitable for administration via enteral feeding tube and must be free of unsafe excipients. We report on the challenges, considerations and outcome of an extremely premature neonate with congenital pre-extensively drug-resistant tuberculosis who was successfully treated with second-line anti-tuberculosis medications. Child-friendly formulations were procured where available, and extemporaneous compounding of clofazimine, moxifloxacin and prothionamide oral suspensions was undertaken to enable administration of these medications.

Weil's disease in a temperate climate: diagnostic uncertainty and the importance of prompt antibiotic treatment.

A man in his 50s presents with a short history of rigors, back pain and dark urine. This was associated with scleral icterus. He was initially treated as urosepsis due to perinephric fat stranding on his first CT but continued to deteriorate with worsening sepsis requiring intensive care admission. He had a conjugated hyperbilirubinaemia (peak 708 µmol/L) with normal liver enzymes, anaemia, thrombocytopaenia, acute kidney injury requiring filtration and respiratory failure requiring ventilatory support. A subsequent CT revealed mediastinal lymphadenopathy and extensive ground-glass changes with patchy consolidation. When his history was revisited, exposure to rodents was identified, and serological testing for leptospirosis subsequently came back positive. This case explores the causes of hyperbilirubinaemia in leptospirosis, the dangers of tunnel vision in diagnostic medicine and the importance of prompt antibiotic therapy in Weil's disease.

Leishmaniases in Ethiopia: a scoping review protocol to determine the scope of research and remaining gaps.

INTRODUCTION: The leishmaniases are among the group of neglected tropical diseases that cause significant morbidity and mortality each year. Currently, the East Africa region has the highest visceral leishmaniasis burden in the world. Ethiopia is one of the East African countries that reports both visceral and cutaneous forms of the disease. As part of the Nairobi Declaration, Ethiopia showed commitment to the elimination of visceral leishmaniasis by 2030. In this endeavour, it is important to understand the scope of research conducted on leishmaniases in the country and identify where the research gaps exist. Determining the research landscape is vital in the plan towards leishmaniases control and elimination. It will help to reference conducted research, determine if systematic reviews are warranted and help prioritise future research directions. METHODS AND ANALYSIS: This protocol was developed with reference to the JBI Scoping Review Methodology Group's guidance on conducting scoping reviews and the PRISMA-ScR reporting guidelines for scoping reviews. The following databases will be searched: PubMed, Embase via Embase.com, Web of Science Core Collection, Cochrane CENTRAL, Global Index Medicus, ClinicalTrials.gov, the Pan African Clinical Trials Registry and PROSPERO. Locally published literature that may not be indexed in the above-mentioned systems will be identified through team members familiar with the setting. Each record will be dually and blindly reviewed in an abstract-title screen and full-text screen using inclusion-exclusion criteria. Included articles must contain an in-depth discussion of leishmaniasis in Ethiopia. Data extracted will consist of study themes, study types, and categories and subcategories each defined in the developed codebook, in addition to type of leishmania, year of publication, funding source and the number of citations. Results will be reported with summary statistics. ETHICS AND DISSEMINATION: Individual consenting and ethical approvals are not applicable. We plan to disseminate our findings to the appropriate stakeholders.

Safety of high-dose amikacin in the first week of all-oral rifampicin-resistant tuberculosis treatment for the prevention of acquired resistance (STAKE): protocol for a single-arm clinical trial.

INTRODUCTION: An effective rifampicin-resistant tuberculosis (RR-TB) treatment regimen should include prevention of resistance amplification. While bedaquiline (BDQ) has been recommended in all-oral RR-TB treatment regimen since 2019, resistance is rising at alarming rates. This may be due to BDQ's delayed bactericidal effect, which increases the risk of selecting for resistance to fluoroquinolones and/or BDQ in the first week of treatment when the bacterial load is highest. We aim to strengthen the first week of treatment with the injectable drug amikacin (AMK). To limit the ototoxicity risk while maximising the bactericidal effect, we will evaluate the safety of adding a 30 mg/kg AMK injection on the first and fourth day of treatment. METHODS AND ANALYSIS: We will conduct a single-arm clinical trial on 20 RR-TB patients nested within an operational study called ShoRRT (All oral Shorter Treatment Regimen for Drug resistant Tuberculosis). In addition to all-oral RR-TB treatment, patients will receive two doses of AMK. The primary safety endpoint is any grade 3-4 adverse event during the first 2 weeks of treatment related to the use of AMK. With a sample size of 20 patients, we will have at least 80% statistical power to support the alternative hypothesis, indicating that less than 14% of patients treated with AMK experience a grade 3-4 adverse event related to its use. Safety data obtained from this study will inform a larger multicountry study on using two high doses of AMK to prevent acquired resistance. ETHICS AND DISSEMINATION: Approval was obtained from the ethics committee of Rwanda, Rwanda Food and Drug Authority, Universitair Ziekenhuis, the Institute of Tropical Medicine ethics review board. All participants will provide informed consent. Study results will be disseminated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT05555303.

Misidentification of Brucella melitensis as Ochrobactrum species: potential pitfalls in the diagnosis of brucellosis.

We describe a case of brucellosis in a man in his 20s, who presented to the emergency department with a 1-month history of fevers, dry cough and knee pain. Blood cultures were positive after 55 hours and Ochrobactrum daejeonense was identified on matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry. Ochrobactrum spp are Gram-negative organisms that are phylogenetically related to Brucella spp but commercially available MALDI-TOF libraries cannot distinguish between the two genera. Further positive blood cultures for O. daejeonense combined with characteristic growth patterns for Brucella spp led to targeted questioning of the patient regarding potential exposure risks, which revealed a history of consumption of unpasteurised camel milk in the Middle East 3 months earlier. Treatment of brucellosis was initiated and subsequent whole genome sequencing identified the blood culture isolate as Brucella melitensis confirming the diagnosis of brucellosis. This case highlights the challenges in the diagnosis of brucellosis in low-incidence settings.

One Health: opportunities for Defence Engagement (Health).

The One Health concept continues to gain traction as a necessary approach to tackle emerging threats to human, animal and environmental health but has not yet been adopted within Defence Engagement (Health). The health of humans, animals and ecosystems are closely interlinked. The One Health concept recognises this interdependence and seeks to balance and optimise the health of all three through an integrated and unifying approach. With a focus on zoonoses, vectorborne disease, antimicrobial resistance and food safety it encourages collaboration, communication, coordination and capacity building. The UK has made commitments to the One Health approach in the Global Health and Security Agenda, and the Integrated Review. This article explores how the One Health approach could and should be adopted within Defence Engagement (Health) activity to offer the potential for high-impact, low-risk activity while facilitating long-term relationship building.

Hydatid cyst in heart and lung: a rare case with a 5-year follow-up.

This report describes a male in his late 20s who presented with a 2-month history of recurrent haemoptysis and chest pain. A chronic infection, such as tuberculosis, was suspected. He had undergone surgical resection of an intrapericardial hydatid cyst in the past. His blood investigations showed peripheral eosinophilia, and his chest X-ray showed a cystic oval lesion in the left upper zone. A CT pulmonary angiogram revealed filling defects in the bilateral segmental and subsegmental arteries with a cystic lesion in the left upper lobe. Further workup, including bronchoalveolar lavage culture and MRI of the thorax, confirmed the diagnosis of a hydatid cyst of pulmonary echinococcosis. This case illustrates the presentation of multisystemic echinococcosis in a young male with no other risk factors, initially treated with surgical resection and antihelminthic therapy. The disease later recurred, which required prolonged medications, which brought the patient into remission.

Preclinical testing of expired antivenoms and its uses in real-world experience: a systematic review.

INTRODUCTION: Limited access to antivenoms is a global challenge in treating snakebite envenoming. In emergency situations where non-expired antivenoms are not readily available, expired antivenoms may be used to save lives with the risk of deteriorating quality, efficacy and safety. Therefore, we aimed to systematically review and summarise the sparse preclinical evidence of neutralising efficacy of expired antivenoms and real-world experience of using expired antivenoms in humans. METHODS: We searched for articles published until 1 March 2023 in PubMed, Scopus, Web of Science and Embase. Studies demonstrating the preclinical studies evaluating expired antivenoms or studies describing the real-world experience of using expired antivenoms were included. Narrative synthesis was applied to summarise the evidence of expired antivenoms. RESULTS: Fifteen studies were included. Ten were preclinical studies and five were real-world experiences of using expired antivenoms in humans. The expired duration of antivenoms in the included studies ranged from 2 months to 20 years. The quality of expired antivenoms was evaluated in one study, and they met the standard quality tests. Five studies demonstrated that the expired antivenoms' immunological concentration and venom-binding activity were comparable to non-expired ones but could gradually deteriorate after expiration. Studies consistently exhibited that expired antivenoms, compared with non-expired antivenoms, were effective when stored in proper storage conditions. The safety profile of using expired antivenoms was reported in two included studies. However, it was inconclusive due to limited information. CONCLUSION: Even though the quality and efficacy of expired antivenoms are comparable to non-expired antivenoms in preclinical studies, the information is limited in terms of real-world experiences of using expired antivenoms and their safety. Therefore, the use of expired antivenoms may be generally inconclusive due to scarce data. Further investigations may be needed to support the extension of antivenoms' expiration date according to their potential efficacy after expiration.

Granulomatous amoebic encephalitis due to Acanthamoeba spp complicating multidrug-resistant tuberculous meningitis in an immunocompetent individual.

Granulomatous amoebic encephalitis due to Acanthamoeba spp is a rare, near-fatal central nervous system infection. It is often seen in immunocompromised individuals. Here we describe a survivor of this infection who was co-infected with multidrug-resistant tuberculosis. He presented to us with features of meningitis and a history of chronic cough. The chest X-ray was classical for pulmonary tuberculosis. Neuroimaging was suggestive of encephalitis; herpes simplex virus PCR was negative. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis. Wet mounts revealed trophozoites of Acanthamoeba Currently, he is being treated with oral bedaquiline, levofloxacin, linezolid, clofazimine, cycloserine and pyridoxine for tuberculosis. He received intravenous amikacin and oral cotrimoxazole and fluconazole for Acanthamoeba infection for 1 month. The resolution was confirmed by repeating the CSF wet mount, culture and neuroimaging. He was then discharged with oral rifampicin, cotrimoxazole and fluconazole. He is currently under our close follow-up.

Artemisinin herbal combo breakers: navigating malaria treatment's double-edged sword.

Artemisinin-based combination therapies (ACTs) have transformed malaria treatment, boasting high efficacy and tolerability. However, emerging resistance jeopardises their long-term effectiveness. ACTs' ability to target multiple parasite stages mitigates resistance risks, but severe malaria cases may require additional interventions. Research on combining ACTs with adjunctive therapies shows promise, but optimal regimens remain unclear. Vigilant resistance monitoring and innovative approaches are crucial to sustaining ACT efficacy. We highlight the ACTs' benefits, limitations, and potential synergies, emphasising the urgent need for comprehensive strategies to combat malaria's evolving challenges.

Experience of dermatologic biologic therapy use and associated opportunistic infection management in Australia's tropical north.

BACKGROUND/OBJECTIVES: Royal Darwin Hospital (RDH) is the sole public dermatology service in the Northern Territory (NT). Prescription of biologic therapies (BT) in the NT is uniquely challenging, with remote populations carrying a high tropical disease burden. The aim of this audit is to examine the demographics and outcomes of patients on BT for dermatologic conditions. METHODS: Retrospective case note review of patients receiving BT through the RDH Dermatology department between August 2021 and October 2023. Data analysed were demographics, location, dermatological diagnosis and serology status. RESULTS: In this audit, 115 patients were included. Age range of 13-91 years, mean of 51.1 years (±14.7), 52 (45.2%) patients were female and 8 (7.8%) identified as First Nations Australian. A large geographical area was serviced, with a primary address between 1 and 1496 km from RDH. Eighteen patients (15.7%) have discontinued BT completely. There was a statistically significant relationship between cessation of BT and increased distance of primary residence from RDH (p < 0.0007). Eighteen patients (15.7%) required management of infections identified in opportunistic infection screening. These infections were strongyloidiasis, tuberculosis, melioidosis and hepatitis B. CONCLUSIONS: There is significant anxiety surrounding BT and tropical infections, including in returning travellers in southern Australian states. There has been particular interest in strongyloidiasis infection, as dupilumab acts on the Th2 immunity mechanism critical to parasitic infection response. This audit exhibits the unique experience of dermatological care in a tropical setting, demonstrating how BT can be used safely and how, when identified, these tropical infections can be successfully managed.