Age of hepatitis B e antigen loss in Aboriginal, Torres Strait Islander and non-Indigenous residents of tropical Australia; implications for clinical care.

Abstract: This study determined the hepatitis B e antigen (HBeAg) status of people living with chronic hepatitis B (CHB) in Far North Queensland (FNQ), Australia and their age of HBeAg loss. It was hoped that this would provide data to explain the stark difference in the incidence of hepatocellular carcinoma (HCC) between Aboriginal and Torres Strait Islander individuals living with CHB in FNQ, a finding that has been hypothesised to relate to differences in hepatitis B virus genotype. We identified every FNQ resident with CHB, determined their country of birth, their HBeAg status, the age they lost HBeAg and whether they identified as an Aboriginal, a Torres Strait Islander or a non-Indigenous individual. We then ascertained whether these demographic and virological variables were correlated. Of 1,474 individuals living with CHB in FNQ, 278 (19%) were Aboriginal, 507 (34%) were Torres Strait Islanders and 689 (47%) were non-Indigenous. Aboriginal individuals were less likely to be HBeAg positive (26/278, 9%) than Torres Strait Islander (91/507, 18%) and non-Indigenous (126/689, 18%) individuals, p < 0.0001. Aboriginal individuals lost HBeAg at an earlier age (median (interquartile range): 30 (23-39) years) than Torres Strait Islander (38 (29-49) years) and non-Indigenous (36 (29-47) years) individuals, p < 0.0001. Aboriginal individuals with CHB in FNQ are more likely to be HBeAg negative than Torres Strait Islander and non-Indigenous individuals and lose HBeAg at a younger age. This provides a biological basis for local clinicians' observation that Aboriginal individuals with CHB in FNQ are at a lower risk of HCC and data to support the principle of genotype-based care in the region.

Bone and joint infections due to melioidosis; diagnostic and management strategies to optimise outcomes.

BACKGROUND: Melioidosis, a life-threatening infection caused by the gram negative bacterium Burkholderia pseudomallei, can involve almost any organ. Bone and joint infections (BJI) are a recognised, but incompletely defined, manifestation of melioidosis that are associated with significant morbidity and mortality in resource-limited settings. METHODOLOGY/PRINCIPAL FINDINGS: We identified all individuals with BJI due to B. pseudomallei managed at Cairns Hospital in tropical Australia between January 1998 and June 2023. The patients' demographics, their clinical findings and their treatment were correlated with their subsequent course. Of 477 culture-confirmed cases of melioidosis managed at the hospital during the study period, 39 (8%) had confirmed BJI; predisposing risk factors for melioidosis were present in 37/39 (95%). However, in multivariable analysis only diabetes mellitus was independently associated with the presence of BJI (odds ratio (95% confidence interval): 4.04 (1.81-9.00), p = 0.001). BJI was frequently only one component of multi-organ involvement: 29/39 (74%) had infection involving other organs and bacteraemia was present in 31/39 (79%). Of the 39 individuals with BJI, 14 (36%) had osteomyelitis, 8 (20%) had septic arthritis and 17 (44%) had both osteomyelitis and septic arthritis; in 32/39 (83%) the lower limb was involved. Surgery was performed in 30/39 (77%). Readmission after the initial hospitalisation was necessary in 11/39 (28%), 5/39 (13%) had disease recrudescence and 3/39 (8%) had relapse; 4/39 (10%) developed pathological fractures. ICU admission was necessary in 11/39 (28%) but all 11 of these patients survived. Only 1/39 (3%) died, 138 days after admission, due to his significant underlying comorbidity. CONCLUSIONS: The case-fatality rate from melioidosis BJI in Australia's well-resourced health system is very low. However, recrudescence, relapse and orthopaedic complications are relatively common and emphasise the importance of collaborative multidisciplinary care that includes early surgical review, aggressive source control, prolonged antibiotic therapy, and thorough, extended follow-up.

Associations between antiretroviral regimen and changes in blood pressure: results from the D2EFT study.

In this randomised, controlled study in 14 low- and middle-income countries, individuals taking dolutegravir with darunavir/ritonavir for 48 weeks had a greater increase in systolic and diastolic blood pressure than individuals taking two nucleoside reverse transcriptase with darunavir/ritonavir. The difference remained significant after controlling for confounding factors including weight gain.

Lincosamide monotherapy treatment of methicillin-resistant Staphylococcus aureus pneumonia in tropical Australia: a case series.

Existing recommended first-line antibiotic agents for MRSA pneumonia have several shortcomings. We reviewed 29 cases of community- and hospital-acquired MRSA pneumonia managed at our hospital. Lincosamide monotherapy was administered to 21/29 (72%) and was the predominant antibiotic regimen (> 50% course duration) in 19/29 (66%). Patients receiving lincosamide-predominant monotherapy were no more likely to die or require intensive care unit admission than patients receiving vancomycin-predominant monotherapy (5/19 (26%) versus 4/7 (57%), p = 0.19); 5/7 (71%) patients admitted to ICU and 4/5 (80%) bacteraemic patients received lincosamide-predominant monotherapy. MRSA pneumonia can be safely treated with lincosamide monotherapy if the isolate is susceptible.

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.

Significant healthcare resource utilisation in the management of skin and soft tissue infections in the Torres Strait, Australia.

INTRODUCTION: Aboriginal and Torres Strait Islander Peoples (First Nations Australians) living in remote communities are hospitalised with skin and soft tissue infections (SSTIs) at three times the rate of non-First Nations Australians. The Torres Strait in tropical northern Australia has a highly dispersed population mainly comprising First Nations Australians. This study aimed to define the health service utilisation and health system costs associated with SSTIs in the Torres Strait and to improve the quality of regional healthcare delivery. METHODS: The research team conducted a retrospective, de-identified audit of health records for a 2-year period, 2018-2019. The aim was to define health service utilisation, episodes of outpatient care, emergency department care, inpatient care and aeromedical retrieval services for SSTIs. RESULTS: Across 2018 - 2019, there were 3509 outpatient episodes of care for SSTIs as well as 507 emergency department visits and 100 hospitalisations. For individuals with an SSTI, the mean outpatient clinic episode cost $240; the mean emergency department episode cost $400.85, the mean inpatient episode cost $8403.05 while an aeromedical retrieval service cost $18,670. The total costs to the health system for all services accessed for SSTI management was $6,169,881 per year, 3% of the total annual health service budget. CONCLUSION: Healthcare costs associated with SSTIs in the Torres Strait are substantial. The implementation of effective preventative and primary care interventions may enable resources to be reallocated to address other health priorities in the Torres Strait.

Chronic hepatitis B care in regional Australia: implications for clinical practice and public health policy.

BACKGROUND: Australia is struggling to meet its National Hepatitis B Strategy care targets, particularly in nonmetropolitan settings. It is vital to engage priority populations and improve their access to recommended care to reach these targets. AIMS: This retrospective study examined people living with chronic hepatitis B (CHB) in regional North Queensland, Australia, and determined whether their care adhered to current national CHB management guidelines. The analysis aimed to identify gaps in care that might be addressed to improve future outcomes. METHODS: All individuals referred to the gastroenterology clinic at the Townsville University Hospital in regional North Queensland, Australia, for CHB care between January 2015 and December 2020 were identified. Their linkage to care, engagement in care and receipt of guideline-recommended CHB care were determined. RESULTS: Of 255 individuals, 245 (96%) were linked to care; 108 (42%) remained engaged in care and 86 (38%) were receiving guideline-recommended care in 2021. There were 91/255 (36%) who identified as Indigenous Australians. Indigenous status was the only independent predictor of not being linked to care (odds ratio (OR): 0.13 (95% confidence interval (CI): 0.03-0.60), P = 0.01), not being engaged in care (OR: 0.19 (95% CI: 0.10-0.36), P < 0.0001), not receiving guideline-recommended CHB care (OR: 0.16 (95% CI: 0.08-0.31), P < 0.0001) or not being engaged in a hepatocellular carcinoma surveillance programme (OR: 0.08 (95% CI: 0.02-0.27), P < 0.0001). CONCLUSION: Current approaches are failing to deliver optimal CHB care to Indigenous Australians in regional North Queensland. Targeted strategies to ensure that Indigenous Australians in the region receive equitable care are urgently needed.

Utility of rotational thromboelastometry in the management of massive haemorrhage at a regional Australian hospital.

BACKGROUND: Rotational thromboelastometry (ROTEM) allows targeted and individualised blood product replacement. OBJECTIVES: The study aimed to determine the impact of ROTEM-guided transfusion on the clinical course of patients with acute massive haemorrhage in a regional Australian hospital. METHODS/MATERIALS: A retrospective review of all patients with acute massive haemorrhage that compared the characteristics, blood product use, and clinical outcomes of patients with massive haemorrhage before and after the introduction of ROTEM-guided transfusion. RESULTS: In per-protocol analysis, the 31/97 (32%) with ROTEM-guided transfusion used less packed red blood cells (median [interquartile range]: 6 [6-8] vs. 8 [6-12] units, p = 0.03) than patients whose transfusion was not ROTEM-guided. They were also less likely to receive fresh frozen plasma (2/31 [6%] vs. 45/66 [68%], p < 0.0001) or platelets (2/31 [6%] vs. 31/66 [47%], p < 0.0001); they were, however, more likely to receive fibrinogen products (26/31 [84%] vs. 38/66 [58%], p = 0.01). Patients receiving ROTEM-guided transfusion had lower in-hospital mortality (6/31 [19%] vs. 20/66 [30%], odds ratio 0.55 [95% confidence interval]: 0.20-1.55, p = 0.26) although this did not achieve statistical significance in this small cohort. CONCLUSION: ROTEM-guided massive transfusion of patients with acute haemorrhage in this regional Australian hospital led to a reduction in packed red blood cell, fresh frozen plasma, and platelet utilisation and may also have reduced mortality.

Hepatitis B genotypes in Aboriginal and Torres Strait Islander Australians: correlation with clinical course and implications for management.

BACKGROUND: The prevalence of chronic hepatitis B (CHB) in Aboriginal and Torres Strait Islander Australians in Far North Queensland (FNQ) is greater than twice that of the general Australian population. CHB is common in Torres Strait Islanders diagnosed with hepatocellular carcinoma (HCC) - and in Aboriginals with HCC living in the Northern Territory - however, Aboriginals diagnosed with HCC in FNQ very rarely have CHB. The explanation for this apparent disparity is uncertain. AIMS: To determine the HBV genotypes in the FNQ Aboriginal and Torres Strait Islander population and their correlation with clinical phenotype. METHODS: We determined the HBV genotype of Aboriginal and Torres Strait Islander Australians living with CHB in FNQ and correlated this with demographic and clinical findings. RESULTS: 134/197 (68%) enrolled individuals had a sufficient viral load for genotyping. All 40 people with HBV/D genotype had Aboriginal heritage, whereas 85/93 (91%) with HBV/C had Torres Strait Islander heritage (P < 0.0001). Individuals with HBV/D were younger than those with HBV/C (median (interquartile range) age: 43 (39-48) vs 53 (42-66) years, P = 0.0002). However, they were less likely to be HBeAg positive (1/40 (3%) vs 23/93 (25%), P = 0.001). All three HCCs developed in Torres Strait Islanders; two-thirds were infected with HBV/C14; genotyping was not possible in the other individual. All 10 diagnoses of cirrhosis occurred in Torres Strait Islanders, 6/10 were infected with HBV/C14, genotyping was not possible in the other four individuals. CONCLUSIONS: HBV genotypes in Aboriginal and Torres Strait Islander Australians in FNQ differ markedly, which could explain the significant differences in the clinical phenotype in the two populations and might be used to inform cost-effective CHB care in the region.

Case Report: Leptospirosis Complicated by Persistent, Bilateral Sensorineural Hearing Loss.

The clinical manifestations of leptospirosis range from mild to life-threatening and can impact on multiple organ systems. A wide array of neurological manifestations of leptospirosis have been reported, although the pathophysiology of neuroleptospirosis remains incompletely understood. We present a case of leptospirosis complicated by bilateral sensorineural deafness, with nodular meningitis demonstrated in the internal auditory meatus on magnetic resonance imaging. The patient was treated with doxycycline, ceftriaxone, systemic and topical steroids, and hyperbaric oxygen therapy, with modest, but incomplete, improvement.

The Epidemiological, Clinical, and Microbiological Features of Patients with Burkholderia pseudomallei Bacteraemia-Implications for Clinical Management.

Patients with melioidosis are commonly bacteraemic. However, the epidemiological characteristics, the microbiological findings, and the clinical associations of Burkholderia pseudomallei bacteraemia are incompletely defined. All cases of culture-confirmed melioidosis at Cairns Hospital in tropical Australia between January 1998 and June 2023 were reviewed. The presence of bacteraemia was determined and correlated with patient characteristics and outcomes; 332/477 (70%) individuals in the cohort were bacteraemic. In multivariable analysis, immunosuppression (odds ratio (OR) (95% confidence interval (CI)): (2.76 (1.21-6.27), p = 0.02), a wet season presentation (2.27 (1.44-3.59), p < 0.0001) and male sex (1.69 (1.08-2.63), p = 0.02), increased the likelihood of bacteraemia. Patients with a skin or soft tissue infection (0.32 (0.19-0.57), p < 0.0001) or without predisposing factors for melioidosis (0.53 (0.30-0.93), p = 0.03) were less likely to be bacteraemic. Bacteraemia was associated with intensive care unit admission (OR (95%CI): 4.27 (2.35-7.76), p < 0.0001), and death (2.12 (1.04-4.33), p = 0.04). The median (interquartile range) time to blood culture positivity was 31 (26-39) hours. Patients with positive blood cultures within 24 h were more likely to die than patients whose blood culture flagged positive after this time (OR (95%CI): 11.05 (3.96-30.83), p < 0.0001). Bacteraemia portends a worse outcome in patients with melioidosis. Its presence or absence might be used to help predict outcomes in cases of melioidosis and to inform optimal clinical management.

Melioidosis of the Female Genitourinary Tract.

Prostatic abscess is a common manifestation of melioidosis in men, but the characteristics of female genitourinary melioidosis are incompletely defined. There were 453 cases of melioidosis in Far North Queensland, tropical Australia, between January 1998 and April 2023; genitourinary involvement was less common in women than in men (13/140 [9%] versus 76/313 [24%], odds ratio [95% confidence interval]: 0.32 [0.17-0.60], P = 0.0004). In 11 of these 13 (85%) women, other organs were also affected. The two women with disease involving only the genitourinary tract had underlying anatomical abnormalities: one had an ovarian malignancy, the only case to involve the female reproductive system in the cohort, while the other had a urethral diverticulum. In 3 of 13 (23%) women, genitourinary involvement was identified only with computed tomography, emphasizing the importance of early imaging of patients with melioidosis to identify unexpected foci of disease and to inform the optimal duration of antibiotic therapy.

Public health response to an outbreak of meningococcal B disease in a secondary school in Far North Queensland.

This article describes the public health response to an outbreak of meningococcal B disease, linked to a secondary school in Far North Queensland. Tropical Public Health Services in Cairns were notified of three cases of meningococcal disease in the same week in May 2022. The cases occurred in individuals who all attended, or worked in, the same secondary school. All cases were serogroup B and shared the same molecular genotype. The public health response included prompt provision of information, distribution of clearance antibiotics and two doses of MenB-4C vaccine to the entire staff and student population. Antibiotic coverage and vaccination coverage were achieved in 99% and 85% of the student population respectively. Following the intervention, no further cases were detected in the region during the subsequent nine months.

A low burden of severe illness: the COVID-19 Omicron outbreak in the remote Torres and Cape region of Far North Queensland.

A coronavirus disease 2019 (COVID-19) outbreak was declared in the remote Torres and Cape region of Far North Queensland soon after the Queensland border opened for quarantine-free domestic travel in December 2021, with a total of 7,784 cases notified during the first ten-month outbreak period. We report a crude attack rate among residents of 25.6% (95% confidence interval [95% CI]: 25.1-26.1%), a hospitalisation rate of 1.6% (95% CI: 1.3-1.9%) and a crude case fatality rate of 0.05% (95% CI: 0.01-0.13%). Hospitalisation and case fatality rates were similar among First Nations and non-Indigenous people, with double dose COVID-19 vaccination rates higher among First Nations than non-Indigenous people by the end of the outbreak period. We attribute the low burden of severe illness to local community leadership, community engagement, vaccination coverage and recency, and community participation in a local culturally considered COVID-19 care-in-the-home program.

The Incidence of Infection Complicating Snakebites in Tropical Australia: Implications for Clinical Management and Antimicrobial Prophylaxis.

Objective: To define the incidence of infection following snakebite in tropical Australia and the resulting implications for the routine prescription of prophylactic antibiotics. Methods: A retrospective study of all individuals presenting to Cairns Hospital, a tertiary referral hospital in tropical Australia, after a snakebite between December 2013 and October 2020. Results: There were 732 hospitalisations, 720 (98.4%) patients presented within 8 hours of the snakebite, and 29/732 (4.0%) were envenomated. Envenomated patients were more likely to receive empirical antibiotics than nonenvenomated patients (8/29 (27.6%) versus 14/703 (2.0%), p < 0.001), although this was frequently as a bundle of care for critically ill individuals. Superficial skin infection was diagnosed by clinicians in 6/732 (0.8%) patients during their hospitalisation; infection was diagnosed more commonly in envenomated than in nonenvenomated patients (3/29 (10.3%) versus 3/703 (0.4%), p = 0.001). All 3 envenomated individuals diagnosed with infection were believed to have taipan (genus Oxyuranus) bites. Five (83%) of the six patients diagnosed with infection had received empirical antibiotics at presentation; only 1/710 (0.1%) patients who received no antibiotics developed a (superficial) infection. Conclusion: Infection is a very uncommon complication of snakebite in tropical Australia. Individuals bitten by snakes in tropical Australia should not routinely receive antibiotic prophylaxis.

Increased recognition of Q fever aortitis as a chronic manifestation of Q fever in tropical North Queensland, Australia.

Aortitis is a life-threatening, manifestation of chronic Q fever. We report a series of 5 patients with Q fever aortitis who have presented to our hospital in tropical Australia since 2019. All diagnoses were confirmed with polymerase chain reaction (PCR) testing of aortic tissue. Only one had a previous diagnosis of acute Q fever, and none had classical high-risk exposures that might increase clinical suspicion for the infection. All patients underwent surgery: one died and 3 had significant complications. Q fever aortitis may be underdiagnosed; clinicians should consider testing for Coxiella burnetii in people with aortic pathology in endemic areas.

Clinical Manifestations and Genomic Evaluation of Melioidosis Outbreak among Children after Sporting Event, Australia.

Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future.

The aetiology and incidence of infective endocarditis in people living with rheumatic heart disease in tropical Australia.

PURPOSE: To define the incidence and microbiological aetiology of infective endocarditis (IE) in patients with rheumatic heart disease (RHD) in tropical Australia. METHODS: A retrospective study that examined all episodes of IE between January 1998 and June 2021 among individuals on the RHD register in Far North Queensland, Australia. RESULTS: There were 1135 individuals with a diagnosis of RHD on the register during the study period, representing 10962 patient-years at risk. Overall, there were 18 episodes of definite IE occurring in 16 individuals, although only 7 episodes occurred in native valves (11 occurred in prosthetic valves) equating to 0.7 episodes of native valve IE/1000 patient-years. No patient with mild RHD - and only one child with RHD - developed IE during the study period. Despite the study's tropical location, the causative organism was usually typical skin or oral flora. Among individuals with an indication for benzathine penicillin G (BPG) prophylaxis, only 1/6 episodes of IE due to a penicillin-susceptible organism received BPG in the month before presentation. CONCLUSION: Although RHD predisposes individuals to IE, the absolute risk of IE in native valve disease in tropical Australia is low and might be reduced further by improved adherence to secondary BPG prophylaxis.

Diagnostic yield of urine lipoarabinomannan and sputum tuberculosis tests in people living with HIV: a systematic review and meta-analysis of individual participant data.

BACKGROUND: Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests. METHODS: In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337. FINDINGS: We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies. INTERPRETATION: AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples. FUNDING: FIND, the Global Alliance for Diagnostics.