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Introduction In May 2022, the World Health Organisation declared a multi-country monkeypox outbreak in non-endemic countries following cases reported from 12 member states that were not endemic for monkeypox virus. Sources of data Pubmed search. Areas of agreement The virology, epidemiology, transmission, incubation and aspects of infection control are described. Clinical features of previous and current outbreaks are described, with growing observations that the current outbreak presents with clinical features distinct from previous outbreaks. Areas of controversy There are variations in clinical presentations seen in the current outbreak that have not been seen in prior outbreaks. More research is needed to investigate the reasons for these differences. Growing points The higher numbers of HIV-positive patients in the current outbreak has allowed better description of the disease in patients co-infected with HIV and monkeypox. The absence of more severe symptoms in HIV-positive patients in the current outbreak could possibly be due to the fact that most of these patients had well-controlled HIV, although further characterization of this cohort of patients would be useful. Areas for developing research Current treatment and vaccination options have been extrapolated from studies of other Orthopox viruses. There remains a need for more data on the safety and efficacy of these options in the context of monkeypox infections.

Background Healthcare-associated (HCA) SARS-CoV-2 infection is a significant contributor to the spread of the 2020 pandemic. Timely review of HCA cases is essential to identify learning to inform infection prevention and control (IPC) policies and organisational response. Aim To identify key areas for improvement through rapid investigation of HCA SARS-CoV-2 cases and to implement change. Methods Cases were identified based on date of first positive SARS-CoV-2 PCR sample in relation to date of hospital admission. Cases were reviewed using a structured gap analysis tool to identify key learning points. These were discussed in weekly multidisciplinary meetings to gain consensus on learning outcomes, level of harm incurred by the patient and required actions. Learning was then promptly fed back to individual teams and the organisation. Findings Of the 489 SARS-CoV-2 cases admitted between 10th March and 23rd June 2020, 114 suspected HCA cases (23.3%) were reviewed; 58/489 (11.8%) were ultimately deemed to be HCA. Five themes were identified: individual patient vulnerability, communication, IPC implementation, policy issues and organisational response. Adaptations to policies based on these reviews were completed within the course of the initial phase of the pandemic. Conclusion This approach enabled timely learning and implementation of control measures and policy development.

Background Drug-resistant enteric fever is increasingly common in the Indian subcontinent. Correctly determining azithromycin resistance matters where drug-resistant enteric fever is common and oral therapy necessary. Case report In two patients returning from Pakistan to the UK with cephalosporin-resistant Salmonella enterica serovar Typhi, gradient strip testing erroneously indicated azithromycin resistance; the errors were detected by repeat testing and confirmed by whole genome sequencing. Results Both patients were treated with meropenem and, when revised susceptibility results were known, with azithromycin, allowing a switch to oral therapy. Conclusion As cephalosporin resistance becomes more common, azithromycin will be key for treating enteric fever and optimizing practice in susceptibility testing will be crucial. Practitioners should be aware of key steps to minimize error in azithromycin susceptibility testing, and should be alert for possible errors when reported azithromycin resistance is discordant with known prevalence of resistance.

Climate change is already expanding the geographic footprint of arboviral infections. In this article we consider the impact of climate change on three arboviruses with particular consideration of the effect on Europe.

Ivermectin has been shown in in vitro studies to have insecticidal properties against Aedes aegypti adults. This study aimed to assess these properties in vivo. Aedes aegypti survival was not affected by acquiring a blood meal from humans both 5 hours and 24 hours after ingestion of a typical dose of ivermectin

Summary The pancreatic islets of Langerhans regulate glucose homeostasis. The loss of insulin-producing β cells within islets results in diabetes, and islet transplantation from cadaveric donors can cure the disease. In vitro production of whole islets, not just β cells, will benefit from a better understanding of endocrine differentiation and islet morphogenesis. We used single-cell mRNA sequencing to obtain a detailed description of pancreatic islet development. Contrary to the prevailing dogma, we find islet morphology and endocrine differentiation to be directly related. As endocrine progenitors differentiate, they migrate in cohesion and form bud-like islet precursors, or “peninsulas” (literally “almost islands”). α cells, the first to develop, constitute the peninsular outer layer, and β cells form later, beneath them. This spatiotemporal collinearity leads to the typical core-mantle architecture of the mature, spherical islet. Finally, we induce peninsula-like structures in differentiating human embryonic stem cells, laying the ground for the generation of entire islets in vitro.

Aedes albopictus is secondary to Aedes aegypti as a vector of dengue viruses (DENVs) in settings of endemicity, but it plays an important role in areas of dengue emergence. This study compared the susceptibility of these 2 species to DENV infection by performing 232 direct blood-feeding experiments on 118 viremic patients with dengue in Vietnam. Field-derived A. albopictus acquired DENV infections as readily as A. aegypti after blood feeding. Once infected, A. albopictus permitted higher concentrations of DENV RNA to accumulate in abdominal tissues, compared with A. aegypti. However, the odds of A. albopictus having infectious saliva were lower than the odds observed for A. aegypti (odds ratio, 0.70; 95% confidence interval, .52–.93). These results quantitate the susceptibility of A. albopictus to DENV infection and will assist parameterization of models for predicting disease risk in settings where A. albopictus is present.

Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development. A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage. Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible. The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue.

Background A previous genome-wide association study identified 2 susceptibility loci for severe dengue at MICB rs3132468 and PLCE1 rs3740360 and further work showed these mutations to be also associated with less severe clinical presentations. The aim of this study was to determine if these specific loci were associated with laboratory features of dengue that correlate with clinical severity with the aim of elucidating the functional basis of these genetic variants. Methods This was a case-only analysis of laboratory-confirmed dengue patients obtained from 2 prospective cohort studies and 1 randomised clinical trial in Vietnam (Trial registration: ISRCTN ISRCTN03147572. Registered 24th July 2012). 2742 dengue cases were successfully genotyped at MICB rs3132468 and PLCE1 rs3740360. Laboratory variables were compared between genotypes and stratified by DENV serotype. Results The analysis showed no association between MICB and PLCE1 genotype and early viraemia level, platelet nadir, white cell count nadir, or maximum haematocrit in both overall analysis and in analysis stratified by serotype. Discussion The lack of an association between genotype and viremia level may reflect the sampling procedures within the included studies. The study findings mean that the functional basis of these mutations remains unclear. Trial registration ISRCTN ISRCTN03147572. Registered 24th July 2012.

Dengue is a viral disease for which there is currently no therapeutic agent. We investigated the potential of lovastatin in the treatment of dengue. Lovastatin was safe and well tolerated, but did not demonstrate a therapeutic benefit., Background. Dengue endangers billions of people in the tropical world, yet no therapeutic is currently available. In part, the severe manifestations of dengue reflect inflammatory processes affecting the vascular endothelium. In addition to lipid lowering, statins have pleiotropic effects that improve endothelial function, and epidemiological studies suggest that outcomes from a range of acute inflammatory syndromes are improved in patients already on statin therapy. Methods. Following satisfactory review of a short pilot phase (40 mg lovastatin vs placebo in 30 cases), we performed a randomized, double-blind, placebo-controlled trial of 5 days of 80 mg lovastatin vs placebo in 300 Vietnamese adults with a positive dengue NS1 rapid test presenting within 72 hours of fever onset. The primary outcome was safety. Secondary outcomes included comparisons of disease progression rates, fever clearance times, and measures of plasma viremia and quality of life between the treatment arms. Results. Adverse events occurred with similar frequency in both groups (97/151 [64%] placebo vs 82/149 [55%] lovastatin; P = .13), and were in keeping with the characteristic clinical and laboratory features of acute dengue. We also observed no difference in serious adverse events or any of the secondary outcome measures. Conclusions. We found lovastatin to be safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, we found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. Continuing established statin therapy in patients who develop dengue is safe. Chinese Clinical Trials Registration. ISRCTN03147572.

Background Primary health care facilities frequently manage dengue cases on an ambulatory basis for the duration of the patient’s illness. There is a great opportunity for specific messaging, aimed to reduce dengue virus (DENV) transmission in and around the home, to be directly targeted toward this high-risk ambulatory patient group, as part of an integrated approach to dengue management. The extent however, to which physicians understand, and can themselves effectively communicate strategies to stop focal DENV transmission around an ambulatory dengue case is unknown; the matter of patient comprehension and recollection then ensues. In addition, the effectiveness of N,N-diethyl-3-methylbenzamide (DEET)-based insect repellent in protecting dengue patients from Aedes aegypti mosquitoes’ bites has not been investigated. Methodology A knowledge, attitude and practice (KAP) survey, focusing on the mechanisms of DENV transmission and prevention, was performed using semi-structured questionnaires. This survey was targeted towards the patients and family members providing supportive care, and physicians routinely involved in dengue patient management in Southern Vietnam. An additional clinical observational study was conducted to measure the efficacy of a widely-used 13% DEET-based insect repellent to repel Ae. aegypti mosquitoes from the forearms of dengue cases and matched healthy controls. Principal Findings Among both the physician (n = 50) and patient (n = 49) groups there were several respondents lacking a coherent understanding of DENV transmission, leading to some inappropriate attitudes and inadequate acute preventive practices in the household. The application of insect repellent to protect patients and their relatives from mosquito bites was frequently recommended by majority of physicians (78%) participating in the survey. Nevertheless, our tested topical application of 13% DEET conferred only ~1hr median protection time from Ae. aegypti landing. This is notably shorter than that advertised on the manufacturer’s label. No differences in landing time between febrile dengue cases or matched healthy controls (n = 19 experiments) were observed. Conclusion/Significance Our study identifies missed opportunities for primary care physicians to improve public health through communication of strategies that could prevent focal dengue transmission in and around a case household. We advocate better access to more efficient communication methods for physicians and auxilliary health workers, supporting to educate those at high risk of DENV transmission. Our empirical testing of a widely-available 13% DEET-based repellent was limited in its protective efficacy against Ae. aegypti mosquito bites, and therefore DENV transmission, suggesting more frequent application is necessary to be beneficial., Author Summary In endemic countries many dengue cases are managed on an ambulatory basis throughout their illness. Many of these ambulatory cases will be infectious to Ae. aegypti mosquitoes for some period of the febrile phase. A survey of two key actors, physicians who manage dengue cases and the primary caregiver to dengue cases, was performed to assess their knowledge, attitudes and practices on the mechanism of DENV transmission and prevention. In addition, the duration of protection from mosquito landing was measured and compared between febrile dengue patients and healthy volunteers using a locally available, and widely-used 13% N,N-Diethyl-3-methylbenzamide (DEET)-based topical insect repellent. This KAP survey demonstrated an incomplete understanding of DENV transmission among several patients and physicians, leading to some inappropriate attitudes and inadequate preventive practices in the household. This suggests that aspects of the knowledge, communication between physicians and patients about dengue, and what patients have retained from the clinical consultation, can be improved. The use of topical insect repellent to protect patients and relatives from mosquito bites was recommended by a large proportion of physicians. However, the repellent used in this experiment provided only a modest repellent effect to Ae. aegypti mosquitoes, with no difference in protection time when applied to either dengue patients or healthy controls. Future recommendations to patients should continue to promote repellent use, but advocate much more frequent application. To directly target those patients at risk of onward DENV transmission, this research highlights the potential benefits of physicians imparting practicable and effective advice on preventive measures of dengue case management, as part of a holistic approach to dengue control. Finally, findings of this work can provide data for approaching effectively preventive practices for DENV and other flaviviruses transmitted by Aedes spp.

An African HIV-infected patient presented with widespread necrotic lymphadenopathy five months after starting combination antiretroviral therapy (cART) and was thought to have disseminated tuberculosis in the context of an immune reconstitution inflammatory syndrome (IRIS) on the basis of typical imaging appearances and suggestive appearances from a fine needle aspirate of a nodal mass. The patient deteriorated despite empirical antituberculosis therapy and the correct diagnosis of nodal cryptococcal infection was subsequently established by histological examination of a core biopsy from a lymph node. IRIS should be borne in mind when considering the differential diagnosis in a patient who has recently started cART.

Female genital mutilation (FGM) is widely practised in several regions of the world. It is often associated with physical, psychological, sexual and social sequelae. Migration of persons from cultures that actively practice FGM to the UK and other Western countries increases the chances that clinicians will be faced with patients who have undergone this procedure. Clinical presentations often occur against a background of differences in culture and social identity, which may pose a challenge to any form of intervention. Perceptions of normalcy, human rights violation and gender roles may also differ. This paper discusses historical, cultural, gender and identity issues associated with FGM and its psychological and sexual implications.

Dengue is the most common arboviral disease of humans. There is an unmet need for a therapeutic intervention that reduces the duration and severity of dengue symptoms and diminishes the likelihood of severe complications. To this end, there are active discovery efforts in industry and academia to develop interventions, with a focus on small molecule inhibitors of dengue virus replication that are suitable for therapy or chemoprophylaxis. Advancements in animal models of dengue virus infection together with the possibility of a dengue human infection model have further enhanced the platform for dengue drug discovery. Whilst drug discovery efforts gestate, there are ongoing clinical research designed to benefit today's patients, including trials of supportive care interventions, and descriptive studies that should improve the ability of clinicians to make an accurate diagnosis early in the illness course and to identify patients most at risk of progression to severe disease. This review provides a state of the art summary of dengue drug discovery, clinical trials, and supportive allied research and reflects discussions at the 2nd International Dengue Therapeutics Workshop held in Ho Chi Minh City, Vietnam, in December 2013.

We have studied the occurrence, stage specificity and cellular location of key molecules associated with microtubules in Plasmodium falciparum merozoites. Antibodies to gamma tubulin, conventional kinesin and cytoplasmic dynein were used to determine the polarity of merozoite microtubules (mt), the stage specificity of the motor proteins and their location during merozoite development. We conclude that the minus ends of the mts are located at their apical pole. Kinesin was present throughout the lifecycle, appearing as a distinct crescent at the apex of developing merozoites. The vast majority of cytoplasmic dynein reactivity occurred in late merogony, also appearing at the merozoite apex. Destruction of mt with dinitroanilines did not affect the cellular location of kinesin or dynein. In invasion assays, dynein inhibitors reduced the number of ring stage parasites. Our results show that both conventional kinesin and cytoplasmic dynein are abundant, located at the negative pole of the merozoite mt and, intriguingly, appear there only in very late merogony, prior to merozoite release and invasion.

BACKGROUND: A recent genome-wide association study (GWAS) identified susceptibility loci for dengue shock syndrome (DSS) at MICB rs3132468 and PLCE1 rs3740360. The aim of this study was to define the extent to which MICB (rs3132468) and PLCE1 (rs3740360) were associated with less severe clinical phenotypes of pediatric and adult dengue. METHODS: 3961 laboratory-confirmed dengue cases and 5968 controls were genotyped at MICB rs3132468 and PLCE1 rs3740360. Per-allele odds ratios (OR) with 95% confidence intervals (CI) were calculated for each patient cohort. Pooled analyses were performed for adults and paediatrics respectively using a fixed effects model. RESULTS: Pooled analysis of the paediatric and adult cohorts indicated a significant association between MICB rs3132468 and dengue cases without shock (OR = 1.15; 95%CI: 1.07 - 1.24; P = 0.0012). Similarly, pooled analysis of pediatric and adult cohorts indicated a significant association between dengue cases without shock and PLCE1 rs3740360 (OR = 0.92; 95%CI: 0.85 - 0.99; P = 0.018). We also note significant association between both SNPs (OR = 1.48; P = 0.0075 for MICB rs3132468 and OR = 0.75, P = 0.041 for PLCE1 rs3740360) and dengue in infants. DISCUSSION: This study confirms that the MICB rs3132468 and PLCE1 rs3740360 risk genotypes are not only associated with DSS, but are also associated with less severe clinical phenotypes of dengue, as well as with dengue in infants. These findings have implications for our understanding of dengue pathogenesis.

In July, 2012, a 25-year-old man was admitted to our hospital with headache, fever, and reduced consciousness. He had an unremarkable medical history and took no regular medications. He worked as a peanut vendor and before becoming unwell had visited relatives in the countryside. During this time he had attended a wedding and dived for pearls in a freshwater lake. 1 week after returning to the city he developed headache and fever, for which he took paracetamol. The next day his headache worsened in severity and he presented to his local hospital, where staff noted that he was confused. He was given a dose of ceftriaxone to cover bacterial meningitis and was transferred to our hospital. On initial assessment, he had a temperature of 39°C. His Glasgow coma scale score was 10 (M=5, V=2, E=3). His neck was stiff . He had no rash and was haemodynamically stable. Initial blood tests showed raised white cell count of 13·34×109 per L with 89% neutrophils. Lumbar puncture was done, which showed an opening pressure of 38 cm H2O. Cerebrospinal fl uid (CSF) contained 3260 × 103 per mL white cells with 88% neutrophils. CSF protein was 7·9 g/L, and glucose was 0·15 mmol/L. Plasma glucose was 8·62 mmol/L. Gram and Zeil-Neilsen stains were negative. However, on wet mount microscopy numerous amoebae were seen (see fi gure and webvideo). He had already started ceftriaxone and dexamethasone for presumed bacterial meningitis. In view of the CSF fi ndings and history of exposure to freshwater a diagnosis of primary amoebic meningoencephalitis was considered. Amphotericin B and rifampicin were started. Later on the day of admission his condition deteriorated and he required intubation and ventilation. He subsequently went into cardiac arrest and could not be resuscitated. Polymerase chain reaction Lancet 2013; 381: 176

Dengue viruses are the most important arboviruses causing disease in humans. Approximately 3 billion people live in areas of risk, and there are an estimated 50–100 million cases occurring each year. These estimates reflect an enormous burden of morbidity, predominantly affecting urban centres of the developing world. There is currently no specific treatment and disease control is limited to tackling the vector. Despite considerable scientific attention disease pathogenesis remains incompletely understood. A better understanding of dengue virus biology and disease pathogenesis has the potential to pave the way to successful therapeutic interventions. This article aims to review current understanding of virus and vector biology, disease pathogenesis and clinical manifestations and management. Finally the article will consider novel approaches to clinical management and disease control. Key Concepts: Dengue viruses are the most important arboviruses globally. Dengue viruses are a significant cause of morbidity, particularly in the tropics. The pathogenesis of dengue results from both virus and host factors. Clinical management is limited to parenteral fluids, occasional use of blood products and supportive care. Despite a long gestation and theoretical safety concerns a dengue vaccine may soon be a reality. Novel approaches to vector control may aid global disease control efforts. Keywords: dengue; Aedes aegypti; haemorrhagic fever; mosquito; arbovirus; infectious disease

Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage. As a result of this prophylactic platelet transfusions are sometimes advocated for the prevention of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a global survey to assess the different approaches to the use of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity of the responses highlights the variation in clinical practice and lack of an evidence base in this area and underscores the importance of prospective clinical trials to address this key question in the clinical management of patients with dengue., Author Summary A low platelet count is a common feature of dengue infection. It is thought that the platelet count correlates with the severity of the infection and may contribute to the risk of developing haemorrhage, a well-recognised complication of dengue. As a result of this platelet transfusions are used in some settings to reduce the risk of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a survey assessing the use of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received 306 responses from 20 different countries. The striking feature of the survey responses was the heterogeneity of approaches to the use of platelets in dengue. These findings highlight the variation in clinical practice and lack of an evidence base in this area and underscore the importance of conducting prospective clinical trials to address this key question in dengue clinical management.

The British HIV Association (BHIVA) recommends that specialist clinical networks are involved in care of HIV-positive patients admitted to district general hospitals (DGHs) and that transfer to a specialist HIV treatment centre is considered for each patient. We audited our experience of 29 patients transferred to our specialist inpatient unit over a two year period. Fifteen (52%) patients were known to be HIV-infected before admission to the referring hospital. Ten (71%) of 14 patients with newly diagnosed HIV had an opportunistic infection at transfer. At the referring hospital the time taken to diagnose HIV infection ranged from one to 26 days (median = 3.5). Only five patients (17%) were transferred by 72 hours of admission to the referring hospital. The duration of stay at our centre was 1–212 days (median = 15): seven patients (24%) required admission to the intensive care unit. Seven patients died; of these, three had newly diagnosed HIV infection. This audit demonstrates that sick HIV-infected patients transferred to a specialist HIV unit had a poor outcome and lengthy hospital admissions. Our audit supports roll-out of HIV testing to avoid adverse outcomes associated with late diagnosis and development of clinical networks involving specialist HIV treatment centres in order to support provision of HIV care in DGHs.

Staphylococcus aureus bacteraemia is one of the most common serious bacterial infections worldwide. In the UK alone, around 12,500 cases each year are reported, with an associated mortality of about 30%, yet the evidence guiding optimum management is poor. To date, fewer than 1500 patients with S aureus bacteraemia have been recruited to 16 controlled trials of antimicrobial therapy. Consequently, clinical practice is driven by the results of observational studies and anecdote. Here, we propose and review ten unanswered clinical questions commonly posed by those managing S aureus bacteraemia. Our findings define the major areas of uncertainty in the management of S aureus bacteraemia and highlight just two key principles. First, all infective foci must be identified and removed as soon as possible. Second, long-term antimicrobial therapy is required for those with persistent bacteraemia or a deep, irremovable focus. Beyond this, the best drugs, dose, mode of delivery, and duration of therapy are uncertain, a situation compounded by emerging S aureus strains that are resistant to old and new antibiotics. We discuss the consequences on clinical practice, and how these findings define the agenda for future clinical research.

INTRODUCTION: Dengue is a vector-borne viral infection that endangers an estimated 2.5 billion people. Disease caused by dengue ranges from a relatively minor febrile illness to a life-threatening condition characterized by extensive capillary leak. A greater understanding of dengue has the potential to improve both the clinical management of individual cases and the control of the disease. SOURCES OF DATA: We searched the available literature using PubMed, Embase and Web of Science for relevant articles and abstracts. AREAS OF AGREEMENT: Addressing our gaps in the understanding of disease pathogenesis and improving our knowledge of dengue virus biology are necessary in order to develop tools to effectively control, diagnose and treat the disease. AREAS OF CONTROVERSY: The pathogenesis of dengue is multifactorial and depends on both host and virus factors. A more integrated understanding of disease pathogenesis is necessary. AREAS TIMELY FOR DEVELOPING RESEARCH: There are many questions related to disease pathogenesis, development of diagnostics, drug and vaccine development and individual case management that need addressing if the disease is to be successfully tackled.

We describe a case of cutaneous myiasis caused by Cordylobia anthropophaga acquired in the UK from contact with another person's clothes. We propose that this diagnosis should be considered in both returning travellers and also their household contacts.

We describe a case of mixed malaria infection in a returning traveller. We suggest that our patient had a chronic infection with Plasmodium vivax, which reduced the severity of an acute infection with P. falciparum-an example of cross-species immunity.

Patients with HIV frequently present with fever. However, the spectrum of diseases affecting patients with HIV has changed in the era of antiretroviral therapy (ART). Here we present a patient who has an unusual cause for his fever with an eventual diagnosis of adult-onset Still's disease.

Adult patients with tuberculosis (TB) recruited at the chest clinic of the University Teaching Hospital in Lusaka, Zambia, from 2003 to 2004.To identify factors associated with delayed treatment or hospitalisation.A cross-sectional survey of newly identified adult patients with TB.A total of 223 patients were included in the analysis. Patients with smear-negative disease were 2.6 times more likely to be hospitalised than those with smear-positive disease (95%CI 1.28-5.30), while patients with extra-pulmonary disease were 3.42 times more likely to be hospitalised than those with pulmonary disease (95%CI 1.75-6.66). Patients with smear-negative disease were 2.81 times more likely to have experienced overall delay than those with smear-positive disease (95%CI 1.20-6.66).This analysis has demonstrated that patients with extra-pulmonary or smear-negative disease are significantly more likely to be hospitalised. Patients with smear-negative disease are also more likely to have experienced treatment delay. These data reinforce the urgent need for more robust diagnostic tests, particularly for smear-negative and extra-pulmonary disease. As these forms of disease are more likely to be associated with the human immunodeficiency virus (HIV), the data support earlier diagnosis and treatment of HIV infection.