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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic represents an extraordinary medical challenge that has already had massive economic and societal impacts. In contrast to the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus outbreaks, every respiratory physician and intensivist are likely to encounter patients infected with SARS-CoV-2 and need a good understanding of the management of the associated disease, COVID-19. We are facing the first wave of the SARS-CoV-2 pandemic, but the infectivity of the virus and the lack of population immunity suggest future waves are possible. For this article (summarised in table 1), we have used our recent clinical experience of COVID-19 combined with the limited published data to discuss how the clinical presentation relates to pathogenesis, key research questions and particular issues relevant to respiratory medicine. View this table: Table 1 Summary of COVID-19 disease features, the research questions these raise, and potential therapeutic relevance Most infections with SARS-CoV-2 are mild, but a minority of patients develop COVID-19 pneumonia. The main differential diagnosis for COVID-19 is community-acquired pneumonia (CAP), which is also commonly caused by infection with respiratory viruses. However, COVID-19 has several clinical features distinct to CAP, which both indicate the diagnosis and suggest it has distinct mechanisms of pathogenesis. For patients with CAP, symptoms, signs and alveolar consolidation usually develop rapidly after infection, whereas for patients with COVID-19, a 6+-day lag between the start of infective symptoms and admission with pneumonia is usual.1 2 COVID-19 also often causes marked malaise and extrapulmonary symptoms, such as anosmia, headache, myalgia and myocarditis.3 4 The leading cause of death in COVID-19 is respiratory failure from extensive lung injury. This usually presents with …

Background Antiretroviral therapy (ART) has significantly altered the pattern of acute and chronic HIV-related disease. However, it is not clear what this means in terms of respiratory symptoms. We sought to investigate the association between HIV status and respiratory symptoms and how these have changed with the availability of ART. Methods We searched Cochrane, Medline and Embase databases for studies published between 1946 and August 2015 comparing the prevalence of respiratory symptoms in populations with and without HIV infection. We undertook random effects meta-analysis of the main symptoms reported. We studied heterogeneity and completed sensitivity analyses and funnel plots. Results From 5788 unique references identified, 24 papers provided relevant data: 18 documented the prevalence of cough and 11 examined the prevalence of breathlessness among other symptoms reported. Compared with the HIV negative, people living with HIV (PLWH) were more likely to have respiratory symptoms with pooled ORs for the prevalence of cough of 3.05 (95% CI 2.24 to 4.16) in resource-limited populations without access to ART; 2.18 (1.56 to 3.18) in resource-rich populations without access to ART and 1.11 (0.99 to 1.24) in resource-rich populations with access to ART. In resource-rich settings, although the availability of ART was associated with a reduction in the difference between HIV-positive and HIV-negative individuals, PLWH were more likely to report breathlessness, OR 1.39 (95% CI 1.11 to 1.73). Conclusions Respiratory symptoms are more common in PLWH than controls. This association persists although at a reduced level in populations with access to ART.

INTRODUCTION: Consensus on the best treatment regimens for patients with isoniazid-resistant TB is limited; global treatment guidelines differ. We undertook a systematic review and meta-analysis using mixed-treatment comparisons methodology to provide an up-to-date summary of randomised controlled trials (RCTs) and relative regimen efficacy.METHODS: Ovid MEDLINE, the Web of Science and EMBASE were mined using search terms for TB, drug therapy and RCTs. Extracted data were inputted into fixed-effects and random-effects models. ORs for all possible network comparisons and hierarchical rankings for different regimens were obtained.RESULTS: 12 604 records were retrieved and 118 remained postextraction, representing 59 studies-27 standalone and 32 with multiple papers. In comparison to a baseline category that included the WHO-recommended regimen for countries with high levels of isoniazid resistance (rifampicin-containing regimens using fewer than three effective drugs at 4 months, in which rifampicin was protected by another effective drug at 6 months, and rifampicin was taken for 6 months), extending the duration of rifampicin and increasing the number of effective drugs at 4 months lowered the odds of unfavourable outcomes (treatment failure or the lack of microbiological cure; relapse post-treatment; death due to TB) in a fixed-effects model (OR 0.31 (95% credible interval 0.12-0.81)). In a random-effects model all estimates crossed the null.CONCLUSIONS: Our systematic review and network meta-analysis highlight a regimen category that may be more efficacious than the WHO population level recommendation, and identify knowledge gaps where data are sparse.SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42014015025.

Latent TB infection (LTBI) screening and treatment in HIV-positive individuals in the UK is advocated by the British HIV Association (BHIVA) and National Institute for Health and Care Excellence (NICE), although each recommends differing strategies. We undertook an evaluation of UK practice, relating the responses to the local HIV/TB disease burden. 162 of 188 (86%) UK geographical areas responded; only 93/162 (57.4%) offer LTBI testing with considerable heterogeneity in practice, and no difference in HIV/TB burden between areas offering testing and those who do not. Only 33/93 (35.5%) and 6/93 (6.5%) reported full compliance with BHIVA and NICE guidance respectively. A uniform national guideline is required.

Background: The emergence of multidrug-resistant tuberculosis (MDRTB) and extensively drug-resistant tuberculosis (XDRTB) is a threat to global tuberculosis control. Limited information is, however, available on the outcome of XDRTB cases. This study describes the susceptibility to second- and third-line antituberculosis drugs among MDRTB cases and treatment outcome of identified XDRTB cases. Method: The results of second-line antituberculosis drug susceptibility tests in the UK between January 1995 and December 2007 were retrospectively reviewed and clinicians contacted for treatment outcome of XDRTB cases. Participants included all 678 patients with culture-confirmed MDRTB in the UK. The main outcome measures were the proportion of isolates resistant to second-line antituberculosis drugs and treatment outcome for XDRTB cases. Results: Among MDRTB isolates, levels of resistance to amikacin, capreomycin, ciprofloxacin, cycloserine, ethionamide and p-aminosalicylic acid (PAS) were 5.5, 3.4, 5.6, 5.1, 14.0 and 16.7%, respectively. Six XDRTB cases (0.9% of MDR cases) were identified during this period. Two further cases of XDRTB were reported in 2008. Five individuals with XDRTB died of tuberculosis within 3 years of diagnosis and three are still on treatment. Conclusion: Levels of MDRTB remain low, and those of XDRTB very low, in this high income country. The case fatality ratio among XDRTB cases was high despite low levels of HIV co-infection.

Background: Immunological ex vivo assays to diagnose tuberculosis (TB) have great potential but have largely been blood-based and poorly evaluated in active TB. Lung sampling enables combined microbiological and immunological testing and uses higher frequency antigen-specific responses than in blood. Methods: A prospective evaluation was undertaken of a flow cytometric assay measuring the percentage of interferon-γ synthetic CD4+ lymphocytes following stimulation with purified protein derivative of Mycobacterium tuberculosis (PPD) in bronchoalveolar lavage fluid from 250 sputum smear-negative individuals with possible TB. A positive assay was defined as >1.5%. Results: Of those who underwent lavage and were diagnosed with active TB, 95% (106/111) had a positive immunoassay (95% CI 89% to 98%). In 139 individuals deemed not to have active TB, 105 (76%) were immunoassay negative (95% CI 68% to 82%). Of the remaining 24% (34 cases) with a positive immunoassay, a substantial proportion had evidence of untreated TB; in two of these active TB was subsequently diagnosed. Assay performance was unaffected by HIV status, disease site or BCG vaccination. In culture-positive pulmonary cases, response to PPD was more sensitive than nucleic acid amplification testing (94% vs 73%). The use of early secretory antigen target-6 (ESAT-6) responses in 71 subjects was no better than PPD, and 19% of those with culture-confirmed TB and a positive PPD immunoassay had no detectable response to ESAT-6. Conclusions: These findings suggest that lung-orientated immunological investigation is a potentially powerful tool in diagnosing individuals with sputum smear-negative active TB, regardless of HIV serostatus.

Anti-tuberculosis drug regimens are efficacious, but drug intolerance can be severe and may impact on treatment completion rates. The Enhanced Tuberculosis Surveillance (ETS) system is a case register of all new notifications of tuberculosis in England, Wales and Northern Ireland. We conducted a cohort study to estimate the incidence of, and risk factors for, drug intolerance reported through ETS between 2001 and 2010 and to assess its relationship with treatment non-completion. Reports of drug intolerance were found for 868/67 547 (1.28%) patients in the cohort, and important risk factors were female sex, older age, later case report year and white ethnicity. Drug intolerance was associated with an approximate fivefold increased odds of treatment non-completion (p

Cohort review has been used internationally to support tuberculosis (TB) control. We describe its first use in the UK by a London TB service. Improvements were noted in case management and contact tracing, weaknesses identified and important service changes put in place. Key areas of impact were directly observed therapy (DOT) provision (a greater proportion of cases offered DOT, and in response to low uptake resources diverted to create posts responsible for patient-centred DOT delivery), and contact tracing (more contacts per case screened and assessed). Cohort review enables whole system review and improvement. It has subsequently been adopted across the UK.

Active tuberculosis (TB) in the UK predominantly affects the non-UK born, but is generally not manifest at the time of UK entry. Strategies to detect latent TB infection (LTBI) in this population are, therefore, important. To date, targeted screening has focused on TB risk estimates based on the incidence in the country of origin. Using TB incidence in the UK and migration data, we estimated the numbers needed to be tested and treated for LTBI to prevent one case of TB disease. Numbers were the lowest in Somalian and the highest in South African and Filipino migrants, which contrasts with TB rates in these countries. Targeting screening on the basis of incidence in the UK may thus improve effectiveness.

Background: It has been suggested that deterioration of tuberculosis (TB) during appropriate treatment, termed a paradoxical reaction (PR), is more common and severe in HIV positive individuals on highly active antiretroviral therapy (HAART). Method: A study was undertaken to determine the frequency of PR and its associated features in a population of HIV+TB+ patients and a similar sized group of HIV−TB+ individuals. Results: PR occurred in 28% of 50 HIV+TB+ patients and 10% of 50 HIV−TB+ patients. Disseminated TB was present in eight of 13 HIV+TB+ patients and four of five HIV−TB+ patients with PR. In 28 HIV+TB+ patients starting HAART, PR was significantly associated with commencing HAART within 6 weeks of starting antituberculosis treatment (p = 0.03) and was more common in those with disseminated TB (p = 0.09). No association was found between development of PR and baseline CD4 count or CD4 response to HAART. Conclusions: PR is common in HIV infected and uninfected individuals with TB. Early introduction of HAART and the presence of disseminated TB appear to be important in co-infected patients.

Cohort review has been used internationally to support tuberculosis (TB) control. We describe its first use in the UK by a London TB service. Improvements were noted in case management and contact tracing, weaknesses identified and important service changes put in place. Key areas of impact were directly observed therapy (DOT) provision (a greater proportion of cases offered DOT, and in response to low uptake resources diverted to create posts responsible for patient-centred DOT delivery), and contact tracing (more contacts per case screened and assessed). Cohort review enables whole system review and improvement. It has subsequently been adopted across the UK.

WHO standards for tuberculosis (TB) control require monitoring and evaluation of TB control programmes. In London, TB rates have stabilised at 44 per 100,000 since 2005. In 38 urban areas outside London with TB rates above the national average, these continued to rise after 2004, to 28 per 100,000 in 2008 (15% increase). London has the highest proportion of TB cases in certain risk groups, but these are increasing rapidly outside London. Many TB control efforts focus on the capital, but with rates rising elsewhere in the country, this strategy is likely to fail in the long term.

Over the past few years there have been an increasing number of research articles published in Thorax on respiratory tract infections (including tuberculosis) affecting children and adults. Although these articles cover a wide variety of areas, several broad themes can be discerned. These include greater interest in viral respiratory infections (partially stimulated by the recent influenza A pandemic), improved characterisation of who is at risk of community-acquired pneumonia and mycobacterial infection, research into better diagnostics and attempts to develop new or improved scoring scales for a range of respiratory infection syndromes. There have also been a limited number of articles on how to manage patients with respiratory infection, including describing the efficacy of prevention by vaccination. Overall, there has been a discernible emphasis on transferring advances in clinical science to actual clinical practice, with several papers using molecular methodologies or measuring levels of cytokines or other potential biomarkers to improve diagnostic accuracy in patients with lung infection. There have also been manuscripts linking specific pathogen genotypes to infection phenotype, an area that is likely to be increasingly important in explaining some of the variations in severity between patients with respiratory infection. However, many questions remain on the optimum strategies for the management and prevention of pneumonia, bronchiectasis and tuberculosis, and there remains a strong need for further clinical research in order to make substantial improvements in the management of patients with lung infection.

Background The pan London “Find andTreat” tuberculosis (TB) service includes a mobile digital X-ray unit (MXU) screening service which has been shown to be cost effective among hard-to-reach groups (homeless people, substance users and prisoners). This study compared the impact of current practice of hostel staff encouraging MXU screening for TB among homeless people with the addition of peer educators with direct experience of TB and/or homelessness on screening uptake. Design/methods Between February 2012 and October 2013 London homeless hostels accessing MXU TB screening were randomised to intervention or control arms by minimisation, balancing on hostel size (≤43 beds), and previous screening uptake level (≤50%). Sites with a previous MXU uptake of >80% were excluded. At intervention sites, peers worked with hostel staff to encourage screening (through contacting and speaking with residents). The primary outcome was the proportion of eligible residents screened for TB. Blinding of participants and observers was not possible due to the nature of the intervention. Analysis was performed by intention to treat (ITT). Results Of 59 hostels considered for eligibility, 46 were randomised (24 allocated to the control and 22 to the intervention arm – Figure 1). Across all sites, median uptake was 44% (IQR: 26,59). Control hostels had a total of 1192 residents [median uptake 45%, (IQR: 33,55)]. Intervention sites had 1150 residents [median uptake 40%, (IQR: 25,61)]. Using Poisson regression to account for the clustered study design, size of hostel, and previous screening uptake, there was no evidence for peer educators increasing uptake of screening – adjusted risk ratio 0.98% (95% CIs: 0.80,1.20). Conclusion This study found no evidence for peer educators increasing the uptake of MXU TB screening. The wide confidence intervals associated with this result mean that we may be missing a 20% effect, which could be explained by a pragmatic study design where sites were not naive to the intervention as peers had previously been involved in screening sessions at many hostels. This study was supported by NIHR Programme Grant for Applied Research (RP-PG-0407–10340). Trial registration number: ISRCTN17270334.

BACKGROUND: Cytomegalovirus may replicate within the lungs both of recipients of transplants and of patients infected with the human immunodeficiency virus (HIV). A hypothesis formulated by this group was that a host damaging immune response might be provoked by cytomegalovirus infection and cause a severe pneumonitis in recipients of allogeneic transplants, whereas the progressive impairment of cellular immunity in patients with HIV disease would preclude a damaging immune response in the lungs, and thus protect these patients from severe cytomegalovirus pneumonitis. This study set out to discover whether severe cytomegalovirus pneumonitis arises in HIV infected patients. METHODS: Data were prospectively collected on severity of pneumonitis and infectious agents identified in consecutive respiratory episodes in HIV infected patients undergoing diagnostic bronchoalveolar lavage during 20 months. RESULTS: Eighty five episodes of pneumonitis occurred in 68 patients. Cytomegalovirus was identified as the only infectious agent in nine episodes (nine patients). Seven of the episodes were mild; all these patients had CD4 counts below 0.1 x 10(9)/1. The remaining two episodes were severe and ventilatory support was required. In both cases the CD4 counts were above 0.2 x 10(9)/1 and HIV infection appeared to have been acquired shortly before presentation. CONCLUSION: Although rare, severe cytomegalovirus pneumonitis may occur in HIV infected patients. Both patients with severe pneumonitis in this series had relatively well preserved immune function. These findings support the hypothesis that severe cytomegalovirus pneumonitis is an immunopathological condition.

In patients receiving treatment for pulmonary tuberculosis (TB), change in sputum culture from positive to negative is the principal outcome measure of a therapeutic response in both clinical practice1 2 and drug trials.3 Patients will often stop producing sputum early in the course of treatment.4 We have tested the assumption that “no sputum” means that the patient is “culture negative”, as this has never been confirmed experimentally. We prospectively followed 16 patients with newly diagnosed pulmonary TB. Sputum samples were collected at diagnosis, during weeks 1 and 2, at months 1, 2 and 4, and on completing treatment. Those patients who were not producing sputum spontaneously had specimens collected by induction. This was performed in a purpose-built negative pressure isolation chamber (Elwyn E Roberts Isolators, Shropshire, UK) where …

Sputum induction (SI) by inhalation of nebulised hypertonic saline is an efficient and non-invasive way of obtaining samples to assess airway inflammation and diagnose pulmonary infections such as tuberculosis (TB).1 2 Data published on the safety of SI are largely derived from subjects with obstructive lung disease. Yet on this basis a Working Group of the European Respiratory Society (ERS) recommended that all patients undergoing SI should receive pre-procedure bronchodilation with monitoring throughout by either serial forced expiratory volume in 1 s or peak expiratory flow rate (PEFR) measurements.3 Subjects with other respiratory conditions may not be at the …

BACKGROUND: Previous studies have estimated the prevalence of tuberculosis and HIV infection in population subgroups in the UK. This study was undertaken to describe recent trends in the proportion of individuals with HIV infection among reported cases of tuberculosis in England and Wales, and to review the implications for clinical and public health care. METHODS: A population-based matching study using national surveillance databases was used to investigate all persons aged 15 years and over reported with a diagnosis of tuberculosis to the Health Protection Agency in England and Wales in 1999-2003. Record linkage was used to match the national tuberculosis and HIV/AIDS surveillance databases to identify all cases of tuberculosis and determine the proportion of patients with tuberculosis co-infected with HIV. The distribution and characteristics of the cases were determined and the trend examined by year. RESULTS: Of 30,670 cases of tuberculosis reported in England and Wales between 1999 and 2003, an estimated 1743 (5.7%) were co-infected with HIV. There was a year on year increase in the proportion from 3.1% (169/5388) in 1999 to 8.3% (548/6584) in 2003 (p for trend

Background There are high rates of active tuberculosis (TB) in London’s hard to reach groups (homeless people, substance misusers and prisoners). However no systematic data are available regarding the prevalence of latent TB infection (LTBI) and blood borne viruses (BBV) - HIV, Hepatitis B and C (HBV, HCV). Hard to reach groups often present late for healthcare. We undertook a TB/BBV screening programme to assess the prevalence of LTBI and co-infection with BBVs within homeless hostels, drug services and a prison in London. We also investigated management outcomes in those referred on to healthcare services. Design/method Recruitment took place from May 2011–June 2013. Service users screened for TB on a mobile chest x-ray unit and in prison using the static digital x-ray machine were approached and, with consent, blood was drawn for IGRA (Quantiferon In-Tube) and HIV, HCV and HBV. Results were provided to participants with onward referral to healthcare services in line with current guidance. Treatment outcomes were collected via telephone follow up one year post referral for the positive cases. Results Prison (n = 511) (Table 1) LTBI: 65(13%) participants were IGRA positive [3(5%) co-infected with HCV]. Of these, 37(57%) were referred for preventive treatment, 16(43%) did not attend (DNA) appointments and were discharged or were lost to follow up (LFU). Of the 15 who commenced treatment, 9(60%) completed treatment. HCV: 22 participants were positive and referred, of which 11(50%) DNA/LFU, 11(50%) were under review and none commenced treatment. HBV: 10 participants were positive, of which 6(60%) DNA/LFU, 4(40%) were under review and none commenced treatment. There were no HIV positives. Community (N=696) (Table 1) LTBI: 116(17%) participants were IGRA positive [22(19%) co-infected with HCV]. Of the 14(12­%) referred to services, 8(57%) DNA/LFU and 3(21%) commenced treatment (2 completed). HCV: 84 were positive and referred (8 new diagnosis), 42(50%) DNA/LFU/declined referral, and 37(44%) under review. Five (6%) commenced treatment, one completed. HBV: 9 participants had current infection, none started treatment; 6 were under review and 3 DNA/LFU. HIV: 9 participants were positive and known to healthcare services. Conclusion The prevalence of LTBI, BBVs and co-infection within the hard to reach group is high compared to the general population with fewer patients starting TB prophylaxis/HCV treatment. The high overall rates of DNA/LFU (47%) seen indicate that current approaches to onward referral and retention in care for this group appear to be poor and effective measures to improve engagement with clinical services are essential. This study was supported by NIHR Programme Grant for Applied Research (RP-PG-0407–10340).

Rationale Recent discoveries in human genetics have identified mitochondrial mutations which confer a high risk of sensorineural deafness in individuals exposed to aminoglycosides. Successful MDR-TB treatment often requires prolonged use of these agents. There are little data from the UK to inform the use of genetic tests within MDR-TB patients. We set out to survey MDR-TB practice in the UK with an emphasis on injectable drug use, ototoxicity and audiological monitoring practice. Methods Five centres took part in a retrospective study of patients initiating injectable treatment for MDR-TB between 1 January 2004 and 31 December 2009. Data were collected regarding patient characteristics, choice of injectable, methods and frequency of ototoxicity screening and incidence of drug-related complications. Results Treatment for 50 MDR-TB patients was reviewed. 29/50 (58%) patients received amikacin, 11/50 (22%) capreomycin, 4/50 (8%) streptomycin and 6/50 (12%) more than one injectable. Three centres used amikacin as their preferred injectable, two used capreomycin. Audiological screening for ototoxicity was variable. 21/50 (42%) patients received baseline screening within 2 weeks of starting an injectable. 16/50 (32%) patients went on to have monthly audiograms, with the majority screened more infrequently or if symptoms were reported. 12/50 (24%) patients received no screening at any point. Ototoxicity was defined as a 20 dB loss from baseline on audiogram at one test frequency, or a 10 dB loss at two adjacent frequencies, or in the absence of a baseline result, as two or more frequencies below 20 dB. If no audiograms were available, the definition was symptomatic. 14/50 (28%) of patients experienced ototoxicity, with 9/50 (18%) left with persistent hearing loss. Increased age (p=0.02), use of amikacin (p=0.02) and decreased renal function on therapy (p=0.01) were significantly associated with ototoxicity (see Abstract S2 Table 1). No centre routinely tests for mitochondrial DNA mutations. Conclusions There is local variation in both choice of injectable agent and in ototoxicity screening practices between the MDR treatment centres studied. The data suggest capreomycin might be associated with less ototoxicity when compared to amikacin. There are no UK guidelines to inform best practice and better evidence, including clinical and cost-effectiveness studies, is needed to inform the implementation of current technology including genetic testing.

Introduction and Objectives AFD is an X-linked lysosomal storage disorder caused by mutations of the GLA gene. Lack of enzyme results in storage material accumulation within lysosomes, leading to multi-organ pathology. Airflow obstruction has been reported, though there has been no systematic assessment of lung enzyme activity in affected individuals. We therefore undertook a controlled cohort review of UK AFD patients focussing in particular on the relationship between airway and blood intra- and extracellular GLA, and lung pathology. Methods Study subjects and controls were recruited following local Ethics Committee approval. All underwent systematic pulmonary investigation, including lung function testing and sputum induction with 40 ml of 4% hypertonic saline over 20 min via an ultrasonic nebuliser. GLA activity was measured from AFD patients and healthy controls in induced sputum (IS) cells and supernatant using a fluorometric assay. In addition, in AFD patients, GLA activity was measured simultaneously in blood leucocytes and plasma. Results 45 AFD patients with variable severity extra-pulmonary disease were recruited (20 males, 10 smokers). The population had a mean FEV1 of 89% predicted. 20 of 45 (44%) (13 males, 6 smokers) had evidence of airflow obstruction with FEV1/FVC ratio Conclusions Sputum GLA activity is lower in male AFD patients than controls. However AFD subjects had significantly higher GLA activity in lung than blood. Measured airway obstruction in AFD was mild, though common. We speculate that the higher levels of lung enzyme found in AFD patients, on or off enzyme replacement, may contribute to the relative preservation of pulmonary function compared to other organ systems.

Paradoxical reaction (PR) in tuberculosis (TB) is defined as transient worsening of symptoms and signs or the appearance of new lesions after beginning appropriate anti-tuberculosis chemotherapy. Recent studies suggest that PR occurs in 10–35% of patients. It is more common and more severe in HIV co-infected individuals with disseminated disease.1 PR is thought to be an immune mediated phenomenon but the reasons for its occurrence are unknown.1 Infection by Mycobacterium tuberculosis (MTB) results in highly variable outcomes between individuals. The characterisation of MTB strains by molecular typing techniques suggests this may be a reflection of the infecting organism, as well as host response and environmental factors. MTB strains with distinct genotypes have been shown to evoke different immunopathological events in mouse models2 and variable clinical manifestations …

BACKGROUND--It has previously been shown that HIV infected individuals with pneumonitis have identifiable abnormalities in alveolar macrophages obtained by bronchoalveolar lavage (BAL). In particular, alterations in the expression of alveolar macrophage surface antigens associated with macrophage function have been reported. To determine whether these changes reflect HIV infection or the respiratory episode itself, a population of HIV infected patients with no respiratory disease was studied. METHODS--Twenty two HIV antibody positive individuals with a peripheral blood CD4 count of > 400/microliters and 10 healthy volunteer controls underwent bronchoscopy and BAL. Cytospin preparations from the recovered cells were stained using immunoperoxidase and double immunofluorescence techniques with monoclonal antibodies RFD1, RFD7, EBM11/CD68 (mature macrophages), UCHM1/CD14 (monocyte marker), and HLA-DR (RFDR1). Differential cell counts were also performed. RESULTS--There was an increase in overall alveolar macrophage HLA-DR expression in the HIV population. This was not reflected in a change in the percentage of cells staining CD14 (monocytes) or CD68 (mature macrophages) positive. The relative proportions of cells staining RFD1 + RFD7- (inducer cells), RFD1 - RFD7+ (effector cells), and RFD1 + RFD7+ (suppressive cells) were unchanged between HIV and control groups. CONCLUSIONS--In a population of HIV infected individuals with normal CD4 counts and no respiratory disease there was an increase in overall alveolar macrophage HLA-DR expression which occurred independently of any alteration in the relative proportions of alveolar macrophage subpopulations.

Setting and Methods London has high rates and large numbers of TB notifications. Treatment completion is generally Results Subjects receiving SAT had excellent treatment completion rates (91%), with 3% lost to TB service follow-up (Abstract P51 table 1). Those on DOT had a lower completion rate—which at 80% was less than the international standard. Ten per cent of DOT subjects were lost to follow-up (all after transfer out of NCL TB service care). Death rates were threefold higher in the DOT group. After 20 months median follow-up post treatment completion, 3 SAT and 0 DOT patients had been re-treated for TB. Conclusions The risk assessment tool appears to discriminate those patients who can receive SAT; though it should be noted that re-treatment was only required in this group—suggesting possible poor adherence with therapy in some individuals. Subjects on DOT did well within NCL TB service, but were too often lost to follow-up if transferred elsewhere. It is unclear whether this reflects inadequate local data collection and communication by, and with, our service, or genuine loss from healthcare. Either way, this requires urgent attention. The planned introduction of enhanced case management within the London TB model of care may improve this.