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P93 TRENDS IN HOME-BORN TUBERCULOSIS RATES AMONG EUROPEAN COUNTRIES IN COMPARISON TO UK
A Ponnuswamy, S Durairaj, PDO Davies. Liverpool Heart and Chest Hospital, Liverpool, UK
Introduction: Following the government action plan for tuberculosis it has been suggested that a reduction in case rates among the home-born white population in the UK could be used as a measure of a successful tuberculosis control programme. In 2007 we presented data comparing trends in home-born rates of tuberculosis between the USA and the UK. We found that between 1993 and 2005 home-born case rates in the UK remained steady while almost halving in the USA. We have extended the analysis to assess the rates in home-born Europeans against the home-born white population in the UK.
Methods: We analysed data from the EuroTB reports published by the European Centre for Disease Control. We also sought data from the individual country profiles. Detailed data regarding incidence rates among all the European countries have started as recently as 2000–1. The data collection changed in 2004 with the expansion of the European Union. Minor differences do exist in the way data are collected by individual member countries. To achieve the most accurate comparison across countries we have extracted data from 2002 to 2006 for selected western European countries: Austria, Belgium, Denmark, France, Germany, Italy, The Netherlands, Portugal and the UK.
Results: Portugal had by far the highest home-born case rates, 38/100 000 in 2002, but also had the highest annual rate of decline over the 5 years analysed: 1.63. The home-born rates in 2002 varied from 9.4 for Austria to 2.1 for The Netherlands and were 3.4 for the UK. Annual tuberculosis case rates among the home-born population were found to be decreasing within most of Europe, varying from 1.63 (Portugal) to 0.02 (Denmark). In contrast, three countries showed a small increase in annual case rates: the UK 0.05, The Netherlands 0.03 and France 0.02.
Conclusions: In contrast to many European countries the UK is experiencing an increase in its home-born cases as well as foreign-born cases. This may indicate a need for an improved tuberculosis control programme.
P94 OBSERVATIONS FROM A TUBERCULOSIS SCREENING CLINIC: NICE, BUT NOT ENOUGH?
H Patel, C Sobajo, C Bell, C Hardy. Manchester Royal Infirmary, Manchester, UK
Cases of tuberculosis have risen dramatically at magnetic resonance imaging (MRI), from 44 cases in 1996 to 144 in 2007. The number of patients requiring screening has likewise increased at a time when tuberculin skin testing changed from Heaf to Mantoux, interferon gamma release assay (IGRA) tesing was introduced and the new NICE guidelines came into effect. Contacts of all cases of tuberculosis are screened, along with new entrants in a weekly nurse-led clinic (TBSC) run by two WTE nurses.
Methods: A retrospective audit of all cases invited to the TBSC throughout 2007 was carried out to monitor the overall activity of the clinic and adherence to the NICE guidelines.
Results: Of the 1621 invited to the clinic, 873 (54%) attended, comprising 684 contacts (79% of those invited) and 189 new entrants (25%). The mean age was 23 years. Investigations included 661 Mantoux tests, 114 IGRA tests and 303 chest x rays. 573 patients had a visible BCG scar or documentation of vaccination, 207 had no evidence of BCG vaccination and 93 were indeterminate. Of 424 with previous BCG who had a Mantoux test, 288 had a reading of 0 mm and a further 35 had a reading <6 mm induration (76% negative). Of 59 patients with a Mantoux reading that was positive according to the NICE guidelines, 41 (69%) had a positive IGRA. With the high Mantoux negativity rate despite previous BCG, 31 patients with a Mantoux induration of 9–14 mm underwent IGRA testing, 15 (48%) of which were positive. All IGRA-positive patients were offered chemoprophylaxis. 112 patients were given BCG vaccination. 14 patients had abnormal chest x rays.
Conclusions: There is a large non-attendance rate, especially among new entrants. Negative Mantoux readings are common after BCG vaccination (76%). A positive Mantoux reading in this cohort was invariably accompanied by a positive IGRA. We have demonstrated high IGRA positivity (48%) in those with Mantoux readings in keeping with previous BCG according to NICE. We believe the NICE algorithm should be urgently reviewed regarding the range of tuberculin sensitivity to trigger IGRA testing.
P95 NURSE-LED FOLLOW-UP CAN DECREASE ATTENDANCES AT THE ADULT TUBERCULOSIS CLINIC WITHOUT DETERIORATION IN OUTCOMES
1M Ogedengbe, 1E Togun, 2FA Post, 3KM Scott, 4V. Graham, 5R. D. Barker. 1Three Boroughs Primary Healthcare Community TB Team, London, UK, 2Academic Department of HIV/GU Medicine, King’s College London, London, UK, 3King’s College London School of Medicine at Guy’s, King’s and St Thomas’s Hospitals Registry, London, UK, 4Department of Respiratory Medicine, Central Middlesex Hospital, London, UK, 5Department of Respiratory Medicine, Kings College Hospital, London, UK
Introduction: The number of patients diagnosed with tuberculosis has increased with an increase in associated outpatient activity. Increased clinic attendances may be associated with crowded waiting rooms, longer waits in outpatients, decreased time for individual patient consultations, less time for teaching, decreased patient satisfaction and increased stress for clinicians. We sought to reduce unnecessary outpatient attendances and provide a more patient-friendly service by passing on large parts of patient care to our dedicated tuberculosis nurses.
Methods: The study was based in an inner city teaching hospital. The intervention included two main changes. First, a protocol was developed for nurse-led follow-up of patients with tuberculosis in the adult tuberculosis clinic. Second, for patients with uncomplicated tuberculosis the prescription for a complete course of treatment was written by a specialist doctor at the time of diagnosis. Medicines were administered to patients by nurses during a combination of clinic appointments and home visits. Patients only came back to clinic at the request of the nurses and at a final appointment. Treatment outcomes were recorded according to WHO/IUATLD guidelines. “Cured” and “treatment complete” were regarded as “successful”, whereas “treatment interrupted”, “died” and “treatment failed” were deemed to be “unsuccessful”. Patients diagnosed between 1 January 2002 and 1 June 2007 were included in the analysis. The intervention started on 1 June 2005. Those who died in hospital, paediatric, known HIV positive, transfers out and those still on treatment were excluded. The number of clinic visits and treatment success were compared before and after the intervention.
Results: 499 patients registered during the study period. Overall, the median number of clinic visits was five, range 1–15. Before nurse-led follow-up the median number of clinic visits was six, and after nurse-led follow-up it fell to three (p<0.001). Treatment success did not change after the initiation of nurse-led follow-up (before 278/297 (94%), after 170/178 (96%), p = 0.4) (see fig).
Conclusion: Nurse-led follow-up appears to be a safe way to manage adults with uncomplicated tuberculosis. It can provide significant benefits to nurses, doctors and students in the tuberculosis clinic.
P96 USE OF THE TUBERCULIN SKIN TEST TO SCREEN HEALTHCARE WORKERS FOR LATENT TUBERCULOSIS INFECTION
1ID Plumb, 1P Miller, 2S Tamne, 1D Creer. 1Barnet and Chase Farm Hospitals NHS Trust, London, UK, 2Royal Free Hampstead NHS Trust, London, UK
Introduction: Previous retrospective analysis in south London found 6.7% of 372 tuberculosis patients were healthcare workers (HCW), presenting a potential risk to patients, other HCW and a challenge to resources. To prevent the development of active disease, current NICE guidance is that treatment for latent tuberculosis infection (LTBI) should be considered in all HCW diagnosed with LTBI. To identify new employees with LTBI, we conduct prospective screening by tuberculin skin test (TST).
Methods: All new employees complete a questionnaire to determine BCG status, the presence of risk factors and history of tuberculosis symptoms. TST is performed and read at 48–72 h for all employees with tuberculosis risk factors, or without a clear history of BCG. Presumed LTBI is diagnosed if the TST is ⩾6 mm in the absence of BCG vaccination, or ⩾15 mm if vaccinated. All patients with increased TST are referred for chest radiograph and clinical assessment. Treatment for presumed LTBI is offered once active disease is excluded.
Results: Over 12 months from July 2007 to June 2008, 1568 employees were screened. Of 1193 for further assessment, three declined TST. Of those tested, 647 (54.3%) were employed as HCW for the trust. 1090 (92%) had prior BCG. The TST was ⩾15 mm in 129 with known previous BCG and ⩾6 mm in 23 with no previous (12) or unknown (11) BCG status. Overall, 152 (12.8%) were diagnosed with presumed LTBI, of whom 64 (42.1%) were HCW. 12 (four HCW) failed to attend clinic. Of the employees reviewed, 56 (24 HCW) agreed to commence chemoprophylaxis for LTBI. No cases of active tuberculosis were identified.
Conclusions: A high prevalence of presumed LTBI was found in new employees. The number of false positive and false negative TST results in this cohort is unknown. The proportion of employees accepting tuberculosis chemoprophylaxis is low. No cases of active tuberculosis were identified. Further evaluation of risk factors and the use of interferon gamma release assays is recommended to identify those requiring screening and chemoprophylaxis.
P97 CAN PATIENT CHARACTERISTICS INCLUDING SYMPTOMS BE USED AS A PROXY FOR THE DIAGNOSIS OF TUBERCULOSIS IN SPUTUM SMEAR-NEGATIVE TUBERCULOSIS IN A POORLY RESOURCED SETTING?
1PDO Davies, 2K Tocque, 2P Cook, 3L Lawson, 4L Cuevas. 1Tuberculosis Unit, Liverpool, UK, 2John Moores University, Liverpool, UK, 3Zankli Clinic, Abuja, Nigeria, 4School Tropical Medicine, Liverpool, UK
Introduction: In poorly resourced settings, when smear microscopy is the only means of diagnosing pulmonary tuberculosis, sputum smear-negative cases pose a diagnostic problem. We have undertaken a study in Abuja, Nigeria, to determine whether patient characteristics available within a short time of presentation could be used to predict whether a smear-negative tuberculosis patient could be diagnosed on a basis other than culture positivity.
Methods: Tuberculosis suspects attending district hospitals of Abuja, Nigeria, were asked to submit three sputum samples for Ziehl–Neelsen microscopy. One sample was cultured using BACTEC. A full history and examination was carried out on all patients and other patient characteristics assessed such as employment and educational status, overcrowding, BCG status, smoking history, body mass index, Karnovsky score and contact and length of exposure to known index cases. Symptoms included cough, haemoptysis, fever, breathlessness, weight loss, night sweats and loss of appetite. Blood tests were also taken including haemoglobin, white cell count, erythrocyte sedimentation rate and lung function tests.
Results: A total of 1321 patients was screened. Of these, 731 were culture positive and for the purposes of the study were defined as having pulmonary tuberculosis. A total of 378 (52%) of these was smear negative. A logisitc regression analysis comparing the 590 smear and culture-negative patients with the 378 smear-negative but culture-positive patients was undertaken. No significant difference in any of the characteristics was found except some symptomatology. The presence of four or five of the listed symptoms was commoner in the tuberculosis confirmed group (odds ratio (OR) 4.2, CI 1.7 to 10.23 for four symptoms and OR 4.7, CI 2.0 to 11.2 for five symptoms) and twice as common for eight symptoms (OR 2.4, CI 1.05 to 6.1). In contrast, patients who were sputum smear positve showed many differences with non-tuberculosis patients such as age, education, frequency of clinical signs and a tenfold difference in symptom score.
Conclusion: Clinical differences between adult patients who have sputum smear-negative tuberculosis and those who do not have tuberculosis are too small to allow the diagnosis of tuberculosis to be made on clinical grounds in a resource-poor setting.
P 98 PREDICTING HIV IN PATIENTS WITH TUBERCULOSIS
1KM Scott, 2E Togun, 2FA Post, 2RD Barker. 1King’s College, London School of Medicine at Guy’s, King’s and St Thomas’s Hospitals, London, UK, 2Kings College Hospital, London, UK
Introduction: Tuberculosis is commonly associated with HIV, especially in patients from sub-Saharan Africa. There is some evidence that the uptake of HIV tests is determined by the enthusiasm of the clinicians who offer the test.1 We evaluated the basic information available at the time of diagnosis of tuberculosis to see which elements might help predict which patients were co-infected with HIV.
Methods: All patients diagnosed with tuberculosis between 1 January 2000 and 1 July 2008 were eligible for the cohort. Age, sex, ethnic group, disease site and a variety of basic blood tests were evaluated in univariate models for their association with a subsequent HIV diagnosis. Factors that were significant in univariate models were entered into a multivariate logistic regression to determine those that predicted a positive HIV test.
Results: There were 972 patients with tuberculosis. HIV status was known for 517 (53%), of which 284 (55%) were men and the majority were black Africans (63%). The mean age was 36 years (SD 9.8). 140 (27%) of this group were HIV positive. In univariate analyses, HIV was associated with black-African ethnic group, age 25–45 years and female sex. HIV tuberculosis was also associated with higher globulin (see fig), alkaline phosphatase, aspartate transaminases, mean corpuscular volume (MCV) and with lower albumin, sodium, haemoglobin, total white cell count, total lymphocyte count, neutrophil count, monocytes, eosinophils, basophils and platelet count. In multivariate models, raised serum globulin was the strongest predictor of a positive HIV test (odds ratio (OR) 21.4 for values above 45 g/dl) with age between 25 and 45 years being the second most effective predictor (OR 4.4). In contrast, black-African ethnic group (OR 1.9) and total lymphocyte count <0.9 (OR 1.6) were relatively weak predictors of HIV. Platelet count, basophils, MCV, haemoglobin and sodium were also independent predictors of HIV status.
Conclusion: This study suggests that simple blood tests can help to assess the HIV risk in tuberculosis patients. In particular, it demonstrates the significance of a raised globulin (particularly over 45 g/l) as a more effective predictor of HIV than either ethnic group or total lymphocyte count.
P99 TUBERCULOSIS-ASSOCIATED VITAMIN D DEFICIENCY IS NOT SECONDARY TO MYCOBACTERIAL DISEASE ACTIVITY
1DW Connell, 2A Lalvani, 1M O’Donoghue, 1OM Kon 1Chest and Allergy Clinic, St Mary’s Hospital, London, UK, 2Tuberculosis Immunology Group, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London, UK
Introduction and Objectives: Vitamin D is thought to play an important role in the immunological control of Mycobacterium tuberculosis. A number of studies have shown vitamin D concentrations in patients with active tuberculosis to be significantly lower than controls. However, it is not known whether vitamin D is deficient as a result of disease activity itself. We hypothesised that if vitamin D deficiency in active tuberculosis is secondary to disease activity, vitamin D levels should increase after curative treatment of tuberculosis. The impact of successful antituberculous therapy on vitamin D levels has not hitherto been systematically assessed, with only one study having partly examined this after 2–3 months treatment in a very small number of patients.
Methods: 25 (OH) vitamin D levels at the beginning of and at the end of 6 months treatment for active disease were measured in an urban tuberculosis clinic. Further demographic data were then analysed.
Results: Paired vitamin D levels at 0 months and 6 months of antituberculous treatment were available for 28 patients. There was no significant change in vitamin D concentration after 6 months antituberculous therapy: the mean vitamin D concentration at the beginning of 6 months of antituberculous therapy was 23.93 mmol/l (95% CI 21.86 to 26); the mean concentration at the end of therapy was 22.44 mmol/l (95% CI 19.71 to 25.17; p = 0.69). Stratification by age, gender and site of tuberculosis had no effect on the results. There was a small significant difference between ethnic groups, with patients from an Indian subcontinent background demonstrating a decrease in vitamin D concentration after treatment, compared with the rest of the cohort (see fig).
Conclusions: These data do not support the hypothesis that vitamin D deficiency in patients with tuberculosis is a direct consequence of disease activity. It does suggest, however, that in some patients, vitamin D levels may in fact fall during treatment. Larger studies are now warranted further to elucidate the interaction of vitamin D and M tuberculosis infection in diverse ethnic groups.
P100 THE CHALLENGES OF DIAGNOSING EXTRAPULMONARY TUBERCULOSIS: WHAT ARE THE CAUSES OF DIAGNOSTIC DELAYS?
B Coker, R Enuechie, A Nundloll, LV Baker. University Hospital Lewisham, London, UK
Tuberculosis incidence in London continues to rise, with a proportionately greater increase in extrapulmonary tuberculosis cases. These cases are clinically more difficult to diagnose and present to a variety of specialties. Delays in diagnosis can result in significant sequelae. In this retrospective study we review the presentation, investigation and management of all adult cases of extrapulmonary tuberculosis notified at University Hospital Lewisham between 1 January 2005 and 31 December 2007, identifying potential diagnostic delays.
Results: 224 tuberculosis cases (191 adults, 33 children) were identified. 79 adults had extrapulmonary tuberculosis: 39 males, 40 females; mean age 39 years (range 16–85); 67 (87%) were non-UK born, median UK residency 4 years. 23 patients (35%) presented to A&E, 56 patients were referred to nine outpatient specialities, only two were referred directly to the tuberculosis service. Duration of symptoms ranged from 2 weeks to 10 years (median 4 months); 74 had local and 35 systemic symptoms. 62 had risk factors for tuberculosis. 3/48 (6%) tested were HIV positive. Initial samples were sent for AFB smear/culture in 46 patients, 64 for MC+S, 56 for histology/cytology, only 38 for all. Repeat samples were required in 29 patients. Tuberculosis was cultured from 35/75 samples sent, five were smear positive, culture negative. Histology/cytology was positive in 47/68. Overall, microbiological or histological confirmation was achieved in 69/79 (87%). Time from first medical contact to treatment ranged from 1 to 824 days (median 42), and from first hospital contact range 1 to 540 days (median 29). Time from diagnostic result to starting treatment varied with presentation and test. 15 started treatment without confirmatory results; 25 started treatment following positive microbiology, 36 following positive histology/cytology (10 with both positive on commencement), 11 following consistent cytology. Overall median delay 2 days for microbiology positivity, 15 days for histology. In 22 cases there was >8-week delay from hospital consultation to starting tuberculosis treatment. Causes for delay included non-diagnostic/inadequate initial specimens, diagnosis not initially considered, patient delay, referral delays, late tuberculosis culture positivity.
Conclusions: Delays in the diagnosis of extrapulmonary tuberculosis are multifactorial, but could be reduced by raising clinician awareness, correct initial investigations and streamlining positive histology results to the tuberculosis team.
P101 NEUTROPHILIA IN TUBERCULOSIS
1A Bandara, 1S Bremner, 2RD Barker, 3G Packe, 1C Griffiths, 1A Martineau. 1Queen Mary’s Barts and The London School of Medine and Dentistry, London, UK, 2King’s College Hospital, London, UK, 3Newham University Hospital Trust, London, UK
Introduction and Objectives: Neutrophilia is present in a proportion of tuberculosis patients at diagnosis, but its significance is not known. We aimed to establish the frequency and determinants of neutrophilia in newly diagnosed tuberculosis patients and to determine whether baseline neutrophilia was of prognostic significance in this group.
Methods: Baseline haematological, biochemical and clinical data of 909 tuberculosis patients who completed treatment and 54 patients in whom tuberculosis caused or contributed to death were compared with those of 160 healthy tuberculosis contacts. A multivariate analysis was conducted to determine whether baseline neutrophilia was independently associated with the risk of death from tuberculosis. Changes in neutrophil count during the intensive phase of therapy were compared between 27 patients who died from tuberculosis versus 19 patients who responded to treatment.
Results: Neutrophilia (peripheral blood neutrophil count >7.5 × 109/l) was more common in newly diagnosed tuberculosis patients than in tuberculosis contacts (175/963 vs 3/160, p<0.001) and mean neutrophil count was higher in newly diagnosed tuberculosis patients than in tuberculosis contacts (5.31 × 109/l vs 4.06 × 109/l, p<0.001). The frequency of neutrophilia in tuberculosis patients varied by ethnic group (present in 28/104 white Europeans, 31/180 south Asians, 18/77 Afro-Caribbeans and 69/439 black Africans at diagnosis, p = 0.03) and disease site (present in 102/482 cases of pulmonary tuberculosis, 14/62 cases of miliary tuberculosis and 57/411 cases of extrapulmonary tuberculosis at diagnosis, p = 0.03). Baseline neutrophilia was more common among patients who subsequently died from tuberculosis versus those who survived (21/54 vs 154/909, p<0.001) and was independently associated with an increased risk of death on multivariate analysis (odds ratio 2.25, 95% CI 1.10 to 4.61). Among tuberculosis patients who responded to therapy, the mean neutrophil count fell during the intensive phase of therapy (from 5.19 × 109/l at baseline to 4.11 × 109/l at 8 weeks). By contrast, patients who subsequently died of tuberculosis experienced an increase in mean neutrophil count over the same period (from 7.54 × 109/l at baseline to 8.10 × 109/l at 8 weeks).
Conclusions: Neutrophilia is common in patients with newly diagnosed tuberculosis and is independently associated with poor prognosis. Further research is needed to establish whether neutrophilia arises as a consequence of severe disease or whether neutrophils may cause immunopathology in active tuberculosis.
P102 CENTRAL NERVOUS SYSTEM TUBERCULOSIS: CLINICAL FEATURES, MANAGEMENT AND LONG-TERM OUTCOME
NF Walker, CJ Kirwan, BR Underwood, J Moore-Gillon, VLC White. Department of Respiratory Medicine, Barts and the London NHS Trust, London, UK
Introduction: We report 10 years experience managing central nervous system tuberculosis. We believe this to be the largest series reported from western Europe in recent years.
Methods: Data on clinical presentation, diagnostic methods and outcome were collected by case note review of 62 patients managed in our hospital from 1995 to 2005, cases to 1999 being previously reported in abstract form.1
Results: 28 patients had tuberculosis meningitis (TBM), 28 cerebral tuberculomata (TBT) and six features of both (TBMT). Median age was 31 years (range 5–68) and 27 (43%) were female. Only five (8%) were UK born, 30 (49%) from sub-Saharan Africa, 24 (39%) Indian sub-continent and three from other countries. HIV status was documented in 24 patients, 14 being HIV positive. Overall, headache was a presenting symptom in 81%, with vomiting (55%) and fever (48%) being common. Neck stiffness was present in only 31% of TBM and confusion in 27%. Seizures were the presentation of 41% of TBT, with 43% having focal neurology and 24% impaired consciousness. Cerebrospinal fluid (CSF) protein was elevated in all cases of TBM, 89% with lymphocytosis and 95% low CSF glucose. CSF was culture positive in seven TBM and five TBMT, with tuberculosis PCR positive in three further cases. Suggestive cerebral imaging was present in all TBT cases, 14 also having cerebral biopsy (nine with suggestive histology, three culture positive). Treatment followed BTS guidelines. Inpatient stay ranged from 6 to 270 days. Mean follow-up was 22 months. 33 patients made a complete recovery (13 TBM, 18 TBT, two TBMT) and four died (three TBM, one TBT). 25 patients had long-term sequelae (12 TBM, nine TBT, four TBMT). There was no difference in outcome between those patients in whom the diagnosis was confirmed microbiologically and/or histologically and those in whom it was based on suggestive clinical, imaging and other laboratory findings.
Conclusions: The TBM and TBT patients were comparable demographically. Clinical presentations were similar to previous reported series, but our mortality was lower. There was significant long-term morbidity and this was independent of whether or not there was laboratory confirmation of the diagnosis.
P103 DIFFICULTIES IN DIAGNOSIS, MANAGEMENT AND OUTCOME OF OCULAR TUBERCULOSIS
1AL Booker, 2B Bradley, 2S Kaul, 3E Graham, 2H Milburn. 1King’s College London, London, UK, 2Department of Respiratory Medicine, Guy’s and St Thomas’ Foundation Trust, London, UK, 3Department of Ophthalmology, Guy’s and St Thomas’ Foundation Trust, London, UK
Ocular tuberculosis (OTB) is a rare disease occurring in <2% of patients with confirmed tuberculosis. The incidence of tuberculosis in developed countries is rising due to increasing levels of immigration and HIV and is a significant cause of ocular pathology in some groups. Early diagnosis and treatment of OTB can prevent ocular morbidity. A lack of specific investigations or pathognomonic symptoms makes diagnosis presumptive and based on exclusion of other systemic diseases and treatment response. Patients may have no systemic manifestations of tuberculosis.
A retrospective study was performed to identify demographic and presenting features of an OTB population, the value of diagnostic investigations and patients’ response to therapy. Twenty-five patients were identified, 22 of whom were born in either south east Asia or Africa. Mean time of residence in the UK before diagnosis was 16.72 (1–42) years. Most common presenting symptoms were orbital pain/discomfort 12/25 (48%), visual loss 11/25 (44%); 11 subjects presented with symptoms in both eyes. The most common diagnosis was severe uveitis. Five patients had evidence or a record of previous tuberculosis, eight had tuberculosis diagnosed at other sites, predominantly the lung. ll had a positive skin tuberculin test. All but one was investigated with a chest x ray; eight had a magnetic resonance imaging scan of the orbit, or orbit and brain. Eight had a tissue biopsy performed; two tested positive for acid-fast bacilli.
Standard tuberculosis treatment was administered for a mean duration of 12.2 (6–30) months, one being treated for multidrug-resistant disease. In some cases, moxifloxacin was substituted for ethambutol. 17 also received systemic immunosuppression but six received topical steroids alone. In nine patients for whom complete data were available, three had poor vision due to scarring, one relapsed, one had their diagnosis changed and four had vision close to pre-disease levels. Eight further patients are still on treatment, four have moved out of the area and three were lost to follow-up.
Due to difficulty of diagnosis, non-specific clinical presentation and high morbidity, OTB must be considered in immigrants coming from areas of high tuberculosis prevalence who present with eye complaints, even when they have no evidence of systemic tuberculosis.
P104 IF PATIENTS WITH PULMONARY TUBERCULOSIS ON TREATMENT STOP EXPECTORATING SPUTUM, ARE THEY GENUINELY CULTURE NEGATIVE?
FMR Perrin, RAM Breen, TD McHugh, SH Gillespie, MCI Lipman. Royal Free Hosptial, London, UK
Introduction and Objectives: In clinical practice and during drug trials for patients with pulmonary tuberculosis change in sputum culture from positive to negative is the principal outcome measure of treatment response. Patients on effective therapy often stop producing sputum at an early stage. This leaves clinicians and triallists uncertain whether the patient is culture negative. Here we have prospectively collected sputum samples, by induction when spontaneous production ceased, to test the hypothesis that “no spontaneous sputum” is equivalent to culture negativity.
Methods: Patients produced sputum at diagnosis, regularly during week 1 of treatment, at week 2, months 1, 2, 4 and at the end of treatment. Spontaneous “spot” samples were obtained until the patient was no longer expectorating sputum, when samples were collected after inhalation of 3% hypertonic saline delivered via an ultrasonic nebuliser for 20 minutes. All samples were homogenised with sputasol and cultured on solid 7H11 Middlebrook agar plates from which total viable colony count was determined. The study received ethical approval.
Results: Eight patients, fully compliant with medication were studied (median age 31 years (range 17–47), seven male, five black African, two white, one Asian, one HIV positive, six tuberculosis sensitive to all first-line agents). In all subjects sputum production ceased and was subsequently sampled by induction. 54 sputum samples were collected, 34 spontaneously and 20 by induction. Four patients stopped producing sputum after one month. The figure shows the bacillary load (log10 cfu/ml) in spontaneous and induced sputum. Only two samples (10%) collected by induction were culture positive. One sample was collected from a patient at week 1 and the 2-week sample was culture negative; the second sample was from a patient in whom the positive induced sample was followed by a positive spontaneous sample one week later. 75% of patients who stopped producing sputum were culture negative by induction.
Conclusions: Our data show that patients who stop producing sputum spontaneously have largely cleared their airway bacillary load. Sputum induction rarely produces positive results in these circumstances and thus lack of sputum after one month of treatment appears to be a useful surrogate for culture negativity.
P105 ETHNIC DETERMINANTS OF PARADOXICAL REACTIONS DURING TUBERCULOSIS THERAPY
1CS Brown, 1RAM Breen, 2C Smith, 3P Ormerod, 4G Bothamley, 1MC Lipman. 1Royal Free Hampstead NHS Trust, London, UK, 2Research Department of Infection and Population Health, University College Medical School, London, UK, 3Royal Blackburn Hospital, East Lancashire Hospitals NHS Trust, London, UK, 4Homerton Hospital, Homerton University Hospital NHS Trust, London, UK
Introduction and Methods: Building on previous work that identified the role of HIV co-infection in the development of a “paradoxical reaction” in tuberculosis treatment, we conducted a multisite study involving three large UK tuberculosis referral centres to determine the relationship between ethnicity and the reported frequency of paradoxical reaction. Both prospective and retrospective data were collected from January 1997 to December 2006. Paradoxical reaction was defined using a standard clinical definition of unexplained (despite extensive investigation) deterioration in symptoms following an initial improvement with antituberculosis treatment.
Results: From a total of 1131 patients treated for tuberculosis, 58 subjects with paradoxical reaction were identified. 55% were male, the median age was 24 years and 5.2% were HIV co-infected. The table shows the site and proportion of paradoxical reactions within different racial groups. Paradoxical reactions occurred at a similar frequency within these populations: 4.3% for south Asians (95% CI 2.0 to 7.9), 4.9% for whites (95% CI 2.6 to 8.4), 5.6% for blacks (95% CI 3.9 to 7.8), 6.0% for east Asians (95% CI 1.7 to 14.6); p = 0.52 (two-tailed Fisher’s exact test). The characteristics of the paradoxical reaction episode were dependent on racial group, with extrapulmonary lymph node involvement found to be higher among south Asians than blacks (p = 0.044). Blacks conversely exhibited somewhat more pulmonary involvement than south Asians and whites (p = 0.15). Blacks and whites also tended to get more systemic symptoms, such as fever and sweating, than Asians (p = 0.13). This, however, may have resulted from increased rates of HIV co-infection in these populations.
Discussion: No difference was seen in the frequency of paradoxical reactions between major racial groups determined by simple ethnic analysis (black, white, south Asian, east Asian). However, the paradoxical reaction site and characteristics did vary significantly between these populations. This information is of relevance to clinicians working with ethnically diverse patients and adds considerably to the evidence base for best-practice monitoring and treatment of tuberculosis-related paradoxical reactions. It is likely that ethnic variations are more complex than those measured in this first analysis and will be explored using more detailed demographic information within this dataset.
P106 COMPLIANCE WITH NATIONAL AND INTERNATIONAL GUIDELINES REGARDING TREATMENT OF ACTIVE MYCOBACTERIUM TUBERCULOSIS INFECTIONS IN DETAINEES AT TWO LONDON IMMIGRATION DETENTION CENTRES
1D Barker, 2P Tsangarides, 1M Haselden. 1Hillingdon Hospital, Uxbridge, UK, 2Hillingdon Primary Care Trust, Hillingdon, UK
Introduction and Objectives: The incidence of infection with Mycobacterium tuberculosis is estimated at 8.8 million worldwide per year. In 2006 there were an estimated 0.5 million cases of multidrug-resistant tuberculosis (MDR-TB).2 The World Health Organisation (WHO) has recently created the Stop TB Partnership, aiming to reduce the incidence of tuberculosis worldwide by 2015. It has identified MDR-TB and extensively drug-resistant tuberculosis (XDR-TB) as potentially “derailing” tuberculosis control.
In 2003, 45% of new cases of tuberculosis reported in England and Wales were from London, with 1.8% of all cases classed as MDR-TB. Hillingdon Hospital serves two local immigration detention centres in west London. BTS guidelines state that those in prison diagnosed with tuberculosis should have directly observed therapy supervised by a chest physician and that “supervision (is) vital”.
The Centers for Disease Control and Prevention in the USA identified that those who are deported before completing the minimum required therapy for tuberculosis are at high risk of developing MDR-TB or XDR-TB and transmitting tuberculosis to others. We hypothesised that a significant number of cases diagnosed with active tuberculosis had their treatment interrupted.
Methods: The London Tuberculosis Register (LTBR) was used to identify cases of newly diagnosed tuberculosis between 1 April 2006 and 1 April 2008 from Harmondsworth and Colnbrook Immigration Detention Centres. Inadequate treatment was defined as a failure to complete treatment to NICE guidelines.
Results: Of 18 cases, 17 (94.4%) were pulmonary tuberculosis and one (5.6%) was abdominal tuberculosis. Only three (16.7%) cases were classified as having completed the recommended treatment course before removal from the Hillingdon area. Nine (50%) cases were deported overseas. The average length of treatment for non-completed cases was 10.1 weeks. 14 (82.4%) of 17 concluded cases were transferred out of the area before completion.
Conclusions: Over 80% of all patients with tuberculosis in the west London immigration detention centres are transferred out of area after starting antituberculosis treatment. The subsequent failure of treatment and disease monitoring is likely to contribute to the growing global problem of MDR-TB and XDR-TB, as well as depriving patients of appropriate healthcare.
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