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Clinical lesson: old diseases may affect older patients
S432 METHOD Between October 1998 and December 2007 patients with Pneumocystis jirovecii detected by immunofluorescence (IF) or polymerase chain reaction (PCR) were identified. A systematic retrospective review of patients’ notes and laboratory records was undertaken.
notes were available for review. In this cohort 75% were receiving chemotherapy or immunomodulatory drugs at presentation. Time from haematological to PCP diagnosis ranged from 36 to 2409 days. 92% were commenced on high-dose co-trimoxazole on average for 12.5 days. 25% received high-dose steroids. For all 22 patients the 30 day mortality was 9%.
CONCLUSIONS RESULTS 22 HIV negative patients were identified; 86% had a haematological malignancy. 59% were male and the median age 46 years. 82% had a bronchoscopy and PCP was detected in 83% by IF. 71% had a lymphocyte count < 1000 mg/dl 7 days pre-diagnosis. 12 sets of
Haematological malignancy is most commonly associated with PCP in the non-HIV setting. Lymphopenia, steroid use and chemotherapy are all risk factors. Further research is needed to identify which patients will benefit from prophylaxis in order to prevent this potentially life threatening infection.
0016 A NATIONAL AUDIT EVALUATING THE MANAGEMENT OF TB IN HIV CO-INFECTED PATIENTS. Matthijs BACKX, Hilary CURTIS, Andrew FREEDMAN and Margaret JOHNSON British HIV Association, Clinical Audit Sub-Committee, United Kingdom
The number of patients with TB who are co-infected with HIV has risen dramatically. In the UK in 2003, approximately 8% of adults with TB were co-infected with HIV. This proportion is higher within certain geographical areas and population groups. The interaction between HIV and TB may result in an atypical presentation especially in patients with advanced immunosupression. The co-infected patient may therefore present a complex diagnostic entity whose management requires specialist knowledge. This audit aimed to assess current practice regarding the management of TB/HIV coinfection in comparison with guidelines, including the ‘BHIVA treatment guidelines for TB/HIV co-infection, 2005’ and the ‘National Collaborating Centre for Chronic Conditions: Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control, 2006’. This audit generated a large amount of data and therefore we have focussed on the most significant findings.
RESULTS
METHOD
Few TB sites completed the survey and casenote data was incomplete because some HIV clinicians did not have access to integrated notes. Over half the patients were diagnosed with HIV before their TB diagnosis. As expected, many had extra-pulmonary disease, making diagnosis and management complex. A significant proportion of patients presented with advanced HIV disease. Many positive smear results were unacceptably delayed compared with a 24 hour, 6 days/ week standard. The TB therapy completion rate fell short of the Chief Medical Officer’s 85% target. Contrary to current guidelines some services do not offer HIV testing to all TB patients.
170 UK HIV treatment sites were invited to complete an online survey and casenote review of HIV/TB coinfected patients. These sites were asked, where applicable, to pass on a survey invitation to their respective TB clinics/units. Patients with TB/HIV co-infection who started treatment for active TB from October 2007 to April 2008 were included in the casenote review. Data were collected from October to December 2008 so most cases had time to complete treatment. Patients who received chemoprophylaxis for latent TB were excluded as were patients where TB was later replaced by a confirmed alternative diagnosis.
Data were obtained for 236 co-infected patients, 74.6% of whom were black African. 131 (55.5%) patients were diagnosed with HIV before seeking care for TB. 163 (69.1%) patients had CD4 counts below 200 cells/mm3, including 90 (38.1%) for whom TB was their HIV indicator disease. 140 (59.3%) patients had extra-pulmonary disease. Of 60 sputum smear positive cases, 25 (41.7%) waited more than 2 days for their smear result. 147 (80.8%) patients completed TB therapy successfully. 124 HIV and 18 TB services completed surveys. 6 of the latter did not routinely offer HIV testing to all adults with TB.
CONCLUSIONS
0017 CLINICAL LESSON: OLD DISEASES MAY AFFECT OLDER PATIENTS Jake DUNNING, Michael RAYMENT, Simon DAVIES and Mark NELSON Chelsea & Westminster NHS Foundation Trust, London, United Kingdom
S433 We decribe an unusual case of fever, chest pain and collapse in an HIV-positive adult.
METHOD A 34 year-old, HIV-positive, black-African patient attended our unit complaining of central, pleuritic chest pain and palpitations over the preceding week. One week earlier she had collapsed and lost consciousness for several minutes. One month prior, she had received 5 days of amoxicillin for purulent pharyngitis. She had been diagnosed HIV-positive in 2004 and commenced antiretrovirals in view of a nadir CD4 count of 176 cell/mm3. Apart from a cholecystectomy, her past medical history was unremarkable, without any HIV-related complications. At the time of presentation, her CD4 count was 459 cells/mm3 with an HIV viral load of <50 copies/ml on tenofovir/emtricitabine and ritonavir-boosted atazanavir.
RESULTS Examination revealed a temperature of 38.3 C and tachycardia. Routine cardiovascular, respiratory, ENT and abdominal
examinations were otherwise unremarkable. Serial ECG’s revealed sinus tachycardia with 1-2 mm ST-elevation in leads V1-V3. The chest radiograph was normal. Transthoracic echocardiography demonstrated an estimated left ventricular ejection fraction of 40% with akinesis of the septum and anteroseptum. Abnormal blood tests included: C-reactive-protein 296 mg/l, ESR 75 mm/h, haemoglobin 9.2 g/dl, total creatine kinase 205 IU/l, troponin-I 3.81mg/l. Routine microbiological cultures of blood, stool, urine and throat swab were negative. TB ELISpot was also negative. Review of archived microbiology results revealed that a Group A Streptococcus had been cultured from a throat swab one month earlier.
CONCLUSIONS Despite the patient’s age, a well-known but uncommon diagnosis was considered in the differential diagnosis. The patient went on to have further blood tests and radiological investigations, and specific empirical therapy was commenced.
0018 HUMAN PROTEOMIC PROFILES IN LATENT AND ACTIVE TUBERCULOSIS Gurjinder SANDHU1, Dimitris ATHANASAKIS2, Carlton EVANS1,3, Barry ELY2, Rosario MONTOYA3, Robert GILMAN3, Teresa VALENCIA3, Rosario SOSA3, Jon FRIEDLAND1,3, Delmiro FERNANDEZ-REYES2 and Dan AGRANOFF1 1 Imperial College London Hammersmith Hospital Campus, London, United Kingdom, 2MRC National Institute for Medical Research, London, United Kingdom, 3Universidad Peruana Cayetano Heredia, Lima, Peru
Distinguishing patients with active tuberculosis (TB) from those with latent TB is an important clinical problem both in affluent countries and resource-poor regions. The SELDI-TOF MS (Surface Enhanced Laser Desorption Ionisation - Time of Flight Mass Spectrometry) platform allows for high throughput detection of multiple proteins in biological fluids. We hypothesise that different clinical manifestations of TB are associated with distinctive proteomic signatures in patient plasma.
METHOD Sample Collection: Plasma samples were collected prospectively in a shanty town in Lima, Peru. Latent and active TB status was defined using the Tuberculin Skin Test (TST), Quantiferon In Tube Gold assay (QFN) and standard culture methodologies including MODS (Microscopic Observation Drug Susceptibility) Spectra Acquisition. Crude plasma and fractionated plasma samples were analysed on weak cationic CM10 chip surfaces using a Biomek 3000 Laboratory Automation Workstation. Spectra were generated using a ProteinChip System 4000 Mass spectrometer. Peak detection and Expression Difference Mapping were performed using proprietary software and data were further analysed using Machine Learning Based methods.
RESULTS Plasma samples were collected from 154 patients with active TB, 112 patients with respiratory symptoms suggestive of TB and 151 healthy
controls. Multiple peaks differed significantly between active TB patients and unhealthy controls. Trained optimal classifiers discriminate between: i) active TB and unhealthy controls with 84% accuracy (87% sensitivity, 79% specificity) in crude plasma and up to 89% accuracy (90% sensitivity, 88% specificity) in fractionated plasma ii) active TB and latent TB with 89% accuracy (90% sensitivity, 89% specificity) iii) latent TB and no TB in healthy controls with 77% accuracy (67% sensitivity, 84% specificity).
CONCLUSIONS SELDI-TOF MS proteomic profiles in combination with trained optimal classifiers accurately discriminate active TB from other respiratory disorders. A number of peaks are statistically significantly different between the two groups and a combination of these could be used as potential biomarkers to aid TB diagnostics. A Support Vector Machine can also discriminate the presence or absence of Latent Tuberculosis in healthy individuals. Proteomic patterns reflect host-pathogen interaction in the development of active and latent TB and can be used as a tool to aid our understanding of the Natural History of Tuberculosis.
notes were available for review. In this cohort 75% were receiving chemotherapy or immunomodulatory drugs at presentation. Time from haematological to PCP diagnosis ranged from 36 to 2409 days. 92% were commenced on high-dose co-trimoxazole on average for 12.5 days. 25% received high-dose steroids. For all 22 patients the 30 day mortality was 9%.
CONCLUSIONS RESULTS 22 HIV negative patients were identified; 86% had a haematological malignancy. 59% were male and the median age 46 years. 82% had a bronchoscopy and PCP was detected in 83% by IF. 71% had a lymphocyte count < 1000 mg/dl 7 days pre-diagnosis. 12 sets of
Haematological malignancy is most commonly associated with PCP in the non-HIV setting. Lymphopenia, steroid use and chemotherapy are all risk factors. Further research is needed to identify which patients will benefit from prophylaxis in order to prevent this potentially life threatening infection.
0016 A NATIONAL AUDIT EVALUATING THE MANAGEMENT OF TB IN HIV CO-INFECTED PATIENTS. Matthijs BACKX, Hilary CURTIS, Andrew FREEDMAN and Margaret JOHNSON British HIV Association, Clinical Audit Sub-Committee, United Kingdom
The number of patients with TB who are co-infected with HIV has risen dramatically. In the UK in 2003, approximately 8% of adults with TB were co-infected with HIV. This proportion is higher within certain geographical areas and population groups. The interaction between HIV and TB may result in an atypical presentation especially in patients with advanced immunosupression. The co-infected patient may therefore present a complex diagnostic entity whose management requires specialist knowledge. This audit aimed to assess current practice regarding the management of TB/HIV coinfection in comparison with guidelines, including the ‘BHIVA treatment guidelines for TB/HIV co-infection, 2005’ and the ‘National Collaborating Centre for Chronic Conditions: Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control, 2006’. This audit generated a large amount of data and therefore we have focussed on the most significant findings.
RESULTS
METHOD
Few TB sites completed the survey and casenote data was incomplete because some HIV clinicians did not have access to integrated notes. Over half the patients were diagnosed with HIV before their TB diagnosis. As expected, many had extra-pulmonary disease, making diagnosis and management complex. A significant proportion of patients presented with advanced HIV disease. Many positive smear results were unacceptably delayed compared with a 24 hour, 6 days/ week standard. The TB therapy completion rate fell short of the Chief Medical Officer’s 85% target. Contrary to current guidelines some services do not offer HIV testing to all TB patients.
170 UK HIV treatment sites were invited to complete an online survey and casenote review of HIV/TB coinfected patients. These sites were asked, where applicable, to pass on a survey invitation to their respective TB clinics/units. Patients with TB/HIV co-infection who started treatment for active TB from October 2007 to April 2008 were included in the casenote review. Data were collected from October to December 2008 so most cases had time to complete treatment. Patients who received chemoprophylaxis for latent TB were excluded as were patients where TB was later replaced by a confirmed alternative diagnosis.
Data were obtained for 236 co-infected patients, 74.6% of whom were black African. 131 (55.5%) patients were diagnosed with HIV before seeking care for TB. 163 (69.1%) patients had CD4 counts below 200 cells/mm3, including 90 (38.1%) for whom TB was their HIV indicator disease. 140 (59.3%) patients had extra-pulmonary disease. Of 60 sputum smear positive cases, 25 (41.7%) waited more than 2 days for their smear result. 147 (80.8%) patients completed TB therapy successfully. 124 HIV and 18 TB services completed surveys. 6 of the latter did not routinely offer HIV testing to all adults with TB.
CONCLUSIONS
0017 CLINICAL LESSON: OLD DISEASES MAY AFFECT OLDER PATIENTS Jake DUNNING, Michael RAYMENT, Simon DAVIES and Mark NELSON Chelsea & Westminster NHS Foundation Trust, London, United Kingdom
S433 We decribe an unusual case of fever, chest pain and collapse in an HIV-positive adult.
METHOD A 34 year-old, HIV-positive, black-African patient attended our unit complaining of central, pleuritic chest pain and palpitations over the preceding week. One week earlier she had collapsed and lost consciousness for several minutes. One month prior, she had received 5 days of amoxicillin for purulent pharyngitis. She had been diagnosed HIV-positive in 2004 and commenced antiretrovirals in view of a nadir CD4 count of 176 cell/mm3. Apart from a cholecystectomy, her past medical history was unremarkable, without any HIV-related complications. At the time of presentation, her CD4 count was 459 cells/mm3 with an HIV viral load of <50 copies/ml on tenofovir/emtricitabine and ritonavir-boosted atazanavir.
RESULTS Examination revealed a temperature of 38.3 C and tachycardia. Routine cardiovascular, respiratory, ENT and abdominal
examinations were otherwise unremarkable. Serial ECG’s revealed sinus tachycardia with 1-2 mm ST-elevation in leads V1-V3. The chest radiograph was normal. Transthoracic echocardiography demonstrated an estimated left ventricular ejection fraction of 40% with akinesis of the septum and anteroseptum. Abnormal blood tests included: C-reactive-protein 296 mg/l, ESR 75 mm/h, haemoglobin 9.2 g/dl, total creatine kinase 205 IU/l, troponin-I 3.81mg/l. Routine microbiological cultures of blood, stool, urine and throat swab were negative. TB ELISpot was also negative. Review of archived microbiology results revealed that a Group A Streptococcus had been cultured from a throat swab one month earlier.
CONCLUSIONS Despite the patient’s age, a well-known but uncommon diagnosis was considered in the differential diagnosis. The patient went on to have further blood tests and radiological investigations, and specific empirical therapy was commenced.
0018 HUMAN PROTEOMIC PROFILES IN LATENT AND ACTIVE TUBERCULOSIS Gurjinder SANDHU1, Dimitris ATHANASAKIS2, Carlton EVANS1,3, Barry ELY2, Rosario MONTOYA3, Robert GILMAN3, Teresa VALENCIA3, Rosario SOSA3, Jon FRIEDLAND1,3, Delmiro FERNANDEZ-REYES2 and Dan AGRANOFF1 1 Imperial College London Hammersmith Hospital Campus, London, United Kingdom, 2MRC National Institute for Medical Research, London, United Kingdom, 3Universidad Peruana Cayetano Heredia, Lima, Peru
Distinguishing patients with active tuberculosis (TB) from those with latent TB is an important clinical problem both in affluent countries and resource-poor regions. The SELDI-TOF MS (Surface Enhanced Laser Desorption Ionisation - Time of Flight Mass Spectrometry) platform allows for high throughput detection of multiple proteins in biological fluids. We hypothesise that different clinical manifestations of TB are associated with distinctive proteomic signatures in patient plasma.
METHOD Sample Collection: Plasma samples were collected prospectively in a shanty town in Lima, Peru. Latent and active TB status was defined using the Tuberculin Skin Test (TST), Quantiferon In Tube Gold assay (QFN) and standard culture methodologies including MODS (Microscopic Observation Drug Susceptibility) Spectra Acquisition. Crude plasma and fractionated plasma samples were analysed on weak cationic CM10 chip surfaces using a Biomek 3000 Laboratory Automation Workstation. Spectra were generated using a ProteinChip System 4000 Mass spectrometer. Peak detection and Expression Difference Mapping were performed using proprietary software and data were further analysed using Machine Learning Based methods.
RESULTS Plasma samples were collected from 154 patients with active TB, 112 patients with respiratory symptoms suggestive of TB and 151 healthy
controls. Multiple peaks differed significantly between active TB patients and unhealthy controls. Trained optimal classifiers discriminate between: i) active TB and unhealthy controls with 84% accuracy (87% sensitivity, 79% specificity) in crude plasma and up to 89% accuracy (90% sensitivity, 88% specificity) in fractionated plasma ii) active TB and latent TB with 89% accuracy (90% sensitivity, 89% specificity) iii) latent TB and no TB in healthy controls with 77% accuracy (67% sensitivity, 84% specificity).
CONCLUSIONS SELDI-TOF MS proteomic profiles in combination with trained optimal classifiers accurately discriminate active TB from other respiratory disorders. A number of peaks are statistically significantly different between the two groups and a combination of these could be used as potential biomarkers to aid TB diagnostics. A Support Vector Machine can also discriminate the presence or absence of Latent Tuberculosis in healthy individuals. Proteomic patterns reflect host-pathogen interaction in the development of active and latent TB and can be used as a tool to aid our understanding of the Natural History of Tuberculosis.