A centralised electronic Multidrug-Resistant Tuberculosis Advisory Service: the first 2 years.

Multidrug-resistant tuberculosis (MDR-TB, defined as resistance to at least both rifampicin and isoniazid) has become a serious problem in the United Kingdom. As it is uncommon, no one clinician has sufficient experience of it to be confident in providing the best management for the patient. The model of a centralised system of management, such as is used in the Baltic countries, would seem a suitable method to adapt to the United Kingdom. With the agreement of the relevant professional organisations, a virtual electronic expert panel, the UK Multidrug-Resistant Tuberculosis Service, has been developed. This body gives advice via a secure website on MDR-TB patients referred by e-mail by clinicians across the country managing MDR-TB cases. In the first 2 years of operation, advice was sought on 60 patients with culture-proven MDR-TB (54% of the UK total). The number of clinicians accessing the advisory service increased from 27 in 2008 to 33 in 2009. Patients of non-UK origin accounted for 90% of all cases, including all four extensively drug-resistant tuberculosis cases. A central electronic virtual committee providing advice via a secure website has proved to be practical, economical and efficient. It could provide a model for MDR-TB management in other countries and for the management of other uncommon diseases.

Resistance to first-line tuberculosis drugs in three cities of Nigeria.

OBJECTIVES: To determine the levels of resistance to first-line tuberculosis drugs in three cities in three geopolitical zones in Nigeria. METHODS: A total of 527 smear-positive sputum samples from Abuja, Ibadan and Nnewi were cultured on BACTEC- MGIT 960. Drug susceptibility tests (DST) for streptomycin, isoniazid, rifampicin and ethambutol were performed on 428 culture-positive samples on BACTEC-MGIT960. RESULTS: Eight per cent of the specimens cultured were multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) with varying levels of resistance to individual and multiple first-line drugs. MDR was strongly associated with previous treatment: 5% of new and 19% of previously treated patients had MDR-TB (OR 4.1 (95% CI 1.9-8.8), P = 0.001) and with young adult age: 63% of patients with and 38% without MDR-TB were 25-34 years old (P = 0.01). HIV status was documented in 71%. There was no association between MDR-TB and HIV coinfection (P = 0.9) and gender (P > 0.2 for both). CONCLUSIONS: MDR-TB is an emerging problem in Nigeria. Developing good quality drug susceptibility test facilities, routine monitoring of drug susceptibility and improved health systems for the delivery of and adherence to first- and second-line treatment are imperative to solve this problem.

Sex differences in the clinical presentation of urban Nigerian patients with pulmonary tuberculosis.

BACKGROUND: Differences in clinical presentation of tuberculosis (TB) have been reported in different age groups, gender and in different parts of the world. Study of gender differences in clinical presentation of patients will assist in targeting those at higher risk and ensure successful TB control planning. OBJECTIVE: To describe the differences in clinical presentation and risk factors for TB in male and female Nigerian patients with pulmonary tuberculosis (PTB). METHODS: Patients with cough of more than three weeks duration attending hospitals in Abuja, Nigeria were interviewed with a structured questionnaire. After clinical examination, sputum samples were examined by smear microscopy and one sample was cultured. Haematological examination, serum chemistries, HIV serology, and chest X-ray evaluation were also evaluated. RESULTS: Of 1186 patients who had sputum culture, 731 (62%) were positive for TB: 437 (60%) males and 394 (40%) females. The mean (SD) age of males was significantly greater than that of females, 34 (11) vs. 31 (12) years, rp = 0.001. Male patients were more likely to be employed and better educated than women. More men than women smoked cigarettes. Women were more likely to be co-infected with HIV and less likely to be smear-positive than men. Male patients had more severe radiological disease. CONCLUSION: More men than women appear to present with TB at hospitals in Abuja. Male patients were older and are more likely to have smear-positive TB, whereas, female patients were more likely to be co-infected with HIV.

The diagnosis and misdiagnosis of tuberculosis.

There are two worlds when it comes to the diagnosis of tuberculosis (TB). One world has only smear microscopy at its disposal. There may also be some radiological facilities, usually at the patients' expense. The other world has all modern techniques available, including culture, nucleic acid amplification, molecular diagnostics and sophisticated radiological techniques such as computed tomography and positron emission tomography scanning. The ability to diagnose or misdiagnose TB will vary across these two worlds. In this review, we provide an overview of clinical, radiological, molecular and immunological diagnosis of TB and highlight the common difficulties and pitfalls in TB diagnosis.

The clinical impact of nucleic acid amplification tests on the diagnosis and management of tuberculosis in a British hospital.

BACKGROUND: Nucleic acid amplification tests (NAAT) based on PCR provide rapid identification of Mycobacterium tuberculosis and the detection of rifampicin resistance. Indications for their use in clinical samples are now included in British tuberculosis guidelines. METHODS: A retrospective audit of patients with suspected mycobacterial infection in a Liverpool hospital between 2002 and 2006. Documentation of the impact of NAAT usage in acid fast bacillus (AFB) microscopy positive samples on clinical practice and the influence of a multidisciplinary group on their appropriate use, compared with British guidelines. RESULTS: Mycobacteria were seen or isolated from 282 patients and identified as M tuberculosis in 181 (64%). NAAT were indicated in 87/123 AFB positive samples and performed in 51 (59%). M tuberculosis was confirmed or excluded by this method in 86% of tested samples within 2 weeks, compared with 7% identified using standard methods. The appropriate use of NAAT increased significantly over the study period. The NAAT result had a clinical impact in 20/51 (39%) tested patients. Culture results suggest the potential for a direct clinical impact in 8/36 (22%) patients in which it was indicated but not sent and 5/36 (14%) patients for whom it was not indicated. Patients managed by the multidisciplinary group had a higher rate of HIV testing and appropriate use of NAAT. CONCLUSIONS: There were significant clinical benefits from the use of nucleic acid amplification tests in this low prevalence setting. Our data suggest that there would be additional benefit from their use with all AFB smear positive clinical samples.

Short-term bleach digestion of sputum in the diagnosis of pulmonary tuberculosis in patients co-infected with HIV.

The bleach digestion of sputum may improve the yield of smear microscopy but has not been validated in patients with HIV. Therefore we assessed the performance of bleach-digested smear microscopy among patients with HIV. One thousand three hundred and twenty one patients with chronic cough submitted three sputum samples for direct smear microscopy and were offered HIV tests. One sample was selected for a bleach-digested smear and another one was cultured. Patients were classified as having 'definite' (>or=2 positive smears), 'very likely' (smear-negative, culture- positive), 'less likely' (one smear-positive, culture-negative) and 'unlikely' (smear and culture negative) tuberculosis (TB). In all, 566/1045 (54%) patients were HIV positive and 731/1186 (62%) were culture positive. The digested smears were positive in 123/125 (98%) 'definite', 4/118 (3%) 'very likely' and 1/174 'unlikely' TB patients with HIV and in 125/127 (98%) 'definite', 2/74 (3%) 'very likely', 4/4 'less likely' and 2/127 'unlikely' TB without HIV. Three direct smears identified 252 (57%) and one digested smear 254 (57%) of the 444 patients with 'definite' or 'very likely' TB. One bleach-digested smear performed similarly to three direct smears. Both methods were less sensitive in HIV-positive patients. Further studies are needed to compare the performance of the two methods under operational conditions.

Pleural tuberculosis.

Pleural effusions in tuberculosis are commonly seen in young adults as an immunological phenomenon occurring soon after primary infection. However, the epidemiology and demographics of tuberculous pleurisy are changing due to the impact of HIV co-infection and the increasing number of pleural effusions seen as part of re-activation disease. Pleural biopsy for histology and culture is the mainstay of diagnosis with closed needle biopsy adequate in the majority of cases. Techniques such as PCR of biopsy specimens and the role of pleural fluid ADA are still being evaluated as a diagnostic aid. Tuberculous empyema is less commonly seen in the western world and the diagnostic yield from pleural fluid here is greater than in "primary" effusions. Treatment with appropriate antituberculous chemotherapy is generally successful though there is currently insufficient evidence to recommend the routine use of corticosteroids in this condition.

Microbiological validation of smear microscopy after sputum digestion with bleach; a step closer to a one-stop diagnosis of pulmonary tuberculosis.

BACKGROUND: Smear microscopy is relatively insensitive for the diagnosis of TB. The digestion of sputum with household bleach prior to smear preparation has been reported to improve its sensitivity. This method has not been validated. METHODS: Seven hundred and fifty six patients with symptoms suggestive of pulmonary TB (PTB) were asked to submit 3 sputum specimens for direct microscopy. One specimen was selected at random for culture and another specimen was digested to prepare a further smear. The WHO case definition (>or=2 positive smears or one positive smear and positive culture) was used to compare the sensitivity and specificity of the smears. FINDINGS: Four hundred and fifty five (60%) patients were culture-positive. Of these, 235 (31%) had "definite" PTB and 223 (29%) "very likely" PTB (smear-negative, culture-positive). The WHO case definition identified 51% (235/458) of the patients with "definite" or "very likely" PTB. One digested smear detected 219 (93%) of the 235 patients with "definite" PTB and 10 patients with "very likely" PTB (sensitivity (95%CI) 50% (45-55%); specificity 99% (97-100%)). The positive and negative predictive values for one digested smear were 98% (95-99%) and 56% (52-60%) respectively, which were not different (p>0.5) to the WHO case definition (100% and 57%, respectively). INTERPRETATION: One bleach-digested smear is as sensitive and specific as the WHO case definition for the diagnosis of PTB.

Smoking and tuberculosis: the epidemiological association and immunopathogenesis.

There is increasing evidence of a link between tuberculosis and smoking. This paper reviews the epidemiological evidence from the UK, China, India and the USA, summarizing some of the main papers which indicate an association. Where an association has been found there seems to be an increase in tuberculosis case rates of between two- and four-fold for those smoking in excess of 20 cigarettes a day, but it may be difficult to control for other factors, particularly alcohol consumption. The final part of the paper reviews possible mechanisms. A likely possibility is that nicotine turns off the production of TNF-alpha by the macrophages in the lungs, rendering the patient more susceptible to the development of progressive disease from latent Mycobacterium tuberculosis infection.

Risk factors for tuberculosis.

The risk of developing tuberculosis is dependent on both the risk of being infected and the risk of infection leading on to active disease. The former will depend on the incidence of tuberculosis in the community where the individual lives or works. The latter will depend on many factors impinging on the individual both genetic and environmental. The greatest single risk factor for developing tuberculosis from infection is concurrent HIV infection. Where these two infections are prevalent tuberculosis case rates have risen dramatically and will continue to do so unless either infection can be curtailed.

Decreasing tuberculosis case fatality in England and Wales, 1988-2001.

SETTING: Despite declining tuberculosis mortality per head of population, there was little change in tuberculosis case fatality in England and Wales from 1974 to 1987. OBJECTIVE: To determine the trend in tuberculosis case fatality for England and Wales from 1988 to 2001. DESIGN: Annual deaths to notifications ratios (DNRs) for tuberculosis were calculated using published notification and mortality data, and analysed by age group and three disease sites (central nervous system [CNS], respiratory and other). DNRs for seven disease sites (miliary, bone and joint, CNS, respiratory, genitourinary, gastrointestinal and other) were calculated for 1998 and 1999 combined, using additional data from the enhanced tuberculosis surveillance programme. RESULTS: DNR for all ages and disease sites combined fell from 9.26% in 1988 to 5.59% in 2001 (r = -0.90; 95%CI -0.97 - -0.70). DNRs for 1998-1999 combined were 41% for miliary disease, 17% for bone and joint disease, 8% for CNS disease, 7% for respiratory disease, 2% for genitourinary and gastrointestinal disease and 0.6% for other disease. CONCLUSIONS: Some of the decrease in DNRs may be due to improving notification rates. True declines in overall case fatality reflect increases in the proportion of tuberculosis patients in younger age groups and with low mortality extra-pulmonary disease.