High early death rate in tuberculosis patients in Malawi.

SETTING: Thirty-eight district and mission hospitals in Malawi. OBJECTIVES: In patients registered with all types of tuberculosis (TB) in 1997 to determine 1) treatment outcomes, and 2) when in the course of anti-tuberculosis treatment TB deaths occurred. DESIGN: A retrospective study using information from TB registers, health centre registers, TB treatment cards and TB ward admission books. RESULTS: A total of 16,004 patients were registered with all types of TB, 6471 with smear-positive pulmonary tuberculosis (PTB), 5305 with smear-negative PTB and 4228 with extra-pulmonary tuberculosis (EPTB). Of patients with all types of TB, 3720 (23%) died: death rates were 22% in smear-positive PTB, 26% in smear-negative PTB and 22% in EPTB. Month of death was known in 3371 patients (91% of those who died) and day of death in 3326 patients (89% of those who died). In patients who died, 19% of deaths occurred by day 7 and 41% by the end of the first month of treatment. A higher proportion of early deaths occurred in patients with smear-negative PTB and EPTB and in relation to increasing age. CONCLUSIONS: There was a high overall death rate in TB patients registered in 1997, with 40% of deaths occurring in the first month of treatment. Strategies to combat this problem are needed.     

Childhood tuberculosis in Malawi: nationwide case-finding and treatment outcomes.

SETTING: All 43 non-private hospitals (three central, 22 [corrected] district and 18 [corrected] mission) in Malawi that register and treat adult and paediatric TB cases. OBJECTIVE: To assess the rate, pattern and treatment outcome of childhood TB case notifications in Malawi in 1998. DESIGN: Retrospective data collection using TB registers, treatment cards and information from health centre registers. Information was collected on number of cases, types of TB and treatment outcomes using standardised definitions. RESULTS: There were 22,982 cases of TB registered in Malawi in 1998, of whom 2,739 (11.9%) were children. Children accounted for 1.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extra-pulmonary TB (EPTB). Estimated rates of TB in children were 78/ 100,000 in those aged less than one year, 83/100,000 in those aged 1-4 years and 33/100,000 in those aged 5-14 years. A significantly higher proportion of TB cases was diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. Treatment completion was best (76%) and death rates lowest (11%) for the 127 children with smear-positive PTB. CONCLUSION: Childhood TB is common in Malawi and treatment outcomes are poor. Research should be directed towards improved diagnosis and follow-up of children with TB, and the National TB Programme should support appropriate management of childhood contacts of smear positive PTB cases.     

The diagnosis of smear-negative pulmonary tuberculosis: the practice of sputum smear examination in Malawi.

SETTING: Forty hospitals in Malawi (3 central, 22 district and 15 mission) performing smear microscopy and registering tuberculosis patients. OBJECTIVE: To determine, in patients aged 15 years or above, 1) the proportion with smear-negative pulmonary tuberculosis (PTB) who had sputum smears examined, 2) the number of sputum smears examined per patient, and 3) the proportion of patients registered with smear-positive and smear-negative PTB. DESIGN: Data collection during three 6-month periods, from January 1997 to June 1998, using tuberculosis registers, laboratory sputum registers and quarterly reports. RESULTS: Of 6301 smear-negative PTB patients, 84% had sputum smears examined, the rate increasing from 76% in January-June 1997, to 85% in July-December 1997, to 89% in January-June 1998. Of patients who submitted sputum (where the number of smears was recorded), 99% had two or more smears examined and 93% had three smears examined. In district and mission hospitals performance improved over time, while in central hospitals results were more variable. During the same 18-month period 21 422 patients aged 15 years or more were registered with PTB: 59% with smear-positive PTB and 41% with smear-negative PTB; this pattern was similar in each 6-month period. CONCLUSION: The study suggests that it is reasonable to aim for a target of 90% or more of smear-negative PTB patients having sputum smears examined.     

全国初治涂阴肺结核病例登记现状分析

目的分析全国各省初治涂阴肺结核病例登记现状,为评价初治涂阴肺结核病例诊断质量提供依据。方法根据2004—2005年全国结核病防治规划报表中初治涂阴和初治涂阳肺结核病例登记资料,分析各省2年初治涂阴肺结核病例登记率变化和增长幅度;统计各省及不同地区初治涂阴与初治涂阳肺结核病例登记率;对各省初治涂阴与初治涂阳肺结核病例登记率进行直线回归分析。结果2005年全国登记初治涂阴肺结核病例316 405例,登记率为24.27/10万,各省登记率在6.01/10万72.17/10万;2005年登记初治涂阴病例数比2004年增加了19.9%,其中2个省登记数呈负增长,其余各省登记数增长了0.5%62.3%;2005年全国初治涂阳病例登记率是涂阴病例登记率的1.5倍,其中23个省初治涂阳病例登记率高于涂阴病例登记率,8个省相反;初治涂阴病例占初治涂阳病人登记率的比例,京津沪地区为149.28%,非项目地区为83.6%,项目地区为50.3%;对涂阳和涂阴病例登记率进行直线回归分析,回归方程y=22.342+0.563 6x。结论对初治涂阴肺结核患者实行免费政策后,全国涂阴肺结核病例登记率提高。但各省初治涂阴病例登记率和增长幅度以及涂阴病例登记率与涂阳病例登记率的比例悬殊。由于涂阴病例诊断困难,对于涂阴病例登记率高或增长幅度大的地区,特别在DOTS执行时间短和人力资源有限的地区,应对涂阴病例诊断质量予以进一步检查和评价。     

Conversion rate at two-month follow-up of smear-positive tuberculosis patients in Burkina Faso.

SETTING: Burkina Faso, West Africa. OBJECTIVE: 1) To determine the trend of sputum smear conversion rates at the 2-month follow-up of new smear-positive tuberculosis (TB) patients; and 2) to compare conversion rates in cured TB patients and treatment failures. DESIGN: Retrospective cohort study based on TB registers from all 80 diagnostic and treatment centres from 1995 to 2003. The conversion rate was defined as the number of negative results divided by the number of smear-positive patients for whom the 2-month follow-up examination was completed. RESULTS: The 2-month follow-up completion rate was 92.1%; it increased from 86.3% in 1996 to 94.3% in 2003. The conversion rate was 82.9%, increasing from 76.3% in 1995 to 87.9% in 1997 and falling to 80.3% in 2003. The cure rate was higher among patients who were smear-negative at the 2-month follow-up (77.3%) CONCLUSION: The conversion rate was satisfying, but had declined since 1997, which may be a matter of concern. This could be due to patient characteristics such as associated conditions (human immunodeficiency virus, malnutrition) or to drug management (ineffective administration of drugs even under directly observed treatment, insufficient dosages, resistance). Thorough research is needed to elucidate this negative trend.     

Auditing the new decentralised oral treatment regimens in Malawi.

SETTING: All 44 non-private hospitals in Malawi treating tuberculosis (TB) cases in which oral regimens were used allowing patients during the initial phase to receive directly observed treatment (DOT) from health centres or guardians at home. OBJECTIVES: A country-wide audit of the oral regimens to determine: 1) TB ward bed occupancy rates, 2) patient DOT options, 3) patients' knowledge of treatment and 4) treatment outcomes compared to those obtained with previous treatment regimens. DESIGN: Retrospective data collection using registers and treatment cards. Prospective interviews with patients. Inspections of TB wards. RESULTS: There were 1513 TB beds occupied by 807 (53%) TB patients. Over 50% of 4793 patients registered with different types of TB chose guardian-based DOT. For 266 patients with pulmonary TB the correct knowledge about total duration of treatment (45%), all three DOT options (62%) and the months for giving follow-up sputum (16%), was poor. There were differences in treatment outcomes between TB patients on oral compared with previous regimens. With oral regimens, rates of unknown outcome were high. CONCLUSION: Oral treatment regimens are associated with reduced bed occupancy rates on TB wards. However, rates of unknown outcome are increased, and TB control is therefore weakened.     

What causes smear-negative pulmonary tuberculosis in Malawi, an area of high HIV seroprevalence?

SETTING: The Central Hospital and the District Tuberculosis (TB) Registry in Lilongwe, the capital of Malawi. In this setting smear-negative pulmonary tuberculosis (PTB) is diagnosed using clinical and radiographic criteria for TB, and mycobacterial cultures are not routinely available. OBJECTIVE: To determine the proportion of patients being registered for smear-negative PTB treatment in Lilongwe who have TB that can be confirmed microbiologically. DESIGN: Prospective cohort study of patients about to start treatment under operational conditions for smear-negative PTB in Lilongwe between October 1997 and June 1998. Patients referred to the study team underwent a detailed clinical re-assessment, testing for human immunodeficiency virus (HIV), repeat sputum smear microscopy for acid-fast bacilli and mycobacterial cultures of sputum and blood. Bronchoscopy and bronchoalveolar lavage (BAL) were performed and BAL fluid was examined for TB, Pneumocystis carinii and other fungi. RESULTS: Of 352 smear-negative PTB suspects assessed, the diagnosis of TB was confirmed in 137 (39%) cases. Eighty-nine per cent of patients assessed were HIV-positive, of whom 81% met the expanded case definition for the acquired immune-deficiency syndrome (AIDS). CONCLUSION: TB was the most commonly confirmed diagnosis amongst patients about to start treatment for smear-negative PTB in an area of high background HIV seroprevalence.     

Risk factors for delay in the diagnosis and treatment of tuberculosis at a referral hospital in Rwanda.

SETTING: Kigali University Hospital, the main referral centre for TB in Rwanda. OBJECTIVE: To evaluate delays in the diagnosis and treatment of tuberculosis (TB) and associated risk factors. DESIGN: Prospective data collection of patients treated for pulmonary TB (PTB) or extra-pulmonary TB (EPTB) between June and September 2006. RESULTS: Of 104 patients with a mean age of 35 years (range 17-84) recruited into the study, 62% were HIV-positive. EPTB was diagnosed in 60 cases. The median total, health care and patient delays were respectively 57, 28 and 25 days. The health system delay before referral was significantly longer than the delay at our institution (18 vs. 6 days, P<0.0001). Risk factors for a longer health system delay at our institution were smear-negative PTB or EPTB (OR 5.12) and a trial of antibiotics (OR 2.96). The latter was also found to significantly prolong total delay (OR 2.85), as did rural residence (OR 4.86). No significant association was found between patient delay and age, sex, profession or health insurance status. CONCLUSION: Smear-negative PTB and EPTB were associated with longer health system delays. A trial of antibiotics significantly increased the health system delay. Its use, recommended by the World Health Organization in case of smear-negative TB and EPTB in developing countries, needs validation at the tertiary health care level.     

Recurrent tuberculosis: definitions and treatment regimens.

Within the National Tuberculosis Control Programme of Malawi, misunderstandings sometimes occur about the diagnosis and management of recurrent tuberculosis (TB). Patients with smear-positive pulmonary tuberculosis (PTB) who have had a previous, treated episode of smear-negative TB may be registered as 'new cases' rather than relapse cases, and thus denied the benefits of a retreatment regimen. Patients with a recurrent episode of smear-negative PTB or extra-pulmonary TB (EPTB) may also be wrongly registered as 'new cases' rather than recurrent cases. International guidelines about the treatment of recurrent smear-negative PTB and EPTB are not explicit, resulting in confusion about how best to manage these cases. It is suggested that all such cases be considered for re-treatment regimen because of concerns about acquired drug resistance. WHO and IUATLD guidelines on the diagnosis and management of recurrent and relapse TB need to be improved, and operational research studies should be conducted to provide answers to some outstanding questions.     

When are follow-up sputum smears actually examined in patients treated for new smear-positive pulmonary tuberculosis?

SETTING: All 44 non-private hospitals (four central, 22 district and 18 mission) in Malawi that registered and treated tuberculosis (TB) cases, October-December 2001. OBJECTIVES: To determine, in new smear-positive pulmonary tuberculosis (PTB) patients, for the 2-, 5- and 7-month smear examinations, 1) the proportion with smears examined and 2) the actual timing of smear examination. STUDY DESIGN: Retrospective data collection using TB registers, TB treatment cards and laboratory sputum registers. Timing of smear examinations was judged acceptable if 2-month smears were examined at 2 or 3 months, 5-month smears at 4, 5 or 6 months and 7-month smears at 6, 7, 8 or 9 months. RESULTS: Of 1994 patients, for those alive and on treatment, 78% had smears definitely examined at 2 months, 75% at 5 months and 74% at 7 months. Of these, 82% had smears examined at an acceptable time for the 2-month smear, 71% for the 5-month smear and 78% for the 7-month smear. Smears were examined after the 8-month treatment regimen for the 2- and 5-month smear in respectively 2% and 9% of patients. Smears were done more frequently in female than male patients, and in district/mission hospitals than central hospitals. Smears were done at acceptable times more frequently in younger than older patients and in mission/central hospitals than district hospitals. CONCLUSION: During supervision, the actual time of follow-up sputum smear examinations needs to be monitored more closely.     

Direct observation of tuberculosis treatment by supervised family members in Yasothorn Province, Thailand.

SETTING: Yasothorn Province, Thailand. OBJECTIVE: To evaluate the effectiveness of a programme offering the option of direct observation of treatment (DOT) by a supervised family member. METHODS: Review of patient records and district registers in Yasothorn Province after implementation of the revised tuberculosis control strategy. RESULTS: From 1 October 1996 to 30 September 1997, the programme registered 779 patients: 366 smear-positive pulmonary, 357 smear-negative pulmonary, and 56 extra-pulmonary. DOT was given in 243 (66%) smear-positive, 83 (23%) smear-negative, and in 21 (38%) extra-pulmonary cases; the observer was a family member in 299 (86.2%) of the 347 cases. By December 1998, treatment outcomes were determined for the 695 new patients (326 smear-positive, 321 smear-negative, 48 extra-pulmonary) of the 779 registered during the period under study. In new smear-positive patients, cure rates were 184/216 (85.2%, 95% confidence interval [CI] 80.5-89.9) with DOT versus 78/110 (70.9%, 95% CI 62.4-79.4) with self-administration. CONCLUSION: The overall cure rate was 80.4% in a programme in which trained and supervised family members directly observed the treatment of two-thirds of sputum smear-positive patients. Supervised family members may contribute to more widespread effective implementation of the revised tuberculosis strategy in Thailand.     

Defining and assessing the maximum number of visits patients should make to a health facility to obtain a diagnosis of pulmonary tuberculosis.

SETTING: All non-private hospitals in Malawi. OBJECTIVES: To determine 1) how many patients with pulmonary tuberculosis (PTB) exceed the maximum number of visits needed for registration as defined by the National Tuberculosis Control Programme, and 2) the factors associated with this delay. DESIGN: Cross-sectional study interviewing hospitalised patients with new smear-positive and smear-negative PTB. RESULTS: Of 380 patients with PTB admitted to the 44 hospitals visited between April and June 2002, 329 (212 smear-positive and 117 smear-negative PTB) were interviewed: 64 (30%) smear-positive PTB patients needed more than five visits, and 44 (37%) smear-negative PTB patients needed more than six visits before being registered and started on treatment. Factors associated with exceeding the maximum number of visits were the first visit being to a health centre, submission of > 1 set of sputum specimens, and > 1 course of antibiotics. The main consequence of exceeding the maximum number of visits was increased duration of cough and increased time spent at health facilities. CONCLUSION: One third of patients exceed the maximum number of visits for registration of PTB. The main consequence of this is an increased duration of cough and an increased time spent at health facilities. Ways to reduce this delay need to be found.     

Characteristics and outcome of tuberculosis patients whose sputum smears are positive at or after 5 months of treatment.

A country-wide survey was carried out to assess the management of new smear-positive pulmonary TB (PTB) patients whose sputum smears were recorded as positive 5 months or later during treatment. During 2000 and 2001, there were 250 patients, of whom 161 (64%) had positive smears at 5 months and 89 at 7 months. Several inconsistencies and inadequacies in management were identified which need to be remedied: 7% of patients were assessed on one sputum specimen instead of two, and 17% on the basis of one positive smear result; 47% of patients with 5-month positive smears and 52% with 7-month positive smears had sputum smears examined too early or too late; 14% of patients with 5-month positive smears continued treatment, and over 60% of these were recorded as 'cured'.     

Profile of geriatric patients under DOTS in Revised National Tuberculosis Control Programme

BACKGROUND: With an increase in life expectancy and the resultant elderly population, there has been an increase in the number of tuberculosis (TB) cases including those in geriatric age as well. However using Directly Observed Treatment-Short Course (DOTS), all categories of TB patients have been sucessfully treated within the country. A need was felt to study the profile of geriatric TB patients under the Revised National Tuberculosis Control Programme (RNTCP). METHODS: A retrospective study of 7439 patients enrolled under DOTS from January 1996 to March 2001 was carried out in a tertiary care referral institute in Delhi and the profile was analysed in terms of the gender, type of TB and ratio of sputum smear-positive to negative patients for both the younger and geriatric age groups. Further, treatment outcomes of the two age groups were analysed and compared for the 2655 new sputum smear patients. RESULTS: The male : female ratio of 315 geriatric TB patients enrolled under DOTS was observed to be 3 : 1 as against the 1.4 : 1 in younger TB patients. The occurrence of pulmonary TB was significantly higher than extra-pulmonary TB in geriatric age group (16:1) as compared to the younger age group (4:1). The ratio of new smear-positive to smear-negative patients was almost similar in the two age groups. Further, the treatment outcomes of new smear-positive geriatric TB patients in comparison to younger TB patients showed significantly lower sputum conversion (75.3% vs 85.7% respectively) and cure rates (69.2% vs 80.7% respectively), significantly higher exclusion rates from DOTS (2.3% vs 0.15% respectively) and relatively higher default and treatment failure rates. CONCLUSIONS: The present study has identified certain issues in the Indian TB patients of geriatric age. These include a lower reported prevalence amongst females, poor sputum conversion as well as cure rates and higher exclusion as well as default rates. Further studies are needed to address the issues under operational conditions of Indian RNTCP.     

Clinical diagnosis of smear-negative pulmonary tuberculosis: an audit of diagnostic practice in hospitals in Malawi.

SETTING: Thirty-seven hospitals in Malawi. OBJECTIVE: To audit the hospital practice of clinically diagnosing adults with smear-negative pulmonary tuberculosis (PTB). DESIGN: A cross-sectional survey of adults aged 15 years or above who were registered and receiving inpatient treatment for smear-negative PTB. An assessment of each patient was carried out to determine 1) the number of recommended diagnostic guidelines (cough >3 weeks, no response to antibiotics, negative sputum smears and a chest radiograph compatible with PTB) used by hospital staff in making the diagnosis of PTB, and 2) whether the clinical diagnosis of smear-negative PTB was correct according to criteria set by the study. RESULTS: There were 259 patients, 127 men and 132 women, with a mean age of 37 years; 93% had a cough >3 weeks, 95% had received one or more courses of antibiotics, 92% had submitted sputum samples for smear examination and 97% had chest radiographs performed. In 148 (57%) patients, all four diagnostic guidelines were used, and in 238 (92%) patients three or more were used. The diagnosis of smear-negative PTB was considered correct by study criteria in 203 (78%) patients. In the remainder, 22 (8%) were considered to have extrapulmonary TB and 34 (14%) another diagnosis. CONCLUSION: Hospital practices in the diagnosis of smear-negative PTB are reasonable, although there is room for improvement with in-service training and regular audits of practice.     

Mortality rates and recurrent rates of tuberculosis in patients with smear-negative pulmonary tuberculosis and tuberculous pleural effusion who have completed treatment.

SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To follow-up human immunodeficiency virus (HIV) seropositive and HIV-seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB who had completed treatment with two different regimens in Blantyre and Zomba, and to assess rates of mortality and recurrent TB. DESIGN: Patients with smear-negative and pleural TB who had completed 8 months ambulatory treatment in Blantyre or 12 months standard treatment in Zomba and who were smear and culture negative for acid-fast bacilli at the completion of treatment were actively followed every 4 months for a total of 20 months. RESULTS: Of 248 patients, 150 with smear-negative PTB and 98 with pleural TB, who completed treatment and were enrolled, 205 (83%) were HIV-positive. At 20 months, 145 (58%) patients were alive, 85 (34%) had died and 18 (7%) had transferred out of the district. The mortality rate was 25.7 per 100 person-years, with increased rates strongly associated with HIV infection and age >45 years. Forty-nine patients developed recurrent TB. The recurrence rate of TB was 16.1 per 100 person-years, with increased rates strongly associated with HIV infection, having smear-negative PTB and having received 'standard treatment'. CONCLUSION: High rates of mortality and recurrent TB were found in patients with smear-negative PTB and pleural effusion during 20 months of follow-up. TB programmes in sub-Saharan Africa must consider appropriate interventions, such as co-trimoxazole and secondary isoniazid prophylaxis, to reduce these adverse outcomes.     

Effectiveness of community-based directly observed treatment for tuberculosis in an urban setting in Tanzania: a randomised controlled trial.

SETTING: An urban district in Dar es Salaam city with a high tuberculosis (TB) caseload. OBJECTIVE: To evaluate the effectiveness of community-based direct observation of treatment (DOT) using guardians and former TB patients compared to hospital-based DOT in an urban setting in Tanzania. DESIGN: Unblinded randomised control trial conducted in five sites under operational conditions in Temeke district. No changes to existing treatment delivery were made other than randomisation. The main outcome measure was treatment success. Analysis was by intention to treat. FINDINGS: A total of 587 new tuberculosis patients were enrolled. Among enrolled patients, 260 were assigned to community-based DOT using guardians and former TB patients and 327 to health facility-based DOT. Both DOT options gave similar treatment outcomes. Treatment success rate among patients under community and health facility-based DOT were 85% and 83%, respectively (OR 1.17, 95%CI 0.75-1.83). CONCLUSION: Community-based DOT is as effective as health facility-based DOT and can achieve good treatment outcomes, even in countries with well functioning National Tuberculosis Programmes.     

Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control

BACKGROUND: Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program. METHODS: Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire. Survey findings were correlated with notification data extracted from the TB treatment register. RESULTS: Of those surveyed, 174 (23%) tested HIV positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear-negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among HIV-positive and -negative individuals, prevalence of notified smear-positive PTB was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was 2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%, respectively. Estimated duration of infectiousness was similar for HIV-positive and HIV-negative individuals. However, 87% of total person-years of undiagnosed smear-positive TB in the community were among HIV-infected individuals. CONCLUSIONS: PTB was identified in 9% of HIV-infected individuals, with 5% being previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low case-finding rates. DOTS strategy based on passive case finding should be supplemented by active case finding targeting HIV-infected individuals.     

Diagnosing smear-negative tuberculosis using case definitions and treatment response in HIV-infected adults.

OBJECTIVE: To assess the diagnostic utility of expanded case definitions for HIV-associated smear-negative pulmonary tuberculosis (PTB) and extra-pulmonary TB (EPTB), and to derive objective criteria for response to anti-tuberculosis treatment. DESIGN: A prospective cohort study of HIV-infected adults who met expanded clinical case definitions for smear-negative PTB and EPTB. METHODS: All participants were started on rifampicin-based anti-tuberculosis treatment after mycobacterial cultures from multiple sites. At weeks 2, 4 and 8, response to treatment (RTT) was assessed by measuring changes in weight, haemoglobin, C-reactive protein, Karnofsky performance score and symptom count ratio. RESULTS: Of 147 participants enrolled, 105 (71%) were diagnosed with definite (culture-positive) or probable (histological features) TB and 25 (17%) with possible TB (treatment response). The positive predictive value for the most common case definitions ranged from 89% to 96%. Significant improvements in all the RTT parameters occurred in the subjects with confirmed TB (P < 0.001). Clinically relevant RTT criteria were derived, two or more of which were met at week 8 in 97.5% of subjects with confirmed TB, 91.3% of subjects with possible TB and none of the subjects without TB. CONCLUSION: Expanded case definitions could enhance the diagnosis of PTB and EPTB in HIV-infected adults in resource-limited settings. Using objective criteria, RTT can be assessed within 8 weeks of initiating anti-tuberculosis treatment.     

The role of induced sputum in the diagnosis of pulmonary tuberculosis

OBJECTIVES: To determine the sensitivity of referral guidelines for induced sputum in pulmonary tuberculosis (PTB) case detection and determine the diagnostic yield of the test. METHODS: A retrospective analysis of case notes of adult patients referred for induced sputum was carried out at the North Trent Regional Department of Infection and Tropical Medicine, the Royal Hallamshire Hospital, Sheffield, UK. Clinical characteristics were noted on patients referred during a 12-month period in 2001-2002, and of all patients with positive induced sputum results from April 1998 to March 2002. RESULTS: Over a 12-month period 114 patients were referred in our unit for induced sputum sampling. Twelve of the 114 patients had positive sputum cultures giving a positive yield for the test of 10.5%. With strict adherence to our referral guidelines, 10 of the 12 positive cases (83.3%) would have been detected. With modification to the referral guidelines, all 12 microbiologically positive cases would have been detected making the guidelines 100% sensitive in detecting microbiologically positive cases among patients referred with a clinical suspicion of PTB who are unable to self-expectorate. The positive yield for the test would have been increased to 13.2%. In the past 4 years 29 patients had positive induced sputum results. Of these, 11 patients (37.9%) had concurrent microbiological proven extra-pulmonary TB (EPTB) and 10 (34.5%) had past histories of TB infection. Seven patients had chest X-rays reported as normal. CONCLUSIONS: Induced sputum offers a relatively non-invasive investigation for patients with suspected PTB who are unable to bring up sputum. Induced sputum also offers a means of establishing a microbiological diagnosis in some cases of EPTB. An investigative algorithm is suggested.Summary. In an era of increasing drug resistant disease, establishing a microbiological diagnosis of TB is paramount. Sputum induction can be used as an alternative investigation to bronchoscopy in suspected PTB patients who are able to self-expectorate. Induced sputum is a sensitive investigation for suspected PTB patients but with a low diagnostic yield. Referral guidelines are suggested.