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.     

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.     

Evaluation of a unified treatment regimen for all new cases of tuberculosis using guardian-based supervision.

SETTING: Ntcheu District, Malawi, using an oral antituberculosis treatment regimen. OBJECTIVE: To determine whether directly observed treatment (DOT) during the initial phase of treatment supervised either in hospital, at health centres or by guardians in the community, was associated with 1) satisfactory 2-month and 8-month treatment outcomes, and 2) with a reduction of in-patient hospital-bed days. DESIGN: Prospective data collection of all tuberculosis (TB) patients registered between 1 April 1996 and 30 June 1997, with 2-month and 8-month treatment outcomes, sputum smear conversion in smear-positive pulmonary TB patients (PTB) and in-patient hospital-bed days. RESULTS: Among the 600 new patients, 302 had smear-positive PTB, 150 smear-negative PTB and 148 extrapulmonary TB (EPTB). Eight-month treatment completion was 65% for smear-positive PTB patients, which was significantly higher than in patients with smear-negative PTB (45%) and EPTB (54%), due mainly to high 8-month mortality rates. The site of the intensive phase was determined in 596 patients: 178 (30%) received DOT from guardians, 115 (19%) from a health centre and 303 (51%) in hospital. At 2 months, mortality rates were significantly higher in hospitalised patients. Two-month treatment outcomes (including sputum smear conversion rates in smear-positive PTB patients) were similar between patients receiving DOT at health centres or from guardians. Decentralised DOT resulted in a 25% reduction in hospital-bed days in patients alive at 2 months compared with that predicted using the old regimens. CONCLUSION: Decentralising DOT to health centres and to guardians during the intensive phase is associated with satisfactory treatment outcomes.     

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.     

Diagnosis of childhood tuberculosis in Malawi: an audit of hospital practice.

SETTING: All 44 non-private hospitals in Malawi that register and treat children with tuberculosis (TB). OBJECTIVE: To determine 1) clinical features and diagnostic practices in children registered with TB, and 2) the use of the WHO score chart in diagnosis. DESIGN: A cross-sectional study of all children aged 14 years or below in hospital receiving anti-tuberculosis treatment, using reviews of treatment cards, case files and chest X-rays and performing a clinical assessment. RESULTS: There were 150 children, 98 with pulmonary TB (PTB) and 52 with extra-pulmonary TB (EPTB). The median duration of illness was 8 weeks. Most patients had fever, no response to anti-malarial treatment and antibiotics, and 40% had a family history of TB. Nearly 45% had weight for age <60%. Diagnosis was mainly based on clinical features and radiography, with less than 10% having tuberculin skin tests or HIV serology, and very few having other sophisticated investigations. A WHO diagnostic score chart was used in 13 (9%) patients by hospital staff. An independent assessment by the study team found that 61% of patients had a score of 7 or more; this was higher in EPTB than PTB patients. CONCLUSION: Diagnostic practices in children with TB in Malawi are poor, and improvements should be made.     

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.     

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.     

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.     

Clinical and epidemiological evaluation of tuberculosis in Serbia, 1990-2004.

SETTING: Republic of Serbia, excluding Kosovo. OBJECTIVE: To estimate the clinical and epidemiological pattern of tuberculosis (TB) in Serbia during the period 1990-2004. DESIGN: A retrospective analysis of clinical and epidemiological data on TB patients registered in annual TB reports. RESULTS: During the 15-year period, TB incidence levelled off in Serbia. The slightly decreasing trend occurred in both total pulmonary TB (PTB) and laboratory confirmed PTB (PTB+) incidence (P > 0.05), while the trend of extra-pulmonary TB (EPTB) incidence increased slightly (P > 0.05). During the same period, TB mortality showed a significantly decreasing trend (P < 0.05). The mean annual proportion of PTB+ cases among newly reported PTB cases was 62.7%. The mean proportion of EPTB cases among total TB cases was 6.1%. The mean percentage of cases with resistance to at least one anti-tuberculosis drug was 4.8%. CONCLUSION: Thanks to the good organisation and efficient work of anti-tuberculosis dispensaries in Serbia, as well as to the low incidence of AIDS and low frequency of Mycobacterium tuberculosis resistant strains, TB incidence did not increase during the period observed and TB mortality significantly decreased, despite markedly deteriorated socio-economic conditions during the 1990s.     

HIV-1 co-infection in children hospitalised with tuberculosis in South Africa.

SETTING: Hospitals associated with the Department of Paediatrics at the University of the Witwatersrand, Johannesburg, South Africa. OBJECTIVES: To define the prevalence of human immunodeficiency virus (HIV) co-infection and differences in clinical presentation between HIV-infected and non-infected hospitalised children with tuberculosis. DESIGN: Children were prospectively enrolled between August 1996 and January 1997. RESULTS: Of 161 children enrolled, 42% were HIV-infected, including 67/137 with pulmonary tuberculosis (PTB) and 1/24 with extra-pulmonary disease (EPTB). Positive microscopy or bacteriology did not differ by HIV status for children with either PTB or EPTB. Although age did not differ between HIV-infected and non-infected children with PTB, non-HIV-infected children with EPTB were significantly older than those with PTB only (median age 32 months vs 14.5 months, P = 0.004). Chronic weight loss, malnutrition and the absence of BCG scarring were more common in HIV-infected children with PTB. HIV-infected children were also more likely to show cavitation (P = 0.001) and miliary TB (P = 0.01) on chest X-ray. Reactivity to tuberculin (> or = 5 mm and > or = 10 mm in HIV-infected and non-infected children, respectively) was significantly lower in HIV-infected children, as were CD4+ lymphocyte levels. The mortality rate during the study was 13.4% in HIV-infected children compared with 1.5% in non-HIV-infected children (P = 0.03). CONCLUSIONS: There is a high prevalence of HIV co-infection in children with TB. Progressive PTB and death are more common in HIV-infected children. Tuberculin skin testing is of limited use in screening for TB in HIV-infected children even when using a cut-point of > or = 5 mm.     

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.     

Benefit of amoxicillin in differentiating between TB suspects whose initial AFB sputum smears are negative.

SETTING: Out-patient dispensary in Conakry, Guinea, West Africa. OBJECTIVE: To differentiate between pulmonary tuberculosis (PTB) and non-PTB diseases among 204 acid-fast bacilli (AFB) smear-negative adult TB suspects. DESIGN: We derived scores from clinical, serological and radiological findings among PTB suspects aged > or = 15 years who, after having had three AFB-negative smears, were treated for 10 days with amoxicillin (AMX, 1.5 g/day). RESULTS: At the selected cut-off score from model 1 (clinical), sensitivity for PTB was 95%, specificity 40%, negative predictive value (NPV) 84%, and positive predictive value (PPV) 69%. Comparable values from model 2 (clinical + serological + radiological) were: sensitivity 99%, specificity 45%, NPV 97%, and PPV 71%. Results from AMX were better: sensitivity 92%, specificity 93%, NPV 94%, and PPV 91%. Of the 117 suspects who failed to respond clinically and radiographically to AMX and remained AFB smear-negative, 110 (94%) had PTB, confirmed either by positive culture (73 patients) or response to anti-tuberculosis treatment (37 patients). CONCLUSION: The clinical and radiographic response to AMX is better than derived scores at differentiating between PTB and non-PTB in TB suspects presenting to a dispensary in Guinea, a low HIV-seroprevalence country.     

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.     

Manifestations and outcome of extra-pulmonary tuberculosis: impact of human immunodeficiency virus co-infection.

SETTING: Metropolitan New Orleans. OBJECTIVE: To determine the impact of human immunodeficiency virus (HIV) co-infection on the manifestations and outcome of extra-pulmonary tuberculosis (EPTB). DESIGN: Retrospective analysis of 136 patients diagnosed with EPTB between 1 January 1993 to 31 December 2001. Characteristics of EPTB were compared by HIV serostatus. RESULTS: Of those tested for HIV (n = 87), 42.5% were seropositive. Except for a higher frequency of disseminated TB among co-infected persons, the manifestations, laboratory diagnostic yield and outcome of EPTB were similar between HIV-infected and non-infected persons. The overall fatality rate was 20%; HIV-infected patients had a three-fold higher mortality compared to non-infected persons. In multivariate logistic regression analysis, factors associated with death were: HIV-seropositive (adjusted odds ratio [aOR] 5.2, 95% CI 1.1-24.65) compared to HIV-seronegative, disseminated and meningeal compared to lymphatic disease (aOR 16.87, 95% CI 12.31-123.34), and lack of TB treatment compared to receipt of TB treatment (aOR 29.23, 95% CI 14.47-191.23). CONCLUSION: Manifestations of EPTB were non-specific and did not differ between HIV-infected and non-infected persons. Severe disease, lack of TB treatment and HIV co-infection were associated withdeath. Approaches are needed to reduce EPTB morbidity and mortality, especially among HIV-infected persons.     

Comparison of extra-pulmonary and pulmonary tuberculosis cases: factors influencing the site of reactivation.

SETTING: Mycobacterium tuberculosis bacilli spread by the hematogenous route during primary infection and reactivate later. OBJECTIVE: To compare factors influencing the reactivation site. DESIGN: A total of 236 pulmonary tuberculosis (PTB) and 139 extra-pulmonary TB (EPTB) cases were compared in terms of age, co-morbid disease, immunosuppressive drug use, history of contact with a PTB case in a close relative, history of tuberculosis, smoking habit and alcohol intake. RESULTS: The sex ratio of EPTB and PTB cases was significantly different (P < 0.001): respectively 74% of EPTB cases and 34% of PTB cases were females; 53.3% of PTB cases and 23% of EPTB cases were smokers (P < 0.001); and the disease appeared within the first 5 years after contact in 23.7% of EPTB cases compared to 72.6% in PTB cases (P < 0.001). In logistic regression analysis, gender (OR = 3.69), smoking habit (OR = 0.54) and interval between contact and disease (OR = 1.07) were found to influence the reactivation site. CONCLUSION: The probability of PTB development was higher in males, in smokers and within the first 5 years of contact. In contrast, the probability of EPTB development was higher in females and after 5 years of contact.     

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。     

Extra-pulmonary tuberculosis at a regional hospital in Thailand

The purpose of this study was to analyze the cases of extra-pulmonary tuberculosis (EPTB) at Maharat Nakhon Ratchasima Hospital, a tertiary care regional hospital in Northeast Thailand. There were 398 cases of EPTB (46.9%) and 450 cases of pulmonary tuberculosis (PTB) (53.1%). The mean age of EPTB patients (47.58 years) was lower than that of PTB patients (51.6 years) (p < 0.01). Human Immunodeficiency Virus (HIV) seropositivity was found in 50 cases of EPTB (12.6%) and 55 cases of PTB (12.2%) which was not significantly different. The common sites of extra-pulmonary involvement were the lymph nodes (29.7%), followed by the pleura (27.4%), the bones and spine (25.1%), the meninges and brain (4.5%), the pericardium (3.5%) and the gastrointestinal tract (3.0%). Disseminated TB occurred in only 8 cases (2.0%). HIV seropositivity rates were more common in disseminated TB (OR 41.51, 95% CI 4.98-34.5), TB of the meninges and brain (OR 4.47, 95% CI 1.57-12.6) and TB of the lymph nodes (OR 3.49, 95% CI 1.86-6.54) and were less common in TB of the bones and spine (OR 0.05, 95% CI 0.01-0.37) and TB of the pleura (OR 0.24, 95%CI 0.09-0.63).     

Accuracy of an interferon-gamma release assay to detect active pulmonary and extra-pulmonary tuberculosis.

OBJECTIVE: To examine the performance of an interferon-gamma (IFN-gamma) release assay (QuantiFERON-TB 2G assay [QFT-G]) to detect Mycobacterium tuberculosis infection in a Japanese general hospital, for the diagnosis of active pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (EPTB). DESIGN: We prospectively examined the performance of QFT-G in 194 patients suspected of active TB. Diagnosis was confirmed by 1) positive M. tuberculosis cultures, or 2) clinical manifestations or laboratory or pathological findings consistent with active TB and response to specific therapy. RESULTS: Three patients with indeterminate QFT-G results were excluded. Among the remaining 191 patients, 77 had active TB. When the cut-off concentration of IFN-gamma was set at 0.35 IU/ml, as recommended by the manufacturer, the assay was positive in 69 patients and negative in 122. The sensitivity of the assay was 76.6% in all patients, 74.5% in the 47 patients with PTB and 80.0% in the 30 patients with EPTB. The overall specificity of the assay was 91.2%. CONCLUSION: Although the specificity of the QFT-G to detect active TB was high and its sensitivity low, it was as accurate for the detection of active EPTB as for PTB when the 0.35 IU/ml INF-gamma cut-off concentration was used.     

Extra-pulmonary manifestations in a large metropolitan area with a low incidence of tuberculosis.

BACKGROUND: The increases in extra-pulmonary tuberculosis (EPTB) have been largely due to human immunodeficiency virus co-infection. The rates of EPTB have remained constant despite the decline in pulmonary tuberculosis (PTB) cases. OBJECTIVE: To evaluate covariates associated with EPTB. METHODS: A 4-year cohort of EPTB patients was compared with PTB cases. Enrollees were assessed for TB risk, medical records were reviewed, and Mycobacterium tuberculosis isolates were fingerprinted. RESULTS: We identified 538 EPTB cases (28.6%) in a total of 1878 enrollees. The most common sites of infection were lymph nodes (43%) and pleura (23%). EPTB cases included 320 (59%) males, 382 (71%) patients were culture-positive, and 332 (86.9%) patient isolates were fingerprinted. Fewer EPTB than PTB patients belonged to clustered M. tuberculosis strains (58% vs. 65%; P = 0.02). A multivariate model identified an increased risk for EPTB among African Americans (OR = 1.9, P = 0.01), HIV-seropositive (OR = 3.1, P < 0.01), liver cirrhosis (OR = 2.3, P = 0.02), and age <18 years (OR = 2.0, P = 0.04). Patients with concomitant pulmonary and extra-pulmonary infections were more likely to die within 6 months of TB diagnosis (OR = 2.3, P < 0.01). CONCLUSIONS: African American ethnicity is an independent risk factor for EPTB. Mortality at 6 months is partly due to the dissemination of M. tuberculosis and the severity of the underlying co-morbidity.