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Diagnosis of tuberculosis in children using a polymerase chain reaction.

We investigated the value of the polymerase chain reaction (PCR) in the diagnosis of active tuberculosis in children and evaluated the relationship between PCR results in children with tuberculous infections and mediastinal adenopathies detected by computerized tomography (CT-Scan). This was a controlled, blinded, prospective study comparing nested PCR, mycobacterial cultures and the clinical diagnosis based on 350 clinical specimens from 117 children referred for evaluation of suspected pulmonary tuberculosis. All children with tuberculous infection but without active disease underwent a chest CT-scan to detect the presence of mediastinal adenopathies not evident on chest x-ray. The sensitivity of PCR was 56.8% in children with clinically active disease (culture: 37.8%; smears: 13.5%). A major advantage of PCR over cultures was noted when there was no parenchymal involvement on chest radiograph and when the patient was undergoing anti-tuberculous treatment. There were nine specimens with false-negative PCR results due to the presence of amplification reaction inhibitors. PCR was positive in five children with tuberculous infection without active disease and these children presented mediastinal adenopathies on the CT-scan that were not evident on chest radiography. There were no false-positive PCR results in the control groups of children. We conclude that nested PCR is a rapid and sensitive method for the early diagnosis of tuberculosis in children. It is especially useful when the diagnosis of active tuberculosis is difficult. In our study children with tuberculous infection without apparent disease who have positive PCR results have mediastinal adenopathies on CT-scan.

Child↗

Fine-needle aspiration cytology in tuberculous lymphadenitis of patients with and without HIV infection.

A study of the cytologic features and role of fine-needle aspiration cytology (FNAC) in tuberculous lymphadenitis (TBL) of 21 patients with HIV (group 1) and 21 patients without HIV (group 2) infection was undertaken. Four cytologic patterns were observed, of which necrotizing lymphadenitis (42.9%) and necrotizing suppurative lymphadenitis (28.6%) were predominant in group 1 while necrotizing granulomatous lymphadenitis (47.7%) and granulomatous lymphadenitis (23.8%) were more common in group 2. No pattern was found specific for either group. Zeihl-Neelsen-stained cytology smears of group 1 showed a much higher percentage of positively (61.9%) and a higher density of acid-fast bacilli than group 2. Definitive diagnoses of TBL on FNAC could be provided in 61.9% of group 1 as against 9.5% of group 2. The need for culture or biopsy for definitive diagnosis was higher in group 2. In suspected TBL, diagnostic efficacy can be improved and the need for surgical biopsy reduced if material collected on FNA is also used for culture.

AIDS-Related Opportunistic Infections↗

Protective value of BCG vaccination in children in Bangkok, Thailand.

The protective effect of bacille Calmette-Guérin (BCG) vaccination against tuberculosis is controversial. In a study, 330 patients less than 12 years of age with tuberculosis, 52.1% of whom had had BCG vaccination, were compared with a control group of 1106 patients free of tuberculosis, 81% of whom had BCG vaccination. The occurrence of disseminated forms of tuberculosis, tuberculous meningitis, tuberculous peritonitis, and tuberculosis of bone and joints in BCG-vaccinated patients was quite low. With BCG vaccination, the incidence of the disseminated form of tuberculosis was significantly lower than that of pulmonary tuberculosis with pulmonary parenchymal lesions, primary pulmonary complexes, and pleural effusion. Tuberculous peritonitis was significantly less frequent than pulmonary tuberculosis with pulmonary parenchymal lesions, enlarged hilar glands, pulmonary primary complex, and pleural effusions. The study demonstrated that BCG gave an overall protective effect of 74% and that a major effect of this immunity was to produce a localized form of tuberculosis.

Adolescent↗

Serological response of tuberculosis patients to antigen 60 of BCG.

Two ELISA tests (IgG and IgM) for the serodiagnosis of tuberculosis, both based on antigen 60 (A60) of M. bovis BCG, were applied to 1,644 controls and patients to analyse the immune response in different forms of this infectious disease. Out of 200 healthy individuals, 148 being tuberculin--positive BCG-vaccinated adults, only 10 contacts--nurses of the pneumology department and laboratory technicians of the mycobacterial laboratory--were found positive for anti-A60 IgG. One quarter of hospitalized patients affected by non-tuberculous pneumopathies (194 in total) were found weakly positive for anti-A60 IgG. We suppose that these positive cases have suffered from inapperant infections and are in a "persistent state". Out of 344 cases of primary pulmonary tuberculosis, 88% were positive for anti-A60 IgG and 75% for the corresponding IgM. Among 97 cases of primary extra-pulmonary tuberculosis, 94% were found IgG positive and 33% IgM positive. The difference between active and inactive post-primary (chronic) tuberculosis was striking: about 100% of both pulmonary and extra-pulmonary cases (367 altogether) had high titers of anti-A60 IgG but IgM positivity was observed in only 15% of the cases, whereas in inactive and quiescent noncavitary tuberculosis (442 cases), 57% of the patients were weakly positive for anti-A60 IgG and none were positive for IgM. Kinetics of synthesis of anti-A60 IgG and IgM were analysed in primary and post-primary (chronic) active tuberculosis. The IgM tracing immune response to A60 was shorter and lower during primary tuberculosis as compared to post-primary tuberculosis. Our findings point to the high prognostic value of the A60- ELISA test for tuberculosis. Anti-A60 IgM mark initial stages of the disease or reactivation processes whereas anti-A60 IgG last longer than IgM and provide an evaluation of the intensity of the infectious process. Repeated serological tests allow monitoring of the course of the infection and the efficacy of therapy. The test is negative in healthy BCG-vaccinated persons (tuberculin-positive) and healed tuberculous infection cases. The combined use of both IgG and IgM tests helps in the correct diagnosis of "false positive" cases.

Adolescent↗

Case report 654: Disseminated tuberculosis.

A case of disseminated tuberculosis with a psoas abscess and associated destruction of bone in a 28-year-old man has been presented. Multiple skeletal lesions and hilar adenopathy were observed. The initial diagnosis from pathological specimens was equivocal, since acid-fast bacilli were not demonstrated. However, special stains of biopsy specimens subsequently confirmed the diagnosis. The initial radiographs suggested disseminated malignancy. Good therapeutic results were obtained, utilizing surgical and chemotherapeutic methods. This case demonstrates the ability of disseminated tuberculosis to mimic other disease processes and shows the difficulty that may exist in establishing a diagnosis of tuberculosis, even with biopsy specimens.

Adult↗

Identification of AIDS-related tuberculosis with concordant gallium-67 and three-hour delayed thallium-201 scintigraphy.

Concordant gallium-67 and thallium-201 uptake has been described in malignant lesions. More recently, 201Tl accumulation has been described in some benign conditions. The authors report three HIV-positive patients who underwent 67Ga and 201Tl scintigraphy. These studies revealed concordant 67Ga and 201Tl uptake and tumour was erroneously diagnosed. All three patients were finally diagnosed as having tuberculosis.

AIDS-Related Opportunistic Infections↗

Value of the lateral chest radiograph in tuberculosis in children.

The value of the lateral chest radiograph, often considered a useful adjunct in the detection of hilar adenopathy, was evaluated in a prospective study of 449 children assessed for tuberculosis. Of these children 298 presented to the hospital with signs and symptoms suggestive of tuberculosis, while 151 were investigated in a regional clinic solely because they were in close contact with an adult household member on treatment for tuberculosis. Tuberculosis was confirmed by culture in 176 of the 449 children (39%). In 40 of these (23%) hilar adenopathy was visible on frontal and lateral view, in 19 of the 176 confirmed cases (11%) only on a frontal view and in 22 (13%) on a lateral view only. Probable tuberculosis was diagnosed in a further 140 of the 449 children (31%), and hilar adenopathy was visible on frontal and lateral views in 39 of these children (28%), on the frontal view only in 8 (6%) and on the lateral view only in 27 (19%). In the symptomatic children investigated in the hospital, and the asymptomatic children investigated in the clinic, hilar adenopathy was detected on the lateral chest radiograph only in 36 (12%) and 14 (9%) cases respectively. Lateral chest radiographs will considerably improve the accuracy of the diagnosis of childhood tuberculosis.

Child↗

Sero diagnosis of tuberculosis in children using two ELISA kits.

The diagnosis of childhood tuberculosis is based on circumstantial evidence in the absence of a gold standard in the majority of cases. Sero-diagnosis offers scope for an early diagnosis in a variety of clinical conditions and is simple to perform. A number of mycobacterial antigens have been used for antibody detection assays and several are available as kits in the market. This study was done to evaluate the value of antibody detection kits (ELISA) against the A60 antigen and 38 kDa antigen of Mycobacterium tuberculosis in the diagnosis of childhood tuberculosis at the outpatient department of the Institute of Social Paediatrics, Government Stanley Hospital in collaboration with Tuberculosis Research Centre, Chennai. Thirty five children with pulmonary tuberculosis, 7 with TB lymphadenitis and 22 healthy controls were studied. In addition to routine investigations including gastric lavage for AFB culture, serum antibodies against the A60 and 38 kDa antigens were assayed using commercially available ELISA kits. With A60, IgM serum levels were positive in 74% of pulmonary TB cases, 57% of TB lymphadenitis cases and 50% of controls. A60 IgG was positive in 17% of pulmonary TB, 86% of TB lymphadenitis and 14% of controls. The 38 kDa IgG antibody was positive in 37% of pulmonary and 86% of TB lymphadenitis cases and 27% of controls. Among 10 culture confirmed cases, A60 IgM was positive in 8, A60 IgG in 3 and 38 kDa IgG in 5 patients. The sensitivity of the tests ranged between 29% and 71% and specificity between 50% and 86%. Although the numbers are small, the results suggest that serodiagnosis using the currently available antigens of M. tuberculosis is unlikely to be a confirmatory test for tuberculosis in children.

Child↗