Reduced sensitivity of tuberculosis serodiagnosis in patients with AIDS in Uganda

Daniel, Thomas M.; Sippola, A A; Okwera, Alphonse; Kabengera, Sam; Hatanga, E.; Aisu, T.; Nyole, Sam; Byekwaso, F.; Vjecha, Michael J.; Ferguson, Lavenia E.; Kataaha, Peter; Mugerwa, Roy D.

doi:10.1016/0962-8479(94)90099-x

Cited by 26 publications

(11 citation statements)

References 10 publications

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“…However, the percent positivity of antibody detection for the HIV-infected tuberculous patient population is lower than that for the entire tuberculous patient population (Table 1 and Table 2). These findings were similar to those presented in other reports, in which the sensitivity dropped from 62% for non-HIV-infected tuberculous patients to 28% for HIV-infected tuberculous patients (14). It has been reported that no antibody is detected by an immunochromatographic test (ICT) for tuberculosis in any of the serum samples of HIV-infected patients coinfected with M. tuberculosis or mycobacteria other than M. tuberculosis (30).…”

Section: Discussionsupporting

confidence: 79%

Evaluation of an In-House-Developed Radioassay Kit for Antibody Detection in Cases of Pulmonary Tuberculosis and Tuberculous Meningitis

Kameswaran

Shetty

Ray

et al. 2002

Clin Vaccine Immunol

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A radioassay for the detection of antitubercular antibody has been developed. The technique involves the addition of 125 I-labeled Mycobacterium tuberculosis antigen as a tracer, diluted clinical sample (serum or cerebrospinal fluid [CSF]), and heat-inactivated Staphylococcus aureus to capture the antibody, incubation for 4 h, and quantitation of the amount of antibody present in the sample. A total of 330 serum samples from patients with pulmonary tuberculosis and 138 control serum samples from individuals who were vaccinated with M. bovis BCG and from patients with pulmonary disorders of nontubercular origin were analyzed. Also, 26 CSF samples from patients with tuberculous meningitis and 24 CSF samples as controls from patients with central nervous system disorders of nontuberculous origin were analyzed. Sensitivities of 80 and 73% were observed for patients with pulmonary tuberculosis and tuberculous meningitis, respectively, and specificities of 90 and 88% were seen for the two groups of patients, respectively. The sensitivity was lower, however, for human immunodeficiency virus-infected patients coinfected with M. tuberculosis. The control population could be differentiated from the patient population. This assay is rapid and user friendly and, with its good sensitivity and specificity, should benefit the population by providing diagnoses early in the course of disease and, hence, permit the early administration of appropriate chemotherapy.Tuberculosis, caused by Mycobacterium tuberculosis, represents a major health problem worldwide. It is estimated that almost one-third of the entire world's population is exposed to this disease (26). In 1993, the World Health Organization declared tuberculosis a global emergency and estimated that by the start of the new millennium there would be more than 1 billion newly infected individuals and more than 17 million deaths due to this disease if control programs were not implemented properly. These control programs are dependent on good tests for early diagnosis, constant monitoring of disease status, and response to and completion of treatment.The diagnosis of tuberculosis has never been simple, especially in children and in patients with extrapulmonary tuberculosis, from whom clinical specimens for microscopy and culture are not easily obtained. Even in patients with pulmonary tuberculosis, diagnosis by microscopy is rather insensitive and culture is time-consuming.Since the mid-1970s radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) techniques have been developed for the detection of M. tuberculosis antigen and anti-M. tuberculosis antibody from clinical specimens, and these assays have various degrees of sensitivity and specificity (1, 2, 4, 7, 8, 13, 21-25, 28, 36-39, 41, 43). Almost all the assays developed at the Laboratory Nuclear Medicine Section of the Bhabha Atomic Research Centre require the detection of both antigen and antibody from clinical samples (1, 2, 21-23, 36-38). With the incidence of tuberculosis being on the rise and with the added...

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Section: Discussionsupporting

confidence: 79%

Evaluation of an In-House-Developed Radioassay Kit for Antibody Detection in Cases of Pulmonary Tuberculosis and Tuberculous Meningitis

Kameswaran

Shetty

Ray

et al. 2002

Clin Vaccine Immunol

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“…The specificities provided by all of the above antigens were high (range, 89% to 100%). However, only 6 (20%) studies involved controls with nontuberculous respiratory disease (23,35,37), while 14 (47%) studies involved either healthy volunteers or asymptomatic HIV-infected individuals without TB (35,37,103,108). In 10 (33%) studies, the control group involved HIV-infected individuals whose clinical status ranged from asymptomatic to symptomatic with opportunistic infections other than TB (69).…”

Section: Resultsmentioning

confidence: 99%

“…Thirty studies evaluating antigens (all proteins) in HIV-infected TB patients were identified; all studies involved sputum smear-positive patients. Of the total, 23 (77%) studies evaluated assays for the detection of IgG and/or IgA antibodies (23,35,37,69,103,108), four studies evaluated assays for the detection of IgM (69,103). Four studies based on multiple-antigen combinations are described in more detail below (35,37,108).…”

Section: Resultsmentioning

confidence: 99%

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Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

Steingart

Dendukuri

Henry

et al. 2009

Clin Vaccine Immunol

170

137

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The failure to diagnose tuberculosis (TB) accurately and rapidly is a key challenge in curbing the epidemic (45,88,116). Sputum microscopy, currently the sole diagnostic test in most areas where TB is endemic, has several limitations; in particular, the sensitivity compared with that of culture is variable (80,97,104,116), multiple patient visits are required (56,93,114), considerable technical training is necessary, and the procedure is labor-intensive (45, 65). Antibody detection tests (serological tests) are used for the diagnosis of many infectious diseases and could potentially improve the means of diagnosis of TB. These tests measure the presence of specific antibodies (most often immunoglobulin G [IgG]) directed against immunodominant antigens of the pathogen in question. Compared with microscopy, antibody detection methods may enable the rapid diagnosis of TB, as these tests have the advantages of speed (results can be available within hours), technological simplicity, and minimal training requirements. In addition, these tests can be adapted to point-of-care formats that can be implemented at lower levels of health services in low-and middle-income countries (21,22,57,65).Efforts to develop antibody detection tests for the diagnosis of TB have been under way for decades, and the performance of these tests has been well described (13,17,22,32,40,47,48,52,60,64,100,107). Several systematic reviews of these tests have been published (discussed below) (28,94,95).First-generation antibody detection tests were based on crude mixtures of constituents and products of Mycobacterium tuberculosis, for example, culture filtrate proteins and purified protein derivative, the preparation used in the tuberculin skin test. Several of these early tests had low specificities, as the tests contained antigens shared among different bacterial species (1,22,48,57). During the past two decades, an increased understanding of humoral immune responses to M. tuberculosis and the new tools of

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“…TB9.7 is frequently recognized by TB patients coinfected with HIV. A large proportion of TB patients are coinfected with HIV, and it has been reported that HIV-positive patients generally have lower levels of M. tuberculosis-specific antibodies than HIV-negative patients (13). The sensitivities obtained with TB16.3, TB9.7, TB15.3, and TB51 were therefore compared with samples from HIV-negative and HIV-positive TB patients (Table 5).…”

Section: Resultsmentioning

confidence: 99%

Assessing the Serodiagnostic Potential of 35 Mycobacterium tuberculosis Proteins and Identification of Four Novel Serological Antigens

et al. 2005

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Improved diagnostic reagents are needed for the detection of Mycobacterium tuberculosis infections, and the development of a serodiagnostic test would complement presently available diagnostic methods. The aim of the present study was to identify novel serological targets for use for the future serodiagnosis of tuberculosis (TB). We cloned and expressed 35 M. tuberculosis proteins as recombinant proteins in Escherichia coli and analyzed their serodiagnostic potentials. By a two-step selection process, four superior seroantigens, TB9.7, TB15.3, TB16.3, and TB51, were identified, none of which has been described before. The four novel antigens were tested with panels of sera from smear-positive and smear-negative TB patients from areas both where TB is endemic and where TB is not endemic, with recognition frequencies ranging from 31 to 93% and with a specificity of at least 97%. The single most potent antigen was TB16.3, which had a sensitivity of 48 to 55% with samples from Danish resident TB patients and a sensitivity of 88 to 98% with samples from African TB patients. Importantly, the TB16.3 and the TB9.7 antigens were recognized by more than 85% of the samples from TB patients coinfected with human immunodeficiency virus, a patient group for which it is in general difficult to detect M. tuberculosis-specific antibodies.Approximately one-third of the world's population is infected with Mycobacterium tuberculosis, and 7 million to 8 million new cases of tuberculosis (TB) occur each year (49). The majority of TB cases occur in developing countries with limited resources, and today, the diagnosis of TB largely depends upon clinical examination and radiographic findings, confirmed by sputum smear microscopy and bacterial culture. Culture is not useful as a first-line means of diagnosis due to the long cultivation period required for M. tuberculosis (6 to 8 weeks); therefore, confirmation of the diagnosis relies on sputum smear examinations. However, smear microscopy has a sensitivity of only 50 to 60%, and the detection rate in children and patients coinfected with human immunodeficiency virus (HIV) is even lower (for a review, see reference 41).To improve the diagnosis of TB, more rapid diagnostic techniques have been investigated in recent years. These methods include the detection of M. tuberculosis components in clinical specimens by PCR and immune reactions, based on the cellmediated immune (CMI) response or on humoral immune responses. The in vitro CMI-based tests allow the early detection of latently infected individuals and are of tremendous value for contact tracing and screening of high-risk groups in a setting of low endemicity (10, 16). However, this method is not suitable as an alternative to culture and microscopy in developing countries, as large proportions of the populations in these countries are likely to be latently infected with M. tuberculosis (24).A serological test is an attractive diagnostic method because it is rapid, easy to perform, and robust and can easily be implemented under the cond...

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Reduced sensitivity of tuberculosis serodiagnosis in patients with AIDS in Uganda

Cited by 26 publications

References 10 publications

Evaluation of an In-House-Developed Radioassay Kit for Antibody Detection in Cases of Pulmonary Tuberculosis and Tuberculous Meningitis

Evaluation of an In-House-Developed Radioassay Kit for Antibody Detection in Cases of Pulmonary Tuberculosis and Tuberculous Meningitis

Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

Assessing the Serodiagnostic Potential of 35 Mycobacterium tuberculosis Proteins and Identification of Four Novel Serological Antigens

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