Two billion people are infected with Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), worldwide. Ten million to 20 million of the infected individuals develop disease per year. TB is a treatable disease, provided that it is diagnosed in a timely manner. The current TB diagnostic methods are subjective, inefficient, or not cost-effective. Antibody-based blood tests can be used efficiently and cost-effectively for TB diagnosis. A major challenge is that different TB patients generate antibodies against different antigens. Therefore, a multiplex immunoassay approach is needed. We have developed a multiplex panel of 28 M. tuberculosis antigen-coated microbeads. Plasma samples were obtained from over 300 pulmonary TB patients and healthy controls in a country where TB is endemic, Pakistan. Multiplex data were analyzed using computational tools by multivariate statistics, classification algorithms, and cluster analysis. The results of antibody profile-based detection, using 16 selected antigens, closely correlated with those of the sputum-based diagnostic methods (smear microscopy and culture) practiced in countries where TB is endemic. Multiplex microbead immunoassay had a sensitivity and specificity of approximately 90% and 80%, respectively. These antibody profiles could potentially be useful for the diagnosis of nonpulmonary TB, which accounts for approximately 20% of cases of disease. Since an automated, high-throughput version of this multiplex microbead immunoassay could analyze thousands of samples per day, it may be useful for the diagnosis of TB in millions of patients worldwide.More than one-third of the world's population is infected with Mycobacterium tuberculosis (7, 26a). Annually, 10 million to 20 million of these individuals develop clinical symptoms, and about 2 million die of tuberculosis (TB) (4, 17a). The infected host typically mounts a vigorous immune response (25). Nevertheless, 10% of all infections result in active disease within 2 years. Another 10% of cases may experience disease after a latent phase spanning many years (8, 17a). Several Mycobacterium species (e.g., M. tuberculosis, M. bovis, and M. africanum) can infect and cause disease in humans (2, 24). In about 80% of active TB cases, direct involvement of the lung results in pulmonary disease (4a). However, M. tuberculosis can spread to other organs. In approximately 20% of cases, M. tuberculosis may cause nonpulmonary disease in various organ systems (urogenital system, nervous system, digestive system, skeletal system, etc.) with or without the lung involvement (7,18). TB is a treatable disease, provided that a timely and appropriate diagnosis is made (4a). Commonly used sputumbased methods for pulmonary TB diagnosis are subjective, insensitive, and/or inefficient. Furthermore, for the detection of pediatric pulmonary TB, a major limitation is that children often have difficulty producing usable quantities of sputum.Sputum smear acid-fast bacillus (AFB) microscopy is recommended by the World Health Organizatio...

BackgroundDelay in diagnosis and treatment of tuberculosis (TB) may enhance the chances of morbidity and mortality and play a key role in continuous transmission of the bacilli. The objective of this study was to describe health care seeking behavior of suspected TB patients and initial diagnostic work up prior to consultation and diagnosis at National TB Center (NTC).FindingsInterviews of 252 sputum smear positive patients were taken from NTC, Rawalpindi. The duration between on-set of symptoms and start of treatment was considered as the total delay and correlated with general characteristics of TB patients. The proportion of males and females were 49.6% and 50.4% with median age of 25 and 24 years respectively. A median delay of 56 days (8 weeks) was observed which was significantly associated with age, cough and fever. More than 50% of the current patients had a history of contact with previously diagnosed TB patients. The majority of patients (63%) visited health care providers within three weeks of appearance of symptoms but only thirty five percent were investigated for TB diagnosis.ConclusionCough and fever are being ignored as likely symptoms of TB by patients as well as health care providers resulting in delay. Engaging private practitioners through public private mix (PPM) approach for expansion of TB diagnosis and increasing public awareness could be more beneficial to reduce delay.