No abstract

SummaryThe impact of intestinal helminth infection on Mycobacterium tuberculosis (MTB)-specific immune responses during active tuberculosis (TB) is not known. We investigated the role of intestinal helminth infection in anti-MTB immunity by evaluating both cellular phenotype and cytokine profiles in patients with TB and patients with concomitant TB and intestinal helminth infection (TB + Helm) during TB therapy. Twenty-seven per cent of TB patients enrolled for the study were co-infected with at least one intestinal helminth. At baseline, absolute frequencies of leucocytes, monocytes and eosinophils from TB and TB + Helm patients differed from healthy subjects. Concomitant intestinal helminth infection in TB + Helm patients had a negative impact (P < 0·05) on absolute frequencies of CD3 + , CD4 natural killer (NK) T and CD4+ CD25 high T cell subsets when compared to either TB patients or healthy controls. Differences in CD4 + T cell frequencies were accompanied by lower interferon (IFN)-g and elevated and sustained interleukin (IL)-10 levels in whole blood (WB) cultures from TB + Helm compared to TB patients. In addition to a depressed anti-MTB immunity, TB + Helm patients also presented with more severe radiological pulmonary disease, with a significant difference (P = 0·013) in the number of involved lung zones at the end of TB treatment. The above data may indicate that concomitant intestinal helminth infection in patients with newly diagnosed TB skews their cytokine profile toward a T helper 2 response, which could favour persistent MTB infection and a more protracted clinical course of the disease.

Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-␥) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-␥ levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-␥ levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-␥ immunoreactivities in serum followed kinetics in sputum. TNF-␣, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-␥, however, TNF-␣ and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.Despite efforts to improve diagnosis and treatment, tuberculosis (TB) remains a major health problem worldwide, especially in developing countries. Obstacles to TB control include the long duration of therapy and the lack of concrete markers indicating success or failure of treatment early during the course of active disease.Sputum culture conversion following 8 weeks of treatment has been used as a surrogate of response to antituberculous chemotherapy (16). However, cultures require up to 6 weeks to perform and, therefore, are not ideally suited for real-time assessment of response to treatment. By contrast, assessment of immunological parameters in biological fluids can be accomplished within days of sample collection and, if validated as a surrogate marker, may be particularly useful in settings where the activity of short-term administration of new drugs (early bactericidal activity studies) or of immunoadjuvants to standard anti-TB therapy is tested. Further, identifying immunological parameters that correlate with culture sterilization may provide important information about host factors most relevant to anti-Mycobacterium tuberculosis (MTB) immunity.Since TB predominantly affects the lung, assessment of specimens recovered from this site may best reflect the interaction between the host and MTB during active disease. Fiber optic bronchoscopy and bronchoalveolar lavage (BAL) has been used to assess anti-MTB immunity in situ (18,19). However, this invasive technique cannot be applied serially during treatment. As a result we investigated alternative approaches for evaluating anti-MTB immune responses ...

A ligase chain reaction DNA amplification method for direct detection of Mycobacterium tuberculosis (Abbott LCx MTB) in respiratory specimens was evaluated. Results from LCx MTB Assay were compared with those from acid fast bacilli smear, culture, and final clinical diagnosis for each patient. A total of 297 respiratory specimens (sputum and bronchial lavage) from 193 patients were tested. The sensitivity, specificity, positive predictive value and negative predictive value of LCx vs culture were 92.7%, 93%, 67.8% and 98.7%, respectively. When compared to the clinical final diagnosis, the sensitivity, specificity, PPV and NPV for LCx were 88.9%, 96.8%, 86.5% and 97.4%, respectively. The sensitivity of LCx MTB assay was 75% for smear-negative, culture positive samples. The results indicate that LCx MTB assay is a rapid, simple and valuable technique as a complementary tool for the diagnosis of tuberculosis.