Neil W. Schluger

Treatment of multidrug-resistant pulmonary tuberculosis with interferon-γ via aerosol

Summary Background Multidrug-resistant tuberculosis (MDR-TB) is associated with substantial morbidity, despite drug therapy. Interferon-γ, a cytokine produced mainly by CD4 T lymphocytes, can activate alveolar macrophages, important effector cells in host immunity against Mycobacterium tuberculosis . We investigated safety and tolerability of aerosolised interferon-γ in patients with MDR-TB, and assessed its efficacy in terms of sputum-smear grades. Methods We did an open-label trial of aerosol interferon-γ given to five patients with smears and cultures positive for pulmonary MDR-TB, despite documented adherence to therapy. The patients received aerosol interferon-γ 500 μg three times a week for 1 month. Safety and tolerability were assessed, and, as well as routine clinical assessments, sputum samples for smear and culture were collected at entry and weekly. Computed tomography scans of the chest were done at baseline and after therapy ended. Findings Interferon-γ was well tolerated by all patients. In all five, bodyweight stabilised or increased. Sputum acid-fast-bacillus smears became negative in all patients, and the time to positive culture increased (from 17 to 24 days, not significant), which suggested that the mycobacterial burden had decreased. The size of cavitary lesions was reduced in all patients, 2 months after treatment had ended. Interpretation Preliminary data suggest that aerosol interferon-γ is a well-tolerated treatment that may be useful as adjunctive therapy in patients with MDR-TB who are otherwise not responding well to therapy.

Peripheral-blood-based PCR assay to identify patients with active pulmonary tuberculosis

BACKGROUNDnThere is a need for rapid diagnosis of pulmonary tuberculosis. We have previously used a PCR to detect circulating Mycobacterium tuberculosis DNA in blood samples from patients (mostly HIV-infected) with pulmonary tuberculosis. We have now prospectively investigated the role of this blood-based PCR assay for diagnosis of this disease in a clinical setting.nnnMETHODSnOur PCR assay is specific for the IS6110 insertion element of the M tuberculosis complex of organisms. We used it to test peripheral blood from 88 consecutive patients admitted to a chest ward with suspected pulmonary tuberculosis. Personnel who carried out the assay did not know the results of any clinical investigations and ultimate diagnosis, and clinicians did not know the PCR results. Results of the PCR assay were compared with the final clinical diagnosis. A subgroup of 15 patients had blood samples assayed serially to track the PCR signal over time.nnnFINDINGSn41 patients had a final clinical diagnosis of tuberculosis, and the cases were typical of those seen at our hospital: HIV infection was common, and most cases were not sputum-smear positive for acid-fast bacilli. The PCR assay correctly identified 39 of 41 patients with proven pulmonary tuberculosis, 26 (63%) of whom were sputum-smear negative. There were five patients in whom a positive PCR result did not accord with the final clinical diagnosis, and two of the 44 negative PCR results were classified as false negatives. The overall sensitivity and specificity of the PCR assay for a diagnosis of tuberculosis was 95% and 89%, respectively. In 15 patients with pulmonary tuberculosis and a positive blood assay,the PCR result remained positive after 1 month of therapy, but had reverted to negative in 13 of the 15 by 4 months of therapy.nnnINTERPRETATIONnWe conclude that peripheral-blood-based PCR detection for the diagnosis of tuberculosis is a technically feasible approach that has a potentially important role in the diagnosis of pulmonary tuberculosis.

Amplification of DNA of Mycobacterium tuberculosis from peripheral blood of patients with pulmonary tuberculosis

Sputum examination for rapid diagnosis of pulmonary tuberculosis is not always satisfactory. We examined peripheral blood with the polymerase chain reaction (PCR). Blood samples were collected from 8 consecutive patients with suspected pulmonary tuberculosis and from 18 healthy controls, half of whom were tuberculin skin-test positive. All 8 patients had evidence of circulating Mycobacterium tuberculosis DNA in the lymphocyte fraction of peripheral blood, and positive sputum cultures indicating active pulmonary tuberculosis. None of the healthy controls had positive PCR results. This PCR technique may prove useful for the rapid diagnosis of tuberculosis.

EARLY RESPONSES TO INFECTION : CHEMOKINES AS MEDIATORS OF INFLAMMATION

Chemokines are a superfamily of small related protein molecules that are secreted by a variety of cells and that have, among their diverse biological properties, the ability to recruit a wide range of immune cells to the sites of infection and disease. Chemokines are secreted in response to bacterial, viral, parasitic, and mycobacterial pathogens. Our recent progress in understanding the patterns of chemokine secretion in response to various pathogens and their impact on disease manifestations is likely to lead to the development of novel therapeutic approaches for a variety of serious infections.

Spinal tuberculosis in patients with human immunodeficiency virus infection: Clinical presentation, therapy and outcome

SETTINGnBellevue Hospital, a large public hospital in New York City.nnnOBJECTIVEnTo discern the clinical characteristics of spinal tuberculosis (Potts disease) in patients with the human immunodeficiency virus (HIV).nnnDESIGNnReview of all cases of spinal tuberculosis seen at the hospital from 1988 to 1995, with comparison of HIV-positive and HIV-negative cases. Chart reviews for all cases were performed and information regarding signs and symptoms, neurological findings, laboratory and radiographic data, medical and surgical treatment and eventual outcome were recorded.nnnRESULTSnWe collected 26 cases of tuberculosis of the spine between July 1988 and June 1995. Seven of our 26 patients (27%) were HIV seropositive. Six of these were PPD+ on presentation. When compared with HIV-negative patients, those with HIV and spinal tuberculosis had similar clinical presentations; most patients had a diagnosis made with percutaneous needle aspiration biopsy of clinically involved areas, and open procedures added little diagnostic information. Most were treated without surgery, and response to antituberculosis therapy was uniformly good.nnnCONCLUSIONnWe conclude that clinical presentations of spinal tuberculosis are similar in HIV-positive and -negative patients, and good outcomes can be expected with regard to mycobacterial disease.