John L. Johnson

OBJECTIVE: Controlled trials have failed to show an effect of Mycobacterium vaccae immunotherapy on treatment outcome and mortality in patients with tuberculosis (TB); however, several studies have suggested improvement in radiographic clearing and resolution of cavitary disease. METHODS: To assess the effect of M. vaccae immunotherapy on radiographic healing in pulmonary TB, chest X-rays from three randomized placebo-controlled trials of M. vaccae given as a single injection during the first 2 weeks of treatment were interpreted by a single, masked assessor using a standard scheme. Endpoints were the overall degree of radiographic improvement or deterioration and changes in cavitary disease at the end of anti-tuberculosis treatment and follow-up. RESULTS: Of 1018 patients (478 HIV-infected; 540 HIV-uninfected) with an end of treatment or end of follow-up X-ray analyzed, 496 received M. vaccae and 522 received placebo. There was no difference in radiographic improvement or deterioration or cavitary disease at the end of treatment or follow-up comparing the M. vaccae and placebo groups. Results were similar comparing HIV-infected and HIV-uninfected patients. CONCLUSION: Adjunctive immunotherapy of drug-susceptible pulmonary TB with M. vaccae during the first 2 weeks of treatment did not improve radiographic responses to treatment or resolution of cavitary disease.

Interleukin (IL)-2 has a central role in regulating T cell responses to Mycobacterium tuberculosis. Adjunctive immunotherapy with recombinant human IL-2 was studied in a randomized, placebo-controlled, double-blinded trial in 110 human immunodeficiency virus–seronegative adults in whom smear-positive, drug-susceptible pulmonary tuberculosis was newly diagnosed. Patients were randomly assigned to receive twice-daily injections of 225, 000 IU of IL-2 or placebo for the first 30 days of treatment in addition to standard chemotherapy. Subjects were followed for 1 year. The primary endpoint was the proportion of patients with sputum culture conversion after 1 and 2 months of treatment. After 1 month, the proportion of patients for whom sputum culture converted to negative was 17% for the IL-2 group compared with 30% in the control group (p = 0.14; χ2). After 2 months, 77% in the IL-2 group were culture negative compared with 85% of those receiving placebo (p = 0.29, χ2). Results were similar when patients with isoniazid monoresistance were included in the analysis. There were no differences in weight gain and no improvement in fever, cough, and chest pain between groups. One patient in each arm relapsed. IL-2 did not enhance bacillary clearance or improvement in symptoms in human immunodeficiency virus–seronegative adults with drug-susceptible tuberculosis.

Gross aspiration of liquid or particulate matter into the lung can result in severe hypoxemia, pulmonary infiltrates in dependent lung regions, fever, and leukocytosis. The initial lung injury is primarily due to inflammatory mediators rather than infection. The responsible bacterial pathogens differ between community-acquired and nosocomial aspiration pneumonia. Many aspiration pneumonias are mixed aerobic-anaerobic infections. Enteric gram-negative bacilli and S aureus are more common in nosocomial aspiration pneumonia. Current treatment guidelines support initial empirical antibiotic therapy in patients with severe aspiration pneumonia pending culture results. Appropriate initial treatment improves outcome. Antimicrobial therapy for aspiration pneumonia is often empirical and should be based on patient characteristics, the setting in which aspiration occurred, the severity of pneumonia, and available information regarding local pathogens and resistance patterns.

Hemoptysis is a frightening symptom for patients and often is a manifestation of significant underlying disease. The chest radiograph, history and examination findings, comorbid illnesses, and demographic factors guide evaluation of patients with minor hemoptysis. Massive hemoptysis occurs in less than 5% of patients with hemoptysis and is almost always due to serious pulmonary or systemic illness. Massive hemoptysis is a life-threatening event that requires ICU admission and urgent bronchoscopic evaluation for lateralization or localization of the bleeding site. Management should be individualized and requires prompt consultation with appropriate cardiothoracic surgery, pulmonary medicine, anesthesia, and interventional radiology staff. The availability of endobronchial techniques and bronchial arterial embolization has enhanced our ability to control massive bleeding short-term and decreased the need for emergency surgical treatment. Massive hemoptysis may recur without warning. Prompt workup and treatment are required for all patients.

Tuberculosis is responsible for more female deaths around the earth than any other infectious disease. Reports have suggested that responses to tuberculosis may differ between men and women. We investigated gender related differences in the presentation and one year outcomes of HIV-infected adults with initial episodes of pulmonary tuberculosis in Uganda. We enrolled and followed up a cohort of 105 male and 109 female HIV-infected adults on treatment for initial episodes of culture-confirmed pulmonary tuberculosis between March 1993 and March 1995. A favorable outcome was defined as being cured and alive at one year while an unfavorable outcome was not being cured or dead. Subjects were followed-up by serial medical examinations, complete blood counts, serum β2 microglobulin, CD4+ cell counts, sputum examinations, and chest x-rays. Male patients were older, had higher body mass indices, and lower serum β2 microglobulin levels than female patients at presentation. At one year, there was no difference between male and female patients in the likelihood of experiencing a favorable outcome (RR 1.02, 95% CI 0.89–1.17). This effect persisted after controlling for symptoms, serum β2 microglobulin, CD4+ cell count, and severity of disease on chest x-ray (OR 1.07, 95% CI 0.54–2.13) with a repeated measures model. While differences existed between males and females with HIV-associated pulmonary tuberculosis at presentation, the outcomes at one year after the initiation of tuberculosis treatment were similar in Uganda. Women in areas with a high HIV and tuberculosis prevalence should be encouraged to present for screening at the first sign of tuberculosis symptoms.

National Tuberculosis Treatment Centre, Mulago Hospital, Kampala, Uganda. To assess the efficacy of a daily, self-administered 8-month rifampicin-containing regimen for the treatment of pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV) infected adults. Treatment outcomes in patients with pulmonary TB treated with a single 8-month regimen and followed in a prospective epidemiological study. Two hundred and sixty-five HIV-infected and 26 non-HIV-infected adults with initial episodes of pulmonary tuberculosis were treated with 2 months of daily isoniazid (INH), rifampicin (RMP), ethambutol and pyrazinamide followed by 6 months of daily INH + RMP. Median follow-up was 17.8 months. Ninety-five per cent of the HIV-infected and all of the non-HIV-infected patients who had sputum examined were sputum culture negative after 2 months of treatment. Twenty-two HIV-infected and no non-HIV-infected patients died during treatment. Relapse rates were 8.4% (5.9 per 100 person-years of observation [PYO], 95%CI 3.2-8.6) among HIV-infected patients and 4.5% (2.1/100 PYO, 95%CI 0-7.8) for non-HIV-infected patients. Adverse drug reactions occurred in 37% of the HIV-infected patients; most were minor and self-limiting. An 8-month RMP-containing regimen was well tolerated and effective in the treatment of HIV-infected adults with initial episodes of pulmonary TB. Relapse rates were similar to those reported with 6-month short-course regimens in HIV-infected individuals. Decisions about the duration of anti-tuberculosis treatment for HIV-infected adults must balance programme resources and the likelihood of poor compliance with longer regimens with the potential for a modest decrease in relapses with longer treatment.

What is the proper course of action when pneumonia symptoms seem to linger? Is the disease running a typical course, or is further evaluation needed? Dr Johnson addresses these important questions with an outline of risk factors for delayed resolution and a detailed listing of diagnostic considerations. He also discusses reasonable timing of further studies and the usefulness of radiography and fiberoptic bronchoscopy.

Tuberculosis is currently an enormous global health problem. In industrialized countries in Western Europe and North America, tuberculosis case rates are low and an increasing proportion of cases now occur in foreign-born individuals and in marginalized populations, including the homeless, prisoners, drug users, and persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). In contrast, the burden of tuberculosis in sub-Saharan Africa continues to grow, largely fueled by the HIV pandemic and poor public health infrastructure. Use of the World Health Organization’s (WHO) directly observed therapy, short course (DOTS) strategy has been successful in improving outcomes and preventing the emergence of acquired drug resistance in several African countries; however, case rates are increasing throughout most of the region. It is clear that control of tuberculosis in Africa is closely linked to control of HIV and AIDS. Substantial external donor support and innovative approaches to enhance interactions between HIV/AIDS prevention and treatment efforts and tuberculosis control programs will be needed to improve the current tuberculosis situation in Africa. The purpose of this review is to provide a synopsis of recent developments in these areas and to serve as a reference source for interested readers.

Adjunctive immunotherapy with heat-killed Mycobacterium vaccae was studied in a randomized, placebo-controlled trial of 120 non-human immunodeficienc