Rapid Diagnosis of Pulmonary Tuberculosis
Rapid Diagnosis of Pulmonary Tuberculosis
The purpose of this study is to test whether a saline nebulization (breathing in a mist of
 moist air through a mask) will help an individual cough up a better sputum sample to test for
 tuberculosis (TB). In addition, this study will test whether samples obtained with saline
 nebulization are better at finding TB in people with HIV infection. The study will enroll up
 to 600 individuals, aged 12 and older, with suspected pulmonary TB. Participants will be
 asked to cough up a sample of sputum into a container. Then, participants will be asked to
 breathe a mist of moist air from an oxygen mask followed by moist salty air, which will help
 individuals to cough up a second sputum sample. This mist of moist air will contain
 salbutamol, a medicine to help open up the airways. The sputum samples will be sent to a
 laboratory to test for TB. Additionally, participants will be tested for HIV with a blood
 sample collection. Participants will be involved in study related procedures for up to 61
 days.
Early case detection, treatment, and prompt household contact investigation, depend on rapid
 microbiological confirmation, by direct smear microscopy of acid-fast bacilli, in patients
 with suspected pulmonary tuberculosis. Since delayed diagnosis may result in death due to
 lack of appropriate therapy, rapid microbiological diagnosis is especially critical in
 HIV-infected persons. Improved rapid diagnostic methods are also crucial for the success of
 epidemiological studies; trials of preventative interventions, such as novel vaccines; and
 therapeutic interventions, since the diagnostic endpoints of such trials may require
 microbiological confirmation of tuberculosis. In clinical practice, early therapeutic
 intervention might reduce the risk of death, especially in patients co-infected with HIV. In
 this study, researchers propose to test a simple diagnostic modality for rapid diagnosis of
 pulmonary tuberculosis in HIV-infected and HIV-uninfected adolescents and adults. Researchers
 will test whether induced sputum will improve the diagnostic yield of smear positive
 tuberculosis. This low-cost technology augments spontaneous sputum production by inhalation
 of a nebulized saline solution. The primary objective of this study is to quantify and
 compare the diagnostic yield of smear positive tuberculosis from induced sputum, with that of
 routine sputum, in HIV-infected patients with suspected tuberculosis. Researchers believe
 that induced sputum will increase the diagnostic yield from direct smear microscopy in this
 patient population. The secondary objective of the study is to quantify and compare the
 diagnostic yield of smear positive tuberculosis from induced sputum, with that of routine
 sputum, in all patients with suspected tuberculosis, regardless of HIV status. Researchers
 believe that induced sputum will increase the diagnostic yield from direct smear microscopy
 in all patients in this population, regardless of HIV status. Approximately 1200 individuals
 (male or female gender), aged 12 years and older, with suspected pulmonary tuberculosis, will
 be screened in order to enroll 600 eligible participants at 2 district health services
 clinics near the town of Worcester, Western Cape Province, South Africa. Informed consent for
 participation will be sought from adolescents and adults with suspected pulmonary
 tuberculosis who present to public sector community health services for investigation. A
 rapid HIV test, with pre- and post-test counseling, will be performed. A routine spontaneous
 expectorated sputum sample and an induced sputum sample (obtained after nebulization of
 sterile 5% saline via mask) will be collected. A second routine sputum will be collected on
 the following morning. Direct smear microscopy and mycobacterial culture of sputum will be
 performed in an accredited microbiology laboratory. HIV rapid test results will be used to
 classify participants for evaluation of the primary outcome, positive direct smear
 microscopy, and the secondary outcome, positive culture of M. tuberculosis. Diagnostic yields
 for each routine and induced sputum sample will be calculated, as a proportion of all
 patients who are culture-positive for M. tuberculosis, and compared in a pair-wise and
 sequential manner. Results will be reported as differences in yield and 95% confidence
 intervals for the difference in those proportions. The primary endpoint will be sputum direct
 smear microscopy positive for acid-fast bacilli. The secondary endpoint will be sputum
 culture positive for Mycobacterium tuberculosis. Study duration will be 4 years with
 individual subject participation approximately 8 weeks.
Inclusion Criteria:

 Adolescents and adults with suspected pulmonary tuberculosis who are referred, or
 self-refer, to health services clinics for investigation for tuberculosis, will be eligible
 to participate.

 Exclusion Criteria:

 -  Failure to obtain informed consent (including failure to consent for either sputum
 collection procedures or failure to consent for HIV testing);

 -  Age less than 12 years;

 -  A history of asthma;

 -  A history of heart disease;

 -  A history of cardiac arrhythmia;

 -  Inability to tolerate sputum induction procedures;

 -  Inability to return for study follow-up visit;

 -  Need for hospital-based in-patient treatment or supplemental oxygen therapy;

 -  Other acute or chronic lung disease that may compromise lung function;

 -  Current anti-tuberculous therapy.