Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pilot Roll Out of the Xpert MTB/Rif for the Diagnosis of Pulmonary Tuberculosis in Two Municipalities in Brazil: a Stepped Wedge Trial
Brief Summary: Diagnosis of tuberculosis (TB) is a challenge because sputum smear, the most rapid and inexpensive test, often fails to detect the disease, in around 20 to 30% of cases. Culture of sputum yields a correct diagnosis in up to 90% of cases, but results are only available in 4 to 8 weeks, depending on the method. A new test (Xpert MTB/Rif) based on a rapid technique, named polymerase chain reaction (PCR), detects TB in less than 2 hours over 95% of cases, in addition to identification of cases resistant to certain drugs used to treat TB. The test is expensive, but several studies have demonstrated its accuracy, and since most steps are automatized, savings can be expected from human resources work. The aims of our study are (1) to evaluate this tool as a substitute test for sputum smears in routine conditions; (2) evaluate if it is cost-effective, meaning that effectiveness of the test may outweigh the extra cost, and (3) evaluate the acceptability of the test among patients and health care workers.


Options:
A: Inclusion Criteria:

* Aged ≤ 12 years old (reported)
* HIV-1 positive (for example, two rapid HIV-1 antibody tests for children \>18 months and not breastfeeding, or one HIV-1 DNA/RNA test for children ≤18 months or who are breastfeeding)
* Not currently receiving antiretroviral therapy (history of pMTCT does not affect eligibility)
* Eligible to receive ART, according to current WHO guidelines
* Caregiver plans to reside in study catchment area for at least 6 months (reported)
* Caregiver provides sufficient locator information

Exclusion Criteria:

* Suspected meningitis, any other central nervous system infection, or encephalitis
B: Inclusion criteria:

1. Children aged 2 to 59 months
2. Newly hospitalized for severe pneumonia defined using WHO criteria as cough or difficulty in breathing with:

   1. Peripheral oxygen saturation \< 90% or central cyanosis, or
   2. Severe respiratory distress (e.g. grunting, nasal flaring, very severe chest indrawing), or
   3. Signs of pneumonia, defined as cough or difficulty in breathing with fast breathing (tachypnea) and/or chest indrawing, with any of the following danger signs:

      * Inability to breastfeed or drink,
      * Persistent vomiting
      * Lethargy or reduced level of consciousness
      * Convulsions,
      * Stridor in calm child
      * Severe malnutrition
3. Informed consent signed by parent/guardian

Exclusion criteria:

- Ongoing TB treatment or history of intake of anti-TB drugs in the last 6 months
C: Inclusion Criteria:

* Age ≥18 years;
* HIV-1 infection as documented at any time prior to trial entry, as per national testing procedures;
* CD4 \<100 cells/mm3;
* No history of antiretroviral drug use (except transient ART for PMTCT);
* Able to correctly understand the trial and to sign the informed consent.

Exclusion Criteria:

* HIV-2 co-infection;
* Contra-indication to efavirenz;
* Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>5 times the upper limit of normal;
* Creatinine clearance \<50 ml/min;
* Overt evidence that TB treatment should be started immediately;
* History of TB treatment in the past 5 years;
* Ongoing TB chemoprophylaxis (isoniazid preventive therapy);
* Any condition that would lead to differ ART initiation (e.g. acute condition requiring investigations and/or treatment prior to ART initiation);
* Current pregnancy or breastfeeding.
D: Inclusion Criteria:

laboratories -and not subjects - will be randomized. All laboratories will start doing smears, when indicated by randomization, they will switch to Xpert MTB/Rif. There are no inclusion or exclusion criteria for the labs. Sputum specimens from non-diagnostic (follow up) patients, second samples for diagnostic tests, insufficient volume/visible blood specimens will be excluded from the Xpert testing.

Answer: D