Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients

Inclusion Criteria: INDEX CASE * Men and women age greater than or equal to 18 years. * Pulmonary MDR-TB defined as: * Confirmation of rifampin/rifampicin (RIF) resistance and INH resistance by * adequate source documentation (including date of testing, test methodology, and test results) of RIF and INH resistance from a licensed/nationally approved\* referral program, OR * if either or both results are unknown or not adequately documented (as noted above), then confirmation must be obtained using a DAIDS-approved laboratory that operates according to Good Clinical Laboratory Practices (GCLP) guidelines and participates in an appropriate external quality assurance (EQA) program. * \*NOTE: The term "licensed/nationally approved" refers to a laboratory that has been certified or licensed by an oversight body within that country and approved for RIF and/or INH resistance testing. * NOTE: Pre-XDR and XDR TB are not exclusionary. See the A5300B/I2003B/PHOENIx MOPS for study-approved molecular and phenotypic methods. * Started MDR-TB treatment within the past 90 days. * Ability and willingness of the index case to provide informed consent to access the HH and approach HH members for evaluation. * HH of index case has at least one reported HHC. HOUSEHOLD CONTACTS If any member(s) of the HH is/are not eligible or do not want to participate, all other eligible TB contacts within the HH can still participate. * Currently lives or lived in the same dwelling unit or plot of land and shares or has shared the same housekeeping arrangements as the index case and who reports exposure within 90 days prior to the index case starting MDR-TB treatment. Also, shared greater than 4 hours of indoor airspace with the index case during any one-week period prior to the index case starting MDR-TB treatment. * HHCs must be in one of the following high-risk groups: * All children 0 to less than 5 years old at the time of enrollment, regardless of LTBI or HIV status; * Adults, adolescents, and children greater than or equal to 5 years of age who are LTBI test positive (either TST-positive (greater than or equal to 5 mm) or IGRA-positive), and whose HIV status is negative, indeterminate, or unknown, and who are not non-HIV immunosuppressed; * NOTE: Both TST and IGRA testing are required for screening unless TST testing is not available due to global shortages or in-country supply challenges, but only one positive test is required for eligibility. * Adults, adolescents, and children greater than or equal to 5 years of age who are HIV-infected or are non-HIV immunosuppressed (defined as receiving anti-tumor necrosis factor (TNF) treatment, or being solid organ or hematologic transplant recipients), regardless of LTBI test status. * HIV-1 infection status must be documented as positive, negative, indeterminate or unknown for all HHCs. Unknown status includes those who previously tested HIV negative but the test was performed more than one year ago. HIV testing will be offered to all HHCs with negative of unknown status. For adults (18 years and older), HIV-1 infection must be documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load greater than 1000 copies/mL. Two or more plasma HIV-1 RNA viral loads of greater than 1,000 copies/mL are also acceptable as documentation of HIV infection. More information is available on this criterion in the protocol. * The following specific laboratory values for infants, children, and adults obtained within 30 days prior to study entry by any DAIDS-approved non-US laboratory. * Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm\^3 * Hemoglobin greater than or equal to 7.4 g/dL * Platelet count greater than or equal to 50,000/mm\^3 * Creatinine less than or equal to 2 × upper limit of normal (ULN) * Potassium level greater than or equal to 3.0 mEq/L * Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) less than or equal to 3 × ULN * Total bilirubin less than or equal to 2.5 × ULN (Note: if on atazanavir (ATV), total bilirubin greater than 2.5 x ULN is permitted if direct bilirubin less than or equal to 2.5 × ULN) * Albumin greater than 3 g/dL * NOTE: Participants with results from other laboratory tests that are outside the normal range may be eligible for the study, at the discretion of the site investigator, if not considered to be an obstacle to entry. * For females of reproductive potential, negative serum or urine pregnancy test within 7 days prior to study entry by any DAIDS-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs. * NOTE: Reproductive potential is defined as: * Girls who have reached menarche or * Women who have had menses within the past 12 consecutive months and who do not have an FSH greater than 40 IU/L or * Women who have had menses within the past 24 consecutive months if an FSH measurement is not available * Women who have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral salpingectomy). * Female participants who are participating in sexual activity that could lead to pregnancy must agree to use one reliable form of contraceptive (i.e., hormonal contraceptive, condoms, IUD, diaphragm with spermicide, or cervical cap with spermicide) while receiving study treatments. * NOTE: Female participants who are not of reproductive potential, as defined above, or whose male partner(s) have undergone successful vasectomy with documented azoospermia or have documented azoospermia for any other reason, are eligible without requiring the use of contraceptives. Participant-reported history is acceptable documentation of menopause, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. * For infants (0 to 1 year of age), weight greater than or equal to 2.5 kg at screening. * Ability and willingness of participant or legally-authorized representative (legal guardian or biological parent) to provide informed consent or assent as appropriate. * Chest radiograph without evidence of active TB performed within 70 days prior to study entry for HHCs greater than or equal to 2 years of age and within 30 days prior to study entry for HHCs less than 2 years of age. * QTcF interval less than or equal to 460 ms within 30 days prior to study entry as confirmed by the central ECG reading center. * Enrollment of the HHC within 30 days after the index case is enrolled. In the event that a HHC is suspected of having TB, then this window for enrollment may be extended from within 30 days to within 70 days to allow for TB testing of the HHC. Exclusion Criteria: INDEX CASE * Has previously enrolled into the A5300B/I2003B/PHOENIx trial as an index case or HHC, or is a member of a HH which has previously enrolled into the A5300B/I2003B/PHOENIx trial. HOUSEHOLD CONTACTS * Current confirmed or probable or possible pulmonary or extrapulmonary TB, based on the following criteria: the current ACTG Diagnosis Appendix 100 for adults and for children of greater than or equal to 15 years of age; or the modified pediatric TB definitions for children less than 15 years of age as described in the A5300B/I2003B/PHOENIx MOPS. * Receipt of more than 30 cumulative days of INH, rifamycin, fluoroquinolone, or DLM in the 90 days prior to study entry. * History of or current liver cirrhosis at any time prior to study entry. * Evidence of acute hepatitis, such as abdominal pain, nausea and vomiting, jaundice, dark urine, and/or light stools within 90 days prior to study entry. * Peripheral neuropathy greater than or equal to Grade 2 within 90 days prior to study entry according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. * Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation. * Current cardiovascular disorder that is clinically relevant in the opinion of the site investigator, including but not limited to heart failure, coronary heart disease, second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (in both male and female participants), arrhythmia, or tachyarrhythmia. * Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. * Serious illness requiring systemic treatment including parenteral therapy (e.g., antibiotics) and/or hospitalization within 30 days prior to study entry. * Currently receiving other medication with potential for adverse drug-drug interactions, including QT prolongation. Please see the study protocol for a list of prohibited medications. * Taken an investigational drug or vaccine within 30 days prior to study entry. * Has a clinical condition that in the site investigator's opinion would interfere with study participation. * Has enrolled into a TB vaccine or TB preventive therapy or TB therapeutic trial, including the A5300B/I2003B/PHOENIx trial, in the two years prior to study entry. * Not expected to be able to complete 96 weeks of study follow-up (e.g., seasonal or migrant workers or students who may not stay in the area).