Tuberculosis / TB (Mycobacterium Tuberculosis)

There is an increased risk of Tuberculosis among HIV - infected children (13) and infact co-infection with HIV occurred in up to 48% of children with culture proven TB (14, 15). Extra pulmonary and miliary TB are more common among younger children.

Children usually get TB from an infected close adult and disease in children is usually a primary infection rather than reactivation disease (16). An asymptomatic child with a positive Mantoux test suggests a latent infection and all latent infections should be treated to prevent the disease. Drug resistance TB is on the rise and thus contacts to drug resistant TB should be treated with the assumption that any newly diagnosed infection is similarly drug resistant.
If there is any patient with Tuberculosis then all exposed family members should be screened for TB to find secondary TB cases and patients with latent TB infection.

Clinical features

Pulmonary TB : May be non-specific symptoms such as fever, weight loss, failure to thrive and cough. Features of presentation in HIV infected children is similar to those among non HIV infection.

Young children present with localized pulmonary infiltrates with hilar adenopathy. 25% of children may have more than 1 lobe involved. Middle lobe collapse and consolidation may result due to endobronchial tuberculosis. Older children and adolescents may present with cavitatory tuberculosis. Cavitatory upper lobe tuberculosis is more common in those with CD4 counts >200/mm3, whereas hilar /mediastinal adenopathy and diffuse pulmonary infiltrates (without cavitation) are more common in those with CD4 counts <200/mm3.

Extrapulmonary TB : Common sites involved are lymph nodes, Disseminated TB, CNS FB, Bone TB and TB of the serosal surfaces.

When to suspect TB
Suspect TB if the child has:

1. Contact with adult who has Pulmonary TB
2. Fever for more than 1 week
3. Chronic cough (more than 3 weeks)
4. Ongoing weight loss or poor weight gain.

• Mantoux test
• Gastric lavage isolation / sputum for culture and smear
• Radio logical - Chest X-ray.

• Culture of affected body fluid or tissue obtained by fine needle aspiration or biopsy.

Mantoux test / MT (Tuberculin test) : Can be done from 3 months onwards using 5 TU PPD injected intradermally. Induration more than 5 mm is considered positive in HIV infected children. However, negative test may be seen in over 50% of children with tuberculosis. Thus, a negative test does not exclude TB.

Gastric lavage / sputum examination : Though acid fast stained sputum smears are positive in 50-70% of adults with Pulmonary TB, children with TB disease rarely produce sputum voluntarily and have a low bacterial load (17). Three consecutive morning gastric aspirates have a yield of about 30-70% and have a better yield on culture.

Other fluids and tissues for culture : Bronchoalveolar lavage (BAL), lung biopsy, lymph node biopsy, serosal fluids and CSF. Specimens should be cultured for 2-6 weeks either by radiometric culture methods (Bactec) or culture on L-J medium. Antimycobacterial drug sensitivity should be done on the initial positive culture if treatment fails or relapse occurs. If no organism is isolated from the specimen of the child, drug sensitivity test can be done on the isolate from the source case.

Chest X-ray

• Localized pulmonary infiltrates with hilar adenopathy
• Middle lobe collapse and consolidation
• Pleural effusion
• In older children and adults - cavitatory tuberculosis

Treatment

Treatment of TB in HIV infected child is the same as that for an HIV uninfected child. However, modified treatment duration schedule and medications are recommended for specific instances. Treatment of TB should be initiated 4-8 weeks before initiating ART. For children already on ART, the child's ART regimen should be reviewed and altered if needed to ensure optimal treatment for both TB and HIV and to minimize potential side effects as well as drug interactions. For HIV infected children with active pulmonary disease, the minimum recommended duration of ATT is 9 months, for children with extrapulmonary disease involving the bones or joints, CNS or military disease, the minimum recommended duration of treatment is 12 months (22, 23, 24). For the first 2 months of treatment. Directly Observed Therapy (DOT) is recommended as a daily schedule. For the continuation phase, DOT may be given two or three times weekly.
Initial treatment (induction phase) consists of 4 drug regimen consisting of Isoniazid (INH), Rifampicin (RIF), Pyrazinamide (PZA) and either Ethambutol (ETB) or Streptomycin for 2 months followed by continuation phase for 7-10 months with INH and Rifampicin.
Rifampicin induces hepatic cytochrome P 450 enzymes and accelerates clearance of drugs such as PIs and NNRTIs resulting in sub-therapeutic levels of the drug. Thus, concurrent administration of rifampicin and single PIs excepted boosted PI is not recommended (25). Also concomitant administration of rifampicin with efavirenz (and also nevirapine) is possible with dose adjustment. Rifabutin can be used as an alternative to Rifampicin for children on HAART, but it is not available in India.

Drug resistant Tuberculosis
For treatment of drug-resistant TB, a minimum of three drugs should be given, including at least 2 bactericidal drugs to which the organism is susceptible. For INH resistant tuberculosis, a regimen containing Rifampicin, Pyrazinamide and Ethambutol may be used for the full duration of treatment (9-12 months). Intermittent therapy may be used after daily therapy for the initial 8 weeks. For tuberculosis resistant only to rifampicin, a 9-12 month regimen consisting of INH+ETB+PZA and streptomycin for the first 2 months is recommended.
In Multidrug resistant tuberculosis (i.e. resistant to INH and RIF) aggressive treatment with a regime that contains an amino glycoside or capreomycin and a fluoroquinolone is recommended. The duration of therapy must be at least 24 months after culture conversion.
In children with HIV and TB coinfection, periodic monitoring of liver enzymes is advised. Mild elevations in serum transaminases (e.g., 2-3 times upper limit of normal) does not require discontinuation of the drugs. All patients should be monitored monthly for clinical and bacteriological response. For patients with pulmonary TB, Chest X-rays should be obtained after 2-3 months of therapy to evaluate response. Hilar adenopathy might persist for as long as 2-3 years despite successful ATT and is not a criteria for continuation of ATT.
Adjunctive use of steroids is indicated in patients with TBM, Serosal TB, Miliary TB and endobronchial tuberculosis.

Prophylaxis

• All HIV infected children with positive MT test and no evidence of active TB or no history of previous treatment for TB should be treated for latent TB.Regimen - 6 months of INH / Rifampicin (INH alone may be given if resistance to INH is less than 5% in the general population).
• HIV infected children in close contact with person with Open TB should be treated for latent TB regardless of their MT test and previous treatment for TB after excluding active TB. Regimen - 6 months of INH / Rifampicin (INH alone may be given if resistance to INH is less than 5% in the general population).
• Secondary prophylaxis is a child who has been successfully treated for TB should not be given.
• Routine TB prophylaxis for HIV infected children is not recommended.