*4.5.5. Treatment of paediatric TB/HIV co-infection*

is insufficient evidence to demonstrate whether steroids are effective in tuberculous pleural

**Maximum Dosage (mg/kg/dose)**

**Times/wk**

**Mode of Action Daily Two or Three**

Isoniazid Bactericidal 10–15 (300 mg) 20–30 (900 mg) Rifampin Bactericidal and sterilizing 10–20 (600 mg) 10–20 (600 mg) Pyrazinamide Sterilizing 20–40 (2,000 mg) 50 (2,000 mg) Ethambutol Bacteriostatic 15–25 (1,200 mg) 30–50 (2,500 mg)

Ethionamide or prothionamide Bactericidal 15–20 (1,000 mg) NA

Ciprofloxacin 20–40 (1,500 mg)

Kanamycin 15–30 (1,000 mg) Amikacin 15–30 (1,000 mg) Capreomycin 15–30 (1,000 mg)

**Table 1.** First- And Second-Line Antituberculosis Drugs And Recommended Dosages In Children

Streptomycin Bacteriostatic 20–40 (1,000 mg) NA Fluoroquinolones Bactericidal NA

Aminoglycosides Bacteriostatic NA

Cycloserine or terizidone Bacteriostatic 10–20 (1,000 mg) NA Para-aminosalicylic acid Bacteriostatic 200–300 (10 g) NA

Anti-tuberculosis treatment rarely fails in children and, if it does, every effort should be made to find the most likely cause. In settings where the prevalence of drug resistance is low the commonest cause is failure to properly take the medications, which can occur even during DOT, if supervision is not complete. It is important to remember that non-adherence has a differential diagnosis; there are psychologic, sociologic, religious, economic, and practical reasons why people are non-adherent and one must deal with all these issues for chemotherapy to be successful. With treatment interruption the child may be restarted on the original treatment regimen while ensuring adequate supervision, as the risk of developing drug resistance is small in children with paucibacillary disease. If an immune-competent child presents with a new episode of tuberculosis more than 6 months after completing treatment

effusion.

*4.5.4. Retreatment*

**First-line drugs**

408 Tuberculosis - Current Issues in Diagnosis and Management

**Second-line drugs**

NA = not applicable. Source: Marais et al., (2006).

The high risk of HIV-infected children to progress to disease after infection justifies the use of preventive chemotherapy in children who are latently infected. However, the difficult issue in endemic areas is how to deal with the ever-present risk of undocumented re-infection within the community. The prevention or reversal of severe immune compromise by using highly active antiretroviral therapy (HAART) should preclude the need for repeated or continuous preventive chemotherapy, although the risk for tuberculosis probably remains higher than in HIV-uninfected children. The cellular immune response assists with organism eradication and therefore it is not unexpected that disease relapse has been documented in HIV-infected children. The value of prolonging the treatment duration from 6 to 9 months, to ensure organism eradication in HIV-infected children, is under investigation. During a repeat episode both relapse and reinfection should be considered and every effort should be made to establish a culture-confirmed diagnosis and to do drug susceptibility testing (Marais et al., 2006).

When initiating treatment (curative treatment or RIF-containing preventive therapy) in HIVinfected children already receiving HAART or for whom HAART is contemplated, it should be appreciated that the rifamycins, especially RIF, and some of the nonnucleoside reverse transcriptase inhibitors and/or protease inhibitors may cause significant drug interactions. HIV-infected children may also develop particularly pronounced paradoxical reactions after the institution of HAART, because of immune reconstitution inflammatory syndrome. Recommendations on optimal drug combinations are frequently revised. The most recent recommendations can be obtained from the Centers for Disease Control and Prevention website, at [http://www.cdc.gov/nchstp/tb/].

Latest WHO recommendations advise starting antiretroviral therapy (ART) once anti-TB therapy (ATT) is established (after a period of 2-8 weeks) for all WHO clinical Stage Four HIVinfected children and Stage Three children with advanced or severe immunosuppression. For children in WHO clinical stage with mild or no immunosuppression, ART may be deferred until 6 months of ATT are completed (WHO, 2006). On-going prospective trials involving adults and children in TB/HIV endemic countries might provide future guidelines for the ideal timing of the initiation of anti-retroviral therapy (ART) in patients with HIV receiving TB therapy. There is already evidence from prospective trials that shows that high mortality is associated with TB in advanced stages of HIV-disease in children who do not receive ART promptly. Further research is required to improve our understanding of immune reconstitu‐ tion disease (IRD) in children (Walters et al., 2006). Also, therapeutic drug monitoring (TDM), where available, should be undertaken when children are receiving concomitant ART and ATT. TDM data from ethnically similar children in resource-rich countries may in the future inform dosing recommendations in resource-poor settings where TDM is not available.
