8. Conclusion

In a prospective study, two of 41 children receiving tailored preventive therapy developed TB (confirmed and probable TB) compared to 13 of 64 children not receiving preventive treatment (OR 0.2, 95% CI 0.04–0.94) [49]. However, WHO has not recommended any form of preventive therapy for MDR contact cases. Based on the available evidence and the probability of increased likelihood to develop active TB disease following recent infection, strict clinical observation and close monitoring for the development of active TB disease for at least 2 years is preferred over the provision of preventive treatment for contacts of MDR-TB cases [1].

Clinical management of latent tuberculosis infection should also address such concomitant risk factors as illicit-drug use, alcohol abuse, and smoking through opioid-substitution treatment and counseling about alcohol and smoking cessation, respectively. Acceptance of and adherence to the full course of latent tuberculosis treatment must be encouraged. In a study conducted in the United States and Canada, 17% of persons who were offered treatment for latent infection refused it [1]. Treatment completion varies widely (from 19 to 96%), and the reasons for non-completion need to be fully assessed [1]. The use of various incentives to promote treatment initiation and adherence, depending on the specific need of the person being treated, should be considered. Peer education, counseling, people-friendly services, and properly trained service providers boost confidence and may improve adherence to treatment [1].

The lengthy duration of treatment reduces patient compliance, while the potential occurrence of serious adverse events such as hepatitis, further discourages patients' and providers' accep-

INH has the major disadvantage of potential serious adverse events. Of particular concern is hepatotoxicity, as this is difficult to detect, and can be fatal. Surveillance studies have confirmed that hepatotoxicity is quite common in patients taking INH and can be severe resulting in up to 1 per cent mortality in older patients [53].The relative risk for developing hepatotoxicity associated with isoniazid compared with placebo were 3.45 (95% CI, 1.49–7.99) for 12 weeks of treatment, 4.59 (95% CI, 2.03–10.39) for 24 weeks of treatment, and 6.21 (95% CI,

In another randomized trial, rates of grade 3 and 4 adverse events were significantly lower with 4RIF than 9INH [54]. Grade 3–4 hepatotoxicity occurred in 4% of patients taking 9INH

Comparison of drug toxicity of INH and Rifampicin has been studied in many trials. Rates of hepatotoxicity among patients receiving isoniazid were 5.2, 3.7, 34 and 11.4% compared to

In PREVENT TB study, rates of grade 3 and 4 hepatotoxicity were 4.9 and 1.0% in the rifapentine plus isoniazid arm and 5.5 and 1.1% in the isoniazid-only arm, respectively [57]. The RR for grade 3 or 4 hepatotoxicity was 0.90 (95% CI, 0.75–1.08). Mortality from hepatotoxicity was reported to be 1.0% among patients on isoniazid and 0.8% on those on isoniazid plus

rates among patients treated with rifampicin (0.0, 0.7 and 4.4%, respectively) [55, 56].

7. Adverse effects of LTBI treatment

2.79–13.79) for 52 weeks of treatment in the IUAT trial [34].

compared to less than 1% in those taking 4RIF [54].

tance of this therapy [50–52].

178 Advances in HIV and AIDS Control

Identification and early chemoprophylaxis for LTBI can prevent reactivation TB and thus reduce both TB morbidity and transmission of TB in the community. In low TB-burden countries LTBI detection and IPT are important strategies for TB eradication. Diagnosis of LTBI is based on either TST or TB IGRA. The test preferred usually depends on the financial support available for public health programmes. In high TB- burden countries, LTBI detection and treatment can contribute to decreasing TB burden and transmission and also emergence of drug resistant TB. Here the guidelines are pretty straightforward and IPT should be offered to all children less than 5 years who have contact with pulmonary TB cases or HIV-positive individuals. INH is the preferred drug for LTBI and a 9-month regimen is considered optimal. However, careful clinical monitoring is required to detect drug induced liver injury early and also to ensure adherence to therapy. Clinical trials in different parts of the world have shown that this effort is worth it.
