Adjunctive Therapies in MDR-TB Treatment

Nutritional Support

In addition to causing malnurition, MDR-TB can be exacerbated by poor nutritional status, low body mass index and severe anaemia. Without nutritional support, patients can become enmeshed in a vicious cycle of malnutrition and disease , especially those already suffering from baseline hunger.

The second-line drugs may also further decrease the appetite, making adequate nutrition a greater challenge. Nutritional support can take the form of providing free staple foods, and whenever possible should include a source of protein. Vitamin B6 (pyridoxine) should also be given to all patients receiving cycloserine or terizidone to prevent adverse neurological effects. Vitamin (especially vitamin A) and mineral supplements can be given in areas where a high proportion of the patients have deficiencies. If minerals (zinc, iron, calcium, etc.) are given, they should be administered at a different time from the fluoroquinolones, as they can interfere with the absorption of these drugs.

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Corticosteroids

The use of corticosteroids in MDR- TB patients can be beneficial in cases of severe respiratory insufficiency and central nervous system involvement. Corticosteroids may also alleviate symptoms in patients with an exacerbation of obstructive pulmonary disease. Injectable corticosteroids are often used initially when a more immediate response is needed.

Directly Observed Treatment-Short Course (DOTS)-Plus Strategy

DOTS is a key ingredient in the tuberculosis control strategy. In populations where MDR- TB is endemic, the outcome of the standard short-course regimen remains uncertain. Unacceptable failure rates have been reported and resistance to additional agents may be induced. As a consequence, there have been calls for well-functioning DOTS programmes to provide additional services in areas with high rates of MDR- TB. These "DOTS-plus for MDR- TB programmes may need to modify all five elements of the DOTS strategy:

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• The treatment may need to be individualized rather than standardised
• Laboratory services may need to provide facilities for on-site culture and antibiotic susceptibility testing
• Reliable supplies of a wide range of expensive second-line agents
• Operational studies would be required to determine the indications
• Financial and technical support from international organizations and Western governments would be needed in addition to that obtained from local governments

The DOTS Plus strategy is part of the extended DOTS strategy recommended by the WHO. WHO has established a Working Group on DOTS-Plus for MDR- TB, to develop policy guidelines for the management of MDR- TB and to develop protocols for pilot projects intended to assess the feasibility of MDR- TB management under programme conditions.

The WHO has also established a unique partnership known as the Green Light Committee (GLC)in an attempt to promote access to and rational use of second-line antituberculosis drugs for the treatment of MDR- TB.

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Mono- and Poly-Resistant Strains (Drug-Resistant Tuberculosis other than MDR-TB)

WHO does not recommend the inclusion of specific efforts to diagnose mono- and poly-resistant strains of TB in routine DOTS programmes. However, cases with mono- or poly-resistance will be identified during the course of case-finding for MDR- TB.

Table 4 gives suggested regimens for different DST patterns. When using this table, it is essential to consider whether resistance has been acquired to any of the drugs that will be used in the recommended regimen. Table 4 assumes that pyrazinamide susceptibility is being tested, which is not the case for many countries. If DST of pyrazinamide is not being carried out, pyrazinamide cannot be depended upon as being an effective drug in the regimen. In such situations, regimens from Table 4 that assume the TB strain to be resistant should be used. Some clinicians would add pyrazinamide to those regimens because a significant percentage of patients could benefit from the drug.

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Recent Emergence of XDR- TB

In March 2006, the World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC) reported extensively drug-resistant tuberculosis as a serious, emerging threat to public health and TB control, raising concerns of TB epidemics with severely restricted treatment options that could jeopardize the gains made in global TB control. Furthermore, XDR- TB poses specific challenges to global control of HIV/AIDS and could compromise the progress already made in many countries towards universal access to HIV treatment and prevention.