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University of Verona Ospedale Civile Maggiore Verona, Italy
Correspondence to: Benedetta Allegranzi, MD, DTM&H, Divisione Clinicizzata di Malattie Infettive, Ospedale Civile Maggiore, P.le Stefani 1, 37126 Verona, Italy; e-mail: benedetta. allegranzi{at}univr.it
To the Editor:
Following several reports of severe liver injury, the American Thoracic Society and the Centers for Infection Control and Prevention recently recommended to discontinue the use of rifampin plus pyrazinamide (RZ) as treatment for latent tuberculosis (LTB).1 Considering the limited choice of drugs proven effective for this purpose, in our opinion this advice, though judicious and precautionary, is a cause of major concerns. In the United States, the implementation of mandatory screening and treatment for LTB in immigrants from high-prevalence countries actually encounters relevant difficulties because of the variable isoniazid (INH) resistance patterns among different countries, and of possible severe hepatotoxicity associated with antituberculosis drugs. High primary INH resistance rates have been registered among immigrants from Vietnam, South Korea, Haiti, the Philippines, and China. In fact, a decision analysis model predicted that RZ would be the most effective and the least expensive option for immigrants from Vietnam, Haiti, and the Philippines.2
This issue may be even more cogent in Europe, given the massive migratory flows from low-income countries and considering that, unlike the United States, HIV-positive legal immigrants, who are at higher risk for active tuberculosis, are not expelled. The European framework for tuberculosis control and elimination, including the recommendation of using INH for LTB treatment in specific groups, has been recently published.3 Nevertheless, in different European countries the origin of the immigrants’ population may vary, and consequently the level of INH resistance too. For instance, in a multicenter study4 in Italy, in 2000 primary INH resistance in immigrants was reported to be 9.4%. In a survey of patients referred to the General Hospital of Verona from January 2000 to June 2003, among 231 isolates of Mycobacterium tuberculosis, 28 of 41 of strains (68.3%) resistant to at least one antituberculosis drug were from immigrants (23.9% of cases in this category of patients). Overall resistance to INH was detected in 23 strains (9.9%); 60.8% of these were isolated in immigrants from the African continent (mainly Senegal, Ghana, Ivory Coast, and Nigeria) who were infected by INH-resistant strains in 22.2% of cases. These data highlight that in the area of Verona, the INH resistance rate among immigrants is much higher compared to the national level. Therefore, the use of INH as LTB treatment could be inadequate in nearly one of four African immigrants. We believe that it is essential to evaluate the origin of immigrants in a specific area while preparing national and local guidelines for LTB treatment because of the possibility of different resistance patterns. Considering the high level of INH resistance in some endemic areas, regimens including rifampin should be recommended. Nevertheless, following the recent withdrawal of the RZ regimen in the United States, new options for LTB treatment are urgently needed. In the meantime, based on a cost-effectiveness evaluation, we would suggest that in young immigrants from high tuberculosis prevalence countries with known high INH resistance, especially if at increased risk, such as HIV-positive subjects, RZ could be still considered in absence of any hepatopathy.
References
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