GENETIC ANALYSIS OF DRUG-RESISTANT STRAINS1

Emergence of Beijing Strain

In South Africa and most of the world, three standardized methods are being adopted to classify TB strains by genotype. Warren and his colleagues have been applying these methods in numerous settings throughout South Africa to elucidate the mechanisms driving the drug-resistant TB epidemic in different regions.

An early study revealed a complex population structure of drug- resistant strains in the Western Cape Province of South Africa, with some strain genotypes being highly dominant (i.e., Beijing, LAM, and Low Copy Clade) (Streicher et al., 2001). A more detailed examination of this data set demonstrated the evolutionary history of an outbreak strain (DRF 150) (Victor et al., 2007). The study found that isoniazid resistance occurred first, followed by streptomycin resistance. With the subsequent introduction of rifampicin, many of these strains acquired rifampicin resistance on different occasions. Most important, the strains that had acquired additional mutations conferring resistance to ethambutol and pyrazinamide were the most dominant.

At about the same time, a preliminary study found that the Beijing/R220 strain was widespread in the Western Cape (Johnson et al., 2006). Warren and his colleagues conducted a follow-up study of the drug-resistant strains in the Western Cape to determine whether there had been a change in the drug-resistant TB epidemic from 2002–2003 to 2005–2006 ( Johnson et al., 2010). The number of identified cases was found to be doubling approximately every 8 years. Of significant concern was their observation that 90 percent of all drug-resistant cases tested were smear positive and thus indicative of being highly infectious, leading to extensive transmission. Stratification of the data by drug resistance pattern showed that the observed increase was strongly driven by MDR TB. The Beijing/R220 strain contributed to 42 percent of this increase, with a doubling time of 2.4 years (Johnson et al., 2010).

A third outbreak strain was identified in an urban setting in Cape Town, South Africa (van Rie et al., 1999). This strain (strain U) is a member of the Beijing genotype and showed a doubling time of approximately 5 years. Thus, as in KwaZulu-Natal (see Chapter 2), the increase in drug-resistant TB in the Western Cape Province was driven by a small number of specific strains. The implication is that the current TB control program is unable to prevent ongoing transmission of these highly resistant strains.

Studies from the Eastern Cape are limited. An initial study showed the spread of an atypical Beijing strain (Strauss et al., 2008). This finding was

1

This section is based on the presentation of Rob Warren, Stellenbosch University.



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