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. 2010 Feb;16(2):264-71.
doi: 10.3201/eid1602.090968.

Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa

Alistair D Calver  1 , Alecia A Falmer, Megan Murray, Odelia J Strauss, Elizabeth M Streicher, Madelene Hanekom, Thelma Liversage, Mothusi Masibi, Paul D van Helden, Robin M Warren, Thomas C Victor
Affiliations

Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa

Alistair D Calver et al. Emerg Infect Dis. 2010 Feb.

Abstract

We investigated the emergence and evolution of drug-resistant tuberculosis (TB) in an HIV co-infected population at a South African gold mine with a well-functioning TB control program. Of 128 patients with drug-resistant TB diagnosed during January 2003-November 2005, a total of 77 had multidrug-resistant (MDR) TB, 26 had pre-extensively drug-resistant TB (XDR TB), and 5 had XDR TB. Genotyping suggested ongoing transmission of drug-resistant TB, and contact tracing among case-patients in the largest cluster demonstrated multiple possible points of contact. Phylogenetic analysis demonstrated stepwise evolution of drug resistance, despite stringent treatment adherence. These findings suggested that existing TB control measures were inadequate to control the spread of drug-resistant TB in this HIV co-infected population. Diagnosis delay and inappropriate therapy facilitated disease transmission and drug-resistance. These data call for improved infection control measures, implementation of rapid diagnostics, enhanced active screening strategies, and pharmacokinetic studies to determine optimal dosages and treatment regimens.

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Figures

Figure 1
Figure 1
Venn diagram of number of potential contacts by type among patients in the largest multidrug-resistant tuberculosis (MDR TB) cluster, South Africa, 2003–2005. Each circle represents potential places of contact: shaft, mine shaft (work); residence, place of residence; hospital, hospitalization at the same time as another MDR TB case-patient.
Figure 2
Figure 2
Phylogenetic history of the largest multidrug-resistant tuberculosis (MDR TB) cluster, South Africa, 2003–2005. Genetic data from isolates from 40 of the 42 case-patients were analyzed. The phylogenetic tree was constructed by using the neighbor joining algorithm (PAUP 4.0*; Sinauer Associates, Sunderland, MA, USA) and was rooted to the H37Rv wild-type DNA sequence (ANC) (20). The gene and the codon conferring resistance are indicated at the internal node where they occurred. Bootstrap values are shown in brackets at the internal nodes. The sequential evolution of resistance to HRZE and Ofx is indicated. The date of MDR TB diagnosis follows each case number. The 3 XDR TB cases are indicated in boldface. H, isoniazid, R, rifampin, E, ethambutol, Z, pyrazinamide, Ofx, ofloxacin.
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