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

Calver AD, Falmer AA, Murray M, Strauss OJ, Streicher EM, Hanekom M, Liversage T, Masibi M, van Helden PD, Warren RM, Victor TC - Emerging Infect. Dis. (2010)

Bottom Line: Phylogenetic analysis demonstrated stepwise evolution of drug resistance, despite stringent treatment adherence.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.

View Article: PubMed Central - PubMed

Affiliation: West Vaal Hospital, Orkney, South Africa.

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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2958014&req=5

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.

Mentions: Phylogenetic reconstructions of the isolates included in the largest identified a single genetically distinct progenitor MDR TB strain (Figure 2). This strain acquired resistance to pyraziamide on 2 separate occasions and both of these strains were subsequently transmitted. Thereafter, ethambutol resistance evolved independently in several different cases. Sequencing of the gyrA gene showed that ofloxacin resistance subsequently evolved on 6 separate occasions, resulting in 15 cases of pre–XDR TB. One of these pre–XDR TB strains then evolved to XDR TB and caused disease in a single patient (patient 27). An additional XDR TB strain evolved independently (lacking gyrA mutations) (patient 41) and subsequently spread to a contact (patient 141).


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

Calver AD, Falmer AA, Murray M, Strauss OJ, Streicher EM, Hanekom M, Liversage T, Masibi M, van Helden PD, Warren RM, Victor TC - Emerging Infect. Dis. (2010)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2958014&req=5

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.
Mentions: Phylogenetic reconstructions of the isolates included in the largest identified a single genetically distinct progenitor MDR TB strain (Figure 2). This strain acquired resistance to pyraziamide on 2 separate occasions and both of these strains were subsequently transmitted. Thereafter, ethambutol resistance evolved independently in several different cases. Sequencing of the gyrA gene showed that ofloxacin resistance subsequently evolved on 6 separate occasions, resulting in 15 cases of pre–XDR TB. One of these pre–XDR TB strains then evolved to XDR TB and caused disease in a single patient (patient 27). An additional XDR TB strain evolved independently (lacking gyrA mutations) (patient 41) and subsequently spread to a contact (patient 141).

Bottom Line: Phylogenetic analysis demonstrated stepwise evolution of drug resistance, despite stringent treatment adherence.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.

View Article: PubMed Central - PubMed

Affiliation: West Vaal Hospital, Orkney, South Africa.

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.

Show MeSH
Related in: MedlinePlus