Background
Tuberculosis (TB) patients with multiple
episodes of anti-TB treatment represent an important source of TB transmission,
as well as a serious threat to the control of drug resistant TB, due to the
high risk of multidrug and extensively drug resistance (MDR/XDR) and elongating
infectiousness of this patient group. In this study we analyzed the possible
risk of development and transmission of MDR and XDR in TB patients with
multiple episodes of previous treatment history.
Methods
The study subjects were pulmonary TB
patients who had at least two episodes of previous anti-TB treatment. A total
of 166 eligible patients were identified from 10 counties/districts distributed
in east, west, north, south and central China. Drug susceptibility test (DST)
was performed by proportion method on LJ-media for the 1st line anti-TB drugs
and a line probe assay was used to detect mutations related to resistance of
the key 2nd-line drugs. Genotyping of M. tuberculosis (Mtb) was
performed with MIRU-VNTR and Spoligotyping.
Results
Resistances to 1st-line drugs was
observed in 122 (73.5 %) of the 166 Mtb isolates with 97 (58.4 %)
being MDR-TB. Mutations relevant to 2nd-line drug resistance was seen in 63
isolates, including 35 MDR-TB isolates (30 pre-XDR, 5 XDR-TB). The Spoligotyping
revealed 83.1 % Mtb isolates belonged to the Beijing family. The MIRU-VNTR
based genotyping revealed 32 (19.3 %) of patients were infected with more
than one strain. The number of previous TB treatment episode was found being
significantly associated with the risk of MDR-TB and XDR-TB. Among the
remaining 134 patients infected with a single Mtb strain, MIRU-VNTR revealed a
high homogeneity of strain especially within Beijing family despite the
polymorphic variations along with geographic locations.
Conclusions
The high genetic relatedness and risk of
MDR-TB and subsequent pre-XDR and XDR-TB among repeatedly treated patients
suggest the establishment of M/XDR Mtb in this specific patient population. It
highlights the urgent needs of providing DST of both 1st- and 2nd-line drugs
before and during the medication in China’s MDR-TB control program.
Furthermore, the possibility of infection with multiple strains should also be
considered to be associated with the drug resistance, which calls for the
modification of treatment regimen.
Below: The mini spanning tree
analysis of the 134 M.tb isolates from the patient with single strain
infection. Each circle represents a unique genotype and a single bigger circle
represents the cluster containing more than two isolates. Different color indicated
the different drug resistant pattern. Note: MDR, multidrug resistance; XDR,
extensively drug resistance; FQR, fluoroquinolones resistance; INJR, injective
drug resistance; DS, drug sensitive; DR, drug resistance
Full article at: http://goo.gl/aJwpO4
By:
Affiliated with
Department of
Epidemiology, School of Public Health, Fudan University
Key Laboratory
of Public Health Safety, Fudan University, Ministry of Education
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