New data suggest that differences in the Mycobacterium tuberculosis genome play a role in both relapse and reinfection of tuberculosis.
“In this large population-based study with active follow-up, relapses were rare after the first 2 years and were associated with drug resistance and lineage-3 genotypes,” the researchers wrote in The Journal of Infectious Diseases. “Reinfections occurred at a more constant rate, were largely restricted to HIV-positive individuals, and were not more likely to be due to different lineages from the index episode, but were due to lineage-2 genotypes more often than would be expected by chance.”
From 1996 to 2010, researchers from the faculty of epidemiology and population health at the London School of Hygiene & Tropical Medicine followed patients in northern Malawi with TB after treatment completion. All cultures from 1996 to 2008 had undergone RFLP molecular testing. The investigators performed whole genome sequencing on the available cultures from 1996 to 2010 and evaluated genetic factors associated with relapse and reinfection.
A recurrence was defined as a relapse if there were 10 or fewer single nucleotide polymorphisms (SNPs) different from the original sample and as a reinfection if there were more than 100 SNPs different. Among patients (n=1,471) in the original study who had follow-up information available, 139 had a laboratory-confirmed recurrence.
Seventy-five patients had paired samples from the original infection and the recurrent infection, either with RFLP testing, whole genome sequencing or both. Among those, 55 were due to a relapse; 46 were defined from the SNPs and nine were defined from the RFLP. Twenty were due to a reinfection; 14 were defined from SNPs and six from RFLP. For the 42 pairs that had RFLP testing and whole genome sequencing, conclusions were similar for both tests. The remaining 64 recurrences were unclassified.
Most relapses occurred within the first 2 years and were not associated with age, sex or HIV status. Lineage-3 strains were associated with a higher relapse rate. Reinfections occurred at a constant rate over time and were associated with a positive HIV status.
“The use of whole genome sequencing surmounts some of the potential problems with older techniques: excluding mixed infections, and knowing how much change to allow when comparing specimens from different episodes of disease,” the researchers wrote. “It validated our earlier results with RFLP and allows the genomic associations with relapse and reinfection to be examined directly.”
Disclosure: The researchers report no relevant financial disclosures.