Mixed tuberculosis infection due to reactivation of a latent MDR strain
triggered by a recent infection with a susceptible strain
ECCMD
1167
Laura Pérez-Lago1, Miguel Martínez-Lirola2, Marta Herranz1,Yurena Navarro1, María Jesús Rúiz-Serrano1, Emilio Bouza1, Darío García de Viedma1
1Hospital
General Universitario Gregorio Marañón, Madrid, Spain; 2Complejo Hospitalario Torrecárdenas, Almería, Spain.
1.Description of the case
POTENTIAL REACTIVATION OF MDR-TB
2. Analysis of resistance pattern
Genotype
MTBDR Plus
2014
2011
TB-diagnosis
Woman
Romanian born
47 year-old
HIV negative
Alcoholic
MDR-TB
Household contact
(Husband)
The 2014 case was studied as part of the contact trace of a 2011 MDR case. She was PPD
positive and BCG vaccinated, and did not show any radiological finding or clinical symptoms.
Prophylaxis was not prescribed. She was attended three times in the hospital along 2012 and
2103 and no symptoms were observed before her final diagnosis in 2014.
Study
case
MGIT-SIRE
Study
case
MIRU 53
Resistant to Rifampin and Isoniazid
4. Epidemiological tracking of the coinfecting strains
MIRU-VNTR analysis and comparison with population-based MIRU-database
MIRU 47
2
MDR strain
4
3
Electropherograms showing double alelles in two representative loci
Plating with
Isoniazid
Study case: MIXED
INFECTION
Susceptible strain
Susceptible
223132253633233433437223
226132233333242212226423
98%
IDENTICAL PATTERNS
223132253633233433437223
IDENTICAL PATTERNS
226132233333242212226423
2011
2
Clear-wt pattern
combined with a
faint-mutant
pattern
Rifampin
susceptible
The susceptible and MDR coinfecting strains were
separated by subculturing +/- INH
Plating without
Isoniazid
rpoB katG katG
MUT3 WT MUT1
Interpretation: Potential MDR/susceptible mixed infection
Single colony analysis
Identification of double alleles in 12 loci
rpoB
WT8
Study
case
GeneXpert
3. Confirmation of a MDR/susceptible mixed infection
MIRU-VNTR analysis
2011
MDRcase
Discrepant results
Background and Objective: The application of genotyping to the analysis of infection by
Mycobacterium tuberculosis (MTB) has enabled us to identify mixed infections involving more than one
strain. These are assumed to be restricted to areas of high prevalence owing to overexposure to more
than 1 infectious case or to sequential superinfection. Our aim was to investigate a representative case of
mixed tuberculosis infection in an area of moderate incidence (Almería, SouthEast Spain) in order to
determine the underlying causes.
Contact: [email protected]
Resistant
2%
MDR-TB
Household contact
Four cases
living in the
same area
2008
2011
2011
CONCLUSIONS
The mixed infection we report most likely corresponded to a reactivation of a latent MDR strain coincidental with a recent infection with a susceptible circulant strain.
The integration of clonal analysis, molecular epidemiology, and patient data could help us to clarify the reasons behind complex infections by MTB in regions with a moderate incidence of TB.
Funding: Plan Estatal de I+D+I 2013-2016, ISCIII (PI 12/02080, 13/01207) and FEDER.
2014