Absence of an association between Mycobacterium tuberculosis genotype and clinical features in children with tuberculous meningitis.
OBJECTIVE
Animal studies point to increased virulence of certain mycobacterial strains, notably those of the Beijing genotype. There are limited data on mycobacterial genotypic diversity in children with tuberculous meningitis (TBM). We investigated mycobacterial genotypic diversity in children with TBM and analyzed the relationship among genotype, clinical presentation and outcome.


METHODS
Data were extracted from an ongoing prospective study on children with confirmed TBM from 1992 through 2003 at a referral hospital in the Western Cape Province, South Africa. Mycobacterial isolates were genotyped by standardized restriction fragment length polymorphism methodology. Clinical data at diagnosis, inflammatory progression during the first month of antituberculosis therapy and neurologic outcomes after 6 months of therapy were analyzed according to the principal genetic group of the strain and the presence of the Beijing strain, respectively.


RESULTS
Fifty-nine children were included (median age at diagnosis, 23 months); 37 presented with stage II and 22 with stage III presented with TBM. At completion of antituberculosis therapy, 6 children were neurologically normal, 22 were moderately neurologically impaired, 23 were severely neurologically impaired and 6 children died; detailed outcomes were not available in 2 children. All 3 principal genetic groups were represented (group 1, 27.1%; group 2, 59.3%; group 3, 13.6%); the most prevalent strains were of the Beijing genotype (family 29; 25.4%), followed by family 28 (10.2%) and family 11 (8.5%). Predictors of poor neurologic outcome included advanced disease at diagnosis and male gender. There was no association between the principal genetic group of the strain or the presence of the Beijing genotype, and clinical presentation or outcome.


CONCLUSIONS
We found no association between Mycobacterium tuberculosis genotypes and clinical presentation or outcome.
Maree
Freda
F
Desmond Tutu TB Centre, Department of Pediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa.
Hesseling
Anneke C
AC
Schaaf
H Simon
HS
Marais
Ben J
BJ
Beyers
Nulda
N
van Helden
Paul
P
Warren
Robin M
RM
Schoeman
Johan F
JF
D000293:Adolescent; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005000:Ethionamide / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007538:Isoniazid / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D011718:Pyrazinamide / Q000627:therapeutic use; D012189:Retrospective Studies; D012293:Rifampin / Q000627:therapeutic use; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000188:drug therapy / Q000382:microbiology*
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D011718:Pyrazinamide; D005000:Ethionamide; D007538:Isoniazid; D012293:Rifampin