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Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) of TLR4 and TLR9 are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPs TLR4 rs4986790 (896A > G) and TLR9 rs187084 (−1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes in TLR4 was significantly higher in patients with Haemophilus influenzae meningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2–5.4; p = 0.021), whereas the frequency of variant genotypes in TLR9 was significantly lower in patients with H. influenzae meningitis than controls (OR, 0.4; 95% CI, 0.2–0.9; p = 0.036). No such differences were found with other causative pathogens, such as Streptococcus pneumoniae and Neisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variant TLR4 genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52–109.80; p = 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07–131.49; p = 0.044) than those with the wild-type TLR4 genotype. Our study suggests an association between H. influenzae meningitis and genetic variation between TLR4 and TLR9 in Angolan children.

This study examined whether gene polymorphisms for toll‐like receptor 10 (TLR10) associated with the susceptibility to and outcomes of bacterial meningitis (BM) in Angolan children. The study cohort consisted of 190 BM patients and the determination of ten single‐nucleotide polymorphisms (SNPs) by Sanger sequencing. Patients with BM caused by Streptococcus pneumoniae who carried the following variants of TLR10 SNPs exhibited an increased risk of coexisting pneumonia: rs10004195 (T > A) (p = 0.025), rs10856837 (G > A) (p = 0.018) or rs11096956 (G > T) (p = 0.010). Yet, TLR10 SNPs rs11466652 (A > G), rs10856837 (G > A) and rs11096956 (G > T) influenced the protein levels in the cerebrospinal fluid (CSF). Moreover, compared with the wild type, patients with pneumococcal meningitis carrying a variant genotype of TLR10 SNP rs11466648 (A > G) exhibited an increased risk of developing blindness (p = 0.025), whereas patients with TLR10 SNP rs10004195 (T > A) exhibited a lower risk of convulsions at admission (p = 0.039) and a lower risk of altered consciousness (p = 0.029). This study suggests a relationship exists between coexisting pneumonia, protein levels in CSF, blindness, convulsions and an altered consciousness with genetic variations of TLR10 in BM in Angolan children.

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