Chemokine responses are increased in HIV-infected Malawian children with invasive pneumococcal disease.
BACKGROUND
Chemokines play an important role in the recruitment and regulation of leukocyte traffic during bacterial infection. The aims of this study were to investigate the chemokine response to invasive pneumococcal disease (IPD) and to examine the influence of HIV infection on the chemokine response, pneumococcal bacterial loads, and outcome.


METHODS
We prospectively studied 95 children with IPD, and blood and cerebrospinal fluid (CSF) samples were taken at admission for the determination of chemokines, interferon-gamma (IFNgamma), and pneumococcal bacterial loads.


RESULTS
Plasma CXCL8 and CCL2, CSF CXCL8 and CCL4, and IFNgamma were significantly higher in HIV-infected children than in HIV-uninfected children. Blood and CSF pneumococcal bacterial loads correlated with plasma and CSF chemokines, respectively, and were higher in HIV-infected children compared with HIV-uninfected children. Among HIV-infected children, plasma concentrations of CXCL8 and CCL2 were significantly higher in nonsurvivors than in survivors, but CCL5 was significantly lower. HIV-infected and HIV-uninfected children with IPD had higher concentrations of chemokines (except CCL5) than acutely ill HIV-infected and HIV-uninfected children with no detectable bacterial infection. Male gender and low plasma CCL2 concentrations were shown to be independently associated with survival.


CONCLUSIONS
Chemokines, in particular CCL2, are associated with survival in IPD and correlate with pneumococcal bacterial loads, disease presentation, and outcome.
Carrol
Enitan D
ED
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. edcarrol@liv.ac.uk
Mankhambo
Limangeni A
LA
Balmer
Paul
P
Nkhoma
Standwell
S
Banda
Daniel L
DL
Guiver
Malcolm
M
Jeffers
Graham
G
Makwana
Nick
N
Molyneux
Elizabeth M
EM
Molyneux
Malcolm E
ME
Smyth
Rosalind L
RL
Hart
C Anthony
CA
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D019742:Chemokines, CC / Q000097:blood / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D015658:HIV Infections / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000097:blood / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000097:blood / Q000134:cerebrospinal fluid; D011008:Pneumococcal Infections / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D016133:Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics; D016019:Survival Analysis
D000900:Anti-Bacterial Agents; C066507:CCL4 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D004269:DNA, Bacterial; D016209:Interleukin-8; D007371:Interferon-gamma