Detection of antibody responses against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins in children with community-acquired pneumonia: effects of combining pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness

Abstract

We evaluated the effects of combining different numbers of pneumococcal antigens, pre-existing antibody levels, sampling interval, age, and duration of illness on the detection of IgG responses against eight Streptococcus pneumoniae proteins, three Haemophilus influenzae proteins, and five Moraxella catarrhalis proteins in 690 children aged <5 years with pneumonia. Serological tests were performed on acute and convalescent serum samples with a multiplexed bead-based immunoassay. The median sampling interval was 19 days, the median age was 26.7 months, and the median duration of illness was 5 days. The rate of antibody responses was 15.4 % for at least one pneumococcal antigen, 5.8 % for H. influenzae, and 2.3 % for M. catarrhalis. The rate of antibody responses against each pneumococcal antigen varied from 3.5 to 7.1 %. By multivariate analysis, pre-existing antibody levels showed a negative association with the detection of antibody responses against pneumococcal and H. influenzae antigens; the sampling interval was positively associated with the detection of antibody responses against pneumococcal and H. influenzae antigens. A sampling interval of 3 weeks was the optimal cut-off for the detection of antibody responses against pneumococcal and H. influenzae proteins. Duration of illness was negatively associated with antibody responses against PspA. Age did not influence antibody responses against the investigated antigens. In conclusion, serological assays using combinations of different pneumococcal proteins detect a higher rate of antibody responses against S. pneumoniae compared to assays using a single pneumococcal protein. Pre-existing antibody levels and sampling interval influence the detection of antibody responses against pneumococcal and H. influenzae proteins. These factors should be considered when determining pneumonia etiology by serological methods in children.

Effect of Pneumococcal Conjugate Vaccine on the Natural Antibodies and Antibody Responses Against Protein Antigens From Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in Children With Community-acquired Pneumonia

“…The included unvaccinated children had similar demographic and serological characteristics when compared with the PNEUMOPAC cohort, whose data have been previously published. 19 The comparison of the baseline clinical features for vaccinated and unvaccinated children demonstrated no significant difference between the study subgroups, as shown in Table 1.…”

Community-acquired pneumonia among children: the latest evidence for an updated management

“…20 Infecções bacterianas típicas também foram pesquisadas, com a quantificação de títulos específicos de IgG: de 690 pacientes com amostras de soro pareadas disponíveis para esses ensaios, a taxa de respostas de anticorpos foi de 15,4% para pelo menos um antígeno da proteína pneumocócica, 5,8% para H. influenzae e 2,3% para M. catarrhalis, a taxa de detecção de anticorpos foi significativamente aumentada para pelo menos uma dessas três bactérias para 20,4%. 21 Foram também investigadas infecções bacterianas atípicas: a infecção aguda por M. pneumoniae foi diagnosticada pela detecção de anticorpos IgM específicos na amostra de soro convalescente, infecções agudas por Chlamydia pneumoniae e Chlamydia trachomatis foram diagnosticadas pela detecção de anticorpos IgM específicos ou mudanças significativas nos títulos de IgG ou IgA; foram diagnosticadas infecções agudas por M. pneumoniae (86/787; 10,9%), C. pneumoniae (79/733; 10,8%) e C. trachomatis (3/28; 10,7%) e 147 (20,1%), 731 pacientes investigados para essas três bactérias tinham infecção aguda por pelo menos uma dessas três bactérias (18 pacientes tinham testes concomitantemente positivos para infecção aguda por M. pneumoniae e C. pneumoniae). 22 Com base nos dados supracitados, é possível observar que os vírus respiratórios têm sido cada vez mais implicados na etiologia da PAC na infância, juntamente com o reconhecimento de que as infecções virais foram mais frequentes do que as bacterianas, mesmo em países em desenvolvimento.…”

Serological diagnosis of pneumococcal infection in children with pneumonia using protein antigens: A study of cut-offs with positive and negative controls

“…Furthermore, Jiménez-Munguía et al also described that the levels of specific IgG against PcpA were three times lower in sera of children with pneumonia collected up to 10 days of disease, when compared to that of negative controls (Jiménez-Munguía et al, 2015). Similar results were found for the evaluation of antibody responses in a cohort of 690 children with non-severe community-acquired pneumonia, in which PcpA and PcsB were the antigens with the highest rate of antibody response detection (Borges et al, 2015).…”

“…Invasive pneumococcal pneumonia was diagnosed by the isolation of S. pneumoniae on blood culture (9 patients) or by the detection of pneumococcal DNA in the buffy-coat (4 patients) using PCR with the ply primers. Data about this study group have been previously published elsewhere (Nascimento-Carvalho et al, 2008;Borges et al, 2015).…”