RESUMEN
Identifying the transmission sources and reservoirs of Streptococcus pneumoniae (SP) is a long-standing question for pneumococcal epidemiology, transmission dynamics, and vaccine policy. Here we use serotype to identify SP transmission and examine acquisitions (in the same household, local community, and county, or of unidentified origin) in a longitudinal cohort of children and adults from the Navajo Nation and the White Mountain Apache American Indian Tribes. We found that adults acquire SP relatively more in the household than other age groups, and children 2-8 years old typically acquire in their own or surrounding communities. Age-specific transmission probability matrices show that transmissions within household were mostly seen from older to younger siblings. Outside the household, children most often transmit to other children in the same age group, showing age-assortative mixing behavior. We find toddlers and older children to be most involved in SP transmission and acquisition, indicating their role as key drivers of SP epidemiology. Although infants have high carriage prevalence, they do not play a central role in transmission of SP compared with toddlers and older children. Our results are relevant to inform alternative pneumococcal conjugate vaccine dosing strategies and analytic efforts to inform optimization of vaccine programs, as well as assessing the transmission dynamics of pathogens transmitted by close contact in general.
Asunto(s)
Portador Sano/epidemiología , Portador Sano/transmisión , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/transmisión , Streptococcus pneumoniae/inmunología , Adolescente , Adulto , Arizona/epidemiología , Portador Sano/microbiología , Niño , Preescolar , Estudios de Cohortes , Composición Familiar , Femenino , Humanos , Indígenas Norteamericanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Infecciones Neumocócicas/microbiología , Factores de Riesgo , Adulto JovenRESUMEN
Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12-23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3-45%; P < 0·01), 19F (21-66%; P < 0·01) and 23F (13-36%; P = 0·02), but not serotypes 6B (24-42%; P = 0·24) and 14 (21-40%; P = 0·06). Correlations between antibodies and memory B cells were weak. Carriage of serotype 19F at enrolment was associated with poor memory B cell responses against this serotype at subsequent time-points (day 30: non-carriers, 82% versus carriers, 0%, P < 0·01; day 210: non-carriers, 72% versus carriers, 33%, P = 0·07). PHiD-CV is capable of inducing memory B cells against some of the component pneumococcal capsular polysaccharides.
Asunto(s)
Linfocitos B/efectos de los fármacos , Proteínas Bacterianas/inmunología , Proteínas Portadoras/inmunología , Infecciones por Haemophilus/prevención & control , Vacunas contra Haemophilus/inmunología , Inmunoglobulina D/inmunología , Memoria Inmunológica/efectos de los fármacos , Lipoproteínas/inmunología , Vacunación , Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Antibacterianos/sangre , Linfocitos B/inmunología , Linfocitos B/microbiología , Proteínas Bacterianas/química , Proteínas Portadoras/química , Femenino , Infecciones por Haemophilus/sangre , Infecciones por Haemophilus/inmunología , Infecciones por Haemophilus/microbiología , Vacunas contra Haemophilus/administración & dosificación , Haemophilus influenzae/química , Haemophilus influenzae/clasificación , Haemophilus influenzae/inmunología , Humanos , Inmunidad Humoral/efectos de los fármacos , Inmunoglobulina D/química , Lactante , Kenia , Lipoproteínas/química , Masculino , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/inmunología , Serotipificación , Resultado del Tratamiento , Vacunas ConjugadasRESUMEN
Previous work divided serotype III group B streptococci (GBS) into 3 major phylogenetic lineages (III-1, III-2, and III-3) on the basis of bacterial DNA restriction digest patterns (RDPs). Most neonatal invasive disease was caused by III-3 strains, which implies that III-3 strains are more virulent than III-2 or III-1 strains. In the current studies, all RDP III-3 and III-1 strains expressed hyaluronate lysase activity; however, all III-2 strains lack hyaluronate lysase activity, because the gene that encodes hyaluronate lysase, hylB, is inactivated by IS1548. Subtractive hybridization was used to identify 9 short DNA sequences that are present in all the III-3 strains but not in any of the III-2 or III-1 strains. With 1 exception, these III-3-specific sequences were not detected in nonserotype III GBS. These data further validate the RDP-based subclassification of GBS and suggest that lineage-specific genes will be identified, which account for the differences in virulence among the lineages.