Immunogenicity and serotype-specific efficacy of a 9-valent pneumococcal conjugate vaccine (PCV-9) determined during an efficacy trial in The Gambia.

This study aimed to determine the immunogenicity of a 9-valent pneumococcal conjugate vaccine (PCV-9) in a subgroup of Gambian children enrolled in a large vaccine efficacy trial. To place the antibody results in context, in this paper we also report previously unpublished data on serotype-specific clinical vaccine efficacy from the main trial. In the sub-study, a single 2-4 ml venous blood specimen was collected from 212 Gambian children 4-6 weeks after the administration of a third dose of PCV-9 or placebo. IgG antibodies to pneumococcal serotype 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F polysaccharides were measured by ELISA. The proportions of infants with antibody concentrations above 0.2, 0.35 and 1.0 microg/ml, and the geometric mean concentrations (GMCs) of anti-pneumococcal polysaccharide antibodies were substantially higher for each serotype in children who received three doses of PCV-9 than those in the placebo group. Among PCV-9 recipients, GMCs ranged between 2.61 and 11.09 microg/ml with the highest being against serotype 14 and the lowest against 9V polysaccharide. The estimated overall protective antibody level for all nine serotypes, based on the vaccine efficacy against vaccine-type invasive pneumococcal disease (IPD) of 77% (95% CI: 51, 90) observed in the trial, was 2.3 microg/ml (95% CI: 1.0, 5.0). The PCV-9 studied was immunogenic in a Gambian population where it was also found to be efficacious.

Childhood asthma and fruit consumption.

The present authors investigated whether wheezing is less common in children who consume more apples and other fruits. A population-based survey of 2,640 primary school children aged 5-10 yrs was carried out in Greenwich (South London, UK). Information about asthma symptoms and fruit consumption was obtained by means of a questionnaire. After controlling for potential confounding variables, eating bananas at least once a day (compared with less than once a month) was negatively associated with current wheeze (odds ratio 0.66; 95% confidence interval 0.44-1.00) and ever wheeze (0.69 (0.50-0.95)), but not with ever asthma (0.80 (0.56-1.14)). Drinking apple juice from concentrate at least once a day (compared with less than once a month) was also negatively associated with current wheeze (0.53 (0.34-0.83)), weakly associated with ever wheeze (0.74 (-0.54-1.02)), but not associated with ever asthma. Consumption of apples, other fruits and orange juice was not significantly associated with asthma symptoms. No association was found between eating fresh apples and asthma symptoms in the study population, but some evidence was found to suggest that a higher consumption of apple juice from concentrate and bananas may protect against wheezing in children.

The transplacental transfer of IgG subclasses: influence of prematurity and low birthweight in the Gambian population.

Having established previously that prematurity in The Gambia is associated with impaired maternofetal transfer of some specific antibodies, we investigated the influence of low birthweight and prematurity on placental transfer of IgG subclasses in 180 Gambian mothers and their newborn babies. A physician-blinded, cross-sectional study of 180 mother-baby pairs was carried out in the labour ward of Bansang Hospital, The Gambia. Paired maternal and cord serum samples were collected from mothers and their newborns. Serum IgG subclass levels were measured by laser nephelometry. Placental transfer of all IgG subclasses was significantly reduced in preterm newborns compared with term newborns (p < 0.01). In low birthweight (LBW) babies, the transfer of IgG1 (p = 0.03) and IgG2 (p < 0.01) subclasses, but not IgG3 and IgG4, was significantly reduced. In preterm neonates with an adequate birthweight and term neonates with a low birthweight, all IgG subclasses were transferred with reduced efficiency, but IgG1 and IgG2 subclasses were transferred with significantly less efficiency than IgG3 and IgG4. These results confirm that prematurity and low birthweight are associated with impaired placental transfer of IgG1 and IgG2 subclasses in this Gambian population. This impairment might explain the susceptibility of these newborns to certain polysaccharide-encapsulated organisms.

Materno-foetal transfer of H. influenzae and pneumococcal antibodies is influenced by prematurity and low birth weight: implications for conjugate vaccine trials.

The influence of prematurity and low birth weight (LBW) on transplacental transfer of Haemophilus influenza type B and Streptococcus pneumoniae antibodies was assessed in 213 mothers and their neonates from Gambia. Paired maternal and cord serum samples were tested for specific IgG antibody titres for H. influenza and S. pneumococcus antigens using enzyme linked immunosorbent assay. Prematurity and LBW was significantly associated with reduced placental antibody transfer for these antigens.The reduced materno-foetal transfer of these antibodies in this vulnerable population of babies may further predispose them to more bacterial infections. These findings are of practical importance to the vaccination strategies.

Influence of placental malaria infection and maternal hypergammaglobulinaemia on materno-foetal transfer of measles and tetanus antibodies in a rural west African population.

Placental malaria infection jeopardizes pregnancy outcome, and its influence may also impair the transplacental transfer of some antibodies. Two hundred and thirteen Gambian mother-baby pairs were studied to determine the influence of placental malaria infection and maternal hypergammaglobulinaemia on transplacental transfer of measles and tetanus antibodies in Gambian population. Placental blood and tissue were collected for placental malaria diagnosis. Cord and maternal sera were tested for total IgG concentration by laser nephelometry and for IgG antibody to tetanus toxoid and measles by ELISA. The prevalence of placental malaria infection was 51.1%. Mothers whose placentae were parasitized had a significantly higher mean total serum IgG (22.0 g/L vs 11.3 g/L, p < 0.001) and measles antibody level (4.02 IU/mL vs 1.21 IU/mL, p < 0.01), but not tetanus antibody, than mothers with non-parasitized placentae. Results of multiple regression analysis showed that placental malaria infection and maternal hypergammaglobulinaemia were associated with the reduction of 72% (95% CI 67.84) and 86% (95% CI 76.91) in transplacental transfer of measles antibody respectively but did not influence the transfer of tetanus antibody. It is concluded that the combined influence of placental malaria infection and maternal hypergammaglobulinaemia is significantly associated with the transfer of impaired measles antibody in this population.

The influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental transfer of antibodies and IgG subclasses in a rural West African population.

Two hundred thirteen mother-baby pairs in The Gambia were studied to determine the influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental antibody transfer. Antibody transfer for herpes simplex virus 1 (HSV-1), respiratory syncytial virus (RSV), and varicella-zoster virus (VZV) was significantly reduced by placental malaria infection by 69%, 58%, and 55%, respectively. Maternal hypergammaglobulinemia was associated with a significant reduction in antibody transfer for HSV-1, RSV, VZV, and pneumococcus by 89%, 90%, 91%, and 88%, respectively. In addition, placental malaria infection was associated with a significant reduction in transfer of IgG1, IgG2, and IgG4 (P<.01, P=.01, and P=.03, respectively) but not of IgG3 (P=.59). Maternal hypergammaglobulinemia significantly impaired the transfer of IgG1 and IgG2 (P=.01) but not of IgG3 or IgG4 (P=.62 and P=.59, respectively). Placental malaria infection and maternal hypergammaglobulinemia were associated with reduction in the transplacental transfer of these specific antibodies, IgG1, and IgG2 in this Gambian population.

Peripheral gangrene complicating Salmonella typhi septicaemia in a Gambian infant.

A 1-year-old malnourished boy, who presented with Salmonella typhi septicaemia with a 4-day history of febrile illness, dehydration and severe anaemia, developed bilateral dry gangrene of the hands and feet. Although he improved appreciably, he suffered auto-amputation of the distal phalanges of the left foot after 3 weeks of illness. A high index of suspicion and prompt treatment is highly critical in the treatment of septicaemia in young children.