Pneumococcal antibody concentrations and carriage of pneumococci more than 3 years after infant immunization with a pneumococcal conjugate vaccine.

BACKGROUND: A 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose schedule, protected Gambian children against pneumococcal disease and reduced nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7) on antibody and nasopharyngeal carriage of pneumococci 3-4 years after primary vaccination. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a subsample of children who had received 3 doses of either PCV-9 or placebo (controls) into this follow-up study. Pre- and post- PCV-7 pneumococcal antibody concentrations to the 9 serotypes in PCV-9 and nasopharyngeal carriage of pneumococci were determined before and at intervals up to 18 months post-PCV-7. We enrolled 282 children at a median age of 45 months (range, 38-52 months); 138 had received 3 doses of PCV-9 in infancy and 144 were controls. Before receiving PCV-7, a high proportion of children had antibody concentrations >0.35 µg/mL to most of the serotypes in PCV-9 (average of 75% in the PCV-9 and 66% in the control group respectively). The geometric mean antibody concentrations in the vaccinated group were significantly higher compared to controls for serotypes 6B, 14, and 23F. Antibody concentrations were significantly increased to serotypes in the PCV-7 vaccine both 6-8 weeks and 16-18 months after PCV-7. Antibodies to serotypes 6B, 9V and 23F were higher in the PCV-9 group than in the control group 6-8 weeks after PCV-7, but only the 6B difference was sustained at 16-18 months. There was no significant difference in nasopharyngeal carriage between the two groups. CONCLUSIONS/SIGNIFICANCE: Pneumococcal antibody concentrations in Gambian children were high 34-48 months after a 3-dose primary infant vaccination series of PCV-9 for serotypes other than serotypes 1 and 18C, and were significantly higher than in control children for 3 of the 9 serotypes. Antibody concentrations increased after PCV-7 and remained raised for at least 18 months.

Immunogenicity and safety of a meningococcal A conjugate vaccine in Africans.

BACKGROUND: Group A meningococci are the source of major epidemics of meningitis in Africa. An affordable, highly immunogenic meningococcal A conjugate vaccine is needed. METHODS: We conducted two studies in Africa to evaluate a new MenA conjugate vaccine (PsA-TT). In study A, 601 children, 12 to 23 months of age, were randomly assigned to receive PsA-TT, a quadrivalent polysaccharide reference vaccine (PsACWY), or a control vaccine (Haemophilus influenzae type b conjugate vaccine [Hib-TT]). Ten months later, these children underwent another round of randomization within each group to receive a full dose of PsA-TT, a one-fifth dose of PsACWY, or a full dose of Hib-TT, with 589 of the original participants receiving a booster dose. In study B, 900 subjects between 2 and 29 years of age were randomly assigned to receive PsA-TT or PsACWY. Safety and reactogenicity were evaluated, and immunogenicity was assessed by measuring the activity of group A serum bactericidal antibody (SBA) with rabbit complement and performing an IgG group A-specific enzyme-linked immunosorbent assay. RESULTS: In study A, 96.0% of the subjects in the PsA-TT group and 63.7% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline; in study B, 78.2% of the subjects in the PsA-TT group and 46.2% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline. The geometric mean SBA titers in the PsA-TT groups in studies A and B were greater by factors of 16 and 3, respectively, than they were in the PsACWY groups (P<0.001). In study A, the PsA-TT group had higher antibody titers at week 40 than the PsACWY group and had obvious immunologic memory after receiving a polysaccharide booster vaccine. Safety profiles were similar across vaccine groups, although PsA-TT recipients were more likely than PsACWY recipients to have tenderness and induration at the vaccination site. Adverse events were consistent with age-specific morbidity in the study areas; no serious vaccine-related adverse events were reported. CONCLUSIONS: The PsA-TT vaccine elicited a stronger response to group A antibody than the PsACWY vaccine. (Funded by the Meningitis Vaccine Project through a grant from the Bill and Melinda Gates Foundation; Controlled-Trials.com numbers, ISRCTN78147026 and ISRCTN87739946.).

Prospects and challenges with introduction of a mono-valent meningococcal conjugate vaccine in Africa.

Epidemic meningococcal meningitis is a priority disease for prevention and control in Africa. The current World Health Organization (WHO) approach to the control of meningitis epidemics is based on early detection of cases and emergency vaccination of the population at risk with meningococcal polysaccharide (PS) vaccines. But this is a tall order for the developing nations of Africa where experts operate from an ineffective health system. Although the widespread use of meningococal polysaccharide vaccines has had a major and much appreciated public health impact on the disease it has not prevented epidemics of this dreaded infection. The current partnership between WHO and the PATH aims to develop, evaluate and introduce an appropriate and affordable meningococcal conjugate vaccine that could potentially provide for a means of preventing epidemic meningitis caused by N. meningitidis group A. In this paper, we review the prospects and challenges facing the introduction of the mono-valent conjugate vaccine in Africa.

Household decision-making process and childhood cerebral malaria in The Gambia.

Mortality from childhood cerebral malaria remains unacceptably high in endemic regions. This survey was conducted between June and December 2001 among 69 primary caregivers of children admitted for cerebral malaria in Bansang Hospital, Central River Division (CRD), The Gambia to describe decision-making process at the family level that could have impact on malaria mortality. Thirty two percent of children presented in coma after 24 h of onset of illness. The eldest person in the compound or the father was responsible for taking decision on when hospital treatment was necessary in 85% of the cases. Mothers who were the primary caregivers made such decisions only in 7% of the cases. Cultural norms in a community are important factors affecting preferences at the household level and could influence important medical decisions. This survey suggests that patriarchs and/or fathers are important target groups for health education and project implementation programs.

Dissociation between tuberculin skin test and in vitro IFN-gamma responses following neonatal BCG vaccination.

The in vitro IFN-gamma response to tuberculin was recently proposed as a correlate of vaccine-induced immunity to tuberculosis. IFN-gamma also plays a central role in the tuberculin skin test (TST), commonly used as a marker of mycobacterial infection. However, the use of TST as a marker of immunity to tuberculosis is limited for reasons ascribed mainly to interference by environmental mycobacteria. We prospectively investigated the relationship between the TST and cytokine responses to BCG in early infancy, a cohort with relatively low exposure to environmental mycobacteria. Neonatal BCG vaccination induced positive TST responses and predominant IFN-gamma responses to tuberculin in most newborns. However, the production of IFN-gamma, IL-5 and IL-13 was similar in TST responders and non-responders, and there was no significant correlation between the size of TST response and cytokine production. These results indicate that the IFN-gamma assay provides different information than TST in BCG-vaccinated newborns and could be a better marker of vaccine-induced immunity.

The epidemiology and consequences of maternal malaria: a review of immunological basis.

Millions of women who become pregnant in malaria-endemic areas are at increased risk of contracting malaria infection that jeopardises the outcome of pregnancy. The complication of this infection for mother and baby are considerable. In absence of any other reason, it was thought that the increased risk of infection during pregnancy was related to suppression of pre-existing malaria immunity. Although this concept is plausible, the significantly higher risk of maternal malaria and consequences in primigravidae compared with multigravidae suggests that there are more to mere immunosuppression in pregnancy. The mechanisms underlying some of the striking epidemiological and clinical features of malaria in pregnancy could be related to differences in the strains of parasite populations infecting pregnant women occasioned by the cyto-adherent properties of human placenta, presence or absence of anti-adhesion antibodies acquired from previous pregnancies or the elevated production of some pro-inflammatory cytokines in response to parasitisation of human placenta. Malaria infection of placenta causes a shift from Th2 to Th1 cytokine profile that may be detrimental to pregnancy. The increased susceptibility in the first pregnancy can be explained by the absence of anti-adhesion antibody in the primigravida that is being exposed for the first time to a different strain of malaria parasite sub-population that adhere exclusively to chondroitin sulphate A and hyaluronic acid (HA) in the placenta. In reviewing the epidemiology and consequences of maternal malaria, we have highlighted possible immunological and molecular basis that could account for the higher impact of malaria in pregnancy especially among primigravidae. These factors could be the basis for future research and vaccine formulation.

Influence of placental malaria infection on foetal outcome in the Gambia: twenty years after Ian Mcgregor.

Malaria infection in pregnancy has serious health consequences among mothers and offspring. The influence of placental malaria infection on foetal outcome was studied in a Gambian rural setting where few pregnant women take antimalarial chemoprophylaxis. During July-December 1997, three hundred thirteen mother-newborn pairs (singletons only) were consecutively recruited into a study of the effects of placental malaria infection on the outcome of pregnancy. Placental blood and tissue were collected at delivery. Babies were clinically assessed until discharge. The overall prevalence of placental malaria infection was 51.1% by placental histology and 37.1% by blood smear. The primigravid women were more susceptible to placental malaria than the multigravidae (65.3% vs 44.7%, p=0.01). Placental malaria was significantly associated with pre-term deliveryand intrauterine growth retardation (p<0.01), and there was a four-fold risk of delivering low-birth-weight babies if mothers had parasitized placentae [OR=4.42, 95% confidence interval (CI) 2.10-9.27]. A reduction of mean birth-weight of babies by 320 g was associated with placental malaria infection (p<0.001). Similarly, a two-fold risk of stillbirth delivery (OR=2.22, 95% CI 1.04-4.72) was observed among the infected mothers. The findings showed that there was still an overall poor foetal outcome associated with placental malaria infection. The findings of this study confirm the findings of an earlier study by McGregor in the Gambia that the low birth-weight rate is significantly higher if the placenta is parasitized. In addition, this study observed that the high stillbirth and prematurity rates were associated with placental malaria infection. The findings of the present study suggest undertaking of effective malaria-control strategies during pregnancy, such as use of insecticide-impregnated bednets, intermittent and early treatment for malaria, and antimalarial chemoprophylaxis, in the Gambia.