[Show abstract][Hide abstract] ABSTRACT: Background. Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. Methods. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. As a pilot experiment we extracted RNA from blood samples before, and 6 weeks after, vaccination to analyze the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analyzed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. Results. We found very few transcripts to alter systematically. Those that did mainly belonged to the Interferon (IFN) signalling pathway. We scrutinized this pathway as well as the Interleukin (IL) pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. Conclusion. The transcriptome changes following DTP booster vaccination were subtle, but although the material was small, it was possible to identify sub groups that deviate from each other, mainly in the IFN response.
Scandinavian journal of clinical and laboratory investigation 05/2013; 73(4). DOI:10.3109/00365513.2013.783229 · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective Vitamin A supplementation (VAS) is estimated to reduce all-cause mortality by 24%. Previous studies indicate that the effect of VAS may vary with vaccination status. The authors evaluated the effect of VAS provided in campaigns on child survival overall and by sex and vaccination status at the time of supplementation.
Design Observational cohort study.
Setting and participants The study was conducted in the urban study area of the Bandim Health Project in Guinea-Bissau. The authors documented participation or non-participation in two national vitamin A campaigns in December 2007 and July 2008 for children between 6 and 35 months of age. Vaccination status was ascertained by inspection of vaccination cards. All children were followed prospectively.
Outcome measures Mortality rates for supplemented and non-supplemented children were compared in Cox models providing mortality rate ratios (MRRs).
Results The authors obtained information from 93% of 5567 children in 2007 and 90% of 5799 children in 2008. The VAS coverage was 58% in 2007 and 68% in 2008. Mortality in the supplemented group was 1.5% (44 deaths/2873 person-years) and 1.6% (20 deaths/1260 person-years) in the non-supplemented group (adjusted MRR=0.78 (0.46; 1.34)). The effect was similar in boys and girls. Vaccination cards were seen for 86% in 2007 and 84% in 2008. The effect of VAS in children who had measles vaccine as their last vaccine (2814 children, adjusted MRR=0.34 (0.14; 0.85)) differed from the effect in children who had diphtheria–tetanus–pertussis vaccine as their last vaccine (3680 children, adjusted MRR=1.29 (0.52; 3.22), p=0.04 for interaction).
Conclusion The effect of VAS differed by most recent vaccination, being beneficial after measles vaccine but not after diphtheria–tetanus–pertussis vaccine.
BMJ Open 01/2012; 2(1):e000448. DOI:10.1136/bmjopen-2011-000448 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Combined vaccination with diphtheria-tetanus-pertussis (DTP) and measles vaccine (MV) has been associated with increased mortality in observational studies. Among children missing MV and a dose of DTP and oral polio vaccine (OPV), we conducted a randomised trial of providing MV+DTP+OPV simultaneously, as currently recommended, or MV+OPV only, and examined the effect on morbidity and growth. We hypothesised that the MV+OPV group would experience less morbidity and grow better. Due to previous observations of sex differences in the non-specific effects of vaccinations, we analysed all data stratified by sex.
At the Bandim Health Project in Guinea-Bissau, 568 children who were due to receive MV and who were missing either DTP3 or DTP booster were enrolled in the study. A subgroup of 332 children was followed intensively to register adverse events and infections in the first month after vaccination. A subgroup of 276 children was followed every third month for a year to monitor growth. All children were followed for one year for infectious diseases, consultations, and hospitalisations.
As expected, adverse events were more common in the MV+DTP+OPV group; diarrhoea and use of medication were increased among girls but not among boys (both p=0.02, test of interaction between DTP and sex). Febrile disease with vesicular rash, as well as consultations and hospitalisations tended to be more common in the MV+DTP+OPV group than in the MV+OPV group; the hazard ratio (HR) for febrile disease with vesicular rash was 1.86 (1.00; 3.47). The strongest tendencies for more febrile diseases and hospitalisations in the MV+DTP+OPV group were found in girls. Overall, growth did not differ by randomisation group. However, results differed by sex. Girls in the MV+DTP+OPV group had a consistent pattern of worse z-scores for weight, height, and mid-upper-arm-circumference (MUAC) than girls in the MV+OPV group. The effect was opposite for boys, with boys in the MV+OPV group faring worse than those in the MV+DTP+OPV group, the interaction test for sex and DTP being significant for weight at 6 and 9 months, for MUAC at 12 months and for weight-for-height at 3 and 9 months after randomisation.
This is the first randomised trial of the non-specific effects of DTP and supports that these effects may be sex-differential and of clinical and anthropometric importance. Combined vaccination with DTP+MV+OPV may be detrimental for girls.
[Show abstract][Hide abstract] ABSTRACT: Increased mortality and morbidity with intracellular pathogens has been reported in females with diphtheria-tetanus-pertussis (DTP) as their most recent vaccination. Within a randomised trial, we investigated the effect of DTP on Chlamydia pneumoniae serology. Eighteen-month-old children were randomised to DTP booster and oral polio vaccine (OPV) or OPV only. Blood samples collected from 523 children at baseline and six months later were analysed for C. pneumoniae antibodies. The C. pneumoniae IgG seroprevalence was high, with 12% positive at 18 months of age. Loss of IgG positivity was common during follow-up (25/65 (38%)), and was associated with lower weight-for-age. DTP did not affect the incidence of IgG seroconversion or IgM positivity. Among normal-weight children, DTP vaccination was associated with an increase in C. pneumoniae infection for females, whereas the trend was the opposite among males (p=0.05, test of interaction between sex and DTP). Among DTP-vaccinated children, the male-female risk ratio was 2.23 (95% CI=0.88-5.66) for IgG seroconversion and 0.0 (95% CI=0.0-0.77) for IgM positivity. The overall C. pneumoniae seroprevalence in young children was high even though loss of IgG positivity was common. We found sex differences in IgG seroconversion and in IgM positivity among DTP-vaccinated children.