1. |
- Benn, Christine Stabell, et al.
(author)
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Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial
- 2008
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In: BMJ (International Edition). - 0959-8146. ; 336:7658, s. 1416-1416
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Journal article (peer-reviewed)abstract
- Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Design Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering approximately 90 000 inhabitants. Participants 4345 infants due to receive BCG. Intervention Infants were randomised to 50 000 IU vitamin A or placebo and followed until age 12 months. Main outcome measure Mortality rate ratios. Results 174 children died during follow-up (mortality=47/ 1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival. Registration Clinical trials NCT00168597.
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2. |
- Roth, Adam, et al.
(author)
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Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau
- 2010
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In: BMJ: British Medical Journal. - : BMJ. - 1756-1833. ; 340
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Journal article (peer-reviewed)abstract
- Objective To determine whether BCG revaccination at 19 months of age reduces overall child mortality. Design Randomised trial, with follow-up to age 5. Setting A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inhabitants. Participants 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrolment. Intervention BCG vaccination or no vaccination (control). Main outcome measure Hazard ratios for mortality. Results 77 children died during follow-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrolment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrolment (hazard ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrolment (1.78, 1.04 to 3.04). Conclusions There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions.
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3. |
- Aaby, Peter, et al.
(author)
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Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial
- 2012
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In: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 97:8, s. 685-691
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Journal article (peer-reviewed)abstract
- Background Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants. Methods 2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit. Results Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls. Conclusion Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.
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4. |
- Aaby, Peter, et al.
(author)
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Randomized Trial of BCG Vaccination at Birth to Low-Birth-Weight Children: Beneficial Nonspecific Effects in the Neonatal Period?
- 2011
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 204:2, s. 245-252
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Journal article (peer-reviewed)abstract
- Background. Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG. Methods. In the period 2004-2008 we recruited 2320 LBW children in Bissau. The children were visited at home at 2, 6, and 12 months of age. With a pretrial infant mortality of 250 per 1000, we hypothesized a 25% reduction in infant mortality for LBW children. Results. Infant mortality was only 101 per 1000 during the trial. In the primary analysis, infant mortality was reduced insignificantly by 17% (mortality rate ratio [MRR] = .83 [.63-1.08]). In secondary analyses, early BCG vaccine was safe with an MRR of .49 (.21-1.15) after 3 days and .55 (.34-.89) after 4 weeks. The reduction in neonatal mortality was mainly due to fewer cases of neonatal sepsis, respiratory infection, and fever. The impact of early BCG on infant mortality was marked for children weighing <1.5 kg (MRR = .43 [.21-.85]) who had lower coverage for diphtheria-tetanus-pertussis vaccinations. Conclusions. Though early BCG did not reduce infant mortality significantly, it may have a beneficial effect in the neonatal period. This could be important for public health because BCG is often delayed in low-income countries.
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5. |
- Aaby, Peter, et al.
(author)
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Vaccinia scars associated with better survival for adults. An observational study from Guinea-Bissau
- 2006
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 24:29-30, s. 5718-5718
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Journal article (peer-reviewed)abstract
- BACKGROUND: Live vaccines including BCG and measles may have non-targeted beneficial effects on childhood survival in areas with high mortality. The authors therefore undertook a survey of vaccinia scars to evaluate subsequent mortality. SUBJECTS: Based on a population census, a cohort of 1893 adults in urban Guinea-Bissau was examined in 1998 and followed until 2002. MAIN OUTCOME MEASURE: All cause mortality, excluding accidents. RESULTS: The median age of vaccinia vaccinations had been 16-18 years. Adults with a vaccinia scar had a mortality ratio (MR) of 0.60 (0.41-0.87) compared to those without any scar. The effect was stronger for women. Mortality decreased with each additional vaccinia scar (MR=0.73 (0.56-0.95)). Among 502 individuals with information on HIV infection, the age-adjusted HIV-2 prevalence was 2.45 (1.06-5.65) for those with a vaccinia scar. Control for district, ethnic group, schooling, place of birth, quality of housing and HIV status had little effect on the estimate. Since vaccinia and BCG scars could have been confused, mortality for adults with vaccinia and/or BCG scar was compared to those without, the MR being 0.61 (0.41-0.89). CONCLUSION: Known cultural or socio-economic factors possibly associated with access to vaccination had no influence on the mortality ratio for having a vaccinia scar. Hence, vaccinia vaccination may have a prolonged beneficial effect on adult survival.
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6. |
- Andersen, Andreas, et al.
(author)
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The immunological effect of revaccination with Bacille Calmette-Guerin vaccine at 19 months of age
- 2013
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 31:17, s. 2137-2144
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Journal article (peer-reviewed)abstract
- Background: Bacille Calmette-Guerin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination. Methods: Children were randomized to BCG or nothing. Blood was sampled 6-11 weeks after randomization (early sample group) or 5-9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-gamma, interleukin (IL)-13, tumor-necrosis-factor (TNF)-alpha, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied. Results: Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-gamma (geometric mean ratio (GMR) = 4.54 (95% confidence interval: 3.13-6.58)) and IL-13 (GMR = 1.43 (1.00-2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR = 1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-alpha/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p = 0.03). In children without MN, BCG was associated with reduced TNF-alpha response in the early sample group (p = 0.006), and increased IL-10 in the late sample group (p = 0.03). Conclusion: BCG revaccination resulted in a strong IFN-gamma response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-alpha and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP-booster before enrolment and children who had not received MN, i.e. the group of children which also had lower mortality after BCG revaccination. (C) 2013 Elsevier Ltd. All rights reserved.
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7. |
- Diness, Birgitte R., et al.
(author)
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Effect of high-dose vitamin A supplementation on the immune response to Bacille Calmette-Guerin vaccines
- 2007
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In: American Journal of Clinical Nutrition. - 1938-3207. ; 86:4, s. 1152-1159
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Journal article (peer-reviewed)abstract
- Background: Vitamin A supplementation (VAS) at birth has been associated with decreased mortality in Asia. Bacille Calmette-Guerin (BCG) vaccine is given at birth in tuberculosis-endemic countries. Previous studies suggest that VAS may influence the immune response to vaccines. Objective: Our objective was to examine whether VAS influences the immune response to simultaneously administered BCG vaccine. Design: Within a randomized trial of 50 000 IU vitamin A or placebo Given with BCG vaccine at birth in Guinea-Bissau, 27 10 infants were examined for BCG scar formation and delayed-type hypersensitivity (DTH) to purified protein derivative of Mycobacterium tuberculosis (PPD) at 2 and 6 mo of age. The ex vivo cytokine response to PPD was measured in 607 infants. Results: At 2 mo of age, 39% (43% of the boys and 34% of the girls) responded to PPD. The prevalence ratio of a measurable PPD reaction for VAS compared with placebo recipients was 0.90 (95% CI: 0.80, 1.02) for all infants. 0.81 (95% CI: 0.69, 0.95) for boys, and 1.04 (95% CI: 0.86, 1.26) for girls. At 6 mo of age, 42% of the infants responded to PPD. No difference was observed between VAS and placebo recipients. The prevalence of BCG scar was not affected by VAS. The ex vivo interferon-gamma response to PPD was increased by VAS (means ratio: 1.40: 95% CI: 1.03, 1.91). Conclusions: VAS with BCG vaccination does not appear to interfere with the long-term immune response to BCG. However, VAS temporarily altered the DTH reaction to PPD in boys at 2 mo of age, suggesting sex differences in the immunologic response to VAS Given with BCG. This trial was registered at www.clinicaltrials.gov as #NCT00168597.
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8. |
- Poulsen, Anja, et al.
(author)
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Varicella zoster in Guinea-Bissau: intensity of exposure and severity of infection
- 2005
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In: Pediatric Infectious Disease Journal. - 1532-0987. ; 24:2, s. 102-107
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To describe the epidemiology of and risk factors for severe chickenpox in Guinea- Bissau. METHODS: A prospective household study in a semiurban area of the capital. Severity was assessed by number of pox, fever response and presence of pneumonia. Severity was compared for the first case in a house, that is, the index case, and the secondary cases infected at home. RESULT: We identified 1539 cases of chickenpox. The median age was lower for boys and secondary cases (both P < 0.03); 44.6% of children were 1-4 years of age. The likely minimum interval between index and secondary cases was 10 days; most secondary cases occurred 14-17 days after the index case. The length of the incubation period was related to the intensity of exposure (P < 0.01). The number of pox was higher for secondary cases (P < 0.01) and was related to intensity of exposure (P < 0.01). Secondary cases had higher fever and more frequently pneumonia (relative risk, 2.17; 95% confidence interval, 1.54-3.08). Children with pneumonia were younger and had more pox. Nutritional status was not related to severity. CONCLUSIONS: Age and intensity of exposure are important determinants for severity of chickenpox infection. The length of the incubation period depends on intensity of exposure, suggesting that the dose of infection might be important.
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9. |
- Sartono, Erliyani, et al.
(author)
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Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment
- 2010
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:5
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Journal article (peer-reviewed)abstract
- Background: Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. Methods and Findings: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-gamma (p = 0.004) and a tendency for lower IL-10 (p = 0.054) in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR) of having a PPD reaction being 0.75 (0.58-0.98), p = 0.033, and with a tendency for reduced likelihood of having a BCG scar (0.95 (0.91-1.00), p = 0.057)). Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05), p = 0.012. Conclusions: This study is the first to address the consequences for the immune response to BCG of simultaneous administration with OPV. Worryingly, the results indicate that the common practice in low-income countries of administering OPV together with BCG at birth may down-regulate the response to BCG vaccine.
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