Community cohort study of rotavirus and other enteropathogens: are routine vaccinations associated with sex-differential incidence rates?

OBJECTIVE: Community studies in West Africa have demonstrated that routine vaccinations may have non-targeted effects, the female-male mortality ratio being reduced after administration of BCG and increased after diphtheria-tetanus-pertussis (DTP). We examined whether immunisation status was associated with infection with rotavirus and other enteropathogens. METHODS: We recruited 200 children shortly after birth and followed them until 2 years of age with weekly morbidity interviews and stool sampling. Vaccination status for each child was classified according to the most recent vaccination as documented by vaccination card. MAIN OUTCOME MEASURES: The female-male incidence rate ratios (IRR) of infection with an enteropathogen and of enteropathogen-associated diarrhoea were estimated for children according to whether they had received BCG or DTP as their last vaccination. RESULTS: For children who received BCG as their last vaccine, the adjusted female-male IRRs for primary rotavirus-infection and diarrhoea were 1.05 (95% CI: 0.21-5.28) and 0.0 (95% CI: 0-3.02), respectively. For children who received DTP as their last vaccine, the adjusted female-male IRRs were 1.93 (0.89-4.21) and 1.92 (0.70-5.32), respectively, for rotavirus-associated infection and diarrhoea. Restricted to the rotavirus season, the female-male IRRs for rotavirus infection and diarrhoea were 2.56 (1.17-5.63) and 2.63 (0.94-7.34), respectively. The female-male IRR for rotavirus-associated diarrhoea differed significantly among BCG and DTP recipients (p=0.02). Infections with enteropathogens not associated with diarrhoea were associated with lower female-male IRRs after BCG of 0.82 (0.55-1.23) and higher female-male IRRs after DTP vaccination of 1.32 (1.03-1.70) for primary infection (p=0.05). Though there were few infections with other diarrhoea-causing enteropathogens, these were also associated with a lower female-male IRR after BCG of 0.62 (0.26-1.52) and a higher female-male IRR after DTP vaccination of 1.51 (1.04-2.20) for all infection. CONCLUSION: Routine immunisations may affect morbidity for non-targeted infections. As in studies of infant mortality, BCG is associated with lower risk for girls, whereas, DTP is associated with higher risk for girls relative to boys.     

Age-specific changes in the female-male mortality ratio related to the pattern of vaccinations: an observational study from rural Gambia

BACKGROUND: According to studies from Guinea-Bissau and Senegal, live vaccines may reduce the female-male mortality ratio (MR) whereas inactivated vaccines increase this ratio. We used data from The Gambia to examine whether similar tendencies could be found in a different setting. SETTING: Forty villages in the Farafenni area in rural Gambia. SUBJECTS: A population of 17,000 was followed with demographic surveillance between 1998 and 2002; 537 children less than 5 years of age died in this period. METHODS: We used two vaccination surveys and community mortality data to examine, first, the female-male mortality ratio (MR) in the age groups in which DTP and MV are recommended and have a high coverage. Second, using vaccination cards seen post-mortem, we examined the distribution of live or inactivated vaccines as last vaccination in different age groups. Third, we examined the effect of DTP and MV administered simultaneously. MAIN OUTCOME MEASURES: The female-male MR in different age groups and for different vaccines. RESULTS: Vaccination coverage was high for BCG, third dose of DTP (DTP3) and MV, reaching a level of 80-90% within a few months of the recommended age of vaccination. First, the female-male MR was 0.93 (0.63-1.38) in the first 2 months of life when children had received no vaccination or the combination of BCG, HBV and OPV. From 2 to 8 months of age, with DTP and HBV being the main vaccinations, the female-male MR was 1.28 (0.86-1.89). Between 9 and 17 months of age, with MV as the main vaccination, this ratio dropped to 0.73 (0.50-1.07), a significant inversion of the female-male MR (p=0.045). Second, using information from vaccination cards of dead children, boys who died at 2-4 months of age were more likely to have received live BCG and girls to have received inactivated DTP and HBV as last vaccination (p<0.001). At 5-8 months of age, essentially all dead children had received DTP as last vaccination and the female-male MR was 1.68 (0.96-2.93), whereas the MR was 0.70 (0.43-1.15) at 12-17 months of age when nearly all dead children had received MV (p=0.022). Third, compared with the general population of children who had received MV, dead children who had received MV were more likely to have received DTP3 simultaneously with MV (relative risk (RR)=5.59 (2.10-14.8)) or after MV (RR=2.61 (1.13-6.05)). CONCLUSION: Most children dying at a specific age had received the recommended vaccines. BCG and MV as last vaccination was associated with a low female-male MR, whereas DTP as last vaccination was associated with a high female-male MR. These trends are consistent with observations from other African countries.     

Divergent female-male mortality ratios associated with different routine vaccinations among female-male twin pairs

BACKGROUND: Observational studies have suggested that vaccinations have non-specific effects that differ by sex. In the absence of randomized trials, studies of female-male twin pairs would allow us to investigate whether an intervention had sex-specific effects on survival. We therefore examined mortality patterns among female-male twin pairs according to vaccination status. Design We identified female-male twin pairs using the population registers from one urban district and three rural studies from Guinea-Bissau and Senegal and examined the female-male mortality ratio (MR) according to the last vaccine received among pairs in which a death occurred before 18 months of age. As background information, we examined sex- and age-specific mortality patterns in the pre-vaccination era. Subjects In all, 626 female-male twin pairs identified between 1978 and 2000. RESULTS: There was no sex difference in mortality for boys and girls in the pre-vaccination era. In the combined analysis of all studies, the female-male MR was 0.25 (95% CI: 0.05, 0.93) for pairs having received Bacille Calmette-Guerin (BCG) as the last vaccine, 7.33 (95% CI: 2.20, 38.3) for pairs having received diphtheria, tetanus, pertussis (DTP) as the last vaccine, and 0.40 (95% CI: 0.04, 2.44) for pairs having received measles vaccine as the last vaccine. The female-male MR varied significantly for BCG compared with DTP (exact test of homogeneity, P < 0.001) and for DTP compared with measles vaccine (exact test of homogeneity, P = 0.001). CONCLUSION: Non-specific effects of routine vaccinations are likely to be important and influence sex-specific mortality patterns in areas with high mortality. The effects of vaccines need to be considered in the planning of immunization programmes for low-income countries.     

Vaccination status and sequence of vaccinations as risk factors for hospitalisation among outpatients in a high mortality country

Background

Most developing countries are implementing the WHO immunisation programme. Although vaccines reach most children, many modifications of the recommended schedule are observed in practice. We investigated the association between vaccination status and risk of hospitalisation in Guinea-Bissau.

Methods

From May 2003 to May 2004, all consultations of children less than five years of age at the outpatient clinic of the paediatric ward at the national hospital in Bissau were registered. For each consultation, information was collected about the child's name, sex, age and socio-cultural conditions, as well as diagnosis and whether the child was hospitalised. Information about vaccinations was also registered from the child's vaccination card. We analysed the association between vaccination status and risk of hospitalisation in age intervals according to the pre-dominant vaccines. We particularly emphasised the comparison of those who had received the recommended vaccination for the age groups and those who were delayed and only had the previous vaccinations. We also examined those who had received the vaccines out of sequence.

Results

Information about vaccinations was available for 11,949 outpatient children of whom 2219 (19%) were hospitalised. Among children less than 3 months of age, unvaccinated children compared to BCG children had as expected a higher risk of hospitalisation; controlled for important determinants of hospitalisation, the hospitalisation risk ratio (HRR) was 1.99 (95% CI 1.37-2.89). In contrast, there was no difference in the HRR for children aged 1 ½ -8 months who were delayed and had only received BCG compared to those who as recommended had received diphtheria-tetanus-pertussis (DTP) vaccine after BCG (HRR = 1.10 (0.77-1.59)). In the age interval 9-17 months of age, children who were delayed and had only received DTP had significantly higher risk of hospitalisation compared with children who as recommended had measles vaccine (MV) as the most recent vaccination (HRR = 1.39 (1.16-1.66)). Having received DTP after MV (HRR = 1.60 (1.15-2.24)) or MV and DTP simultaneously (HRR = 1.51 (1.16-1.97)) was also associated with higher risk than MV only as most recent vaccination. In contrast, the children aged 18-59 months who as recommended had received a DTP booster after MV did not have lower risk of hospitalisations compared with children who were delayed and had received only MV (RR = 0.90 (0.75-1.07)). After 9 months of age, there was a significant difference in the female-male HRR for children who had MV (HRR = 0.85 (0.72-1.00)) or DTP (HRR = 1.08 (0.96-1.22)) as most recent vaccination (p = 0.02, test of interaction).

Conclusion

Following the recommended vaccination schedule for BCG and MV is associated with a reduced risk of hospitalisation but this is not the case for DTP and booster DTP. Receiving DTP simultaneously with MV or after MV is associated with increased risk of hospitalisation. Vaccines have sex-differential effects on the risk of hospitalisation.     

Routine vaccinations and child survival in a war situation with high mortality: effect of gender

Non-specific effects of vaccination may be different for boys and girls. Due to the sequential administration of vaccines, it is difficult to separate the effect of different vaccines. We tested sex-specific effects of diphtheria, tetanus, pertussis (DTP) and polio vaccines and measles vaccines during the recent war (1998) in Guinea-Bissau when there was no functioning immunisation programme in the country. The study included 1491 children aged 1-17 months in four urban districts in Bissau. Vaccination status had been assessed in the study area in the 3 months before the war. The effect of DTP and polio vaccines was assessed for children who had not received measles vaccine. The effect of measles vaccine was evaluated for children aged 6-17 months. Compared with measles-unvaccinated children, measles-vaccinated children had lower mortality (mortality ratio (MR)=0.44 (95% CI 0.20-1.00)), the difference being marked for girls (0.25 (0.09-0.71)) but not for boys (0.84 (0.26-2.75)) (test of homogeneity, P=0.095). If measles cases were censored in the analysis, the mortality ratio for vaccinated and unvaccinated children was 0.38 (0.16-0.89). DTP and polio-vaccinated children did not have lower mortality than unvaccinated children. The female-male mortality ratio for DTP and polio-vaccinated children was 3.08 (1.11-8.56) and 0.63 (0.28-1.40) for measles-vaccinated children, a significant inversion of the ratios (test of homogeneity, P=0.013). The divergent female-male mortality ratios are unlikely to be explained by a selection bias going in different directions for different vaccines. The reduction associated with measles vaccination was unrelated to prevention against measles infection. Non-specific effects of vaccination should be assessed separately for boys and girls. Taking these effects into consideration may have implications for child mortality patterns in developing countries.     

The sequence of vaccinations and increased female mortality after high-titre measles vaccine: trials from rural Sudan and Kinshasa

OBJECTIVE: West African studies have hypothesized that increased female mortality after high-titre measles vaccine (HTMV) was due to subsequent diphtheria-tetanus-pertussis (DTP) and inactivated polio vaccine (IPV) vaccinations. We tested two deductions from this hypothesis in HTMV studies from rural Sudan and Kinshasa; first, there should be no excess female mortality for HTMV recipients when DTP was not given after HTMV and second, excess female mortality should only be found among those children who received DTP after HTMV. STUDIES: The Sudanese trial randomised 510 children to Edmonston-Zagreb (EZ) HTMV, Connaught HTMV or a control vaccine (meningococcal). Both the Connaught HTMV and the control group received standard measles vaccine at 9 months. In the Kinshasa study 1023 children received one dose of HTMV at 6 months or two doses at 312 and 912 months of age. FINDINGS: First, the Sudan trial is one of the few randomised studies of measles vaccine; the EZ HTMV group had lower mortality between 5 and 9 months of age than controls, the mortality ratio (MR) being 0.00 (p = 0.030). This effect was not due to prevention of measles infection. Second, both studies provided evidence that HTMV per se was associated with low mortality. In a combined analysis comparing both HTMV groups with controls, the HTMV groups had a MR of 0.09 (0.01-0.71) between 5 and 9 months of age. In Kinshasa, the HTMV recipients who did not receive simultaneous DTP had an annual mortality rate of only 1.0% between 6 months and 3 years of age. Third, the female-male MR was related to subsequent DTP vaccinations. In Kinshasa, the female-male MR was only 0.40 (0.13-1.27) among the HTMV recipients who did not receive further doses of DTP. In Sudan, the female-male mortality ratio in the EZ group was 3.89 (95% CI 1.02-14.83) and the female-male MR increased with number of doses of DTP likely to have been given during follow-up (trend, p = 0.043). Fourth, in Kinshasa, mortality was higher among children who had received HTMV and DTP simultaneously than among children who had received HTMV alone (MR = 5.38 (1.37-21.2)). CONCLUSIONS: Measles vaccine is associated with non-specific beneficial effects. When not given with DTP, HTMV per se was associated with low mortality. Increased female mortality was not found among children who did not receive DTP after HTMV. Hence, our deductions were supported and the sequence or combination of vaccinations may have an effect on sex-specific mortality patterns in low-income countries.     

Non-specific and sex-differential effects of vaccinations on child survival in rural western India

Background

Studies from Africa have suggested marked non-specific effects (NSEs) of routine vaccinations with effects on child survival. There have been few studies from Asia. We re-analyzed a study from Maharashtra, India, which had collected information on vaccinations during infancy and survival until 5 years of age.

Design

4138 children born between 1987 and 1989 were visited at home every three months to collect information on nutritional status and vaccinations. Since nutritional status was a determinant of time to vaccinations, we adjusted for nutritional status in the analyzes of the association between vaccinations and mortality.

Setting

45 contiguous villages in Shirur Administrative Block in Pune District.

Main outcome measures

Mortality rate ratios (MRR) for different vaccination status groups.

Results

The study area has male preferential treatment, but the female–male mortality ratio varied between age groups with different pre-dominant vaccines; it was high in the age group in which diphtheria–tetanus–pertussis (DTP) vaccine predominates and low in the age group in which measles vaccine (MV) is given. Children who followed the WHO recommended schedule of first BCG and then DTP vaccination were vaccinated earlier than other children (p < 0.01). Two-thirds of the children had received BCG and DTP out-of-sequence, i.e. BCG and DTP simultaneously or BCG after DTP. Children who received BCG and DTP simultaneously or BCG as most recent vaccination had significantly lower mortality than children having DTP as the most recent vaccination, the mortality rate ratio being 0.15 (0.03–0.70).

Conclusions

BCG out-of-sequence may be associated with lower mortality than DTP as the most recent vaccination. Given the public health implications, this possibility should be tested in randomized trials. Excess female mortality may also be related to vaccination policy.     

Oral polio vaccination and low case fatality at the paediatric ward in Bissau, Guinea-Bissau

Oral polio vaccine (OPV) and diphtheria-tetanus-pertussis (DTP) vaccines are given simultaneously in routine immunisation programmes in developing countries. It is therefore difficult to determine the separate effects of these vaccines on survival. We used the shortage of DTP vaccine in Bissau to examine the impact of OPV on the case fatality at the paediatric ward in Bissau. For 719 children less than 5 years of age whose vaccination card had been seen at admission and who had not yet received measles vaccine, having received OPV only was associated with a case fatality of 6% compared with 15% for children having received combined DTP and OPV vaccinations, the case fatality ratio (CFR) being 0.29 (95% confidence interval (CI) 0.11-0.77). Even if children fleeing the hospital were assumed to have died shortly after leaving the hospital, the case fatality would still be lower for children having received OPV only (CFR = 0.41; (95% CI 0.20-0.81)). The tendency was similar for children hospitalised with pneumonia, diarrhoea, and presumptive malaria. Control for background factors had no impact on the estimate. In areas with high mortality, OPV administered alone may have non-specific beneficial effects or DTP may have a negative effect for children who had received both DTP and OPV.     

DTP with or after measles vaccination is associated with increased in-hospital mortality in Guinea-Bissau

BACKGROUND: The sequence of routine immunisations may be important for childhood mortality. Three doses of diphtheria-tetanus-pertussis vaccine (DTP) should be given at 6, 10, and 14 weeks and measles vaccine (MV) at 9 months of age. The sequence is not always respected. We examined in-hospital mortality of children having received DTP with or after measles vaccine. SETTING: The only paediatric ward in Bissau, Guinea-Bissau. PARTICIPANTS: Children hospitalised during two periods in 1990-1996 and 2001-2002 who had received MV prior to hospitalisation. MAIN OUTCOME MEASURE: The all-cause case fatality at the hospital for children aged 6-17 months. RESULT: The case fatality was increased for children who had received DTP with or after measles vaccine compared with children who had received measles vaccine as the most recent vaccine, the ratio being 2.53 (1.37-4.67) and 1.77 (0.92-3.41) in the two periods, respectively. The combined estimate was 2.10 (1.34-3.28). These results were not explained by differences in nutritional status, number of doses of DTP or discharge policy. CONCLUSION: Administration of DTP with, or after MV, may reduce the beneficial effect of MV.     

Non-specific effects of diphtheria tetanus pertussis vaccination on child mortality in Cebu, The Philippines

BACKGROUND: To determine the non-specific effects of diphtheria, tetanus and pertussis (DTP) vaccination and sex on mortality before 30 months of age among those who received Bacille Calmette Guerin (BCG) vaccine in a high mortality area. METHODS: This analysis used a longitudinal study of child survival monitoring the use of primary care services, morbidity and mortality in Metro Cebu, The Philippines. Participants included 14 537 children under 30 months of age who received a BCG vaccination from July 1988 to January 1991. The main outcome measure was all-cause mortality. RESULTS: Mortality before 30 months of age was 57% lower among BCG-vaccinated children who received DTP vaccination than BCG-vaccinated children who did not receive DTP vaccination {hazard ratio (HR) for vaccinated vs unvaccinated 0.43 [95% confidence interval (CI) 0.21-0.88]}. Females had lower mortality rates [HR = 0.19 (0.04-0.86), P = 0.03] than males among DTP-unvaccinated children. The protective effect of DTP vaccination was more pronounced in males [HR 0.32 (0.14-0.73)] than in females [HR 0.86 (0.18-4.23)]. DTP vaccination increased (interaction term P = 0.08) the female-to-male mortality ratio to 0.76 (0.52-1.12). CONCLUSIONS: Among BCG-vaccinated children under 30 months of age, DTP vaccination is associated with improved survival. The increased female-male mortality ratio is associated with reduced mortality among males following DTP vaccination rather than increased mortality among female children.     

Fewer out-of-sequence vaccinations and reduction of child mortality in Northern Ghana

BackgroundStudies suggest that diphtheria-tetanus-pertussis (DTP) vaccine administered simultaneously with measles vaccine (MV) or DTP administered after MV are associated with higher child mortality than having MV-after-DTP3 as most recent vaccination. We tested this in Northern Ghana where the prevalence of such out-of-sequence vaccinations has declined.MethodsUsing annual cohort data of children aged 12–23 months from 1996 to 2012 and Cox proportional hazards models, we assessed survival in relation to the most recent vaccination status within the next 12 months and until five years of age. We assessed whether mortality in children aged 12–59 months was higher when the most recent vaccine was non-live (DTP) rather than live (MV or OPV).ResultsOut-of-sequence vaccinations with DTP-containing vaccines and MV declined from 86% in 1989 to 24% in 1996 and 0.7% in 2012. Between 1996 and 2012, 38 070 children had their vaccinations status assessed: the adjusted hazard ratio (HR) for out-of-sequence vaccinations (DTP >= MV) compared with the recommended sequence of MV-after-DTP3 was 1.42(1.06–1.90) during the first 12 months after assessment of vaccination status and 1.29(1.03–1.60) with follow-up to five years of age; the HR was 2.58(1.14–5.84) before OPV or MV campaigns and 1.37(1.02–1.85) after the campaigns.ConclusionOut-of-sequence vaccinations with DTP and MV are associated with higher mortality than MV as most recent vaccination; the effect is unlikely to be due to confounding. Hence, the reduction in out-of-sequence vaccinations may have lowered child mortality. It is recommended not to give DTP with MV or DTP after MV.     

The introduction of diphtheria-tetanus-pertussis vaccine and child mortality in rural Guinea-Bissau: an observational study

BACKGROUND: and objective Previous studies from areas with high mortality in West Africa have not found diphtheria-tetanus-pertussis (DTP) vaccine to be associated with the expected reduction in mortality, a few studies suggesting increased mortality. We therefore examined mortality when DTP was first introduced in rural areas of Guinea-Bissau in 1984-1987. Setting Twenty villages in four regions have been followed with bi-annual examinations since 1979. SUBJECTS: In all, 1657 children aged 2-8 months. Design Children were weighed when attending the bi-annual examinations and they were vaccinated whenever vaccines were available. DTP was introduced in the beginning of 1984, oral polio vaccine later that year. We examined mortality for children aged 2-8 months who had received DTP and compared them with children who had not been vaccinated because they were absent, vaccines were not available, or they were sick. MAIN OUTCOME MEASURE: Mortality over the next 6 months from the day of examination for vaccinated and unvaccinated children. RESULTS: Prior to the introduction of vaccines, children who were absent at a village examination had the same mortality as children who were present. During 1984-1987, children receiving DTP at 2-8 months of age had higher mortality over the next 6 months, the mortality rate ratio (MR) being 1.92 (95% CI: 1.04, 3.52) compared with DTP-unvaccinated children, adjusting for age, sex, season, period, BCG, and region. The MR was 1.81 (95% CI: 0.95, 3.45) for the first dose of DTP and 4.36 (95% CI: 1.28, 14.9) for the second and third dose. BCG was associated with slightly lower mortality (MR = 0.63, 95% CI: 0.30, 1.33), the MR for DTP and BCG being significantly inversed. Following subsequent visits and further vaccinations with DTP and measles vaccine, there was no difference in vaccination coverage and subsequent mortality between the DTP-vaccinated group and the initially DTP-unvaccinated group (MR = 1.06, 95% CI: 0.78, 1.44). CONCLUSIONS: In low-income countries with high mortality, DTP as the last vaccine received may be associated with slightly increased mortality. Since the pattern was inversed for BCG, the effect is unlikely to be due to higher-risk children having received vaccination. The role of DTP in high mortality areas needs to be clarified.     

Routine vaccinations associated with divergent effects on female and male mortality at the paediatric ward in Bissau, Guinea-Bissau

Several studies have suggested that routine childhood immunisations may have non-specific effects on mortality. To examine which disease categories might be affected, we investigated whether immunisation status had an impact on the case fatality for hospitalised children. Between 1990 and 1996, the Bandim Health Project maintained a register of all children from the study area hospitalised at the paediatric ward of the central hospital in Bissau, Guinea-Bissau. The study included 2079 hospitalised children aged 1.5-17 months coming from the Bandim study area. Among children whose vaccination card had been seen at admission, the case fatality ratio for measles-vaccinated children versus measles-unvaccinated children was 0.51 (0.27-0.98), the beneficial effect being significantly stronger for girls than for boys (test of interaction, p=0.050). The protective effect of measles vaccine remained unchanged when hospitalised measles cases were excluded from the analysis (0.49 (0.26-0.94)). The effect of measles vaccine was strongest for children with pneumonia (MR=0.28 (0.07-0.91)) and presumptive malaria (MR=0.40 (0.13-1.18)). For measles-vaccinated children, the female to male case fatality ratio was 0.54 (0.28-0.97). Among children having received diphtheria-tetanus-pertussis (DTP) and oral polio (OPV) as the last vaccines, girls had higher case fatality than boys, the mortality ratio being 1.63 (1.03-2.59). The female to male ratios were significantly inversed for DTP and OPV versus measles vaccine (test of interaction, p=0.003). These results remained unchanged if 1-month post-discharge deaths were included in the analysis, and in multivariate analyses controlling for determinants of mortality. In conclusion, measles vaccine was associated with reduced mortality from diseases other than measles, the beneficial effect being stronger for girls than for boys. On the other hand, DTP and OPV vaccine were associated with higher case fatality for girls than for boys. Understanding the divergent non-specific effects of common vaccines may contribute to better child survival in developing countries.     

The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination

Unexpectedly, we found no overall beneficial effect on mortality in a randomised trial of vitamin A supplementation (VAS) or placebo administered with BCG vaccine at birth in Guinea-Bissau. We conducted an explorative analysis to examine whether subsequent diphtheria–tetanus–pertussis (DTP) vaccinations had modified the effect of VAS at birth. VAS was associated with a weak tendency for decreased mortality as long as BCG was the most recent vaccination, the mortality rate ratio being 0.86 (0.48–1.54); 0.82 (0.32–2.08) in girls and 0.89 (0.43–1.88) in boys. However, after DTP vaccination VAS at birth was associated with increased mortality in girls (2.19 (1.09–4.38)), whereas no difference was seen for boys (0.90 (0.44–1.82)) (p = 0.08 for equal effect of VAS in the two sexes if DTP is the last vaccine). The explanation for the lack of beneficial effect in our setting may have been that VAS at birth interacted negatively with subsequent DTP vaccinations in girls.     

BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria-tetanus antigens.

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria-tetanus-pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria-tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40-4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25-2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02-1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria-tetanus antigens (OR=0.42 (0.28-0.63), OR=0.77 (0.60-0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19-2.19)). DTP vaccination was associated with less anergy to diphtheria-tetanus antigens (OR=0.40 (0.32-0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria-tetanus antigens (OR=0.36 (0.26-0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria-tetanus antigens (OR=0.40 (0.16-0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria-tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.     

Benefits of routine immunizations on childhood survival in Tari, Southern Highlands Province, Papua New Guinea

BACKGROUND: Non-specific beneficial as well as deleterious effects of childhood immunizations have been reported in areas of high mortality. This study aimed to determine the effects of diphtheria-tetanus-whole-cell-pertussis (DTP), BCG, hepatitis B, and measles vaccines on mortality in the highlands of Papua New Guinea (PNG). METHODS: Demographic events for children born in 1989-1994 who were under monthly demographic surveillance in Tari were recorded from birth until age 2 years, out-migration, death, or the end of the study period. Data on BCG, hepatitis B, DTP, measles and pneumococcal polysaccharide vaccination were collected monthly from clinic records. To allow for different characteristics of immunized and non-immunized children, analysis included conditioning on a propensity score for vaccination, adjusting for differences in children's background characteristics. RESULTS: In all, 101/3502 children (3%) who had at least one vaccine died between ages 29 days and 24 months were compared to 112/546 (21%) who had none. BCG was associated with lower mortality in the 1-5 month age group (hazard ratio [HR] = 0.17, 95% CI: 0.09, 0.34), measles vaccine with lower mortality at age 6-11 months (HR = 0.42, 95% CI: 0.17, 1.01), and pneumococcal polysaccharide vaccine with lower mortality at age 12-23 months (HR = 0.42, 95% CI: 0.19, 0.93). One or more doses of DTP was associated with lower overall mortality (HR = 0.27, 95% CI: 0.16, 0.44), particularly in the 1-5 month age group (HR = 0.19, 95% CI: 0.10, 0.34), and also in those who had had prior BCG (HR = 0.45, 95% CI: 0.22, 0.91). CONCLUSION: Routine immunizations are effective in reducing overall mortality in young children in an area of high mortality. In particular, DTP, whether considered separately or in addition to BCG, was associated with a lowering of overall mortality, in contrast to findings reported from Guinea-Bissau.     

Do selective immunisation against tuberculosis and hepatitis B reach the targeted populations? A nationwide register-based study evaluating the recommendations in the Norwegian Childhood Immunisation Programme

BackgroundSelective immunisation is an alternative to universal vaccination if children at increased risk of disease can be identified. Within the Norwegian Childhood Immunisation Programme, BCG vaccine against tuberculosis and vaccine against hepatitis B virus (HBV) are offered only to children with parents from countries with high burden of the respective disease. We wanted to study whether this selective immunisation policy reaches the targeted groups.MethodsThe study population was identified through the Norwegian Central Population Registry and consisted of all children born in Norway 2007–2010 and residing in Norway until their second birthday, in total 240,484 children. Information on vaccinations from the Norwegian Immunisation Registry, and on parental country of birth from Statistics Norway, was linked to the population registry by personal identifiers. The coverage of BCG and HBV vaccine was compared with the coverage of vaccines in the universal programme.ResultsAmong the study population, 16.1% and 15.9% belonged to the target groups for BCG and HBV vaccine, respectively. Among children in the BCG target group the BCG vaccine coverage was lower than the coverage of pertussis and measles vaccine (83.6% vs. 98.6% and 92.3%, respectively). Likewise, the HBV vaccine coverage was lower than the coverage of pertussis and measles vaccine in the HBV target group (90.0% vs. 98.6% and 92.3%, respectively). The coverage of the targeted vaccines was highest among children with parents from South Asia and Sub-Saharan Africa. The coverage of vaccines in the universal programme was similar in targeted and non-targeted groups.ConclusionsChildren targeted by selective vaccination had lower coverage of the target vaccines than of vaccines in the universal programme, indicating that selective vaccination is challenging. Improved routines for identifying eligible children and delivering the target vaccines are needed. Universal vaccination of all children with these vaccines could be considered.     

Using surveys of schoolchildren to evaluate coverage with and opportunity for vaccination in Costa Rica]

OBJECTIVE: To identify differences in the level of coverage of and opportunity for vaccination among schoolchildren in three areas in Costa Rica with different characteristics: an urban area (with the highest level of socioeconomic development of the three areas), a rural area (with a medium level of socioeconomic development), and a border area (a rural area in northern Costa Rica, on the border with Nicaragua, with the lowest level of socioeconomic development and the highest proportion of foreign immigrants). METHODOLOGY: Following selection of schools by proportional probability, surveys were used with children chosen at random from the first and second grades of elementary schools in the three areas: urban (961 students), rural (544 students), and border (811 students). The data on the vaccines that had been administered were obtained from the children's vaccination cards. Differences among the three areas were evaluated: (1) in the coverage with BCG; with three doses of diphtheria-tetanuspertussis vaccine (DTP3); with three doses of oral polio vaccine (OPV3); with the first dose of measles-mumps-rubella vaccine (MMR1); and with the second dose of MMR vaccine (MMR2) and (2) in the "opportunity" for the children having received DTP1 + OPV1 before 3 months of age, DTP3 + OPV3 before 7 months of age, and DTP4 + OPV4 + MMR1 before 24 months of age. RESULTS: Out of all the students who had been selected, 80% of them in the urban area had a vaccination card, 73% did in the rural area, and 72% did in the border area (P < 0.05). The coverage levels for BCG, DTP3, and OPV3 were each over 95% in both the urban area and the rural area; however, the coverage levels were significantly lower (P < 0.05) in the border area: BCG, 83%; OPV3, 88%; and DTP3, 88%. Coverage with MMR1 and MMR2 was similar in the three areas. The percentage of schoolchildren with two or more doses of measles vaccine was 98% in the urban area, 92% in the rural area, and 85% in the border area (P < 0.05). In terms of opportunity, 90% of the children had received DTP1 + OPV1 before 3 months of age in the urban area, 89% had in the rural area, and 80% had in the border area (P < 0.05). The percentage of application of the complete basic schedule (DTP4 + OPV4 + MMR1) before 24 months of age was 93% in the urban area, 95% in the rural area, and 84% in the border area (P < 0.05). CONCLUSIONS: The border area had lower coverage of and opportunity for the basic schedule of vaccines, except for MMR. Follow-up campaigns for measles eradication have increased the coverage of the initial and booster doses in all three areas, but the increase has been greatest in the urban area. A greater effort should be made to identify children with an incomplete schedule of vaccinations, with priority going to areas that have a high proportion of immigrants.     

Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age

BACKGROUND AND METHODS: measles is a common cause of morbidity and mortality in developing countries. Although the measles-mumps-rubella vaccine (MMR) is currently in use in developed countries, monovalent measles vaccine (MV) is routinely recommended by World Health Organization (WHO) at 9 months of age in Turkey, as in many other developing countries. In this study, 442 Turkish children received MV at 9 months of age and were revaccinated with MMR vaccine at 15 months of age. In the second group 495 children received MMR at 12 months of age with no earlier measles vaccination. Antibodies were measured before the first vaccination and 6 weeks after the MMR. All children had been followed for occurrence of measles infection for 60 months. Two vaccination schedules were compared for immunogenicity and protection rates. CONCLUSIONS: seroconversion and clinical protection rates were significantly higher in children who received only MMR at 12 months of age than in children revaccinated at 15 months of age. Seroconversion rate for measles was 69.9% in children who received MMR at 12 months of age and 90.3% in children revaccinated at 15 months of age (P=0.0003). While there was no measles case in children who were revaccinated, 12 (2.7%) children in the first group acquired measles during the follow-up period. Vaccination at 12 months of age appeared to be better than the current national standard. The late elimination of maternal antibodies and the inhibitory effect of a weak antibody response after the first dose of vaccine at 9 months may explain the better immunogenicity and efficacy of the MMR vaccine given at 12 months of age.     

Acute lower respiratory tract infections and respiratory syncytial virus in infants in Guinea-Bissau: a beneficial effect of BCG vaccination for girls community based case-control study

Among measles unvaccinated infants in Guinea-Bissau, we tested whether case infants with acute lower respiratory tract infection (ALRI), especially ALRI caused by respiratory syncytial virus (RSV), were more likely to be Bacille Calmette Guerin (BCG)-unvaccinated and to have no scar after BCG vaccination than were control infants without symptoms of ALRI. Three hundred and eighty-six case infants with ALRI were identified at a paediatric clinic (N=84), a health centre (N=82), and in a community morbidity surveillance system (N=220). Control infants were matched on sex, age, and district and were also measles unvaccinated. In ALRI case infants, the adjusted OR of being BCG unvaccinated was 2.87 (1.31-6.32), 1.72 (0.48-6.19) in boys and 4.45 (1.48-13.4) in girls. Among BCG vaccinated ALRI case infants, the adjusted OR of having no BCG scar was 1.54 (0.86-2.75), 0.93 (0.45-1.91) in boys and 2.70 (1.21-6.02) in girls. In ALRI case infants with RSV infection, similar trends were observed. BCG vaccination may have a non-targeted protective effect against ALRI, the effect being most marked in girls.