Doses Of Diphtheria-tetanus-pertussis Research Articles

473Preventable pertussis burden in Australia within the first year of life by improving vaccination timeliness

Abstract Background Previous Australian studies have shown that on-time Diphtheria-Tetanus-Pertussis (DTP) vaccination coverage is 50-60% in certain subpopulations. We estimated the potentially preventable burden of pertussis if, 1) the full primary course and, 2) each dose was given on-time. Methods Perinatal, immunisation, pertussis notification, and death data were linked for 1,412,984 infants born in two Australian states in 2000-2012. A DTP dose administered >15 days after the recommended age was categorised as delayed. For aim 1, pertussis rates up to 1-year of age were compared in infants with ≥1 dose delayed versus all doses on-time, using Poisson regression methods. For aim 2, the expected number of cases preventable by each dose was calculated as the product of the number of cases observed during the period of delay and (1 – dose-specific vaccine effectiveness). Results 58% of infants had all primary DTP doses on time. We estimated that 85 (95% CI: 61-109) cases per 100,000 infants, aged 39-days to 1-year, could have been prevented if all infants had been vaccinated on time; 77% of these infants had received ≥1 DTP dose within the first year of life. Estimated preventable burden attributable to delayed DTP1 (58/100,000) was higher than for DTP2 (26/100,000) and DTP3 (15/100,000). Conclusions and Key messages Poor vaccine timeliness, especially delayed DTP1, is a key contributor to the residual burden of pertussis. These findings can inform cost-benefit analyses of targeted programs and public health messaging to reduce delays.

472Long-term effectiveness of 3-dose primary course and 4-year booster dose of pertussis vaccine in Australia

Abstract Background Australia’s National Immunisation Program recommended a 3-dose primary Diphtheria-Tetanus-Pertussis (DTP) vaccination course at 2, 4 and 6 months and a booster dose at 4 years during 2003-2015. We examined vaccine effectiveness by time since doses 3 and 4, as studies to date have shown conflicting results. Methods Perinatal, immunisation, pertussis notification and death data were linked for 1,086,319 infants born in two Australian states in 2003-2012. Administration of DTP doses 3 and 4 from 5.5-7 months and 47-53 months respectively, was considered age-appropriate. Adjusted Cox proportional hazards models with time-varying vaccination status were used to estimate vaccine effectiveness (VE = 1–hazard ratio) against notified pertussis post age-appropriate doses 3 and 4 compared to unvaccinated children, with additional benefit of dose 4 compared to receipt of primary course alone. Results Dose 3 VE declined from 79% (CI 75%-83%) from 0-6 months to 64% (CI 60%-67%) at 6-36 months and 45% (CI 31%-56%) at 36-42 months post-vaccination. Compared to unvaccinated children, VE after dose 4 declined from 83% (CI 80%-86%) at 0-12 months to 67% (CI 60%-72%) and 55% (CI 46%-63%) in the following two 12-month periods post-vaccination. When compared to dose 3, the relative VE for dose 4 was 58% (CI 51%-64%) in 0-18 months post-vaccination. Conclusion and Key messages Our study adds to previous Australian evidence for substantial waning of vaccine induced immunity against pertussis over a 3-year period following dose 3. VE was significantly higher in the 18 months following dose 4 compared to receipt of primary course alone.

Associated Factors for Dropout of First Vs Third Doses of Diphtheria Tetanus Pertussis (DPT) Vaccination in Nepal.

Background Immunization acts as a key intervention to reduce under-five mortality and morbidity. Despite global progress on vaccination, difficulties in the utilization of this service in developing countries have been observed. According to Nepal Demographic and Health Survey (NDHS) 2016, only 78% of children received a complete dose of vaccine among which the first-dose receiver of DPT is 98%, whereas only 83% received a third dose. This study aims to explore the influencing factors of DPT vaccination dropout in Nepal. Methods The explorative study was done through secondary data analysis of NDHS 2016. The KR file was used for the analysis of information for 2883 children. Factors influencing dropout of DPT vaccination were explored against the independent variables such as external environment, predisposing factors, and enabling resources. All the analyses were weighted before the analysis. The descriptive, bivariate, and multivariate analyses were performed. The variables showing collinearity have been removed in the final model. Results A higher dropout was reported in Terai (18.9%) and province 2 (22.0%), among uneducated mothers (18.1%) and uneducated fathers (19.4%), less than once a week internet users (22.2%), the nonradio listener (17.4%), who had <4 ANC visits (22.7%), home delivery (19.2%), no advised SBA (19.1%), long distance to health facility (17.9%), no iron supplementation in pregnancy (24.3%), and PNC by TBA/others (21.1%). All these tested relationships were found statistically significant (P value <0.05). The aOR for dropout was found to be 7.94 (4.07–15.51) for mothers with less than 4 or no ANC visit, long distance to health facility 4.68 (1.98–10.67), province 2 3.53 (1.13–11.03), and mother without formal employment 2.33 (1.52–3.55). Conclusion Factors related to health services, distance, provinces, and socioeconomic status of the family were influencers for vaccine dropout. Targeted intervention towards disadvantaged regions, counseling the mother during ANC, improving the education status of parents, access to the health facility, and use of mass media for advocacy are hereby recommended.

Implementation and adherence of routine pertussis vaccination (DTP) in a low-resource urban birth cohort

IntroductionReliable information on rates of up-to-date coverage and timely administration of routine childhood immunisations are critical for guiding public health efforts worldwide, yet prospective observation of vaccination programmes within individual...

Diphtheria-Tetanus-Pertussis (DTP) Vaccine Is Associated With Increased female-Male Mortality. Studies of DTP administered before and after measles vaccine

The third dose of diphtheria-tetanus-pertussis vaccine (DTP3) is used to monitor immunization programs. DTP has been associated with higher female mortality. We updated previous literature searches for DTP studies of mortality by sex. We examined the female/male (F/M) mortality rate ratio (MRR) with increasing number of doses of DTP and for subsequent doses of measles vaccine (MV) after DTP and of DTP after MV. Eight studies had information on both DTP1 and DTP3. The F/M MRR was 1.17 (95% confidence interval [CI], .88-1.57) after DTP1 and increased to 1.66 (95% CI, 1.32-2.09) after DTP3. Following receipt of MV, the F/M MRR declined to 0.63 (95% CI, .42-.96). In 11 studies the F/M MRR increased to 1.73 (95% CI, 1.33-2.27) when DTP-containing vaccine was administered after MV. F/M MRR increased with increasing doses of DTP. After MV, girls had lower mortality than boys. With DTP after MV, mortality increased again for girls relative to boys. No bias can explain these changes in F/M MRR. DTP does not improve male survival substantially in situations with herd immunity to pertussis and higher F/M MRR after DTP may therefore reflects an absolute increase in female mortality.

Infant, maternal and demographic predictors of delayed vaccination: A population-based cohort study

BackgroundReceiving vaccines at or close to their due date (vaccination timeliness) is a now key measure of program performance. However, studies comprehensively examining predictors of delayed infant vaccination are lacking. We aimed to identify predictors of short and longer-term delays in diphtheria-tetanus-pertussis (DTP) vaccination by dose number and ethnicity. MethodsPerinatal, notification, death and immunisation databases were linked for 1.3 million births in 2000–11 from two Australian states (Western Australia and New South Wales), with follow-up data until 2013. Ordinal logistic regression was used to estimate adjusted relative risks (RR) by degree of delay. Separate models were constructed for each vaccine dose and for Aboriginal and non-Aboriginal children. ResultsEach dose-specific cohort included at least 49,000 Aboriginal and 1.1 million non-Aboriginal children. Delayed receipt was more common among Aboriginal than non-Aboriginal children (eg for the first dose of DTP [DTP1] 19.4 v 8.1%). Risk factors for delayed vaccination were strongest for DTP1, and delayed receipt of DTP1 was a key driver of subsequent delays; every week DTP1 was delayed was associated with a 1.6 to 2-fold increased risk of delayed DTP2 receipt. For DTP1, ≥3 previous pregnancies (the only factor more strongly associated with longer than shorter delays; RR ≥5 compared to no previous pregnancies), and children born to mothers <20 years of age (RR ≥2 compared to ≥35 years) were at highest risk of delay. Other independent predictors were prematurity, maternal smoking during pregnancy, and being born in Western Australia (if Aboriginal) or another country in the Oceania region. ConclusionThe sub-populations at risk for delayed vaccination we have identified are likely generalisable to other high-income settings. Measures to improve their dose 1 timeliness, particularly for children with older siblings, are likely to have significant flow-on benefits for timeliness of later doses.

Experiences and Lessons From Polio Eradication Applied to Immunization in 10 Focus Countries of the Polio Endgame Strategic Plan

Nine polio areas of expertise were applied to broader immunization and mother, newborn and child health goals in ten focus countries of the Polio Eradication Endgame Strategic Plan: policy & strategy development, planning, management and oversight (accountability framework), implementation & service delivery, monitoring, communications & community engagement, disease surveillance & data analysis, technical quality & capacity building, and partnerships. Although coverage improvements depend on multiple factors and increased coverage cannot be attributed to the use of polio assets alone, 6 out of the 10 focus countries improved coverage in three doses of diphtheria tetanus pertussis containing vaccine between 2013 and 2015. Government leadership, evidence-based programming, country-driven comprehensive operational annual plans, community partnership and strong accountability systems are critical for all programs and polio eradication has illustrated these can be leveraged to increase immunization coverage and equity and enhance global health security in the focus countries.

Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage: observational study from Senegal

Diphtheria-tetanus-pertussis (DTP) may be associated with increased female mortality; the effect of co-administration with BCG is not known. Between 1989 and 1997, we examined female and male mortality rates in rural Senegal where 7824 infants received the first dose of DTP and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person-years, but mortality increased with subsequent doses of DTP-IPV to 45/1000 person-years. Among boys, BCG and DTP-IPV1 simultaneously reduced mortality from 72/1000 person-years to 60/1000 person-years and mortality decreased further with subsequent doses of DTP-IPV to 34/1000 person-years. In age-adjusted analyses, female-male mortality rate ratios were 0.83(95% CI 0.50-1.40) among unvaccinated children and 0.58 (95% CI 0.35-0.96) among children vaccinated simultaneously with BCG and DTP-IPV1, but increased to 1.17 (95% CI 0.67-2.03) after DTP-IPV2, and 1.63 (95% CI 0.86-3.10) after DTP-IPV3. Difference in vaccination coverage could not explain these sex-differential patterns; girls had significantly better weight-for-age than boys so nutritional status did not explain the increase in female mortality after DTP-IPV3. Whereas BCG co-administered with DTP-IPV was associated with lower female than male mortality, subsequent DTP-IPV vaccinations were associated with an increase in female mortality relative to male mortality.

Routine childhood vaccination programme coverage, El Salvador, 2011—In search of timeliness

While assessing immunization programmes, not only vaccination coverage is important, but also timely receipt of vaccines. We estimated both vaccination coverage and timeliness, as well as reasons for non-vaccination, and identified predictors of delayed or missed vaccination, for vaccines of the first two years of age, in El Salvador.We conducted a cluster survey among children aged 23–59 months. Caregivers were interviewed about the child immunization status and their attitudes towards immunization. Vaccination dates were obtained from children immunization cards at home or at health facilities. We referred to the 2006 vaccination schedule for children below two years: one dose of BCG (Bacillus Calmette-Guérin) at birth; rotavirus at two and four months; three doses of pentavalent – DTP (diphtheria-tetanus-pertussis), hepatitis B, and Haemophilus influenzae type b (Hib) – and of oral poliomyelitis vaccine (polio) at two, four, and six months; first MMR (measles-mumps-rubella) at 12 months; and first boosters of DTP and OPV at 18 months. Timeliness was assessed with Kaplan–Meier analysis; Cox and logistic regression were used to identify predictors of vaccination.We surveyed 2550 children. Coverage was highest for BCG (991%; 95% CI: 98.8–99.5) and lowest for rotavirus, especially second dose (86.3%; 95% CI: 84.2–88.4). The first doses of MMR and DTP had 991% (95% CI: 98.5–99.6) and 977% (95% CI: 970–985), respectively. Overall coverage was 837% (95% CI: 81.4–86.0); 96.4% (95% CI: 95.4–97.5), excluding rotavirus. However, only 26.7% (95% CI: 24.7–28.8) were vaccinated within the age interval recommended by the Expanded Programme on Immunization. Being employed and using the bus for transport to the health facility were associated with age-inappropriate vaccinations; while living in households with only two residents and in the “Paracentral”, “Occidental”, and “Oriental” regions was associated with age-appropriate vaccinations. Vaccination coverage was high in El Salvador, but general timeliness and rotavirus uptake could be improved.

Timeliness of infant vaccination and factors related with delay in Flanders, Belgium

Achieving high vaccination coverage is a necessary, but not a sufficient indicator of the quality of a vaccination programme, in terms of control and prevention of childhood infectious diseases. For optimal protection of infants, timeliness of vaccination is increasingly recognized as another important target.The aim of this study was to assess the timeliness of measles-mumps-rubella (MMR) and diphtheria-tetanus-pertussis (DTP) vaccination in infants in Flanders (Belgium), and to identify predictors of vaccination delay. The timeliness was assessed using the Kaplan–Meier estimator in three consecutive vaccination coverage surveys among children aged 18–24 months, conducted in 2005, 2008 and 2012, respectively. Factors associated with delayed administration of the vaccines were identified using Cox regression analysis.Over the time period, vaccination coverage for the first dose of MMR ranged from 94.0 to 96.6% and for the third dose of DTP from 97.9 to 98.7%. However, up to 32% (for MMR1) and 95% (for DTP3) of infants received vaccine doses delayed according to the recommended schedule. Although some improvement was achieved over the last decade, further efforts are needed to reach risk groups with delays, more specifically children vaccinated outside the baby well clinics, born from a mother originating from outside the European Union, children with a higher ranking or in families with a lower income.

Non‐specific effects of diphtheria‐tetanus‐pertussis and measles vaccinations? An analysis of surveillance data from Navrongo, Ghana

Studies from low-income countries have suggested that routine vaccinations may have non-specific effects on child mortality; measles vaccine (MV) is associated with lower mortality and diphtheria-tetanus-pertussis (DTP) with relatively higher mortality. We used data from Navrongo, Ghana, to examine the impact of vaccinations on child mortality. Vaccination status was assessed at the initiation of a trial of vitamin A supplementation and after 12 and 24 months of follow-up. Within the placebo group, we compared the mortality over the first 4 months and the full 2 years of follow-up for different vaccination status groups with different likelihoods of additional vaccinations during follow-up. The frequency of additional vaccinations was assessed among children whose vaccination card was seen at 12 and 24 months of follow-up. Among children with a vaccination card, more than 75% received missing DTP or MV during the first 12 months of follow-up, whereas only 25% received these vaccines among children with no vaccination card at enrollment. Children without a card at enrollment had a significant threefold higher mortality over the 2-year follow-up period than those fully vaccinated. The small group of children with DTP3-4 but no MV at enrollment had lower mortality than children without a card and had the same mortality as fully vaccinated children. In contrast, children with 1-2 DTP doses but no MV had a higher mortality during the first 4 months than children without a card [MRR = 1.65 (0.95, 2.87)]; compared with the fully vaccinated children, they had significantly higher mortality after 4 months [MRR = 2.38 (1.07, 5.30)] and after 2 years [MRR = 2.41 (1.41, 4.15)]. Children with 0-2 DTP doses at enrollment had higher mortality after 4 months (MRR = 1.67 (0.82, 3.43) and after 2 years [MRR = 1.85 (1.16, 2.95)] than children who had all three doses of DTP at enrollment. As hypothesised, DTP vaccination was associated with higher child mortality than measles vaccination. To optimise vaccination policies, routine vaccinations need to be evaluated in randomised trials measuring the impact on survival.

Immunization coverage and timeliness of vaccination in Italian children with chronic diseases

Since children with chronic diseases represent a primary target for immunization strategies, it is important that their immunization coverage and timeliness of vaccines is optimal. We performed a study to measure immunization coverage and timeliness of vaccines in children with type 1 diabetes, HIV infection, Down syndrome, cystic fibrosis, and neurological diseases. A total of 275 children aged 6 months–18 years were included in the study. Coverage for diphtheria–tetanus–pertussis (DTP), polio (Pol), and hepatitis B (HBV) vaccines approximated 85% at 24 months, while measles–mumps–rubella (MMR) coverage was 62%. Immunization coverage for seasonal influenza was 59%. The analysis of timeliness revealed that there was heterogeneity among children with different chronic diseases. A proportional hazard model showed that children with HIV infection had the longest time to complete three doses of DTP, Pol, and HBV, and those with neurological diseases received the first dose of MMR later than the other categories. Causes of missing or delayed vaccination mostly included a concurrent acute disease. Children with chronic diseases should be strictly monitored for routine and recommended vaccinations, and health care providers and families should be properly informed to avoid false contraindications.

Diphtheria–tetanus–pertussis vaccine administered simultaneously with measles vaccine is associated with increased morbidity and poor growth in girls. A randomised trial from Guinea-Bissau

Background 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. Methods 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. Results 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. Conclusion 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.

Coverage of recommended vaccines in children at 7–8 years of age in Flanders, Belgium

Evaluation of the coverage of primary diphtheria-tetanus-pertussis (DTP), poliomyelitis, hepatitis B (HBV) and measles-mumps-rubella (MMR) vaccine doses recommended before the age of 18 months in 7-year-old school children in Flanders, Belgium. Meningococcal serogroup C and DT-polio vaccines offered respectively as catch-up and booster vaccinations were also evaluated. Parents of 792 children born in Flanders in 1997 and selected by cluster sampling were interviewed at home in 2005. Vaccination data since infancy were collected retrospectively from vaccination documents and school health records. Coverage rates were 88.0% for the first dose of MMR, and 72.0%, 84.2% and 91.4% for the recommended HBV, DTP and poliomyelitis primary vaccine doses, respectively. These rates included catch-up of missed infant MMR (4.9%) and HBV (6.4%) vaccinations. In addition, 88.3% of the target group received the DT-polio booster dose recommended at 6 years of age and 83.1% a meningococcal C vaccine dose. Preventive public health services as well as private physicians were involved to a varying extent. A lower socioeconomic status of the family was associated with a higher risk of nonvaccination. Vaccinators in Flanders reach children relatively well during infancy and at school age, but catch-up of missed infant vaccine doses, especially MMR, should be optimized.

Humoral immune response after post‐chemotherapy booster diphtheria–tetanus–pertussis vaccine in pediatric oncology patients

The role of post-chemotherapy booster vaccination in pediatric oncology children remains to be established. In this randomized controlled study, we studied the effect of immune responses to diphtheria-tetanus-pertussis (DTP) booster vaccination in children 6 months after completing chemotherapy. Children 1-18 years old with chemotherapy completed for 6 months (baseline) were eligible. Subjects were randomized into vaccine and control group. In the former, three doses of DTP vaccine (Aventis Pasteur Inc., Lyon, France) were administered. IgG antibody titers against diphtheria, tetanus, pertussis, hepatitis B, measles, mumps, and rubella antibodies were measured serially in vaccine and control groups. Subsets of circulating lymphocytes (CD3(+), CD4(+), CD8(+), CD19(+), and CD16/56(+)) were quantified by flow cytometry using fluorescence-labeled monoclonal antibodies. Fifty-six children (28 vaccinees; 28 controls) were enrolled. Protective antibody levels against diphtheria, tetanus, pertussis were found at baseline in 83.6%, 96.5%, 96.1% of them respectively. After three doses of DTP, all vaccinees demonstrated a sustain rise in antibody levels and the antibody titers were significantly higher than control group. 35.8% of subjects were susceptible to measles mumps and rubella infection and 69% showed anti-HBs antibody titer less than protective level up to 18 months after stopping chemotherapy. Post-chemotherapy booster vaccinations produced a strong and sustained effect in humoral immunity against vaccine-preventable infectious diseases.

Seroimmunity to diphtheria and tetanus among mother-infant pairs; the role of maternal immunity on infant immune response to diphtheria-tetanus vaccination.

This study was designed to determine the levels of immunity against diphtheria and tetanus in 110 mothers with/without diphtheria-tetanus toxoid (dT) vaccination during pregnancy and their two-month-old infants before diphtheria-tetanus-pertussis (DTP) immunisation, and also to assess the influence of pre-vaccination passive immunity on the infants' immune response to three doses of DTP vaccination. Sera from 110 mother-infant pairs before DTP vaccination and from 69 infants after receipt of three doses of DTP vaccine were tested to measure antidiphtheria-antitetanus toxin IgG levels, using a commercial enzyme immunoassay. History of dT toxoid vaccination of mothers at pregnancy was recorded. 20% of mothers did not receive dT vaccine. Among these 22 unvaccinated mothers, one (5%) and six (27%) were serologically susceptible to tetanus and diphtheria respectively. The mean concentrations of antibody titers were lower in unvaccinated than in vaccinated mothers: diphtheria 0.78 (0.30) IU/mL vs 0.31 (0.20), and tetanus 1.95 (1.20) IU/mL vs 0.51 (0.45), vaccinated mother vs unvaccinated. All infants (100%) acquired immunity against both infections after receipt of three doses of DTP vaccine. Pre-vaccination passive immunity did not influence the infants' immune response to vaccination: diphtheria 0.95 (0.40) vs 0.89 (0.25), and tetanus 2.30 (1.0) vs 2.30 (0.70), from passive immune infants before vaccination vs those without, respectively. This study showed that diphtheria-tetanus toxoid components of DTP vaccine were highly immunogenic and maternal passive immunity did not affect the infants' immune response to DTP vaccination. Since there is a 23% missed opportunity for dT immunisation, efforts must be made to increase the coverage rate of this highly immunogenic vaccine in order to sustain protection against diphtheria and tetanus in mothers and their infants..

Increased Female-Male Mortality Ratio Associated With Inactivated Polio and Diphtheria-Tetanus-Pertussis Vaccines

The 2-fold increase in female mortality after high-titer measles vaccine may have occurred because many children received diphtheria-tetanus-pertussis (DTP) vaccine or inactivated polio vaccine (IPV) after high-titer measles vaccine. We examined whether DTP vaccine and IPV were associated with increased female mortality when they were the most recent vaccine administered to children who had not received measles vaccine. IPV was used as a control vaccine in 4 randomized trials of early measles vaccination (MV) with enrollment at 4-6 months of age conducted in Guinea-Bissau. Many children had not received all 3 DTP vaccinations before enrollment, and therefore received DTP after IPV or MV. We examined whether DTP vaccination status at enrollment affected the female-male mortality ratio. 9544 children enrolled in 4 trials. The female-male mortality ratio in different vaccine groups. Females had a higher mortality rate than males among children randomized to receive IPV (mortality rate ratio [MR] 1.52, 95% CI 1.02-2.28), but females had a similar mortality rate to males among children randomized to receive MV (MR 1.01, 0.69-1.46) and among children in the IPV group after they had received MV at 9 months of age or later (MR 0.88, 0.68-1.14). Children who had not received a third dose of DTP before enrollment (and were likely to receive DTP after MV or IPV) tended to have a higher mortality than children who had received all 3 doses of DTP (MR 1.30, 0.97-1.73). This effect was seen only among girls (MR 1.61, 1.08-2.40) and not among boys (MR 1.02, 0.67-1.54). Girls had a lower mortality when MV was the most recent vaccine received rather than DTP or IPV (MR 0.49, 0.28-0.87). Randomization to IPV was associated with higher female than male mortality. However, the increased female mortality might result from additional doses of DTP received after enrollment and before measles vaccination.

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 3 1 2 and 9 1 2 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.

The immunization data quality audit: verifying the quality and consistency of immunization monitoring systems.

To evaluate the consistency and quality of immunization monitoring systems in 27 countries during 2002-03 using standardized data quality audits (DQAs) that had been launched within the framework of the Global Alliance for Vaccines and Immunization. The consistency of reporting systems was estimated by determining the proportion of third doses of diphtheria-tetanuspertussis (DTP-3) vaccine reported as being administered that could be verified by written documentation at health facilities and districts. The quality of monitoring systems was measured using quality indices for different components of the monitoring systems. These indices were applied to each level of the health service (health unit, district and national). The proportion of verified DTP-3 doses was lower than 85% in 16 countries. Difficulties in verifying the doses administered often arose at the peripheral level of the health service, usually as the result of discrepancies in information between health units and their corresponding districts or because completed recording forms were not available from health units. All countries had weaknesses in their monitoring systems; these included the inconsistent use of monitoring charts; inadequate monitoring of vaccine stocks, injection supplies and adverse events; unsafe computer practices; and poor monitoring of completeness and timeliness of reporting. Inconsistencies in immunization data occur in many countries, hampering their ability to manage their immunization programmes. Countries should use these findings to strengthen monitoring systems so that data can reliably guide programme activities. The DQA is an innovative tool that provides a way to independently assess the quality of immunization monitoring systems at all levels of a health service and serves as a point of entry to make improvements. It provides a useful example for other global health initiatives.

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

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. 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. Mortality over the next 6 months from the day of examination for vaccinated and unvaccinated children. 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). 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.