Diphtheria-tetanus-pertussis Research Articles

Childhood full and under-vaccination in Nigeria, 2013

BackgroundNigeria’s government is challenged with vaccinating the world’s third largest birth cohort within a culturally and socioeconomically diverse country. This study estimated full childhood immunization coverage in Nigeria and characterizes the association between vaccination status and urbanicity, region of residence, ethnicity, and other factors. MethodsIn 2013, households throughout Nigeria were enrolled in the Demographic and Health Survey which included questions about vaccination. We defined full vaccination of a child as having received a single dose of bacillus Calmete-Guerin (BCG), one dose of measles-containing vaccine (MCV), three doses of diphtheria, pertussis, tetanus (DPT), and four doses of oral polio vaccine (OPV). Using a multinomial logistic regression model, full vaccination and under-vaccination versus non-vaccination was regressed onto various demographic and socioeconomic characteristics. ResultsAmong 5759 children 1 year of age, 25.5% were fully vaccinated, 47.9% were under-vaccinated, and 26.6% had not received any vaccinations. Children were more likely to be fully vaccinated if they belonged to wealthier families, resided in southern regions of the country, were Christian, belonged to the Igbo or Yoruba ethnic group, had mothers who made ≥5 antenatal care visits, delivered at an institution, or were more highly educated. ConclusionsFull vaccination among children in Nigeria is exceptionally low by global standards and certain groups, such as Muslims and individuals in northern regions who are higher risk of non- or under-vaccination should be targeted by vaccination programs. Providing a wide range of health care services for mothers and pregnant women could improve full vaccination of children.

Seroprevalence of Maternal and Cord Antibodies Specific for Diphtheria, Tetanus, Pertussis, Measles, Mumps and Rubella in Shunyi, Beijing

Maternal antibodies contribute to the protection of young infants from infectious diseases during the early life. However, vaccinations for women of child-bearing age are not routine in China. Therefore, we investigated the level of protective immunity against vaccine preventable diseases in pregnant women and newborns in China. A total of 194 paired maternal and cord blood samples were collected in Beijing from 2016 to 2017. Antibodies specific for the antigens covered by diphtheria-tetanus-pertussis (DTP) and measles-mumps-rubella (MMR) vaccine were determined by ELISA (Euroimmun, Lübeck, Germany). The cut off value of ≥0.1 IU/ml (anti-diphtheria), >0.1 IU/ml (anti-tetanus), >40 IU/ml (anti-pertussis toxin), ≥200 IU/l (anti-measles), ≥45 RU/ml (anti-mumps) and ≥10 IU/ml (anti-rubella) were used to assess the percentage of newborns with protective IgG concentrations, respectively. The results revealed that 61.3%, 73.2%, 97.4%, 30.4%, 65.5% and 17.0% of newborns had no protection against diphtheria, tetanus, pertussis, measles, mumps and rubella. Only 1.0% and 23.7% of newborns had protection against all three components of DTP or MMR, respectively. The finding suggested that most of newborns were susceptible to diphtheria, tetanus, pertussis and mumps, almost one-third of this population had no immune protection against measles, and about one-sixth of them were under threat of rubella infection. These data supported the immunization program for DTP and MMR vaccine in women at child-bearing age.

Comparison of the Effects of Drawing Pictures and Inflating Balloons on Anxiety and Pain Caused by Diphtheria-Pertussis-Tetanus Immunization in School-Aged Children

Background: Frequent experience of pain and anxiety can cause neuro-developmental disorders, reduced learning ability, and behavioral problems in children. Objectives: For this reason, the present study aimed at comparing the effects of drawing pictures and blowing up balloons on the anxiety and pain intensity arising from diphtheria-pertussis-tetanus (DPT) immunization (triple vaccine) in school-aged children. Methods: The present study was a quasi-experimental research conducted on children, who had been referred to Ilam clinics for DPT immunization during year 2016. 120 children, who met the inclusion criteria were enrolled in this study. They were randomly divided to three groups, namely experimental group A (drawing pictures before immunization up to its completion), experimental group B (inflating balloons before immunization up to its completion), and control group C (routine care group). The data collection instruments in this study included numeric pain rating scale, behavioral scale of pain responses (for the assessment of the child's pain), Pieri's pictorial anxiety scale, and self-rating scale of clinical phobias (for the assessment of the child's anxiety). The SPSS version 16 (IBM Corp., Armonk, N.Y., USA) was used to analyze the data through descriptive statistics. Results: The results showed that no statistically significant differences were observed in demographic characteristics of children under the study among the groups (P < 0.0.5). The results also showed that the practice of distraction technique via drawing pictures reduced the children's anxiety and pain caused by the vaccine. However, only anxiety decreased in the group that experienced the distraction method through inflating balloons. Additionally, the implementation of this technique did not have a statistically significant effect on the level of perceived pain in patients that inflated balloons (P < 0.05). Conclusions: The implementation of these non-pharmacological and low-cost distraction techniques is suggested to be incorporated in care and treatment routines, particularly in clinical setting. It is also recommended that the personnel receive training in this field and that research be conducted to determine the willingness of health care workers to perform distraction techniques and eliminate the existing barriers.

Impact of Maternal Nutritional Supplementation During Pregnancy on Infant Antibody Response to Diphtheria-Tetanus-Pertussis Vaccine: A Randomized Trial in the Gambia

Background A nutritionally deficient environment during fetal life may impair an infant's ability to mount an optimal immune response to vaccination. We examined the impact of supplementation during pregnancy with multiple micronutrients (MMN) and/or protein-energy (PE) on infant antibody responses to diphtheria-tetanus-pertussis (DTP) vaccination. Methods The Early Nutrition and Immune Development Trial (ISRCTN49285450) randomized 875 pregnant women from rural Gambia to receive one of four nutritional interventions (iron-folate (FeFol) as standard of care), MMN, PE and PE MMN) daily from enrolment (mean gestational age = 13·7±3·3 weeks) until delivery. Antibody responses to DTP administered to infants at 8, 12 and 16 weeks of age were measured in blood collected from a total of 670 and 563 infants at 12 and 24 weeks, respectively. The main outcome was the impact of maternal supplementation on log-transformed antibody titres in infants analysed using regression models with adjustment for confounders. Results At 12 weeks, adjusted mean (95% CI) anti-diphtheria titres were higher in infants born to mothers in the MMN (0·15 (0·13-0·18) IU/ml, p=0·002) and PE MMN (0·14 (0·12-0·16) IU/ml, p=0·028) groups, compared with the FeFol group (0·10 (0·09-0·12) IU/ml). This resulted in 72·2% (96/133) and 64·9% (87/134) of infants with protective anti-diphtheria titres (>0·1IU/ml) from the MMN and PE MMN groups, respectively, compared with 48·1% (64/133) from the FeFol group (p=0·001). Additionally, supplementation with PE MMN enhanced anti-tetanus titres (β=0·12, 95% CI 0·01-0·23, p=0·028) at 12 weeks; and anti-pertussis titres (β=0·26, 95% CI 0·02-0·50, p=0·035) at 24 weeks. Conclusions This study demonstrates that supplementation during pregnancy with MMN or a combination of MMN and PE enhances infant antibody responses to vaccination in rural Gambia. Overall, this research supports interventions that improve nutritional status in pregnancy and promote infant immune development, especially in settings with high rates of infection. Funding: Medical Research Council (UK). Declaration of Interest: No conflict of interest was declared. Ethical Approval: The ENID trial was approved by the joint Gambian Government/MRC Unit the Gambia ethics committee (SCC1126v2). Written informed consent was obtained from all participants. The trial observed Good Clinical Practice Standards and the current version of the Helsinki Declaration. The ENID trial was registered as ISRCTN49285450.

The effect of maternal decisional authority on children's vaccination in East Asia.

Even though they are important determinants for increasing vaccination rates in advanced and developing nations alike, maternal capacity and decisional authority have not been fully elucidated in diverse countries and cultural spheres. This study examined the effects of South Korean, Chinese, and Japanese mothers’ health literacy, self-efficacy, mass media use, and decisional authority on their children’s vaccination after adjustment for their socioeconomic statuses. Computer-assisted web interviews were conducted with married women in their 20s-40s of South Korean, Chinese, or Japanese nationality (n = 1,571). Dependent variables were generated for the following four vaccinations: BCG, diphtheria+pertussis+tetanus (DPT), poliomyelitis (polio), and measles. For statistical processing, cases where all four types of vaccines had been recorded were scored as 1 and other cases were processed as 0. According to the results of the pooled model, we found that for East Asian mothers, decisional authority, self-efficacy, and health literacy all increased the likelihood that they would vaccinate their children. Furthermore, women who searched for health information through media such as the radio were more likely to vaccinate their children. However, when elaborate analyses were conducted by country, there were considerable differences in those characteristics by country. Therefore, this study showed that it is necessary to establish locally tailored strategies in order to raise vaccination rates in the Global Vaccine Action Plan. This study also showed that social contexts must be taken into consideration in order to raise vaccination rates.

Abstract 5638: A tetanus-way of improving synthetic long peptide tumor vaccination

Abstract We have previously identified a natural B cell epitope derived from tetanus toxin named Minimal Tetanus Toxin Epitope (MTTE)[1]. Most healthy individuals have IgG1 antibodies to this peptide sequence but no IgM antibodies. We have assessed the possibility to apply this MTTE sequence in drug development with the intention to create immune complexes and use them as vehicles to carry antigen-material into dendritic cells. Thru a conjugation method three MTTE sequences and a longer synthetic peptide stretch harboring T cell epitopes are linked together. As immune complexes are efficient carriers of antigen material and can promote cross-presentation the aim is to use these conjugates for therapeutic purposes in diseases where a strong cellular immune response should be induced. To further evaluate the MTTE peptide conjugates in drug development we have investigated how a diphtheria, tetanus, pertussis (DTP) vaccination induces antibody titers against the linear tetanus sequence. Herein we have studied the MTTE location in the tertiary structure of the protein, how cancer patients respond with antibody titers against MTTE along with a subsequent T cell response and in vivo anti-tumor responses (mice). In addition we have studied safety in terms of cytokine release assessment pre and post a DTP vaccination. We found that the MTTE sequence is part of an alpha-helix that is externally oriented and thereby accessible for peptide binding. We found that not helper epitope is part of the MTTE sequence and that healthy individuals as well as cancer patients can mount IgG titers against the epitope, this also result in more efficient induction of recall responses post a DTP booster than pre boost. Mice seropositive to the MTTE sequence can mount anti-tumor responses, while this is not seen in seronegative animals. In addition, a cytokine release assessment using a modified chandler loop model with intact complement does not display a broad immediate cytokine release pre or post a DTP booster. We conclude that it is efficacious and safe to make use of a peptide conjugate in a drug development project with the aim to use it as a vaccine strategy. [1] Mangsbo et al. In press. Molecular Immunology 2017 Citation Format: Jan Wouter Drijfhout, Erika Fletcher, Justyna Leja-Jarblad, Iliana Kerzeli, Robert Cordfunke, Gunilla Tornqvist, Frida Lindqvist, Greta Hultqvist, Rob Valentijn, Sam Ladjervardi, Michael Haggman, Gustav Ullenhag, Sara Mangsbo. A tetanus-way of improving synthetic long peptide tumor vaccination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5638.

Uji Efek Antipiretik Ekstrak Etanol Buah Wualae (Etlingera elatior (Jack) R.M. Smith) Terhadap Mencit Jantan (Mus musculus L.) Galur Balb/C

Wualae (Etlingera elatior (Jack) R.M. Smith) empirically been used by people to treat diseases and as food. This research was carried to determine the antipyretic activity of ethanol extracts of Wualae (Etlingera elatior (Jack) R.M. Smith) fruit on male mice (Mus musculus L) Balb/c along with ratio the effects of ethanol extracts of fruit Wualae with paracetamol as a antipyretic. Ethanol extracts of fruit Wualae obtained by maceration method using ethanol 96%. Male mice divided into 6 groups i.e: negative control (Na.CMC), positive control, and the treatment group (ethanol extracts of fruit Wualae 100 mg/KgBW, 200 mg/KgBW, 300 mg/KgBW, dan 400 mg/KgBW). Antipyretic activity tested by using DPT vaccine (Diphtheria Tetanus Pertussis) 0.1 cc intraperitoneally as an inducer and paracetamol 500 mg as a positive control. Temperature measurement determined for 3 hours with a 30 minutes interval. Data analysis was performed by Kruskal Wallis statistical analysis and continued with Mann-Whitney test. The results showed that the effects of ethanol extracts of wualae fruit at dose of 400 mg/KgBW has antipyretic effects with a total decrease of temperature was 1,237oC.Keywords: antipyretic, fever, Etlingera elatior, wualae, mice

Evidence of Increase in Mortality After the Introduction of Diphtheria-Tetanus-Pertussis Vaccine to Children Aged 6-35 Months in Guinea-Bissau: A Time for Reflection?

Whole-cell diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) were introduced to children in Guinea-Bissau in 1981. We previously reported that DTP in the target age group from 3 to 5 months of age was associated with higher overall mortality. DTP and OPV were also given to older children and in this study we tested the effect on mortality in children aged 6-35 months. In the 1980s, the suburb Bandim in the capital of Guinea-Bissau was followed with demographic surveillance and tri-monthly weighing sessions for children under 3 years of age. From June 1981, routine vaccinations were offered at the weighing sessions. We calculated mortality hazard ratio (HR) for DTP-vaccinated and DTP-unvaccinated children aged 6-35 months using Cox proportional hazard models. Including this study, the introduction of DTP vaccine and child mortality has been studied in three studies; we made a meta-estimate of these studies. At the first weighing session after the introduction of vaccines, 6-35-month-old children who received DTP vaccination had better weight-for-age z-scores (WAZ) than children who did not receive DTP; one unit increase in WAZ was associated with an odds ratio of 1.32 (95% CI = 1.13-1.55) for receiving DTP vaccination. Though lower mortality compared with not being DTP-vaccinated was, therefore, expected, DTP vaccination was associated with a non-significant trend in the opposite direction, the HR being 2.22 (0.82-6.04) adjusted for WAZ. In a sensitivity analysis, including all children weighed at least once before the vaccination program started, DTP (±OPV) as the most recent vaccination compared with live vaccines or no vaccine was associated with a HR of 1.89 (1.00-3.55). In the three studies of the introduction of DTP in rural and urban Guinea-Bissau, DTP-vaccinated children had an HR of 2.14 (1.42-3.23) compared to DTP-unvaccinated children; this effect was separately significant for girls [HR = 2.60 (1.57-4.32)], but not for boys [HR = 1.71 (0.99-2.93)] (test for interaction p = 0.27). Although having better nutritional status and being protected against three infections, 6-35 months old DTP-vaccinated children tended to have higher mortality than DTP-unvaccinated children. All studies of the introduction of DTP have found increased overall mortality.

No effect of an additional early dose of measles vaccine on hospitalization or mortality in children: A randomized controlled trial

BackgroundNon-specific effects (NSEs) of vaccines have increasingly gained attention in recent years. Recent studies suggest that live vaccines, such as measles vaccine (MV), have beneficial effects on health, while inactivated vaccines, such as the diphtheria-tetanus-pertussis (DTP) vaccine, may have harmful effects. If this is the case, it should improve child health to move MV closer to the last vaccination with DTP. The objective of this study was to investigate the NSEs of an additional early dose of MV on hospitalization or mortality. MethodsChildren were randomized to receive either the standard MV at 9 months (control) or an additional early dose of MV 4 weeks after the third dose of DTP-containing Pentavalent vaccine and the standard MV at 9 months (intervention). In this analysis of a secondary outcome in the trial, we investigated the effect of the intervention on a composite endpoint of over-night hospitalization with or without recovery, or death without previous hospitalization, in children between 4.5 and 36 months of age in the Nouna HDSS in Burkina Faso. We used Cox proportional hazards regression with repeated events and time since study enrolment as underlying time-scale. ResultsAmong 2258 children in the intervention and 2238 children in the control group we observed a total of 464 episodes of hospitalization or mortality. There was no difference between intervention and control group (HR = 1.00, 95% Confidence Interval (CI) 0.83–1.20). Results from the per-protocol and intention-to-treat analysis were similar. Although no significant, results suggest a possible beneficial effect of early MV in children that had not been exposed to an OPV campaign after enrolment (HR = 0.83, 95% CI 0.55–1.29). ConclusionsWe did not detect any effect of early MV on subsequent hospitalization or mortality. However, possible effects of early MV could have been obscured by NSEs of the frequent OPV campaigns.Registration: The trial was registered at ClinicalTrials.gov, NCT01644721

Effect and cost-effectiveness of educating mothers about childhood DPT vaccination on immunisation uptake, knowledge, and perceptions in Uttar Pradesh, India: A randomised controlled trial

BackgroundTo assess the effect of health information on immunisation uptake in rural India, we conducted an individually randomised controlled trial of health information messages targeting the mothers of unvaccinated or incompletely vaccinated children through home visits in rural Uttar Pradesh, India.Methods and findingsThe study tested a brief intervention that provided mothers face-to-face with information on the benefits of the tetanus vaccine. Participants were 722 mothers of children aged 0–36 months who had not received 3 doses of diphtheria–pertussis–tetanus (DPT) vaccine (DPT3). Mothers were randomly assigned in a ratio of 1:1:1 to 1 of 3 study arms: mothers in the first treatment group received information framed as a gain (e.g., the child is less likely to get tetanus and more likely to be healthy if vaccinated), mothers in the second treatment group received information framed in terms of a loss (e.g., the child is more likely to get tetanus and suffer ill health if not vaccinated), and the third arm acted as a control group, with no information given to the mother. Surveys were conducted at baseline (September 2015) and after the intervention (April 2016). The primary outcome was the proportion of children who had received DPT3 measured after 7 months of follow-up. The analysis was by intention to treat. A total of 16 (2.2%) participants were lost to follow-up. The coverage of DPT3 was 28% in the control group and 43% in the pooled information groups, giving a risk difference of 15 percentage points (95% CI: 7% to 22%, p < 0.001) and a relative risk of 1.52 (95% CI: 1.2 to 1.9, p < 0.001). The information intervention increased the rate of measles vaccination by 22 percentage points (risk difference: 22%, 95% CI: 14% to 30%, p < 0.001; relative risk: 1.53, 95% CI: 1.29 to 1.80) and the rate of full immunisation by 14 percentage points (risk difference: 14%, 95% CI: 8% to 21%, p < 0.001; relative risk: 1.72, 95% CI: 1.29 to 2.29). It had a large positive effect on knowledge of the causes, symptoms, and prevention of tetanus but no effect on perceptions of vaccine efficacy. There was no difference in the proportion of children with DPT3 between the group that received information framed as a loss and the group that received information framed as a gain (risk difference: 4%, 95% CI: −5% to 13%; p = 0.352; relative risk: 1.11, 95% CI: 0.90 to 1.36). The cost per disability-adjusted life year averted of providing information was US$186, making the intervention highly cost-effective with respect to the WHO-recommended threshold of once the gross domestic product per capita (US$793 in the case of Uttar Pradesh). Key study limitations include the modest sample size for this trial, limiting power to detect small differences in the framing of information, and the potential for contamination among households.ConclusionsProviding mothers of unvaccinated/incompletely vaccinated children with information on tetanus and the benefits of DPT vaccination substantially increased immunisation coverage and was highly cost-effective. The framing of the health information message did not appear to matter.Trial registrationThe trial is registered with ISRCTN, number ISRCTN84560580.

Measles Vaccination Supports Millennium Development Goal 4: Increasing Coverage and Increasing Child Survival in Northern Ghana, 1996-2012.

Measles vaccine (MV) administered as the last vaccine after the third dose of diphtheria-tetanus-pertussis (DTP) may be associated with better child survival unrelated to prevention of measles infection. Other studies have shown that MV administered after DTP was more beneficial and was associated with lower mortality compared with DTP administered after MV or DTP administered simultaneously with MV. We compared the difference in mortality between measles vaccinated after DTP3 and measles-unvaccinated children in Navrongo, Ghana. This was a follow-up study involving annual cohort of children aged 9-23 months from 1996 to 2012. We assessed survival in relation to the measles vaccination status within the first 12 months from interview date and until 5 years of age using Cox proportional hazards models. In all, 38,333 children were included in the study. The proportion of children vaccinated with MV-after-DTP3 increased from 45% in 1996 to 95% in 2012. The adjusted hazard ratio (HR) for measles unvaccinated compared with MV-after-DTP3 vaccinated children was 1.38 (1.15-1.66) in the first 12 months after assessment of vaccination status and 1.22 (1.05-1.41) with follow-up to 5 years of age. The national immunization days campaigns with oral polio vaccine or MV might have reduced the effect of being MV-after-DTP3 vaccinated vs MV-unvaccinated. For 12 months of follow-up, the HR before a campaign for MV-unvaccinated children was 1.63 (1.23-2.17) compared to those who received MV-after-DTP3. After the campaign, the HR reduced to 1.23 (0.97-1.54). Stratifying the analysis by sex, measles-unvaccinated boys had a HR of 1.69 (1.33-2.61) compared to measles-unvaccinated girls who had a HR 1.06 (0.79-1.40) during 1-year follow-up. In 1989, only 7% of children in the area had received MV-after-DTP3; the increase in MV-after-DTP3 coverage from 1989 to 2012 may have lowered mortality rate among children aged 9 months to 3 years by 24%. Though an observational study, our findings suggest that measles vaccination, administered in the recommended sequence, is associated with improved child survival and may have contributed importantly to the mortality decline toward the achievement of Millennium Development Goal 4.

Study of Serologic Response Rate to Pertussis after Administration of the Third Dose of Pentavalent Vaccine in Children 12 Months Old in Karaj City, Iran

Background: After substitution of Pentavalent vaccine with diphtheria, tetanus, pertussis (DTP) in the Iranian National Vaccination program with 3 Pentavalent (three times vaccination with Pentavalent vaccine at months 2, 4, and 6) in 2014 and the lack of published research in the field of immunogenicity of pertussis component of this vaccine, the efficacy of pertussis vaccine was studied 6 months after the last dose of Pentavalent vaccine in Iranian infants. Materials and Methods: Five hundred blood samples were collected from healthy one-year-old children who attended 18 health care centers of Karaj, Iran for routine vaccination selected by cluster sampling (2016). Sampling checklists contained demographic information and risk factors. The blood samples were sent to the laboratory for determination of Immunoglobulin G (IgG) and IgA anti-pertussis antibody titer by ELISA method. Data were analyzed by STATA software (version 14.0). Results: 82.7% (n=413) of children (95% confidence interval [CI]: 79.49-86.11) had IgG titer less than 16 IU/ml against pertussis (no immune response), and 17.3% (n=87) had equal or greater than 16 IU/ml IgG titer against pertussis (95% CI: 13.89-20.51). IgA titer against pertussis was less than 8U/ml in all cases. Anti-pertussis IgG geometric mean titer (GMT) was 15.80 U/ml (95% CI: 15.26-16.36), and IgA GMT was 6.26 U/ml (95% CI: 6.22-6.30). There was not a significant correlation between titer of pertussis antibody and demographic factors. Conclusion: Based on low IgG titer in vaccinated children, immunogenicity of pentavalent vaccine in Iranian children needs more investigation. In this study, 100 % of children had negative serologic response (IgA

Tetanus Toxin Antibody Levels in Pre-School Nigerian Children after Three Doses of Diphtheria-Pertussis-Tetanus/Pentavalent Immunization: A Cross-Sectional Study

Background: Post-neonatal tetanus is an important problem. Prevention of tetanus in Nigeria is via immunization with three doses of Diphtheria-Pertussis-Tetanus (DPT)/Pentavalent vaccine at 6, 10 and 14 weeks. The anti-tetanus antibody levels of these children are not known after they had received DPT3/Pentavalent vaccines. Aim: This work was to determine the anti-tetanus antibody (IgG) response in Nigerian children aged six months to five years who had received three doses of DPT vaccine in early infancy. Methods: Children aged six months to five years who were attended to in the University of Calabar Teaching Hospital for acute illnesses were recruited. Their anti-tetanus IgG levels were measured using Enzyme Linked Immunosorbent Assay (ELISA). The optimal cut-off level of ≥0.1 IU/ml was used as the protective level. Data was analysed using the Statistical Package for Social Sciences (SPSS) version 20.0 with simple proportions and percentages. Students’ “t” test and ANOVA were used to compare quantitative variables while Chi-square and Fisher’s exact test were used to compare categorical data. Results: Four hundred and eighteen children participated in the study. The mean IgG antibody level was 1.021 ± 0.9 IU/ml. Four hundred children (95.7%) had protective levels of antibodies. The highest proportion of subjects with protective levels was in infants, 6 - 11 months (99%) and lowest in children aged 36 - 47 months (92.2%). Conclusion: The proportion of children with protective levels was above 90% in all age groups studied. The current national immunization schedule is adequate. Further studies in older age groups are needful.

Comparative tetanus antibody response of Nigerian children to diphtheria-pertussis-tetanus and pentavalent vaccines.

In Nigeria and many parts of the world, the pentavalent vaccine is replacing the diphtheria-pertussis-tetanus (DPT) vaccine in tetanus prevention. The aim of this study was to compare the anti-tetanus immunoglobulin G (IgG) response of children who received DPT with those who received the pentavalent vaccine. A cross-sectional survey of anti-tetanus IgG levels in children aged 6 months to 5 years who received DPT and in children who received the pentavalent vaccine. IgG antibody levels were determined using enzyme-linked immunosorbent assay. The protective level was set at ≥0.1 IU/ml. One hundred and twenty-two out of 130 children (93.9%) who had received DPT had protective levels of anti-tetanus IgG compared to 278 out of 288 children (96.5%) who had received the pentavalent vaccine. The difference was not statistically significant (P = 0.21). The median IgG antibody level in those who received DPT was 1.1 IU/ml (interquartile range (IQR) 0.4-1.8) compared with 0.6 IU/ml (IQR 0.4-1.4) in those who received pentavalent vaccine (P = 0.006), with age being the only predictor of variability in the multivariate analysis. DPT and pentavalent vaccines are equally effective in inducing protective levels of anti-tetanus IgG in children. Vaccination with the pentavalent vaccine, which is the current policy in Nigeria and many other parts of the world, should continue.

Measuring the timeliness of childhood vaccinations: Using cohort data and routine health records to evaluate quality of immunisation services.

To achieve full benefits of vaccination programmes, high uptake and timely receipt of vaccinations are required. To examine uptake and timeliness of infant and pre-school booster vaccines using cohort study data linked to health records. We included 1782 children, born between 2000 and 2001, participating in the Millennium Cohort Study and resident in Wales, whose parents gave consent for linkage to National Community Child Health Database records at the age seven year contact. We examined age at receipt, timeliness of vaccination (early, on-time, delayed, or never), and intervals between vaccine doses, based on the recommended schedule for children at that time, of the following vaccines: primary (diphtheria, tetanus, pertussis (DTP), polio, Meningococcal C (Men C), Haemophilus influenzae type b (Hib)); first dose of measles, mumps and rubella (MMR); and pre-school childhood vaccinations (DTP, polio, MMR). We compared parental report with child health recorded MMR vaccination status at age three years. While 94% of children received the first dose of primary vaccines early or on time, this was lower for subsequent doses (82%, 65% and 88% for second and third doses and pre-school booster respectively). Median intervals between doses exceeded the recommended schedule for all but the first dose with marked variation between children. There was high concordance (97%) between parental reported and child health recorded MMR status. Routine immunisation records provide useful information on timely receipt of vaccines and can be used to assess the quality of childhood vaccination programmes. Parental report of MMR vaccine status is reliable.

Sex-differential effects of diphtheria-tetanus-pertussis vaccine for the outcome of paediatric admissions? A hospital based observational study from Guinea-Bissau.

In spite of protection against the targeted infections, a large volume of observational data indicates that diphtheria-tetanus-pertussis (DTP) vaccine may have a negative impact on overall childhood mortality in low-income countries, especially in girls. In an observational study using data from Bandim Health Project's continuous registration of all admissions to the paediatric ward at the National Hospital Simão Mendes in Bissau, we investigated whether DTP was associated with higher female than male in-hospital mortality (female/male case fatality ratio (F/M CFR)) and whether the CFR comparing DTP-vaccinated and DTP-unvaccinated children differed by sex. We included children aged 6 weeks to 8 months (274 days) admitted to the paediatric ward with a vaccination card seen during admission. From May 2001 to January 2008, 4230 children aged 6 weeks to 8 months were admitted and 3450 (82%; 1997 boys, 1453 girls) presented a vaccination card. The proportion presenting a vaccination card and DTP coverage did not differ by sex. During admission, 16% (200/1250) of the girls and 13% (220/1694) of the boys who had received DTP died. The F/M CFR among the 2944 DTP-vaccinated children was 1.23 (1.03-1.46); while it was 0.95 (0.66-1.38) among the 506 children who had not received DTP. DTP-vaccinated children were older and had better socioeconomic status. Adjusted for age, BCG-vaccination, residence, and maternal education the CFR comparing DTP-vaccinated boys with DTP-unvaccinated boys was 0.84 (0.63-1.11), while the CFR comparing DTP-vaccinated girls with DTP-unvaccinated girls was 1.28 (0.90-1.83) (p = .07 for same effect in boys and girls). Among DTP-vaccinated children, female in-hospital mortality was higher than male in-hospital mortality and DTP-vaccination tended to be associated with higher mortality in girls. The data are consistent with DTP having negative effects on mortality for girls. Further studies are necessary to design the optimal vaccination programme for both sexes.

Negative Correlation between Circulating CD4+FOXP3+CD127- Regulatory T Cells and Subsequent Antibody Responses to Infant Measles Vaccine but Not Diphtheria-Tetanus-Pertussis Vaccine Implies a Regulatory Role.

Regulatory T cells (Tregs) play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4+FOXP3+CD127− Tregs in controlling immunity in infant males and females to vaccination with diphtheria–tetanus–whole cell pertussis (DTP) and/or measles vaccine (MV). We find correlative evidence that circulating Tregs at the time of vaccination suppress antibody responses to MV but not DTP; and Tregs 4 weeks after DTP vaccination may suppress vaccine-specific cellular immunity. This opens the exciting possibility that Tregs may provide a future target for improved vaccine responses in early life, including reducing the number of doses of vaccine required. Such an approach would need to be safe and the benefits outweigh the risks, thus further research in this area is required.

The Residual Vaccine-preventable Burden of Rotavirus Disease.

From July 2007 to June 2015, 61% of rotavirus-positive, vaccine-eligible children were unvaccinated for rotavirus. Of these, 67% of children had received diphtheria-tetanus toxoids-acellular pertussis within the recommended age for rotavirus vaccine initiation. Improving linkage between rotavirus and diphtheria-tetanus toxoids-acellular pertussis administration may impact the residual burden of US rotavirus disease.

Analysis of the association between millennium development goals 4 & 5 and the physician workforce across international economic strata

BackgroundThe Millennium Development Goals (MDGs) are 8 international development goals voluntarily adopted by 189 nations. The goals included health related aims to reduce the under-five child mortality rate by two-thirds (MDG4), and to reduce the maternal mortality ratio by three-quarters (MDG5). To assess the relationship between the healthcare workforce and MDGs 4–5, we examined the physician workforces of countries around the globe, in terms of the Physician Density Level (PDL, or number of physicians per 1000 population), and compared this rate across a number of years to several indicator variables specified as markers of progress towards MDG4 and MDG5.MethodsData for each variable of interest were obtained from the World Bank’s Millennium Development Goals and World Development Indicators databases for 208 countries and territories from 2004 to 2014, representing a ten-year period for which the most information is available. We analyzed the relationships between MDG outcomes and PDL, controlling for national income levels and other covariates, using linear mixed model regression. Dependent variables were logarithmically transformed to meet assumptions necessary for multivariate analysis.ResultsIn unadjusted models, an increase of every one physician per 1000 population (one unit change in PDL) lowered the risk of not being vaccinated for measles-mumps-rubella (MMR) to 29.3% (p < 0.001, 95% CI: 22.2%–38.7%) and for not receiving diphtheria-tetanus-pertussis (DTaP) vaccination rate decreased to 38.5% (p < 0.001, 95% CI: 28.7% - 51.7%). Maternal mortality rate decreased to 76.6% (p < 0.001, 95% CI: 74.3% - 79.0%), neonatal mortality decreased to 58.8% (p < 0.001, 95% CI: 54.8% - 63.2%) and under-5 mortality rate decreased to 52.1% (p < 0.001, 95% CI: 48.0% - 56.4%), with every one-unit change in PDL. Adjusted models tended to reflect unadjusted risk assessments.ConclusionThe maintenance and improvement of the health workforce is a vital consideration when assessing how to achieve global development goals related to health outcomes.

Co-administration of BCG and Diphtheria-tetanus-pertussis (DTP) Vaccinations May Reduce Infant Mortality More Than the WHO-schedule of BCG First and Then DTP. A Re-analysis of Demographic Surveillance Data From Rural Bangladesh

BackgroundWHO recommends BCG at birth and diphtheria-tetanus-pertussis (DTP)-containing vaccine at 6, 10 and 14weeks of age. However, BCG and DTP are often co-administered in low-income countries. The health implications have not been examined. SettingWe reanalysed data from Matlab, Bangladesh, to examine the influence of co-administration on mortality; 37,894 children born 1986-1999 were followed with registration of vaccinations and survival. MethodsUsing Cox models, survival was analysed from 6weeks to 9months of age when measles vaccine is given; 712 children died in this age group. We calculated mortality rate ratios (MRR) for children starting the vaccination schedule with BCG-first, BCG+DTP1-first or DTP1-first. ResultsOnly 17% followed the WHO-schedule with BCG-first. Mortality was 16/1000 person-years for children who initiated the vaccination schedule with BCG+DTP1 but 32/1000 and 20/1000 for children who received BCG-first or DTP-first, respectively. Compared with BCG+DTP1-first and adjusting for background factors, the BCG-first-schedule was associated with 2-fold higher mortality (MRR=1.94 (1.42–2.63)). DTP1 administered after BCG-first was associated with higher mortality than receiving DTP1 with BCG (MRR=1.78 (1.03–3.03)). ConclusionsCo-administration of BCG and DTP may further reduce mortality. Since all observational studies support this trend, co-administration of BCG and DTP should be tested in randomised trials.