Diphtheria-tetanus-pertussis Research Articles

Serum reactome induced by Bordetella pertussis infection and Pertussis vaccines: qualitative differences in serum antibody recognition patterns revealed by peptide microarray analysis.

BackgroundPertussis (whooping cough) remains a public health problem despite extensive vaccination strategies. Better understanding of the host-pathogen interaction and the detailed B. pertussis (Bp) target recognition pattern will help in guided vaccine design. We characterized the specific epitope antigen recognition profiles of serum antibodies (‘the reactome’) induced by whooping cough and B. pertussis (Bp) vaccines from a case–control study conducted in 1996 in infants enrolled in a Bp vaccine trial in Sweden (Gustafsson, NEJM, 1996, 334, 349–355).MethodsSera from children with whooping cough, vaccinated with Diphtheria Tetanus Pertussis (DTP) whole-cell (wc), acellular 5 (DPTa5), or with the 2 component (a2) vaccines and from infants receiving only DT (n = 10 for each group) were tested with high-content peptide microarrays containing 17 Bp proteins displayed as linear (n = 3175) peptide stretches. Slides were incubated with serum and peptide-IgG complexes detected with Cy5-labeled goat anti-human IgG and analyzed using a GenePix 4000B microarray scanner, followed by statistical analysis, using PAM (Prediction Analysis for Microarrays) and the identification of uniquely recognized peptide epitopes.Results367/3,085 (11.9%) peptides were recognized in 10/10 sera from children with whooping cough, 239 (7.7%) in DTPwc, 259 (8.4%) in DTPa5, 105 (3.4%) DTPa2, 179 (5.8%) in the DT groups. Recognition of strongly recognized peptides was similar between whooping cough and DPTwc, but statistically different between whooping cough vs. DTPa5 (p < 0.05), DTPa2 and DT (p < 0.001 vs. both) vaccines. 6/3,085 and 2/3,085 peptides were exclusively recognized in (10/10) sera from children with whooping cough and DTPa2 vaccination, respectively. DTPwc resembles more closely the whooping cough reactome as compared to acellular vaccines.ConclusionWe could identify a unique recognition signature common for each vaccination group (10/10 children). Peptide microarray technology allows detection of subtle differences in epitope signature responses and may help to guide rational vaccine development by the objective description of a clinically relevant immune response that confers protection against infectious pathogens.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-015-0090-3) contains supplementary material, which is available to authorized users.

Resurgence of pertussis at the age of vaccination: clinical, epidemiological, and molecular aspects

ObjectiveReport the incidence, epidemiology, clinical features, death, and vaccination status of patients with whooping cough and perform genotypic characterization of isolates of B. pertussis identified in the state of Paraná, during January 2007 to December 2013. MethodsCross‐sectional study including 1,209 patients with pertussis. Data were obtained through the Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação – SINAN) and molecular epidemiology was performed by repetitive sequence‐based polymerase chain reaction (rep‐PCR; DiversiLab®, bioMerieux, France). ResultsThe incidence of pertussis in the state of Paraná increased sharply from 0.15‐0.76 per 100,000 habitants between 2007‐2010 to 1.7‐4.28 per 100,000 between 2011‐2013. Patients with less than 1 year of age were more stricken (67.5%). Fifty‐nine children (5%) developed pertussis even after receiving three doses and two diphtheria‐tetanus‐pertussis (DTP) boosters vaccine. The most common complications were pneumonia (14.5%), otitis (0.9%), and encephalopathy (0.7%). Isolates of B. pertussis were grouped into two groups (G1 and G2) and eight distinct patterns (G1: P1‐P5 and G2: P6‐P8). ConclusionThe resurgence of pertussis should stimulate new research to develop vaccines with greater capacity of protection against current clones and also encourage implementation of new strategies for vaccination in order to reduce the risk of disease in infants.

Vaccination rates for Tdap are low during pregnancy

A wide disparity exists between states in the percentage of women receiving the tetanus–diphtheria–pertussis (Tdap) vaccination before, during, or after pregnancy, according to a CDC report released in late May. An analysis of data from September to December 2011 showed that among 16 states and New York City, approximately 55.7% of women with live births reported receiving any Tdap vaccination. Rates ranged from 38.2% in New York City to 76.6% in Nebraska.

The Trend of the Extended Program of Immunization (EPI) in Iran from the Beginning (1984) to 2013

Introduction The extended program of immunization (EPI) in Iran is started in 1984, and it played an important and effective role in controlling many infectious diseases in community. The objective of this study was to determine the time trends of vaccination coverage by the type of vaccine among children, in the age group of 0-24 months, in Iran from the beginning of EPI (1984) to 2013. Materials and Methods This study has been conducted as a descriptive analytical research to evaluate the vaccines of extended program of immunization in Iran from 1984 to 2013. The data of this study have been obtained from the World Health Organization and UNICEF. The data of this study included the percentage of coverage for routine vaccines in Iran National immunization program in children, aged 0-24 months. The data analysis has been done by STATA, Version12. Results The coverage of all vaccines has been continuously increased from 1984 to 2013, and now the coverage for all of them is about 99 percent. All coefficients in the regression models are positive and statistically significant (P <0.05). Birth dose of Hepatitis B (HepBB) and third dose of diphtheria–tetanus–pertussis containing vaccine (DPT3) variables with coefficients of 1.52 and 1.34 had the highest rate of increasing during this period, respectively. The first dose of diphtheria–tetanus–pertussis containing vaccine (DPT1) with a coefficient of 0.65 had the lowest coefficient among other variables. Conclusion According to the findings, maintaining the wide coverage, monitoring and updating the program can play an important role to improve children's health, contagious disease prevention, and health promotion.

Spillover effect of HIV-specific foreign aid on immunization services in Nigeria

Health aid to Nigeria increased tremendously in the last decade and a significant portion of the funds were earmarked for HIV-associated programs. Studies on the impact of HIV-specific aid on the delivery of non-HIV health services in sub-Saharan Africa have yielded mixed results. This study assessed if there is a spillover effect of HIV-specific aid on childhood vaccinations in Nigeria. Multivariate logistic regression models were used to estimate the effect of aid disbursements in a previous year on the receipt of vaccines at the individual level in a given year. Estimations were done for approximately 11 700 children using data from demographic and health surveys conducted in Nigeria in 2003 and 2008. US$1 increase in HIV aid per capita was associated with a decrease in the probability of receipt of vaccines by 8-31%: polio first dose decreased by 8%; polio final dose by 9%; diphtheria-pertussis-tetanus (DPT) first dose by 11%; DPT final dose by 19%; measles by 31%; final doses of polio and DPT plus measles vaccine by 8%. HIV-specific aid had a negative spillover effect on immunization services in Nigeria over the study period. Donors may need to rethink their funding strategies in favour of more horizontal approaches.

The Fast Track from a New Practice Recommendation to Nurse Sensitive Indicator

Poster Presentation Purpose for the Program In response to the recent surge in pertussis across the United States, specific recommendations for pregnant women have been made by the Advisory Committee for Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) along with the American College of Obstetricians and Gynecologists (ACOG). Infants younger than age 6 months, who are too young to be vaccinated against pertussis, are the most vulnerable population with the highest mortality from this disease. The recommendations from ACIP and ACOG focus on protecting the newborn directly by targeting vaccination of the pregnant mother (to maximize maternal antibody response and passive immunity transfer to the newborn) and indirectly by cocooning (ensuring up‐to‐date vaccination status of family members and care givers who will be around the newborn). Proposed Change To expedite implementing the evolving recommendations at the bedside in our labor and delivery, antepartum, and mother/infant units by utilizing different areas of focus, including maximizing the Electronic Medical Record (EMR) for patient screening and reporting, initial and ongoing staff education, increased surveillance, implementation of a nurse driven protocol, streamlining availability of the vaccine, and implementing a family and caregiver vaccination program. Implementation, Outcomes, and Evaluation We created a patient screening tool within the admission database in the EMR, developed new reports to accurately assess vaccination status of perinatal patients, provided initial and ongoing staff education and vaccination, increased routine surveillance for adherence, implemented a nurse driven protocol to facilitate administration, streamlined availability of the vaccine on the units, and implemented a family and caregiver vaccination program. During the initial 7‐month period, approximately one half of the eligible patients were vaccinated before admission. We educated, screened for eligibility, and administered the vaccine for the other half. During this period, our tetanus–diphtheria–pertussis (Tdap) vaccination rate increased from 46% to 84%. Initially, we were steadily missing vaccinating between 33% and 54% of the eligible women who came into our facility who said they wanted the vaccine. After identifying nurse barriers to vaccination and implementing a nurse‐driven vaccine protocol we were able to decrease the missed rate to 16% within the first month. Additionally, we partnered with our outpatient pharmacy to pilot a family and caregiver vaccination program. Implications for Nursing Practice Tdap vaccination is nursing sensitive. Screening all perinatal patients for eligibility and implementing a nurse driven protocol positively affects vaccination rates.

Estimated costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy.

Antigens contained in vaccines are inherently unstable biologically; such a characteristic is conferred by their three-dimensional structure. Preserving the ability of the vaccines to protect against disease is necessary to ensure the supervision and monitoring of all steps of the cold chain. DTPa-HBV-IPV/Hib vaccine (Infanrix hexaTM, GSK Vaccines, Belgium) is designed to prevent disease due to diphtheria, tetanus, pertussis (DTP), hepatitis B virus (HBV), poliomyelitis and Haemophilus influenzae type b (Hib); it was first licensed for use in Europe in 2000 and is currently licensed in at least 95 countries. Since October 2013, more than 102 million doses of GSK's DTPa-HBV-IPV/Hib vaccine have been distributed globally, with nearly 15 million doses distributed in Italy. DTPa-HBV-IPV/Hib components are stable up to a temperature of 25°C for 72 hours. Lacking of officially approved stability data may generate some concern in case of cold chain accidents. An analysis based on collected data was carried out to estimate potential costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy in 2014. The analysis, based on real data, documented that the loss for the National Health Service (NHS) was in the range of 100,000 - 400,000 euros in one year. However, the amount of money that in principle could have been lost would have ranged between nearly half and one million euros/year. A substantial loss of money was avoided thanks to the availability of officially approved stability data for GSK's DTPa-HBV-IPV/Hib vaccine.

Association between sudden infant death syndrome and diphtheria-tetanus-pertussis immunisation: an ecological study.

BackgroundSudden infant death syndrome (SIDS) continues to be one of the main causes of infant mortality in the United States. The objective of this study was to analyse the association between diphtheria-tetanus-pertussis (DTP) immunisation and SIDS over time.MethodsThe Centers for Disease Control and Prevention provided the number of cases of SIDS and live births per year (1968–2009), allowing the calculation of SIDS mortality rates. Immunisation coverage was based on (1) the United States Immunization Survey (1968–1985), (2) the National Health Interview Survey (1991–1993), and (3) the National Immunization Survey (1994–2009). We used sleep position data from the National Infant Sleep Position Survey. To determine the time points at which significant changes occurred and to estimate the annual percentage change in mortality rates, we performed joinpoint regression analyses. We fitted a Poisson regression model to determine the association between SIDS mortality rates and DTP immunisation coverage (1975–2009).ResultsSIDS mortality rates increased significantly from 1968 to 1971 (+27% annually), from 1971 to 1974 (+47%), and from 1974 to 1979 (+3%). They decreased from 1979 to 1991 (−1%) and from 1991 to 2001 (−8%). After 2001, mortality rates remained constant. DTP immunisation coverage was inversely associated with SIDS mortality rates. We observed an incidence rate ratio of 0.92 (95% confidence interval: 0.87 to 0.97) per 10% increase in DTP immunisation coverage after adjusting for infant sleep position.ConclusionsIncreased DTP immunisation coverage is associated with decreased SIDS mortality. Current recommendations on timely DTP immunisation should be emphasised to prevent not only specific infectious diseases but also potentially SIDS.

Resurgence of pertussis at the age of vaccination: clinical, epidemiological, and molecular aspects

ObjectiveReport the incidence, epidemiology, clinical features, death, and vaccination status of patients with whooping cough and perform genotypic characterization of isolates of B. pertussis identified in the state of Paraná, during January 2007 to December 2013. MethodsCross-sectional study including 1,209 patients with pertussis. Data were obtained through the Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação – SINAN) and molecular epidemiology was performed by repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab®, bioMerieux, France). ResultsThe incidence of pertussis in the state of Paraná increased sharply from 0.15-0.76 per 100,000 habitants between 2007-2010 to 1.7-4.28 per 100,000 between 2011-2013. Patients with less than 1 year of age were more stricken (67.5%). Fifty-nine children (5%) developed pertussis even after receiving three doses and two diphtheria-tetanus-pertussis (DTP) boosters vaccine. The most common complications were pneumonia (14.5%), otitis (0.9%), and encephalopathy (0.7%). Isolates of B. pertussis were grouped into two groups (G1 and G2) and eight distinct patterns (G1: P1-P5 and G2: P6-P8). ConclusionThe resurgence of pertussis should stimulate new research to develop vaccines with greater capacity of protection against current clones and also encourage implementation of new strategies for vaccination in order to reduce the risk of disease in infants.

Sex-differential and non-specific effects of routine vaccinations in a rural area with low vaccination coverage: an observational study from Senegal.

We examined the potential sex-differential and non-specific effects of bacille Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP) and measles vaccine (MV) in a rural area of Senegal. The 4133 children born in the area between 1996 and 1999 were included in the study. Vaccinations were provided at three health centres. Vaccine information was collected through 3-monthly home visits. The survival analysis compared the effects of BCG and DTP according to the following sequence of vaccinations: BCG-first, BCG+DTP1-first, or DTP1-first. We compared DTP and MV between 9 and 24 months of age, as 9 months is the minimum age for MV. At 12 months the vaccination coverage was 44%, 46% and 9%, respectively, for BCG, DTP1 and MV. Most children received BCG+DTP1-first and this combination was associated with a significantly lower mortality rate ratio (MRR) of 0.69 (0.53-0.89) compared with unvaccinated children. There was no benefit for children receiving BCG-first or DTP1-first. The female-male MRR was 0.79 (0.64-0.96) among unvaccinated children, but was significantly inversed with 1.45 (1.00-2.10) for children receiving DTP vaccination (test of homogeneity, p=0.006). Children who had received DTP simultaneously with MV or DTP after MV had significantly higher mortality (MRR=2.59 [1.32-5.07]) compared with children having MV-only as their most recent vaccination. After 9 months, the female-male MRR was 0.61 (0.31-1.19) for measles-vaccinated children but remained 1.54 (1.03-2.31) for DTP-vaccinated children who had not received MV (p=0.01). The sequence of routine vaccinations is important for the overall impact on child survival and these vaccines are associated with sex-differential effects.

The balance between pro- and anti-inflammatory cytokines in the immune responses to BCG and DTwP vaccines.

Bacillus Calmette-Guérin (BCG) and pertussis vaccines have been found to be insufficient and their further improvement is required. In order to develop improved vaccines, a better understanding of the main pathways involved in the host's protective immunity to the pathogens is crucial. We address the question as to whether the balance between pro- and anti-inflammatory cytokine production might affect the host responses to BCG and diphtheria-tetanus toxoids-whole cell pertussis (DTwP) vaccines. The study population consisted of 118 healthy people, age range 18-30 years, who had been subjected to BCG and DTwP vaccination according to the state policy. Tuberculin skin testing (TST) revealed a delayed type hypersensitivity (DTH) to PPD (purified protein derivative) in 53% volunteers. The variability in development of the BCG-driven DTH to tuberculin prompted us to address a question as to whether Th1/Th2 polarization is involved in the lack of skin responsiveness to PPD. PPD-stimulated blood lymphocytes from TST(+) participants produced significantly more IFN-γ and less IL-10 than lymphocytes from TST(-) volunteers. However, TST(-) volunteers' sera contained more anti-pertussis IgG but not anti-diphtheria toxin IgG. Mycobacterial antigens and particularly PPD induced a higher expression of HLA-DR and co-stimulatory CD80 receptors on DCs from TST(+) than TST(-) participants. BCG but not PPD pulsed DCs from TST(-) volunteers produced significantly more IL-10. Mycobacterial antigen stimulated DCs from TST(+) volunteers induced a more intense IFN-γ production in co-cultures with autologous lymphocytes than the cells from TST(-) participants. Differences among the types of dendritic cell activities contribute to development of tuberculin reactivity in BCG vaccinated volunteers.

Cold Abscess of the Thigh in an Infant

Local and minor adverse reactions to diphtheria-pertussis-tetanus (DPT) vaccination are usually mild and appear within 48 hours of vaccination. We herein report a rare association with intramuscular DPT injection and discuss pertinent issues. Primary tuberculous abscess was the final diagnosis.

Early exposure to thimerosal-containing vaccines and children's cognitive development. A 9-year prospective birth cohort study in Poland.

The controversial topic of the early exposure to mercury is regarding ethylmercury, which is present in the thimerosal-containing vaccines (TCVs). The objective of this study was to determine the relationship between the early exposure to TCVs and cognitive development in children during the first 9 years of life. The cohort included 318 children vaccinated in an early period (neonatal and up to 6 months) against hepatitis B and diphtheria-tetanus-pertussis (DTP) using formulation with or without thimerosal. The children’s development was assessed using the Fagan test (6th month of life), the Bayley Scales of Infant Development (BSID)-II (12th–36th month), the Raven test (5th, 8th year), and the Wechsler Intelligence Scale for Children (WISC-R) (6th, 7th, 9th year). Results were determined by multivariable linear and logistic regression, adjusted to potential confounders. Children exposed and not exposed to TCVs in the neonatal period had similar outcomes of cognitive-developmental tests; only the results of BSID-II at the 36th month and WISC-R at the 9th year were significantly higher for those exposed to TCVs. Developmental test results in children exposed to TCVs up to the 6th month of life also did not depend on thimerosal dose. Conclusion: TCV administration in early infancy did not affect children’s cognitive development.

Lasting immune memory against hepatitis B following challenge 10–11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11–12 months of age

BackgroundThe combined hexavalent diphtheria–tetanus–pertussis–hepatitis B-inactivated poliomyelitis – Haemophilus influenzae type b conjugate vaccine (Infanrix hexa™; DTPa-HBV-IPV/Hib: GlaxoSmithKline Vaccines) induces robust responses to the HBV component when administered at 3, 5 and 11–12 months of age. We assessed long term HBV antibody persistence 10–11 years after primary vaccination in infancy. MethodsAntibody persistence and immune memory were assessed post-primary vaccination at 3, 5, 11–12 months with DTPa-HBV-IPV/Hib, or monovalent HBV vaccine (Engerix™ B, GlaxoSmithKline Vaccines) co-administered with DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in 185 children aged 11–12 years. Blood samples were collected before and 1 month after a challenge dose of Engerix™ B (10μg dose). Results10–11 years after primary vaccination the percentage of subjects with persisting anti-HBs antibody concentrations ≥10mIU/ml was 48.4% in the DTPa-HBV-IPV/Hib group and 58.4% in the DTPa-IPV/Hib+HBV group. After the HBV challenge dose, the percentage with anti-HBs ≥100mIU/ml increased from 14.7% to 93.6% in the DTPa-HBV-IPV/Hib group and 19.1% to 94.4% in the DTPa-IPV/Hib+HBV group. Anti-HBs GMCs increased by at least 187-fold in each group. An anamnestic response (≥4-fold increase in initially seropositive or anti-HBs concentration ≥10mIU/ml in initially seronegative subjects) was observed in 96.8% and 96.6% of subjects in the DTPa-HBV-IPV/Hib and DTPa-IPV/Hib+HBV groups, respectively. No serious adverse events occurred that were considered related to challenge vaccination. ConclusionAdministration of HBV as part of a combination vaccine or as a monovalent vaccine induced long lasting immune memory against HBV in children primed at 3, 5 and 11 months of age. Antibody persistence and immune memory were similar, suggesting that protection afforded by DTPa-HBV-IPV/Hib and monovalent HBV vaccines, is likely to be of similar duration. The administration of HBV challenge dose 10–11 years after the 3, 5, 11–12 months primary schedule induced strong anamnestic responses and was well tolerated.This study is registered at www.clinicaltrials.gov NCT01138098.

Predictors of optional immunization uptake in an urban south Indian population

BackgroundIn Tamil Nadu, India, bacille Calmette–Guérin, diphtheria–tetanus–pertussis, oral poliomyelitis, hepatitis B, and measles vaccines are part of the routine immunization schedule and are available free from government health centers. All other vaccines are optional and available in the private sector at a cost to families. This study assesses immunization rates of routine and optional vaccines and examines parental attitudes toward vaccines in Pallavapuram, Tamil Nadu. MethodsThe cluster sampling method was used to estimate immunization coverage. Seven children 18 to 36 months old were selected from 30 clusters for a total sample of 210 children. Demographics and vaccination data were collected from interviews and immunization records. Predictors of vaccination status were identified with logistic regression models. In addition, 21 parents participated in semi-structured interviews regarding their attitudes toward vaccination. Interviews were analyzed qualitatively for themes. ResultsEighty one percent of children were fully immunized with routine vaccines. However, only 21% received all “major” optional vaccines, defined as 3 doses of Haemophilus influenzae type b vaccine, one dose of measles, mumps, rubella vaccine, and one dose of varicella zoster virus vaccine. Birth in a private hospital (OR 5.6, 95% CI 1.3 to 22.9, P<0.01), higher income (P=0.03), and maternal completion of high school (OR 6.4, 95% CI 1.5 to 27.6, P<0.01) were significant predictors of receiving all major optional vaccines. Elucidated themes from interviews included (1) strong parental support for immunizations, (2) low concern for side effects, and (3) low uptake of optional vaccines due to high cost and lack of awareness. ConclusionsCoverage of optional vaccines is low despite positive attitudes toward immunizations. Efforts to reduce cost and increase awareness of these vaccines particularly among low-income families or to include these vaccines in the routine schedule may increase uptake and reduce morbidity and mortality from vaccine-preventable diseases.

Health system cost of delivering routine vaccination in low- and lower-middle income countries: what is needed over the next decade?

On the eve of the 40th anniversary of launching of the Expanded Programme on Immunization (EPI) in 1974, during the twenty-seventh World Health Assembly (WHA), fundamental questions about the level of financing needed to sustain achievements and scale up the EPI in low- and lower-middle income countries continue to permeate the discourse on the economics of immunization. The answer to this question is all the more important in light of the fact that at the sixty-fifth WHA in 2012, ministers of health embraced the Global Vaccine Action Plan (GVAP) – a 10-year global strategic plan for immunization.1 But how much – and in what areas – are the investments needed for this decade? Today, improved transparency in pricing information allows for relatively accurate vaccine cost estimates.2 Unfortunately, trends in the health system costs of delivering vaccination beyond the cost of the vaccines themselves continue to be poorly understood. During the EPI’s first three decades of existence, they were fairly homogenous. The six basic antigens1 included in the EPI were inexpensive and health system inputs, such as the human resources for vaccination and the vaccine supply chain and logistics infrastructure, accounted for the largest share of total costs in country programmes.3 It was common knowledge that EPI vaccines represented 20% of overall investment in national immunization programmes in low- and lower-middle income countries.4 With the turn of the millennium came a paradigm shift away from this earlier established trend as countries began introducing new vaccines, such as the pentavalent vaccine, a five–in-one combination of the antigens against diphtheria, tetanus and pertussis with those against hepatitis B (HepB) and Haemophilus influenzae type b (Hib).2 During the period from 2000 to 2010, countries rapidly scaled up the use of pentavalent vaccine and, as a result, the total cost of country immunization programmes doubled or tripled.5 Recurrent investments in vaccines suddenly comprised the bulk of immunization programme costs: an average of more than 50% of total investments, and in many cases, well over this average.6 Part of the reason for this rise in the component of the total costs comprised by vaccines was that the incremental health system (i.e. non-vaccine) costs of introducing the pentavalent vaccine were marginal, since this product, despite adding two new antigens – HepB and Hib – to EPI schedules, required no more injections than the previously administered trivalent diphtheria–pertussis–tetanus (DPT) vaccine. In addition, pentavalent vaccines required little additional storage space in the vaccine cold chain.7 Looking ahead, the current decade will see the accelerated introduction into national EPI programmes of additional new, expensive, but highly effective vaccines, such as pneumococcal conjugate vaccine and the vaccines against rotavirus and human papilloma virus (HPV).3 These products are bulkier than the pentavalent vaccine and will require more cold chain storage space and more injections. The health system costs associated with delivering these newer vaccines are likely to outweigh the costs of the vaccines themselves – which reverses the trend in relative importance of vaccine to non-vaccine costs once again.

Costs of vaccine delivery in the Gambia before and after, pentavalent and pneumococcal conjugate vaccine introductions

BackgroundThe Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV) in August 2009 and switched to 13-valent PCV in April 2011. In April 2009 monovalent hepatitis B and combined Diphtheria–Tetanus–Pertussis and Haemophilus influenzae type b vaccines were transitioned to a combined pentavalent vaccine. The current schedule offers three doses of PCV and pentavalent, and continues to give children monovalent hepatitis B vaccine at birth. We estimated the overall costs of the Gambian immunisation programme and the incremental costs of introducing pentavalent and the seven-valent PCV. MethodsTwenty health facilities out of a total of 56 were surveyed. Data collected included number of vaccine doses delivered, staff time spent on vaccine delivery, distance travelled to collect vaccines, and cold chain expansion due to new vaccine introduction. National level data were collected from key informant interviews. Annualised costs were calculated in 2009 US$. ResultsWith a PCV price of US$7 per dose, the incremental costs of introducing PCV was US$1.6 million, equivalent to US$25 per fully immunised child, with systems costs accounting for US$1.90. The switch to pentavalent vaccine resulted in cost savings of US$0.45 per fully immunised child. Total annual costs increased by 45% after the introduction of the new vaccines, amounting to US$ 3.0 million, or US$45 per fully immunised child. ConclusionVaccine prices were the most important determinant of total incremental costs and cold chain expansion the biggest cost component of systems costs.

Timeliness of routine immunization in a population-based Italian cohort of very preterm infants: Results of the ACTION follow-up project

BackgroundAlthough very preterm infants are recommended to receive immunizations, according to their chronological age, immunization start in these infants is often delayed.Aim To measure coverage and timeliness of routine immunizations in Italian very preterm infants and to assess determinants of delay. MethodsWe followed up infants 22–31 completed weeks of gestational age discharged from intensive care. We measured the proportion of children with one dose of diphtheria–tetanus–pertussis–poliohepatitis, B-Hib vaccine (DTP–Pol–HBV-Hib), measles–mumps–rubella vaccine (MMR), conjugate pneumococcal vaccine (Pnc), conjugate meningococcal C vaccine (MenC), and varicella vaccine (Var) by 24 months. We used the Kaplan Meier method and Cox proportional hazard models to estimate the age, at immunization start and determinants of timeliness for each vaccine. ResultsData on 1102 (92.1%) children out of 1196 included in the cohort were analyzed. Immunization start by 24 months of age occurred in 95.9% of children for DTP–Pol–HBV-Hib; 84.0% for MMR; 49.7% for Pnc; 38.5% for MenC; and 4.1% for Var. Eighty-seven percent of participants received the first dose of DTP–Pol–HBV-Hib by 6 months of age, and 66.7% had their first MMR administered by 18 months. Hospitalization was associated with delay for all vaccines with the exception of MenC and Var. Maternal employment was associated with earlier immunization for MMR, Pnc, and MenC. DTP–Pol–HBV-Hib timeliness improved with increasing birthweight and paternal employment and decreased with a larger number of siblings in the household. MMR was delayed in children with cerebral palsy, and in those with a larger number of children in the household. Immunization for Pnc was delayed in children with larger number of siblings. ConclusionsImmunization start for all vaccines was considerably delayed in many very preterm infants. Public health strategies taking into account determinants of delay should be implemented to improve coverage and timeliness of vaccination in this group of infants.

Antipyretic Effect of Cinnamomum burmannii (Nees &amp; T.Nees) Blume Infusion in Fever-induced Rat Models

Background: Fever is a frequent clinical sign encountered in human especially in children. Unfortunately, access to health care and medications (antipyretics) are hampered by shortage of services and affordability, which are accentuated by local resources mainly for those living in remote areas. Therefore, using herbal medicineas an alternative in treating fever should be developed as substituent reliance on synthetic antipyretic. This study is conducted to observe antipyretic effect of Cinnamomum burmannii (Nees &amp; T.Nees) Blume infusion using Diphtheria Tetanus Pertussis (DTP) vaccine-induced fever in rats. Methods: Twenty-eight male Wistar rats (150200 g) were randomly allocated into control and treatment groups. Fever was induced with DTP vaccine intramuscularly injected (0.7 mL/200 g body weight) and 4 hours later, distilled water (5 mL) was administered orally to the control group while the treatment group received 5 mL of 3%, 6%, and 12% of cinnamon infusion. Rectal temperature was measured before the pretreatment, 4 hours afterDTP vaccine-induced fever injection and at a 30-minute interval during 180 minutes after the infusion administration. All procedures and protocols were performed in October 2012 at the Pharmacology Laboratory, Faculty of Medicine, Universitas Padjadjaran, Bandung. Results: Data analysis using the one way analysis of variance (ANOVA) showed significant reduction (p&lt;0.001) of rectal temperature after 30 minutes and Duncan Post-Hoc test showed significant effect for 6% and 12% of cinnamon infusion groups. Conclusion The antipyretic effect of 6% and 12% of Cinnamomum burmannii (Nees &amp; T.Nees) Blume infusion in fever-induced rat models is found in the first 30 minutes. Key words : Antipyretic, Cinnamomum burmannii (Nees &amp; T.Nees) Blume, fever, herbal medicine Efek Antipiretik Infusa Cinnamomum burmannii (Nees &amp; T.Nees) Blume pada Tikus yang Diinduksi Demam Abstrak Latar belakang: Demam merupakan suatu gejala yang sering muncul terutama pada anak-anak. Antipiretik merupakan obat yang sering digunakan untuk meringankan demam, namun akses kepada pelayanan kesehatan dan pengobatan masih belum terjangkau bagi penduduk yang tinggal di daerah terpencil. Menggunakan herbal sebagai alternatif pengobatan demam harus dikembangkan sebagai substituen terhadap ketergantungan pada obat sintetik. Penelitian ini dilakukan dengan tujuan untuk mengetahui efek antipiretik infusa Cinnamomum burmannii (Nees &amp; T.Nees) Blume pada tikus yang diinduksi demam menggunakan vaksin Diphtheria Tetanus Pertussis (DTP). Metode: Penelitian yang dilakukan menggunakan 28 ekor tikus putih jantan galur Wistar yang dikelompokkan secara acak dan diinjeksi dengan vaksin DTP (0.7 mL/200 g BB) secara intramuskular untuk menimbulkan demam. Setelah 4 jam, kelompok kontrol diberikan 5mL air suling per oral dan kelompok uji diberikan infusa Cinnamomum burmannii (Nees &amp; T.Nees) Blume per oral dengan dosis masing-masing 3%/5 mL, 6%/5 mL dan 12%/5 mL. Pengukuran suhu tubuh dilakukan melalui rektal sebelum pemberian vaksin DTP, 4 jam setelah pemberian vaksin DTP dan 30 menit interval setelah perlakuan sampai menit 180. Semua prosedur dan protokol dilaksanakan pada Oktober 2012 di Laboratorium Farmakologi, Fakultas Kedokteran, Universitas Padjadjaran, Bandung. Hasil: Hasil analisis data menggunakan uji ANOVA menunjukkan penurunan yang signifikan (p&lt;0.001) dari suhu rektal pada menit 30 dan dengan uji Duncan Post-Hoc menunjukkan efek yang signifikan pada kelompok yang diberikan 6%/5 ml dan 12%/5 mL infusa Cinnamomum burmannii (Nees &amp; T.Nees) Blume. Pada menit 60–180 tidak ada penurunan yang signifikan (p&gt;0.05) dari suhu rektal, dimungkinkan karena durasi kerja yang singkat dari Cinnamomum burmannii (Nees &amp; T.Nees) Blume. S impulan: Efek antipiretik pada pemberian dosis 6% dan 12% infusa Cinnamomum burmannii (Nees &amp; T.Nees) Blume pada tikus yang diinduksi demam ditemukan pada 30 menit pertama. Kata kunci : Antipiretik, Cinnamomum burmannii (Nees &amp; T.Nees) Blume, demam, pengobatan herbal DOI: 10.15850/amj.v1n2.352

Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau

BackgroundStudies from low-income countries indicate that co-administration of inactivated diphtheria–tetanus–pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP–H. Influenza type B–Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects. MethodsIn 2007–2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6–23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV+YF) or a combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors. ResultsWhile DTP was still used 685 children received MV only and 358 MV+DTP; following the change in programme, 940 received MV+YF only and 348 MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20–8.73). For MV+YF+pentavalent compared with MV+YF only, the adjusted MRR was 7.73 (1.79–33.4). ConclusionIn line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality.