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Sample records for acellular pertussis tdap

  1. Universal tetanus, diphtheria, acellular pertussis (Tdap) vaccination of adults: What Canadian health care providers know and need to know

    PubMed Central

    MacDougall, D; Halperin, BA; MacKinnon-Cameron, D; Li, L; McNeil, SA; Langley, JM; Halperin, SA

    2015-01-01

    The tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in both Canada and the United States. There are few data on the proportion of Canadian adults vaccinated with Tdap; however, anecdotal reports indicate that uptake is low. This study aimed to explore the knowledge, attitudes, beliefs, and behaviors of Canadian health care providers (HCPs) in an attempt to identify potential barriers and facilitators to Tdap uptake. HCPs were surveyed and a geographic and practice representative sample was obtained (N =1,167). In addition, 8 focus groups and 4 interviews were conducted nationwide. Results from the survey indicate that less than half (47.5%) of all respondents reported being immunized with Tdap themselves, while 58.5% routinely offer Tdap to their adult patients. Knowledge scores were relatively low (63.2% correct answers). The best predictor of following the adult Tdap immunization guidelines was awareness of and agreement with those recommendations. Respondents who were aware of the recommendations were more likely to think that Tdap is safe and effective, that their patients are at significant risk of getting pertussis, and to feel that they have sufficient information (p < 0.0001 for each statement). Focus group data supported the survey results and indicated that there are substantial gaps in knowledge of pertussis and Tdap among Canadian HCPs. Lack of public knowledge about adult immunization, lack of immunization registries, a costing differential between Td and Tdap, workload required to deliver the vaccine, and vaccine hesitancy were identified as barriers to compliance with the national recommendations for universal adult immunization, and suggestions were provided to better translate recommendations to front-line practitioners. PMID:26090861

  2. Universal tetanus, diphtheria, acellular pertussis (Tdap) vaccination of adults: What Canadian health care providers know and need to know.

    PubMed

    MacDougall, D; Halperin, B A; MacKinnon-Cameron, D; Li, L; McNeil, S A; Langley, J M; Halperin, S A

    2015-01-01

    The tetanus, diphtheria, and acellular pertussis vaccine (Tdap) is recommended for all adults in both Canada and the United States. There are few data on the proportion of Canadian adults vaccinated with Tdap; however, anecdotal reports indicate that uptake is low. This study aimed to explore the knowledge, attitudes, beliefs, and behaviors of Canadian health care providers (HCPs) in an attempt to identify potential barriers and facilitators to Tdap uptake. HCPs were surveyed and a geographic and practice representative sample was obtained (N =1,167). In addition, 8 focus groups and 4 interviews were conducted nationwide. Results from the survey indicate that less than half (47.5%) of all respondents reported being immunized with Tdap themselves, while 58.5% routinely offer Tdap to their adult patients. Knowledge scores were relatively low (63.2% correct answers). The best predictor of following the adult Tdap immunization guidelines was awareness of and agreement with those recommendations. Respondents who were aware of the recommendations were more likely to think that Tdap is safe and effective, that their patients are at significant risk of getting pertussis, and to feel that they have sufficient information (p < 0.0001 for each statement). Focus group data supported the survey results and indicated that there are substantial gaps in knowledge of pertussis and Tdap among Canadian HCPs. Lack of public knowledge about adult immunization, lack of immunization registries, a costing differential between Td and Tdap, workload required to deliver the vaccine, and vaccine hesitancy were identified as barriers to compliance with the national recommendations for universal adult immunization, and suggestions were provided to better translate recommendations to front-line practitioners. PMID:26090861

  3. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    MedlinePlus

    Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  4. Factors Associated with Intention to Receive Influenza and Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Vaccines during Pregnancy: A Focus on Vaccine Hesitancy and Perceptions of Disease Severity and Vaccine Safety

    PubMed Central

    Chamberlain, Allison T.; Seib, Katherine; Ault, Kevin A.; Orenstein, Walter A.; Frew, Paula M.; Malik, Fauzia; Cortés, Marielysse; Cota, Pat; Whitney, Ellen A. S.; Flowers, Lisa C.; Berkelman, Ruth L.; Omer, Saad B.

    2015-01-01

    BACKGROUND: Improving influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccine coverage among pregnant women is needed. PURPOSE: To assess factors associated with intention to receive influenza and/or Tdap vaccinations during pregnancy with a focus on perceptions of influenza and pertussis disease severity and influenza vaccine safety. METHODS: Participants were 325 pregnant women in Georgia recruited from December 2012 – April 2013 who had not yet received a 2012/2013 influenza vaccine or a Tdap vaccine while pregnant. Women completed a survey assessing influenza vaccination history, likelihood of receiving antenatal influenza and/or Tdap vaccines, and knowledge, attitudes and beliefs about influenza, pertussis, and their associated vaccines. RESULTS: Seventy-three percent and 81% of women believed influenza and pertussis, respectively, would be serious during pregnancy while 87% and 92% believed influenza and pertussis, respectively, would be serious to their infants. Perception of pertussis severity for their infant was strongly associated with an intention to receive a Tdap vaccine before delivery (p=0.004). Despite perceptions of disease severity for themselves and their infants, only 34% and 44% intended to receive antenatal influenza and Tdap vaccines, respectively. Forty-six percent had low perceptions of safety regarding the influenza vaccine during pregnancy, and compared to women who perceived the influenza vaccine as safe, women who perceived the vaccine as unsafe were less likely to intend to receive antenatal influenza (48% vs. 20%; p < 0.001) or Tdap (53% vs. 33%; p < 0.001) vaccinations. CONCLUSIONS: Results from this baseline survey suggest that while pregnant women who remain unvaccinated against influenza within the first three months of the putative influenza season may be aware of the risks influenza and pertussis pose to themselves and their infants, many remain reluctant to receive influenza and Tdap vaccines antenatally. To

  5. Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years.

    PubMed

    Carlsson, R M; Gustafsson, L; Hallander, H O; Ljungman, M; Olin, P; Gothefors, L; Nilsson, L; Netterlid, E

    2015-07-17

    Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20μg) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5μg). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. The adolescent study was registered at ClinicalTrials.gov on 26 March 2009 (NCT00870350). PMID:26057135

  6. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    MedlinePlus

    ... which can cause difficulty breathing, vomiting and disturbed sleep. It can also lead to weight loss, incontinence, and rib fractures. Up to 2 in 100 adolescents and 5 in 100 adults with pertussis are ...

  7. Tdap (Tetanus, Diphtheria and Pertussis) Vaccine: What You Need to Know

    MedlinePlus

    ... Tdap Vaccine What You Need to Know (Tetanus, Diphtheria and Pertussis) Many Vaccine Information Statements are available ... immunize. org/ vis 1 Why get vaccinated? Tetanus, diphtheria and pertussis are very serious diseases. Tdap vaccine ...

  8. CDC update on pertussis surveillance and Tdap vaccine recommendations.

    PubMed

    Clark, Thomas A; Bobo, Nichole

    2012-11-01

    Pertussis is the most poorly controlled bacterial vaccine-preventable disease. Since the early 1980s there has been an increase in reported cases of pertussis. Multiple factors have likely contributed to the increase, including waning immunity, increased recognition, and changes in diagnostic testing and reporting. Of the four combination vaccines used to prevent diphtheria, tetanus, and pertussis, one dose of Tdap should be used to vaccinate preteens as well as teens and adults who have not yet received this booster dose. It is the position of NASN that immunizations, including the Tdap vaccine, are key to primary prevention of diseasefrom infancy through adulthood. The school nurse is in a critical position to create awareness and influence action-related national and state recommendations for the Tdap vaccine. PMID:23193719

  9. Tetanus, diphtheria, and acellular pertussis vaccination among women of childbearing age-United States, 2013.

    PubMed

    O'Halloran, Alissa C; Lu, Peng-Jun; Williams, Walter W; Ding, Helen; Meyer, Sarah A

    2016-07-01

    The incidence of pertussis in the United States has increased since the 1990s. Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination of pregnant women provides passive protection to infants. Tdap vaccination is currently recommended for pregnant women during each pregnancy, but coverage among pregnant women and women of childbearing age has been suboptimal. Data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) and 2013 National Health Interview Survey (NHIS) were used to determine national and state-specific Tdap vaccination coverage among women of childbearing age by self-reported pregnancy status at the time of the survey. Although this study could not assess coverage of Tdap vaccination received during pregnancy because questions on whether Tdap vaccination was received during pregnancy were not asked in BRFSS and NHIS, demographic and access-to-care factors associated with Tdap vaccination coverage in this population were assessed. Tdap vaccination coverage among all women 18-44 years old was 38.4% based on the BRFSS and 23.3% based on the NHIS. Overall, coverage did not differ by pregnancy status at the time of the survey. Coverage among all women 18-44 years old varied widely by state. Age, race and ethnicity, education, number of children in the household, and access-to-care characteristics were independently associated with Tdap vaccination in both surveys. We identified associations of demographic and access-to-care characteristics with Tdap vaccination that can guide strategies to improve vaccination rates in women during pregnancy. PMID:27372388

  10. Tdap (tetanus, diphtheria, pertussis) Vaccine and Pregnancy

    MedlinePlus

    ... Canada, and many other countries. Pertussis (also called whooping cough) is a bacterial illness that usually begins with symptoms like those of the common cold. Severe coughing can develop over several weeks. Fast, heavy ... sound when breathing in. Pertussis is most serious ...

  11. Protecting Newborns by Immunizing Family Members in a Hospital-Based Vaccine Clinic: A Successful Tdap Cocooning Program During the 2010 California Pertussis Epidemic

    PubMed Central

    McBane, Sarah; Wang, Wendy; Sawyer, Mark

    2014-01-01

    Objective Infants are at greatest risk for mortality from pertussis infection. Since 2005, the Advisory Committee on Immunization Practices has recommended a cocooning strategy of vaccinating all close contacts of infants with tetanus, diptheria, and acellular pertussis (Tdap) vaccine to reduce the risk of transmitting pertussis. Difficulties in establishing a complete cocoon have been reported in the literature. We determined whether families of newborns could be fully immunized against pertussis, thereby providing a complete cocoon of protection. Methods Tdap vaccine was offered during visiting hours to contacts aged 7 years and older and to postpartum patients who had not received Tdap vaccine during pregnancy. We then conducted retrospective phone interviews with randomly selected mothers (or other family members) to assess vaccination rates. We compared household vaccination rates during intervention and control periods and the demographic factors associated with Tdap vaccination of all members within the households. Results During the intervention period, 243 postpartum patients and 1,287 other family members of newborns were immunized, with 84.8% of all family members receiving Tdap vaccination. Seventy-six percent of households reported a complete cocoon. In the control group, 52.2% of all family members received Tdap vaccination, and 29.3% of households had a complete cocoon. In the control group, fewer family members completed Tdap vaccination in the larger households than in the smaller households (p=0.008). Conclusion A cocooning strategy can be successfully implemented, such that the majority of newborns leave the hospital with their families fully immunized against pertussis. PMID:24791022

  12. Multiplex immunoassay for in vitro characterization of acellular pertussis antigens in combination vaccines.

    PubMed

    Agnolon, Valentina; Bruno, Cristina; Galletti, Bruno; Mori, Elena; Ugozzoli, Mildred; Pergola, Carlo; O'Hagan, Derek T; Baudner, Barbara C

    2016-02-17

    Vaccines characterization is required to ensure physical, chemical, and biological integrity of antigens and adjuvants. Current analytical methods mostly require complete antigen desorption from aluminum-based adjuvants and are not always suitable to distinguish individual antigens in multivalent formulations. Here, Luminex technology is proposed to improve the analytics of vaccine characterization. As proof of concept, TdaP (tetanus, diphtheria and acellular pertussis) combination, adjuvanted with aluminum hydroxide, was chosen as model formulation to quantify and determine the level of adsorption of acellular pertussis (aP) antigens onto adjuvant surface at the same time. The assay used specific antibodies bound to magnetic microspheres presenting unique digital signatures for each pertussis antigen, allowing the simultaneous recognition of respective antigens in the whole vaccine, avoiding laborious procedures for adjuvant separation. Accurate and reproducible quantification of aP antigens in TdaP vaccine has been achieved in the range 0.78-50 ng/mL, providing simultaneously information on antigen identity, quantity, and degree of adsorption to aluminum hydroxide. The current study could further be considered as a model to set up in vitro potency assays thus supporting the replacement of animal tests accordingly to the 3Rs concept. PMID:26784684

  13. Protection against pertussis by acellular pertussis vaccines (Takeda, Japan): household contact studies in Kawasaki City, Japan.

    PubMed

    Kato, T; Goshima, T; Nakajima, N; Kaku, H; Arimoto, Y; Hayashi, F

    1989-12-01

    To evaluate the vaccine efficacy of an acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was performed by a questionnaire survey of secondary pertussis attacks through family contact in 146 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, acellular vaccine made by Takeda Pharmaceutical Company, which contains a high level of FHA (filamentous hemagglutinin), a low level of PT (pertussis toxin) and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 29 siblings (58.6%) not immunized with pertussis vaccine. On the other hand, 27 siblings immunized with Takeda's acellular vaccine were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.7%). The present study revealed an efficacy rate of 93.7% for Takeda's acellular pertussis vaccine. PMID:2516396

  14. [Protection against pertussis by Japanese T type acellular pertussis vaccine: household contact study in Kawasaki City].

    PubMed

    Kato, T; Matsuyoshi, S; Goshima, T; Nakajima, N; Yamamoto, H; Arimoto, Y; Kaku, H; Hayashi, F

    1989-09-01

    To evaluate the vaccine efficacy of acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was made by a questionnaire from secondary pertussis attack through family contact in 149 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, Takeda's acellular vaccine which contains a high level of FHA, low level of PT and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 29 siblings (58.6%) not immunized with pertussis vaccine. On the other hand of the siblings immunized with Takeda's acellular vaccine 27 were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.4%). The present study revealed an efficacy rate of 94.2% for the Takeda's acellular pertussis vaccine. PMID:2509597

  15. Protection against pertussis by Takeda's acellular pertussis vaccine: household contact studies in Kawasaki City, Japan.

    PubMed

    Kato, T; Kaku, H; Arimoto, Y

    1988-01-01

    To evaluate the vaccine efficacy of an acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was performed by a questionnaire survey of secondary pertussis attacks through family contact in 146 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, Takeda's acellular vaccine which contains a high level of FHA, low level of PT and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 27 siblings (62.9%) not immunized with pertussis vaccine. On the other hand, 26 siblings immunized with Takeda's acellular vaccine were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.8%). The present study revealed an efficacy rate of 93.9% for Takeda's acellular pertussis vaccine. PMID:3078808

  16. Comparison of toxicities of acellular pertussis vaccine with whole cell pertussis vaccine in experimental animals.

    PubMed

    Sato, Y; Sato, H

    1991-01-01

    There is no suitable animal model for pertussis encephalopathy in humans. In this study, we have compared the toxicity of acellular pertussis vaccine with whole cell pertussis vaccine in mice or guinea pigs. Two lots of acellular and two lots of whole cell vaccine produced in different countries were assayed in the test. 1. There was no statistical difference in mouse protective potency between these acellular or whole cell pertussis vaccines. 2. There were no differences in chemical ingredients between acellular and whole cell pertussis vaccines except for protein nitrogen content. The protein nitrogen content of whole cell vaccine was at least three times higher than that of the acellular product. 3. Anti-PT antibody productivity of the acellular vaccine was higher than that of the whole cell vaccine. 4. Anti-agglutinogen antibody productivity of the whole cell vaccine was higher than that of the acellular vaccine. 5. There was no pyrogenic activity with the acellular vaccine, but high pyrogenicity was seen with whole cell vaccine. 6. There was high body-weight decreasing toxicity in mice and guinea pigs by the whole cell vaccine. 7. The mice died when they received whole cell pertussis vaccine iv, but no deaths occurred in the mice which received acellular pertussis vaccine. PMID:1778317

  17. Immunogenicity of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria, tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study.

    PubMed

    John, T; Voysey, M; Yu, L M; McCarthy, N; Baudin, M; Richard, P; Fiquet, A; Kitchin, N; Pollard, A J

    2015-08-26

    This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination. PMID:26165918

  18. Tdap vaccine attitudes and utilization among pregnant women from a high-risk population.

    PubMed

    Dempsey, Amanda F; Brewer, Sarah E; Sevick, Carter; Pyrzanowski, Jennifer; Mazzoni, Sara; O'Leary, Sean T

    2016-04-01

    Infants infected with Bordatella pertussis experience high morbidity and significant mortality. Vaccinating pregnant mothers with the tetanus-diphtheria-acellular pertussis (Tdap) vaccine is a recommended strategy for preventing infant pertussis. This is especially important for mothers living in poverty and from racial and ethnic minority populations as these groups are at increased risk of having a pertussis-affected infant. Using the Health Belief Model as a framework, we surveyed a convenience sample of pregnant mothers representing these high-risk populations to understand factors associated with Tdap vaccine uptake during their pregnancy. Among the 316 mothers surveyed, 82% had gotten or planned to get Tdap that same day even though 63% of the sample had concerns about the safety of the vaccine during pregnancy. Perceived benefits and norms were the Health Belief Model constructs most consistently associated with Tdap vaccination. Although 32% of women reported prior Tdap vaccine receipt, this factor was not associated with Tdap vaccination during the current pregnancy, contrasting studies of vaccination done in non-pregnant populations. Important variations in attitudes were apparent, with Spanish-speaking women significantly more likely to have concerns about the vaccine's safety and efficacy than English-speaking women. This study indicates that among this high-risk population acceptance of Tdap vaccine during pregnancy is high. However, our results suggest that it may be important to modify information conveyed about the safety and importance of Tdap during pregnancy based on individual level factors such as language or acculturation. PMID:26430729

  19. Immunogenicity and safety of a monovalent, multicomponent acellular pertussis vaccine in 15 month-6-year-old German children. Monovalent Acellular Pertussis Vaccine Study Group.

    PubMed

    Stehr, K; Heininger, U; Uhlenbusch, R; Angersbach, P; Hackell, J; Eckhardt, T

    1995-03-01

    Immunization against pertussis has been re-recommended for healthy children in Germany in 1991. In addition the former restriction of immunizing only in the first 2 years of life was abolished. In children born before 1991 immunization rates against pertussis were 15% or less. With the new recommendations physicians are now faced with an increasing demand of parents for catch-up vaccinations in these children. Since they were immunized against diphtheria and tetanus previously monovalent pertussis vaccines are needed for this indication. Therefore a monovalent, multicomponent acellular pertussis vaccine was studied in 249 German children 15 months to 6 years of age. Three doses were administered at 6-10 week intervals. Reactogenicity and antibody responses against the vaccine antigens pertussis toxin (PT), filamentous haemagglutinin (FHA), 69-kd antigen (pertactin) and fimbriae-2 (agglutinogen) were investigated. Local and systemic reactions were minimal in frequency and severity. Antibody responses against all vaccine antigens were pronounced with 93%-100% of vaccinees demonstrating at least four fold titre rises above pre-immunization after the third dose. These findings indicate that this monovalent, multicomponent acellular pertussis vaccine with excellent immunogenicity and low reactogenicity is an appropriate candidate for closing immunization gaps in older children in countries with previously low vaccination rates against pertussis. Based on the results of this study the monovalent acellular pertussis vaccine was licensed in Germany in January 1994. PMID:7758519

  20. [Pertussis vaccines: acellular versus whole cell. Perhaps a return to the past?].

    PubMed

    Cofré, José

    2015-10-01

    The resurgence of pertussis in the world and in our country has questioned the effectiveness of cellular and acellular vaccines. The reason why pertussis has not been controlled or eliminated after 70 years of implementation of the vaccination is probably multifactorial. This article, on the basis of questions and answers, describes the benefits and limitations of both cellular and acellular vaccines and suggests new strategies of vaccination in childhood. It is a fact that the currently applied vaccination does not eliminate the circulation of Bordetella pertussis in the community. Perhaps the introduction of vaccines with live B. pertussis, inhalation, will be able to eliminate the disease around the world. PMID:26633113

  1. Purification design and practice for pertactin, the third component of acellular pertussis vaccine, from Bordetella pertussis.

    PubMed

    Li, Zenglan; Zhang, Yan; Wang, Qi; Li, Zhengjun; Liu, Yongdong; Zhang, Songping; Zhang, Guifeng; Ma, Guanghui; Luo, Jian; Su, Zhiguo

    2016-07-25

    Development of acellular pertussis vaccine (aPV) requires purification of several components from Bordetella pertussis. While the components pertussis toxin (PT) and filamentous hemagglutinin (FHA) have been successfully purified, the third component, pertactin, proves to be a difficult target due to its very low concentration. In order to solve its purification problem, we performed the surface potential analysis with GRASP2 program. The results demonstrated that there are two major charge patches, one negative and one positive, which are located separately on this linear protein. For this special feature, we designed a dual ion exchange chromatography strategy including an anionic exchange and a cationic exchange process for separation of pertactin from the heat extract of B. pertussis. The initial anionic exchange chromatography concentrated the product from 1.7% to 14.6%, with recovery of 80%. The second cationic exchange chromatography increased the purity to 33%, with recovery of 83%. The final purification was accomplished by hydrophobic interaction chromatography, yielding a purity of 96%. The total recovery of the three columns was 61%. Characterization of the purified antigen was performed with CD, intrinsic fluorescence, HP-SEC and western-blot, showing that the purified protein kept its natural conformation and immune-reactivity. The rationally designed process proved to be feasible, and it is suitable for large-scale preparation of the third aPV component pertactin. PMID:27302339

  2. Phase II trial of whole-cell pertussis vaccine vs an acellular vaccine containing agglutinogens.

    PubMed

    Miller, E; Ashworth, L A; Robinson, A; Waight, P A; Irons, L I

    1991-01-12

    An acellular pertussis vaccine containing agglutinogens 2 and 3, pertussis toxin, and filamentous haemagglutinin was developed by the Centre for Applied Microbiology and Research in the UK. 188 infants were entered into a randomised blind trial and received either the acellular or a whole-cell vaccine, combined with diphtheria and tetanus toxoids, in a 3, 5, and 8-10 month schedule. Local reactions were similar in the two groups but significantly fewer infants had systemic symptoms after the acellular vaccine. Mean log-antibody titres to the agglutinogen and toxin components were higher with the acellular than with the whole-cell vaccine. Persistence of antibodies one year after the third dose was also better in the acellular group. PMID:1670725

  3. Comparative biological activities of acellular pertussis vaccines produced by Kitasato.

    PubMed

    Watanabe, M; Izumiya, K; Sato, T; Yoshino, K; Nakagawa, N; Ohoishi, M; Hoshino, M

    1991-04-01

    The quality of 14 lots of acellular pertussis-diphtheria-tetanus (AC-PDT) vaccines manufactured by the Kitasato Institute during the period 1987-1990 were investigated. The geometric means of HSU, LPU, and BWDU were 0.078, 0.257, and 7.33 per ml respectively. The potency was higher than 14 IU per ml. These results indicated the consistency of the Kitasato AC-PDT vaccines. The antibody response to the AC-PDT vaccines was measured in primary and secondary vaccinated mice by ELISA. IgG antibody response to FHA and PT was obtained in all immunized mice (P less than 0.001) after the primary injection. In contrast, IgG antibody response to fimbriae 2 showed a significant titer rise (P less than 0.001) after the booster injection. The results indicated that the Kitasato AC-P vaccines consisted of protein, PT and FHA as the major antigens, and a little agglutinogen as the minor antigen. PMID:1798236

  4. Immunogenicity, safety, and antibody persistence at 3, 5, and 10 years postvaccination in adolescents randomized to booster immunization with a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliomyelitis vaccine administered with a hepatitis B virus vaccine concurrently or 1 month apart.

    PubMed

    Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona

    2015-03-01

    An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This phase II randomized, controlled, and open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n = 145) received Tdap-IPV, followed by a HepB dose 1 month later, and group 2 (n = 135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/ml for diphtheria and tetanus, at a ≥1:8 dilution for poliovirus (serotypes 1, 2, and 3), and ≥10 mIU/ml for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (at or above the lower limit of quantitation), and 72.7% to 95.8% had 4-fold increases in pertussis antibodies at 1 month postvaccination. At 10 years postvaccination, the remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/ml for diphtheria and tetanus, a ≥1:8 dilution for all 3 poliovirus serotypes, and 74.1% to 98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between the groups. These results support the coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after an adolescent booster vaccination. PMID:25540274

  5. Tdap (tetanus, diphtheria and pertussis) vaccine - what you need to know

    MedlinePlus

    ... It can lead to breathing problems, heart failure, paralysis, and death. PERTUSSIS (Whooping Cough) causes severe coughing spells, which can cause difficulty breathing, vomiting, and disturbed sleep. It can also lead to weight loss, incontinence, ...

  6. Tdap (tetanus, diphtheria and pertussis) vaccine - what you need to know

    MedlinePlus

    ... which can cause difficulty breathing, vomiting, and disturbed sleep. It can also lead to weight loss, incontinence, and rib fractures. Up to 2 in 100 adolescents and 5 in 100 adults with pertussis are ...

  7. Should acellular pertussis vaccine be recommended to healthcare professionals?

    PubMed

    Moraes, José Cassio de; Carvalhanas, Telma; Bricks, Lucia Ferro

    2013-07-01

    The aim of this study was to describe recent changes in the epidemiology of pertussis and existing policies regarding recommended and mandatory occupational vaccinations for healthcare professionals (HCPs). The authors carried out an extensive review of references on the PubMed and SciELO databases and the official sites of the World Health Organization, Pan American Health Organization, Centers for Disease Control and Prevention, and Brazilian Ministry of Health, using the keywords pertussis, vaccines and healthcare professionals. Vaccination against pertussis is recommended for HCPs in the United States, Canada, nine European countries, Australia, Hong Kong, Singapore, Costa Rica, Argentina and Uruguay, and in some countries it is compulsory. In Brazil, only one publication discussing the risk of pertussis among HCPs was found. Considering the reemergence of pertussis and the great number of associated hospitalizations and deaths registered in 2011, it is necessary to review public policies regarding HCP pertussis vaccination, particularly among workers in frequent contact with young babies. PMID:23842996

  8. The cell mediated and humoral immune response to vaccination with acellular and whole cell pertussis vaccine in adult humans.

    PubMed

    Petersen, J W; Ibsen, P H; Bentzon, M W; Capiau, C; Heron, I

    1991-10-01

    The cell mediated immune response (CMI) against pertussis antigens following vaccination with the traditional Danish whole cell pertussis vaccine (WC-P) and the Japanese acellular pertussis vaccine (A-PV) JNIH-3 was studied in four adult human volunteers. Vaccination with the A-PV induced an in vitro proliferative response of peripheral blood lymphocytes to pertussis toxin (PT) subunits S2-S4, S3-S4 and S5 and the filamentous hemagglutinin (FHA), and a better serological response to native PT, detoxified PT (dPT) and FHA than the WC-PV. The induced CMI and serological response were followed over a period of 17 weeks, and were not seen to decline during this period. Further, an in vitro proliferative response to Bordetella pertussis agglutinogen 2 and 3 were demonstrated using lymphocytes from recently and not-so-recently pertussis-vaccinated adults. PMID:1797049

  9. Evaluation of respiratory model employing conventional NIH mice to access the immunity induced by cellular and acellular pertussis vaccines.

    PubMed

    Dias, Alexandre Alves de Souza de Oliveira; Boller, Maria Aparecida Affonso; Werneck, Lúcia Maria Correa; Hirata Junior, Raphael; Mattos-Guaraldi, Ana Luíza

    2006-11-01

    The increasing number of pertussis cases reported on the last twenty years and the existence of new acellular vaccines reinforce the need of research for experimental models to assure the quality of available pertussis vaccines. In this study, allotments of whole-cell and acellular pertussis vaccines were tested through the Intranasal Challenge Model (INM) using conventional NIH mice. The results have been compared to those achieved by the "Gold standard" Intracerebral Challenge Model (ICM). In contrast to ICM, INM results did not show intralaboratorial variations. Statistical analysis by Anova and Ancova tests revealed that the INM presented reproducibility and allowed identification and separation of different products, including three-component and four-component accellular pertussis vaccines. INM revealed differences between pertussis vaccines. INM provides lower distress to the mice allowing the reduction of mice number including the possibility of using conventional mice (less expensive) under non-aseptic environment. Thus, INM may be used as an alternative method of verifying the consistence of allotment production, including acellular pertussis vaccines. PMID:17160282

  10. Alternatives to HIST for acellular pertussis vaccines: progress and challenges in replacement

    PubMed Central

    Arciniega, J.; Wagner, L.; Prymula, R.; Sebo, P.; Isbrucker, R.; Descampe, B.; Chapsal, J.M.; Costanzo, A.; Hendriksen, C.; Hoonaker, M.; Nelson, S.; Lidster, K.; Casey, W.; Allen, D.

    2016-01-01

    The ‘International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: Progress and Challenges in the Replacement of HIST’ was held on 24 August 2014, in Prague, Czech Republic, as a satellite meeting to the 9 th World Congress on Alternatives and Animal Use in the Life Sciences. Participants discussed the progress and challenges associated with the development, validation, and implementation of in vitro assays as replacements for the histamine sensitisation test (HIST) for acellular pertussis vaccines. Discussions focused on the consistency approach, the necessary framework for regulatory acceptance of a harmonised method, and recent international efforts towards the development of in vitro assays to replace the HIST. Workshop participants agreed that acceptable alternatives to the HIST should be based on ADP ribosylation-mediated cell intoxication and therefore that the CHO cell clustering assay, which measures cell intoxication, should be further pursued and developed as a possible replacement for the HIST. Participants also agreed to continue ongoing multinational discussions involving national and international standardisation authorities to reach consensus and to organise collaborative studies in this context for assay characterisation and calibration of reference materials. PMID:27506225

  11. Overview of currently available Japanese acellular pertussis vaccines and future problems.

    PubMed

    Kamiya, H; Nii, R

    1988-01-01

    Acellular pertussis diphtheria, tetanus vaccine (APDT) was licensed in 1981 in Japan. This vaccine contains pertussis toxin (PT), filamentous hemagglutinin (FHA) and agglutinogen (AGG) as the main protective antigens. The new APDT vaccine produced by each company differs slightly in composition. There are two representative types of vaccine. One vaccine (B type) contains PT and FHA in a ratio of 1 to 1 and the other one (T type) contains PT and FHA in a ratio of 4 to 1 or 9 to 1 and also contains different amounts of AGG. We have been comparing the effectiveness of these two types of vaccine. The adverse reactions of APDT were local reactions such as redness and swelling, with a few febrile cases. No central nervous system adverse reactions were observed. The antibody protective level of this vaccine is also being investigated. After we changed from conventional vaccine to APDT, the frequency of serious adverse reactions was reduced and the number of pertussis infections also gradually decreased. This vaccine should be used for the children world-wide. PMID:3273618

  12. A novel TLR2 agonist from Bordetella pertussis is a potent adjuvant that promotes protective immunity with an acellular pertussis vaccine.

    PubMed

    Dunne, A; Mielke, L A; Allen, A C; Sutton, C E; Higgs, R; Cunningham, C C; Higgins, S C; Mills, K H G

    2015-05-01

    Bordetella pertussis causes whooping cough, a severe and often lethal respiratory infection in infants. A recent resurgence of pertussis has been linked with waning or suboptimal immunity induced with acellular pertussis vaccines (Pa) that were introduced to most developed countries in the 1990s because of safety concerns around the use of whole-cell pertussis vaccines (Pw). Pa are composed of individual B. pertussis antigens absorbed to alum and promote strong antibody, T helper type 2 (Th2) and Th17 responses, but are less effective at inducing cellular immunity mediated by Th1 cells. In contrast, Pw, which include endogenous Toll-like receptor (TLR) agonists, induce Th1 as well as Th17 responses. Here we report the identification and characterization of novel TLR2-activating lipoproteins from B. pertussis. These proteins contain a characteristic N-terminal signal peptide that is unique to Gram-negative bacteria and we demonstrate that one of these lipoproteins, BP1569, activates murine dendritic cells and macrophages and human mononuclear cells via TLR2. Furthermore, we demonstrated that a corresponding synthetic lipopeptide LP1569 has potent immunostimulatory and adjuvant properties, capable of enhancing Th1, Th17, and IgG2a antibody responses induced in mice with an experimental Pa that conferred superior protection against B. pertussis infection than an equivalent vaccine formulated with alum. PMID:25315966

  13. Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines.

    PubMed

    Isbrucker, R; Daas, A; Wagner, L; Costanzo, A

    2016-01-01

    Current regulations for acellular pertussis (aP) vaccines require that they are tested for the presence of residual or reversion-derived pertussis toxin (PTx) activity using the mouse histamine sensitisation test (HIST). Although a CHO cell clustering assay can be used by manufacturers to verify if sufficient inactivation of the substance has occurred in-process, this assay cannot be used at present for the final product due to the presence of aluminium adjuvants which interfere with mammalian cell cultures. Recently, 2 modified CHO cell clustering assays which accommodate for the adjuvant effects have been proposed as alternatives to the HIST. These modified assays eliminate the adjuvant-induced cytotoxicity either through dilution of the vaccine (called the Direct Method) or by introducing a porous barrier between the adjuvant and the cells (the Indirect Method). Transferability and suitability of these methods for testing of products present on the European market were investigated during a collaborative study organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM). Thirteen laboratories participated in this study which included 4 aP-containing vaccines spiked by addition of PTx. This study also assessed the transferability of a standardised CHO cell clustering assay protocol for use with non-adjuvanted PTx preparations. Results showed that the majority of laboratories were able to detect the PTx spike in all 4 vaccines at concentrations of 4 IU/mL or lower using the Indirect Method. This sensitivity is in the range of the theoretical sensitivity of the HIST. The Direct Method however did not show the expected results and would need additional development work. PMID:27506252

  14. Pertussis vaccination during pregnancy in Vietnam: Results of a randomized controlled trial Pertussis vaccination during pregnancy.

    PubMed

    Hoang, Ha Thi Thu; Leuridan, Elke; Maertens, Kirsten; Nguyen, Trung Dac; Hens, Niel; Vu, Ngoc Ha; Caboré, Raissa Nadège; Duong, Hong Thi; Huygen, Kris; Van Damme, Pierre; Dang, Anh Duc

    2016-01-01

    A pertussis vaccination during pregnancy has recently been adopted in several countries to indirectly protect young infants. This study assessed the effect of adding a pertussis component to the tetanus vaccination, in the pregnancy immunization program in Vietnam. A randomized controlled trial was performed. Pregnant women received either a Tdap (tetanus, diphtheria acellular pertussis) vaccine or a tetanus only vaccine between 19 and 35 weeks' gestational age. Immunoglobulin G (IgG) against tetanus (TT), diphtheria (DT), pertussis toxin (PT), filamentous hemaglutinin (FHA) and pertactin (Prn) were measured using commercial ELISA tests, at baseline, 1 month after maternal vaccination, at delivery, and in infants from cord blood and before and after the primary series (EPI: month 2-3-4) of a pertussis containing vaccine. Significantly higher geometric mean concentrations (GMC) were observed for all 3 measured pertussis antigens in the offspring of the Tdap group, up to 2 months of age. One month after completion of the primary infant vaccination schedule, anti-Prn GMC, but not anti-PT and anti-FHA GMCs, was significantly (p=0.006) higher in the control group. Maternal antibodies induced by vaccination during pregnancy close the susceptibility gap for pertussis in young infants. Limited interference with the infant vaccine responses was observed. Whether this interference effect disappears with the administration of a fourth vaccine dose is further studied. PMID:26529073

  15. Tetanus, diphtheria, pertussis vaccination coverage before, during, and after pregnancy - 16 States and New York City, 2011.

    PubMed

    Ahluwalia, Indu B; Ding, Helen; D'Angelo, Denise; Shealy, Kristen H; Singleton, James A; Liang, Jennifer; Rosenberg, Kenneth D

    2015-05-22

    In June 2011, the Advisory Committee on Immunizations Practices (ACIP) recommended 1 dose of a tetanus, diphtheria, and acellular pertussis (Tdap) vaccine during pregnancy for women who had not received Tdap previously. Before 2011, Tdap was recommended for unvaccinated women either before pregnancy or postpartum. In October 2012, ACIP expanded the 2011 recommendation, advising pregnant women to be vaccinated with Tdap during each pregnancy to provide maternal antibodies for each infant. The optimal time for vaccination is at 27-36 weeks' gestation as recommended by ACIP. In response to ACIP's Tdap recommendation for pregnant women in 2011, CDC added a supplemental question to the Pregnancy Risk Assessment Monitoring System (PRAMS) survey to determine women's Tdap vaccination status before, during, or after their most recent delivery. This report describes overall and state-specific Tdap vaccination coverage around the time of pregnancy using data from 6,852 sampled women who delivered a live-born infant during September-December 2011 in one of 16 states or New York City (NYC). Among the 17 jurisdictions, the median percentage of women with live births who reported any Tdap vaccination was 55.7%, ranging from 38.2% in NYC to 76.6% in Nebraska. The median percentage who received Tdap before pregnancy was 13.9% (range = 7.7%-20.1%), during pregnancy was 9.8% (range = 3.8%-14.2%), and after delivery was 30.9% (range = 13.6%-46.5%). The PRAMS data indicate a wide variation in Tdap vaccination coverage among demographic groups, with generally higher postpartum coverage for non-Hispanic white women, those who started prenatal care in the first trimester, and those who had private health insurance coverage. This information can be used for promoting evidence-based strategies to communicate the importance of ACIP guidelines related to Tdap vaccination coverage to women and their prenatal care providers. PMID:25996094

  16. Cell-Mediated Immune Responses in Four-Year-Old Children after Primary Immunization with Acellular Pertussis Vaccines

    PubMed Central

    Ausiello, Clara M.; Lande, Roberto; Urbani, Francesca; la Sala, Andrea; Stefanelli, Paola; Salmaso, Stefania; Mastrantonio, Paola; Cassone, Antonio

    1999-01-01

    Cell-mediated immune (CMI) responses to Bordetella pertussis antigens (pertussis toxin [PT], pertactin [PRN], and filamentous hemagglutinin [FHA]) were assessed in 48-month-old recipients of acellular pertussis [aP] vaccines (either from Chiron-Biocine [aP-CB] or from SmithKline Beecham [aP-SB]) and compared to CMI responses to the same antigens at 7 months of age, i.e., 1 month after completion of the primary immunization cycle. None of the children enrolled in this study received any booster of pertussis vaccines or was affected by pertussis during the whole follow-up period. Overall, around 75% of 4-year-old children showed a CMI-positive response to at least one B. pertussis antigen, independently of the type of aP vaccine received, and the proportion of CMI responders were at least equal at 48 and 7 months of age. However, longitudinal examination of individual responses showed that from 20 (against PT) to 37% (against FHA) of CMI responders after primary immunization became negative at 48 months of age. This loss was more than compensated for by conversion to positive CMI responses, ranging from 36% against FHA to 69% against PRN, in other children who were CMI negative at 7 months of age. In 60 to 80% of these CMI converters, a lack of decline or even marked elevation of antibody (Ab) titers against B. pertussis antigens also occurred between 20 and 48 months of age. In particular, the frequency of seropositivity to PRN and FHA (but not to PT) was roughly three times higher in CMI converters than in nonconverters. The acquisition of CMI response to B. pertussis antigens in 48-month-old children was not associated with a greater frequency of coughing episodes lasting ≥7 days and was characterized by a prevalent type 1 cytokine profile, with high gamma interferon and low or no production of interleukin-5, reminiscent of cytokine patterns following immunization with whole-cell pertussis vaccine or natural infection. Our data imply that vaccination

  17. Collaborative study for the establishment of a European Phamacopoeia Biological reference preparation for Bordetella pertussis mouse antiserum for serological potency testing of acellular pertussis vaccines.

    PubMed

    Poirier, Bertrand; Bornstein, Nicole; Andre, Murielle; Marmonier, Denis; Pares, Monique; Vanhooren, Gerard; Rautmann, Guy; Behr-Gross, Marie-Emmanuelle; Dobbelaer, Roland; Fuchs, Florence

    2003-03-01

    A collaborative study was organised by the European Directorate For the Quality of Medicines (EDQM) to assess the suitability of a candidate mouse antiserum as a European Pharmacopoeia Biological reference preparation (BRP) for acellular pertussis vaccine potency testing. The candidate antiserum was obtained by immunising mice with a five-component acellular pertussis vaccine: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and Fimbrial 2/Fimbrial 3 (Fim 2&3). The study has been divided into two separate phases. Phase I was a pre-qualification study including three laboratories. This phase was aimed at pre-qualifying the candidate BRP (cBRP) and at documenting the impact of differences in the antibody detection methodology enzyme linked immunosorbent assay (ELISA) procedures on results of pertussis antisera calibration versus the currently used standard US standard pertussis antiserum (mouse) Lot 1 (SPAM-1) (United States Food and Drug Administration (USFDA) reference serum) and the cBRP. As no significant difference between the antibody titres determined by using the different ELISA methodologies was found, a large-scale study enrolling 13 laboratories (Phase II) was carried out, each participant performing its in-house methodology. Its aim was to calibrate the cBRP (in terms of the SPAM-1 reference) and to demonstrate its equivalence or superiority to internal references. The study showed that there was no difference in positive sera titres expressed relative to their corresponding internal reference (homologous situation) or the proposed standard (heterologous situation) reference. The cBRP can, therefore, reliably act as replacement for the in-house reference preparations. Further analysis of the outcome of this study enabled to assign to the cBRP a potency of 39, 138, 34 and 56 ELISA unit per millilitre, respectively, to its anti-PT, anti-FHA, anti-PRN and anti-Fim 2&3 antibody contents. The cBRP has been adopted by the European

  18. Vaccine safety implications of Ontario, Canada's switch from DTaP-IPV to Tdap-IPV for the pre-school booster.

    PubMed

    Klar, Salman; Harris, Tara; Wong, Kenny; Fediurek, Jill; Deeks, Shelley L

    2014-11-12

    Ontario, Canada, replaced the 4-6 year old diphtheria (D, d), tetanus (T), acellular pertussis (aP, ap) and polio (IPV) booster from DTaP-IPV to Tdap-IPV in May 2012. We assessed the impact of this replacement on the rate and types of reported adverse events following immunization (AEFIs). We used AEFIs reported among 4-6 years olds, through the provincial surveillance system, following administration of DTaP-IPV or Tdap-IPV from 2009 to 2013. Reporting rates per 100,000 doses distributed were calculated using publicly funded doses distributed as the denominator. A total of 204 AEFIs were reported (DTaP-IPV, n=182; Tdap-IPV, n=22). AEFI reporting rates were 33.1 and 6.3 per 100,000 doses distributed for DTaP-IPV and Tdap-IPV, respectively. Injection site reaction rate was lower for Tdap-IPV compared with DTaP-IPV (1.7 vs 20.6 per 100,000 doses). The replacement resulted in a decline in the number of reports and AEFI reporting rates, most notably a substantial decrease in injection site reactions. PMID:25252195

  19. Predicting future trends in the burden of pertussis in the 21st century: implications for infant pertussis and the success of maternal immunization.

    PubMed

    van den Biggelaar, Anita H J; Poolman, Jan T

    2016-01-01

    Support is growing for maternal immunization using acellular pertussis (aP) vaccines to prevent severe pertussis disease and deaths among very young, unvaccinated infants. Vaccine effectiveness of maternal immunization is 91% in preventing laboratory-confirmed pertussis in infants aged <3 months. To date, most mothers were primed in childhood with whole-cell pertussis vaccines. Soon, the generation of aP-primed individuals will become the new mothers-to-be. The shorter duration of protection afforded by aP vaccines, which is more pronounced with repeated aP boosters, may lead to increased pertussis circulation among aP-primed parents. Maternal Tdap immunization in aP-primed mothers-to-be may become less effective. Additional measures to protect young infants may eventually be needed, along with new vaccines that induce higher quality and more durable responses. PMID:26559122

  20. T-Cell Immune Response Assessment as a Complement to Serology and Intranasal Protection Assays in Determining the Protective Immunity Induced by Acellular Pertussis Vaccines in Mice

    PubMed Central

    Ausiello, C. M.; Lande, R.; Stefanelli, P.; Fazio, C.; Fedele, G.; Palazzo, R.; Urbani, F.; Mastrantonio, P.

    2003-01-01

    The relative value of antibodies and/or T-cell immune responses to Bordetella pertussis antigens in the immunity induced by acellular pertussis (aP) vaccines is still an open issue, probably due to the incomplete knowledge on the mechanisms of protective immunity to pertussis. The relevance of T-cell immune responses in protection from pertussis has been demonstrated in murine and human models of infection; thus, in this study, the ability of different vaccine preparations of three component (pertussis toxin, filamentous hemagglutinin, and pertactin) aP vaccines to induce T-cell responses was investigated in mice. All vaccine preparations examined passed the immunogenicity control test, based on antibody titer assessment, according to European Pharmacopoeia standards, and protected mice from B. pertussis intranasal challenge, but not all preparations were able to prime T cells to pertussis toxin, the specific B. pertussis antigen. In particular, one vaccine preparation was unable to induce proliferation and gamma interferon (IFN-γ) production while the other two gave borderline results. The evaluation of T-cell responses to pertussis toxin antigen may provide information on the protective immunity induced by aP vaccines in animal models. Considering the critical role of the axis interleukin-12-IFN-γ for protection from pertussis, our results suggest that testing the induction of a key protective cytokine such as IFN-γ could be an additional tool for the evaluation of the immune response induced by aP vaccines. PMID:12853397

  1. Relative Contribution of Th1 and Th17 Cells in Adaptive Immunity to Bordetella pertussis: Towards the Rational Design of an Improved Acellular Pertussis Vaccine

    PubMed Central

    Ross, Pádraig J.; Allen, Aideen C.; Walsh, Kevin; Misiak, Alicja; Lavelle, Ed C.; McLoughlin, Rachel M.; Mills, Kingston H. G.

    2013-01-01

    Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular pertussis vaccines (Pa). One explanation for this is that Pa are less protective than the more reactogenic whole cell pertussis vaccines (Pw) that they replaced. Although Pa induce potent antibody responses, and protection has been found to be associated with high concentrations of circulating IgG against vaccine antigens, it has not been firmly established that host protection induced with this vaccine is mediated solely by humoral immunity. The aim of this study was to examine the relative contribution of Th1 and Th17 cells in host immunity to infection with B. pertussis and in immunity induced by immunization with Pw and Pa and to use this information to help rationally design a more effective Pa. Our findings demonstrate that Th1 and Th17 both function in protective immunity induced by infection with B. pertussis or immunization with Pw. In contrast, a current licensed Pa, administered with alum as the adjuvant, induced Th2 and Th17 cells, but weak Th1 responses. We found that IL-1 signalling played a central role in protective immunity induced with alum-adsorbed Pa and this was associated with the induction of Th17 cells. Pa generated strong antibody and Th2 responses, but was fully protective in IL-4-defective mice, suggesting that Th2 cells were dispensable. In contrast, Pa failed to confer protective immunity in IL-17A-defective mice. Bacterial clearance mediated by Pa-induced Th17 cells was associated with cell recruitment to the lungs after challenge. Finally, protective immunity induced by an experimental Pa could be enhanced by substituting alum with a TLR agonist that induces Th1 cells. Our findings demonstrate that alum promotes protective immunity through IL-1β-induced IL-17A production, but also reveal that optimum protection against B. pertussis requires induction of Th1, but not Th2 cells. PMID:23592988

  2. Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

    MedlinePlus

    Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  3. Persistence of T-cell immune response induced by two acellular pertussis vaccines in children five years after primary vaccination.

    PubMed

    Palazzo, Raffaella; Carollo, Maria; Bianco, Manuela; Fedele, Giorgio; Schiavoni, Ilaria; Pandolfi, Elisabetta; Villani, Alberto; Tozzi, Alberto E; Mascart, Françoise; Ausiello, Clara M

    2016-01-01

    The resurgence of pertussis suggests the need for greater efforts to understand the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of T memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac® vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa® (Infanrix) (Glaxo-SmithKline Biologicals). We evaluated magnitude and duration of T-cell responses to pertussis toxin (PT) by measuring T-cell proliferation, cytokines (IL-2 and IFNγ) production and memory subsets in two groups of children 5 years after primary vaccination. Some of the enrolled children received only primary vaccination, while others had the pre-school boost dose. Positive T-cell responses to PT were detected in 36% of children. Percentage of responsive children, T-cell proliferation and CD4IL-2+ cells were significantly higher in the children primed with Hexavac than in those who received Infanrix vaccine. No major effects of the boost on PT-specific proliferation were observed. Overall, our data documented a persistence of T-cell memory against PT in a minor fraction of children 5 years after primary vaccination. The different responses induced by Hexavac and Infanrix vaccine could rely on differences in PT inactivation process or excipients/adjuvants formulations. PMID:26922984

  4. Knowledge, attitudes, beliefs, and behaviors of pregnant women approached to participate in a Tdap maternal immunization randomized, controlled trial

    PubMed Central

    MacDougall, Donna M.; Halperin, Beth A.; Langley, Joanne M.; McNeil, Shelly A.; MacKinnon-Cameron, Donna; Li, Li; Halperin, Scott A.

    2016-01-01

    ABSTRACT Immunization with pertussis vaccine during pregnancy is recommended in a number of countries to prevent newborn deaths from whooping cough. In some jurisdictions, vaccine uptake during pregnancy is low. We undertook a survey of the knowledge, attitudes, beliefs, and behaviors of pregnant women who had been approached to participate in a randomized, controlled trial of tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy. A total of 346 women completed the survey. Knowledge about pertussis and pertussis vaccine was generally low; the mean number of correct answers was 10.65 out of 19 questions. Attitudes toward maternal immunization were generally favorable; 51.7%–94.7% of women had positive responses to 10 attitudinal statements. Substantial uncertainty was shown in responses to a number of the attitudinal statements related to vaccination during pregnancy; 22.3%–45.7% neither agreed nor disagreed with the statements. Importantly, 89% of women reported that they would get immunized with pertussis vaccine during pregnancy if their physician recommended it. We conclude that a national recommendation to be immunized with pertussis vaccine during pregnancy supported by their physicians' recommendation would be well received by Canadian women. PMID:27176822

  5. Knowledge, attitudes, beliefs, and behaviors of pregnant women approached to participate in a Tdap maternal immunization randomized, controlled trial.

    PubMed

    MacDougall, Donna M; Halperin, Beth A; Langley, Joanne M; McNeil, Shelly A; MacKinnon-Cameron, Donna; Li, Li; Halperin, Scott A

    2016-04-01

    Immunization with pertussis vaccine during pregnancy is recommended in a number of countries to prevent newborn deaths from whooping cough. In some jurisdictions, vaccine uptake during pregnancy is low. We undertook a survey of the knowledge, attitudes, beliefs, and behaviors of pregnant women who had been approached to participate in a randomized, controlled trial of tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy. A total of 346 women completed the survey. Knowledge about pertussis and pertussis vaccine was generally low; the mean number of correct answers was 10.65 out of 19 questions. Attitudes toward maternal immunization were generally favorable; 51.7%-94.7% of women had positive responses to 10 attitudinal statements. Substantial uncertainty was shown in responses to a number of the attitudinal statements related to vaccination during pregnancy; 22.3%-45.7% neither agreed nor disagreed with the statements. Importantly, 89% of women reported that they would get immunized with pertussis vaccine during pregnancy if their physician recommended it. We conclude that a national recommendation to be immunized with pertussis vaccine during pregnancy supported by their physicians' recommendation would be well received by Canadian women. PMID:27176822

  6. Development of a guinea-pig model for potency/immunogenicity evaluation of diphtheria, tetanus acellular pertussis (DTaP) and Haemophilus influenzae type b polysaccharide conjugate vaccines.

    PubMed

    Gupta, R K; Anderson, R; Cecchini, D; Rost, B; Griffin, P; Benscoter, K; Xu, J; Montanez-Ortiz, L; Siber, G R

    1996-01-01

    We have evaluated a guinea pig model for assessing the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines, acellular pertussis vaccine and combination vaccines-consisting of tetanus toxoid (TT), diphtheria toxoid (DT), acellular pertussis vaccine and Hib-TT (Hib-T) conjugate vaccine. The model was based on the United States (US) potency test for TT and DT which requires injection of guinea pigs with a single dose of undiluted vaccine. Guinea pigs showed dose-dependent antibody responses to pertussis toxoid (PTxd) and filamentous haemagglutinin (FHA), two important components of acellular pertussis vaccine. Antibody response of guinea pigs to commercially available Hib conjugate vaccines qualitatively resembled those of human infants. Unconjugated polyribosylribitolphosphate (PRP) was not immunogenic; PRP-D conjugate produced a low antibody response, HbOC, PRP-T (Merieux) and Hib-T (MPHBL) produced a low response to the first dose and a strong anamnestic response to the booster dose. PRP-OMP uniquely produced a strong response after the first dose which was boosted by the second dose. In preliminary experiments, injection of guinea pigs with the combined vaccine formulations consisting of TT, DT, whole cell or acellular pertussis vaccine (Ptxd and FHA) and Hib-T conjugate showed that these vaccines were immunogenic when combined, with some effects on the antibody responses of certain components. This model for testing potency/immunogenicity of combined vaccines substantially reduces the number of animals needed to test each lot of vaccine. To reduce the use of animals in testing vaccines further, we propose the use of a Vero cell assay for titrating diphtheria antitoxin and ELISA for measuring IgG antibody to tetanus toxin. The guinea pig model may also be useful for evaluating combination vaccines. PMID:8785957

  7. Pertussis vaccination during pregnancy: Antibody persistence in infants.

    PubMed

    Vilajeliu, Alba; Ferrer, Laia; Munrós, Jordina; Goncé, Anna; López, Marta; Costa, Josep; Bayas, José M

    2016-07-19

    Maternal pertussis vaccination is associated with higher levels of pertussis antibodies at birth. We assessed the persistence of pertussis antibodies until primary vaccination in infants whose mothers received Tdap (tetanus, diphtheria, acellular pertussis) vaccine during pregnancy. Infants were born at the Hospital Clinic of Barcelona (Spain) in November 2014. Anti-PT IgG was determined by ELISA at delivery, between the first and second month of life, and estimated at 2months of age. The study included 37 infants whose mothers received Tdap between 21 and 38weeks of gestation. Infants presented a decline in GMC of anti-PT IgG between peripartum and follow-up levels, 52.7 (95% CI 34.7-80.2) versus 7.5 (95% CI 4.2-13.3) at 2months of age (p<0.001). The median half-life of maternal antibodies was 47days. More than half (51.4%) the infants presented detectable anti-PT IgG before the start of primary infant vaccination. PMID:27265448

  8. Safety of Tdap vaccine in pregnant women: an observational study

    PubMed Central

    Petousis-Harris, Helen; Walls, Tony; Watson, Donna; Paynter, Janine; Graham, Patricia; Turner, Nikki

    2016-01-01

    Objectives Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination. Design and settings A prospective observational study conducted in 2 New Zealand regions. Participants Women in their 28th–38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration. Telephone interviews were conducted at 48 h and 4 weeks postvaccination. Main outcomes measures Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs). Where available, data have been classified and reported according to Brighton Collaboration definitions. Results 793 women participated with 27.9% receiving trivalent inactivated influenza vaccine concomitantly. 79% of participants reported mild or moderate pain and 2.6% severe pain. Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants. Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%. During the study period, there were 115 adverse events in 113 participants, most of which were minor. At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia). All had variable onset time from vaccination. There were two perinatal deaths. Clinician assessment of all SAEs found none likely to be vaccine related. Conclusions Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine. Trial registration number ACTRN12613001045707. PMID:27091823

  9. Pertussis (Whooping Cough) Vaccination

    MedlinePlus

    ... Tetanus-diphtheria-acellular Pertussis vaccine Pertussis (Whooping Cough) Vaccination Pronounced (per-TUS-iss) Recommend on Facebook Tweet ... The best way to prevent it is through vaccinations. The childhood vaccine is called DTaP. The whooping ...

  10. Protecting Newborns Against Pertussis: Treatment and Prevention Strategies.

    PubMed

    Salim, Abdulbaset M; Liang, Yan; Kilgore, Paul E

    2015-12-01

    Pertussis is a potentially severe respiratory disease, which affects all age groups from young infants to older adults and is responsible for an estimated 195,000 deaths occurred globally in 2008. Active research is ongoing to better understand the pathogenesis, immunology, and diagnosis of pertussis. For diagnosis, molecular assays (e.g., polymerase chain reaction) for detection of Bordetella pertussis have become more widely available and support improved outbreak detection. In children, pertussis vaccines have been incorporated into routine immunization schedules and deployed for pertussis outbreak control. Lower levels of vaccine coverage are now being observed in communities where vaccine hesitancy is rising. Additionally, recognition that newborn babies are at risk of pertussis in the USA and UK has led to recommendations to immunize pregnant women. Among adolescents and older adults in the USA, Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular pertussis (Tdap) Vaccines are recommended, but substantial individual- and system-level barriers exist that will make achieving national Healthy People 2020 targets for immunization challenging. Current antimicrobial regimens for pertussis are focused on reducing the severity of disease, reducing rates of sequelae, and minimizing transmission of infection to susceptible individuals. Continued surveillance for pertussis will be important to identify opportunities for reducing young infants' exposure and reducing the impact of outbreaks among school-aged children. Laboratory-based surveillance for newly emerging strains of B. pertussis will be important to identify strains that may evade protection elicited by currently available vaccines. Efforts to develop new-generation pertussis vaccines should be considered now in anticipation of vaccine development programs, which may require ten or more years to deliver a licensed vaccine. PMID:26542059

  11. The safety and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) booster vaccine in healthy Vietnamese children.

    PubMed

    Anh, Dang Duc; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay

    2016-08-17

    Despite effective infant immunization against pertussis, the disease continues to circulate due to waning immunity. Booster vaccinations against pertussis beyond infancy are widely recommended. In Vietnam, however, no recommendations for pertussis boosters beyond the second year of life exist. This open-label, single-centre study was designed to assess the safety of a single booster dose of reduced-antigen-content-diphtheria-tetanus-acellular-pertussis vaccine (dTpa) in 300 healthy Vietnamese children (mean age 7.9years), who had completed primary vaccination against diphtheria, tetanus and pertussis. Solicited symptoms were recorded for 4days and unsolicited and serious adverse events (SAEs) for 31days post-vaccination. Pain and fatigue were the most common solicited local and general symptoms in 35.0% and 14.0% of children, respectively. Grade 3 swelling occurred in 3 children; no large injection site reactions or SAEs were reported. The dTpa booster vaccine was well tolerated and this study supports its administration in school age Vietnamese children. PMID:27435387

  12. Prevention of pertussis through adult vaccination

    PubMed Central

    Suryadevara, Manika; Domachowske, Joseph B

    2015-01-01

    Pertussis is a vaccine preventable respiratory infection. Young infants are at high risk of developing severe complications from infection. Despite high rates of pediatric vaccine uptake, there continues to be increases in pertussis cases, likely due to waning immunity from childhood vaccine and increased transmission through adults. Currently, pertussis booster vaccine (Tdap) is recommended for unimmunized adults and for women in the third trimester of each pregnancy; yet adult Tdap coverage remains low. Administering Tdap vaccine at non-traditional vaccination clinics and at sites where adults are accessing care for their children are effective in improving adult Tdap uptake. While most are willing to receive vaccine when recommended by their provider, lack of provider recommendation is a major obstacle to immunization. Future studies to understand barriers to provider vaccine recommendations need to be undertaken to develop interventions to improve adult Tdap vaccine uptake and reduce pertussis infection in the susceptible population. PMID:25912733

  13. Pertussis

    PubMed Central

    Gabutti, Giovanni; Azzari, Chiara; Bonanni, Paolo; Prato, Rosa; Tozzi, Alberto E; Zanetti, Alessandro; Zuccotti, Gianvincenzo

    2014-01-01

    Pertussis continues to be an important public-health issue. The high immunization coverage rates achieved, mainly in industrialized countries, have certainly decreased the spread of the pathogen. However, as immunity wanes, adolescents and adults play an important role in the dynamics of the infection. The surveillance system has several limitations and the underestimation of pertussis in adolescents, young adults and adults is mainly related to the atypical clinical characteristics of cases and the lack of lab confirmation. The real epidemiological impact of pertussis is not always perceived. The unavailability of comprehensive data should not hamper the adoption of active prophylactic measures designed to avoid the impact of waning immunity against pertussis. Different immunization strategies have been suggested and/or already adopted such as immunization of newborns, pre-school and school children, adolescents, adults, healthcare workers, childcare workers, pregnant women, cocoon strategy. Prevention of pertussis requires an integrated approach and the adoption of different immunization strategies, with the objective of achieving and maintaining high coverage rates. PMID:25483523

  14. Characterization of the immune response induced by pertussis OMVs-based vaccine.

    PubMed

    Bottero, D; Gaillard, M E; Zurita, E; Moreno, G; Martinez, D Sabater; Bartel, E; Bravo, S; Carriquiriborde, F; Errea, A; Castuma, C; Rumbo, M; Hozbor, D

    2016-06-14

    For the development of a third generation of pertussis vaccine that could improve the control of the disease, it was proposed that the immune responses induced by the classic whole cell vaccine (wP) or after infection should be used as a reference point. We have recently identified a vaccine candidate based on outer membrane vesicles (OMVs) derived from the disease etiologic agent that have been shown to be safe and protective in mice model of infection. Here we characterized OMVs-mediated immunity and the safety of our new candidate. We also deepen the knowledge of the induced humoral response contribution in pertussis protection. Regarding the safety of the OMVs based vaccine (TdapOMVsBp,) the in vitro whole blood human assay here performed, showed that the low toxicity of OMVs-based vaccine previously detected in mice could be extended to human samples. Stimulation of splenocytes from immunized mice evidenced the presence of IFN-γ and IL-17-producing cells, indicated that OMVs induces both Th1 and Th17 response. Interestingly TdapOMVsBp-raised antibodies such as those induced by wP and commercial acellular vaccines (aP) which contribute to induce protection against Bordetella pertussis infection. As occurs with wP-induced antibodies, the TdapOMVsBp-induced serum antibodies efficiently opsonized B. pertussis. All the data here obtained shows that OMVs based vaccine is able to induce Th1/Th17 and Th2 mixed profile with robust humoral response involved in protection, positioning this candidate among the different possibilities to constitute the third generation of anti-pertussis vaccines. PMID:27151884

  15. Licensed pertussis vaccines in the United States

    PubMed Central

    Klein, Nicola P

    2014-01-01

    The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that waning protection following licensed acellular pertussis vaccines have been significant factors in the widespread reappearance of pertussis. PMID:25483496

  16. Rediscovering Pertussis.

    PubMed

    Zlamy, Manuela

    2016-01-01

    Pertussis, caused by Bordetella (B.) pertussis, a Gram-negative bacterium, is a highly contagious airway infection. Especially in infants, pertussis remains a major health concern. Acute infection with B. pertussis can cause severe illness characterized by severe respiratory failure, pulmonary hypertension, leucocytosis, and death. Over the past years, rising incidence rates of intensive care treatment in young infants were described. Due to several virulence factors (pertussis toxin, tracheal cytotoxin, adenylate cyclase toxin, filamentous hemagglutinin, and lipooligosaccharide) that promote bacterial adhesion and invasion, B. pertussis creates a unique niche for colonization within the human respiratory tract. The resulting long-term infection is mainly caused by the ability of B. pertussis to interfere with the host's innate and adaptive immune system. Although pertussis is a vaccine-preventable disease, it has persisted in vaccinated populations. Epidemiological data reported a worldwide increase in pertussis incidence among children during the past years. Either acellular pertussis (aP) vaccines or whole-cell vaccines are worldwide used. Recent studies did not detect any differences according to pertussis incidence when comparing the different vaccines used. Most of the currently used aP vaccines protect against acute infections for a period of 6-8 years. The resurgence of pertussis may be due to the lack of herd immunity caused by missing booster immunizations among adolescents and adults, low vaccine coverages in some geographic areas, and genetic changes of different B. pertussis strains. Due to the rising incidence of pertussis, probable solution strategies are discussed. Cocooning strategies (vaccination of close contact persons) and immunizations during pregnancy appear to be an approach to reduce neonatal contagiousness. During the past years, studies focused on the pathway of the immune modulation done by B. pertussis to provide a basis for the

  17. Rediscovering Pertussis

    PubMed Central

    Zlamy, Manuela

    2016-01-01

    Pertussis, caused by Bordetella (B.) pertussis, a Gram-negative bacterium, is a highly contagious airway infection. Especially in infants, pertussis remains a major health concern. Acute infection with B. pertussis can cause severe illness characterized by severe respiratory failure, pulmonary hypertension, leucocytosis, and death. Over the past years, rising incidence rates of intensive care treatment in young infants were described. Due to several virulence factors (pertussis toxin, tracheal cytotoxin, adenylate cyclase toxin, filamentous hemagglutinin, and lipooligosaccharide) that promote bacterial adhesion and invasion, B. pertussis creates a unique niche for colonization within the human respiratory tract. The resulting long-term infection is mainly caused by the ability of B. pertussis to interfere with the host’s innate and adaptive immune system. Although pertussis is a vaccine-preventable disease, it has persisted in vaccinated populations. Epidemiological data reported a worldwide increase in pertussis incidence among children during the past years. Either acellular pertussis (aP) vaccines or whole-cell vaccines are worldwide used. Recent studies did not detect any differences according to pertussis incidence when comparing the different vaccines used. Most of the currently used aP vaccines protect against acute infections for a period of 6–8 years. The resurgence of pertussis may be due to the lack of herd immunity caused by missing booster immunizations among adolescents and adults, low vaccine coverages in some geographic areas, and genetic changes of different B. pertussis strains. Due to the rising incidence of pertussis, probable solution strategies are discussed. Cocooning strategies (vaccination of close contact persons) and immunizations during pregnancy appear to be an approach to reduce neonatal contagiousness. During the past years, studies focused on the pathway of the immune modulation done by B. pertussis to provide a basis for the

  18. Recommendation for the use of newly introduced Tdap vaccine in Korea

    PubMed Central

    Kim, Kyung Hyo; Kim, Yae-Jean; Kim, Jong-Hyun; Park, Su Eun; Lee, Hoan Jong; Eun, Byung Wook; Jo, Dae Sun; Choi, Eun Hwa; Hong, Young Jin

    2011-01-01

    Pertussis is an acute respiratory infection characterized by paroxysmal cough and inspiratory whoop for over 2 weeks. The incidence of pertussis has decreased markedly after the introduction of DTwP/DTaP vaccine, but the incidence of pertussis has increased steadily among young infant and among adolescents and adults in many countries. Td vaccine was used in this age group but the increase in pertussis has lead to the development of a Tdap vaccine. The Tdap vaccine is a Td vaccine with a pertussis vaccine added and is thought to decrease the incidence and transmission of pertussis in the respective age group. In Korea, two products are approved by the KOREA FOOD & DRUG ADMINISTRATION, which are ADACEL™ (Sanofi-Pasteur, Totonto, Ontario, Canada) and BOOSTRIX® (GlaxoSmithKline Biologicals, Rixensart, Belgium) for those aged between 11-64. This report summarizes the recommendations approved by the Committee on Infectious Diseases, the Korean Pediatric Society. PMID:21738546

  19. Report on the international workshop on alternatives to the murine histamine sensitization test (HIST) for acellular pertussis vaccines: state of the science and the path forward.

    PubMed

    Isbrucker, Richard; Arciniega, Juan; McFarland, Richard; Chapsal, Jean-Michel; Xing, Dorothy; Bache, Christina; Nelson, Sue; Costanzo, Angele; Hoonakker, Marieke; Castiaux, Amélie; Halder, Marlies; Casey, Warren; Johnson, Nelson; Jones, Brett; Doelling, Vivian; Sprankle, Cathy; Rinckel, Lori; Stokes, William

    2014-03-01

    Regulatory authorities require safety and potency testing prior to the release of each production lot of acellular pertussis (aP)-containing vaccines. Currently, the murine histamine sensitization test (HIST) is used to evaluate the presence of residual pertussis toxin in aP containing vaccines. However, the testing requires the use of a significant number of mice and results in unrelieved pain and distress. NICEATM, ICCVAM, their partners in the International Cooperation on Alternative Test Methods, and the International Working Group for Alternatives to HIST organized a workshop to discuss recent developments in alternative assays to the HIST, review data from an international collaborative study on non-animal alternative tests that might replace the HIST, and address the path toward global acceptance of this type of method. Currently, there are three potential alternative methods to HIST. Participants agreed that no single in vitro method was sufficiently developed for harmonized validation studies at this time. It is unlikely that any single in vitro method would be applicable to all aP vaccines without modification, due to differences between vaccines. Workshop participants recommended further optimization of cell-based assays under development. Participants agreed that the next international collaborative studies should commence in 2013 based on discussions during this workshop. PMID:24394373

  20. Th1 versus Th2 T cell polarization by whole-cell and acellular childhood pertussis vaccines persists upon re-immunization in adolescence and adulthood.

    PubMed

    Bancroft, Tara; Dillon, Myles B C; da Silva Antunes, Ricardo; Paul, Sinu; Peters, Bjoern; Crotty, Shane; Lindestam Arlehamn, Cecilia S; Sette, Alessandro

    2016-01-01

    The recent increase in cases of whooping cough among teenagers in the US suggests that the acellular Bordetella pertussis vaccine (aP) that became standard in the mid 1990s might be relatively less effective than the whole-bacteria formulation (wP) previously used since the 1950s. To understand this effect, we compared antibody and T cell responses to a booster immunization in subjects who received either the wP or aP vaccine as their initial priming dose in childhood. Antibody responses in wP- and aP-primed donors were similar. Magnitude of T cell responses was higher in aP-primed individuals. Epitope mapping revealed the T cell immunodominance patterns were similar for both vaccines. Further comparison of the ratios of IFNγ and IL-5 revealed that IFNγ strongly dominates the T cell response in wP-primed donors, while IL-5 is dominant in aP primed individuals. Surprisingly, this differential pattern is maintained after booster vaccination, at times from eighteen years to several decades after the original aP/wP priming. These findings suggest that childhood aP versus wP vaccination induces functionally different T cell responses to pertussis that become fixed and are unchanged even upon boosting. PMID:27212461

  1. Immunogenicity of a combination vaccine containing diphtheria toxoid, tetanus toxoid, three-component acellular pertussis, hepatitis B, inactivated polio virus, and Haemophilus influenzae type b when given concomitantly with 13-valent pneumococcal conjugate vaccine.

    PubMed

    Gimenez-Sanchez, Francisco; Kieninger, Dorothee M; Kueper, Kathrin; Martinon-Torres, Federico; Bernaola, Enrique; Diez-Domingo, Javier; Steul, Kathrin; Juergens, Christine; Gurtman, Alejandra; Giardina, Peter; Liang, John Z; Gruber, William C; Emini, Emilio A; Scott, Daniel A

    2011-08-11

    Two randomized trials of 13-valent pneumococcal conjugate vaccine (PCV13) relative to PCV7 evaluated the immune responses of coadministered antigens comprising Infanrix(®) hexa/Infanrix(®)-IPV+Hib (diphtheria, tetanus, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b). After the 3-dose infant series, immunogenic noninferiority was demonstrated for all concomitantly administered antigens between the PCV13 and PCV7 groups. All antigens elicited good booster responses after the toddler dose except pertussis toxoid; however, 99.6% subjects achieved pertussis toxoid protective antibody level ≥5EU/mL in both groups. These results support the concomitant administration of PCV13 and Infanrix hexa/Infanrix-IPV+Hib as part of routine immunization schedules. PMID:21704105

  2. Bordetella pertussis Strain Lacking Pertactin and Pertussis Toxin

    PubMed Central

    Sen, Kathryn; Weigand, Michael R.; Skoff, Tami H.; Cunningham, Victoria A.; Halse, Tanya A.; Tondella, M. Lucia

    2016-01-01

    A Bordetella pertussis strain lacking 2 acellular vaccine immunogens, pertussis toxin and pertactin, was isolated from an unvaccinated infant in New York State in 2013. Comparison with a French strain that was pertussis toxin–deficient, pertactin wild-type showed that the strains carry the same 28-kb deletion in similar genomes. PMID:26812174

  3. Transcriptome signature for dampened Th2 dominance in acellular pertussis vaccine-induced CD4+ T cell responses through TLR4 ligation

    PubMed Central

    Brummelman, Jolanda; Raeven, René H. M.; Helm, Kina; Pennings, Jeroen L. A.; Metz, Bernard; van Eden, Willem; van Els, Cécile A. C. M.; Han, Wanda G. H.

    2016-01-01

    Current acellular pertussis (aP) vaccines promote a T helper 2 (Th2)-dominated response, while Th1/Th17 cells are protective. As our previous study showed, after adding a non-toxic TLR4 ligand, LpxL1, to the aP vaccine in mice, the Bordetella pertussis-specific Th2 response is decreased and Th1/Th17 responses are increased as measured at the cytokine protein level. However, how this shift in Th response by LpxL1 addition is regulated at the gene expression level remains unclear. Transcriptomics analysis was performed on purified CD4+ T cells of control and vaccinated mice after in vitro restimulation with aP vaccine antigens. Multiple key factors in Th differentiation, including transcription factors, cytokines, and receptors, were identified within the differentially expressed genes. Upregulation of Th2- and downregulation of follicular helper T cell-associated genes were found in the CD4+ T cells of both aP- and aP+LpxL1-vaccinated mice. Genes exclusively upregulated in CD4+ T cells of aP+LpxL1-vaccinated mice included Th1 and Th17 signature cytokine genes Ifng and Il17a respectively. Overall, our study indicates that after addition of LpxL1 to the aP vaccine the Th2 component is not downregulated at the gene expression level. Rather an increase in expression of Th1- and Th17-associated genes caused the shift in Th subset outcome. PMID:27118638

  4. Humoral and cell mediated immune responses to a pertussis containing vaccine in pregnant and nonpregnant women.

    PubMed

    Huygen, Kris; Caboré, Raïssa Nadège; Maertens, Kirsten; Van Damme, Pierre; Leuridan, Elke

    2015-08-01

    Vaccination of pregnant women is recommended for some infectious diseases in order to protect both women and offspring through high titres of maternal IgG antibodies. Less is known on the triggering of cellular immune responses by vaccines administered during pregnancy. In an ongoing study on maternal pertussis vaccination (2012-2014) 18 pregnant women were vaccinated with a tetanus-diphtheria-acellular pertussis (Tdap) containing vaccine (Boostrix®) during the third pregnancy trimester. Sixteen age-matched nonpregnant women received the same vaccine in the same time period. A blood sample was taken at the moment of, but before vaccination and one month and one year after vaccination. Anti-Pertussis Toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxin (TT) and diphtheria toxin (DT) antibodies were measured by ELISA. Cellular immune responses were analyzed using a diluted whole blood assay, measuring proliferation, and cytokine release in response to vaccine antigens PT, FHA, TT, and to pokeweed mitogen (PWM) as polyclonal stimulus. Antibody levels to all five vaccine components increased significantly and to the same extent after vaccination in pregnant and nonpregnant women. One year after vaccination, antibody titres had decreased particularly to PT, but they were still significantly higher to all antigens than before vaccination. In contrast, proliferative and IFN-γ responses were increased to TT, PT, and FHA in nonpregnant women one month after vaccination, whereas in pregnant women only TT specific T cell responses were increased and to a lesser extent than in the control group. One year after vaccination, cellular responses equaled the baseline levels detected prior to vaccination in both groups. In conclusion, a Tdap vaccination can increase vaccine specific IgG antibodies to the same extent in pregnant and in nonpregnant women, whereas the stimulation of vaccine specific Th1 type cellular immune responses with this acellular vaccine

  5. Evaluation of a new syringe presentation of reduced-antigen content diphtheria, tetanus, and acellular pertussis vaccine in healthy adolescents - A single blind randomized trial

    PubMed Central

    Pavia-Ruz, Noris; Abarca, Katia; Lepetic, Alejandro; Cervantes-Apolinar, Maria Yolanda; Hardt, Karin; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay; de la O, Manuel

    2015-01-01

    Reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) vaccine, Boostrix™, is indicated for booster vaccination of children, adolescents and adults. The original prefilled disposable dTpa syringe presentation was recently replaced by another prefilled-syringe presentation with latex-free tip-caps and plunger-stoppers. 671 healthy adolescents aged 10–15 years who had previously received 5 or 6 previous DT(P)/dT(pa) vaccine doses, were randomized (1:1) to receive dTpa booster, injected using the new (dTpa-new) or previous syringe (dTpa-previous) presentations. Immunogenicity was assessed before and 1-month post-booster vaccination; safety/reactogenicity were assessed during 31-days post-vaccination. Non-inferiority of dTpa-new versus dTpa-previous was demonstrated for all antigens (ULs 95% CIs for GMC ratios ranged between 1.03-1.13). 1-month post-booster, immune responses were in similar ranges for all antigens with both syringe presentations. dTpa delivered using either syringe presentation was well-tolerated. These clinical results complement the technical data and support the use of the new syringe presentation to deliver the dTpa vaccine. PMID:26075317

  6. Evaluation of a new syringe presentation of reduced-antigen content diphtheria, tetanus, and acellular pertussis vaccine in healthy adolescents--A single blind randomized trial.

    PubMed

    Pavia-Ruz, Noris; Abarca, Katia; Lepetic, Alejandro; Cervantes-Apolinar, Maria Yolanda; Hardt, Karin; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay; de la O, Manuel

    2015-01-01

    Reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) vaccine, Boostrix™, is indicated for booster vaccination of children, adolescents and adults. The original prefilled disposable dTpa syringe presentation was recently replaced by another prefilled-syringe presentation with latex-free tip-caps and plunger-stoppers. 671 healthy adolescents aged 10-15 years who had previously received 5 or 6 previous DT(P)/dT(pa) vaccine doses, were randomized (1:1) to receive dTpa booster, injected using the new (dTpa-new) or previous syringe (dTpa-previous) presentations. Immunogenicity was assessed before and 1-month post-booster vaccination; safety/reactogenicity were assessed during 31-days post-vaccination. Non-inferiority of dTpa-new versus dTpa-previous was demonstrated for all antigens (ULs 95% CIs for GMC ratios ranged between 1.03-1.13). 1-month post-booster, immune responses were in similar ranges for all antigens with both syringe presentations. dTpa delivered using either syringe presentation was well-tolerated. These clinical results complement the technical data and support the use of the new syringe presentation to deliver the dTpa vaccine. PMID:26075317

  7. Promoting Adult Pertussis Vaccination in the Workplace.

    PubMed

    Luthy, Karlen E; Bainum, Jennifer L; Beckstrand, Renea L; Macintosh, Janelle L B; Eden, Lacey M; Saunders, Brooke

    2016-06-01

    Vaccines are an important disease prevention strategy among individuals of all age groups. Despite the success of vaccinations in preventing communicable diseases, adults, in particular, often have sub-optimal vaccination rates. Consequently, some vaccine-preventable diseases, such as pertussis, are still on the rise in the United States despite the availability of the Tdap vaccine. As most adults can be found in the workplace, occupational and environmental health nurses are in a unique position to encourage employers to promote adequate Tdap vaccination among their employees. As specific resources regarding Tdap vaccination are lacking, the Pertussis Prevention Toolkit was developed to help occupational health nurses promote Tdap vaccination in the workplace. PMID:27217084

  8. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    NASA Astrophysics Data System (ADS)

    May, J. C.; Rey, L.; Lee, Chi-Jen; Arciniega, Juan

    2004-09-01

    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

  9. Mutants of Escherichia coli Heat-Labile Toxin Act as Effective Mucosal Adjuvants for Nasal Delivery of an Acellular Pertussis Vaccine: Differential Effects of the Nontoxic AB Complex and Enzyme Activity on Th1 and Th2 Cells

    PubMed Central

    Ryan, Elizabeth J.; McNeela, Edel; Murphy, Geraldine A.; Stewart, Helen; O'hagan, Derek; Pizza, Mariagrazia; Rappuoli, Rino; Mills, Kingston H. G.

    1999-01-01

    Mucosal delivery of vaccines is dependent on the identification of safe and effective adjuvants that can enhance the immunogenicity of protein antigens administered by nasal or oral routes. In this study we demonstrate that two mutants of Escherichia coli heat-labile toxin (LT), LTK63, which lacks ADP-ribosylating activity, and LTR72, which has partial enzyme activity, act as potent mucosal adjuvants for the nasal delivery of an acellular pertussis (Pa) vaccine. Both LTK63 and LTR72 enhanced antigen-specific serum immunoglobulin G (IgG), secretory IgA, and local and systemic T-cell responses. Furthermore, using the murine respiratory challenge model for infection with Bordetella pertussis, we demonstrated that a nasally delivered diphtheria, tetanus, and acellular pertussis (DTPa) combination vaccine formulated with LTK63 as an adjuvant conferred a high level of protection, equivalent to that generated with a parenterally delivered DTPa vaccine formulated with alum. This study also provides significant new information on the roles of the binding and enzyme components of LT in the modulation of Th1 and Th2 responses. LTK63, which lacks enzyme activity, promoted T-cell responses with a mixed Th1–Th2 profile, but LTR72, which retains partial enzyme activity, and the wild-type toxin, especially at low dose, induced a more polarized Th2-type response and very high IgA and IgG antibody titers. Our findings suggest that the nontoxic AB complex has broad adjuvant activity for T-cell responses and that the ADP-ribosyltransferase activity of the A subunit also appears to modulate cytokine production, but its effect on T-cell subtypes, as well as enhancing, may be selectively suppressive. PMID:10569737

  10. Mutants of Escherichia coli heat-labile toxin act as effective mucosal adjuvants for nasal delivery of an acellular pertussis vaccine: differential effects of the nontoxic AB complex and enzyme activity on Th1 and Th2 cells.

    PubMed

    Ryan, E J; McNeela, E; Murphy, G A; Stewart, H; O'hagan, D; Pizza, M; Rappuoli, R; Mills, K H

    1999-12-01

    Mucosal delivery of vaccines is dependent on the identification of safe and effective adjuvants that can enhance the immunogenicity of protein antigens administered by nasal or oral routes. In this study we demonstrate that two mutants of Escherichia coli heat-labile toxin (LT), LTK63, which lacks ADP-ribosylating activity, and LTR72, which has partial enzyme activity, act as potent mucosal adjuvants for the nasal delivery of an acellular pertussis (Pa) vaccine. Both LTK63 and LTR72 enhanced antigen-specific serum immunoglobulin G (IgG), secretory IgA, and local and systemic T-cell responses. Furthermore, using the murine respiratory challenge model for infection with Bordetella pertussis, we demonstrated that a nasally delivered diphtheria, tetanus, and acellular pertussis (DTPa) combination vaccine formulated with LTK63 as an adjuvant conferred a high level of protection, equivalent to that generated with a parenterally delivered DTPa vaccine formulated with alum. This study also provides significant new information on the roles of the binding and enzyme components of LT in the modulation of Th1 and Th2 responses. LTK63, which lacks enzyme activity, promoted T-cell responses with a mixed Th1-Th2 profile, but LTR72, which retains partial enzyme activity, and the wild-type toxin, especially at low dose, induced a more polarized Th2-type response and very high IgA and IgG antibody titers. Our findings suggest that the nontoxic AB complex has broad adjuvant activity for T-cell responses and that the ADP-ribosyltransferase activity of the A subunit also appears to modulate cytokine production, but its effect on T-cell subtypes, as well as enhancing, may be selectively suppressive. PMID:10569737

  11. Contribution of pertussis toxin to the pathogenesis of pertussis disease.

    PubMed

    Carbonetti, Nicholas H

    2015-11-01

    Pertussis toxin (PT) is a multisubunit protein toxin secreted by Bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. PT in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. PT inhibits G protein-coupled receptor signaling through Gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. But how does this activity of PT contribute to pertussis, including the severe respiratory symptoms of this disease? In this minireview, the contribution of PT to the pathogenesis of pertussis disease will be considered based on evidence from both human infections and animal model studies. Although definitive proof of the role of PT in humans is lacking, substantial evidence supports the idea that PT is a major contributor to pertussis pathology, including the severe respiratory symptoms associated with this disease. PMID:26394801

  12. Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant Seropositivity Against Pertussis

    PubMed Central

    Eberhardt, Christiane S.; Blanchard-Rohner, Geraldine; Lemaître, Barbara; Boukrid, Meriem; Combescure, Christophe; Othenin-Girard, Véronique; Chilin, Antonina; Petre, Jean; de Tejada, Begoña Martinez; Siegrist, Claire-Anne

    2016-01-01

    Background. Maternal immunization against pertussis is currently recommended after the 26th gestational week (GW). Data on the optimal timing of maternal immunization are inconsistent. Methods. We conducted a prospective observational noninferiority study comparing the influence of second-trimester (GW 13–25) vs third-trimester (≥GW 26) tetanus-diphtheria-acellular pertussis (Tdap) immunization in pregnant women who delivered at term. Geometric mean concentrations (GMCs) of cord blood antibodies to recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) were assessed by enzyme-linked immunosorbent assay. The primary endpoint were GMCs and expected infant seropositivity rates, defined by birth anti-PT >30 enzyme-linked immunosorbent assay units (EU)/mL to confer seropositivity until 3 months of age. Results. We included 335 women (mean age, 31.0 ± 5.1 years; mean gestational age, 39.3 ± 1.3 GW) previously immunized with Tdap in the second (n = 122) or third (n = 213) trimester. Anti-PT and anti-FHA GMCs were higher following second- vs third-trimester immunization (PT: 57.1 EU/mL [95% confidence interval {CI}, 47.8–68.2] vs 31.1 EU/mL [95% CI, 25.7–37.7], P < .001; FHA: 284.4 EU/mL [95% CI, 241.3–335.2] vs 140.2 EU/mL [95% CI, 115.3–170.3], P < .001). The adjusted GMC ratios after second- vs third-trimester immunization differed significantly (PT: 1.9 [95% CI, 1.4–2.5]; FHA: 2.2 [95% CI, 1.7–3.0], P < .001). Expected infant seropositivity rates reached 80% vs 55% following second- vs third-trimester immunization (adjusted odds ratio, 3.7 [95% CI, 2.1–6.5], P < .001). Conclusions. Early second-trimester maternal Tdap immunization significantly increased neonatal antibodies. Recommending immunization from the second trimester onward would widen the immunization opportunity window and could improve seroprotection. PMID:26797213

  13. Booster vaccination of pre-school children with reduced-antigen-content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine co-administered with measles-mumps-rubella-varicella vaccine

    PubMed Central

    Ferrera, Giuseppe; Cuccia, Mario; Mereu, Gabriele; Icardi, Giancarlo; Bona, Gianni; Esposito, Susanna; Marchetti, Federico; Messier, Marc; Kuriyakose, Sherine; Hardt, Karin

    2012-01-01

    Background: Pertussis occurs in older children, adolescents and adults due to waning immunity after primary vaccination. Booster vaccination for pre-school children has been recommended in Italy since 1999. In this study (NCT00871000), the immunogenicity, safety and reactogenicity of a booster dose of reduced-antigen content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (dTpa-IPV; GSK Biologicals Boostrix™-Polio; 3-component pertussis) vs. full-strength DTPa-IPV vaccine (sanofi-pasteur—MSD Tetravac™; 2-component pertussis) was evaluated in pre-school Italian children.   Methods: Healthy children aged 5–6 y primed in a routine vaccination setting with three doses of DTPa-based vaccines were enrolled and randomized (1:1) in this phase IIIb, booster study to receive a single dose of dTpa-IPV or DTPa-IPV; the MMRV vaccine was co-administered. Antibody concentrations/titers against diphtheria, tetanus, pertussis and poliovirus 1–3 were measured before and one month post-booster. Reactogenicity and safety was assessed. Results: 305 subjects were enrolled of whom 303 (dTpa-IPV = 151; DTPa-IPV = 152) received booster vaccination. One month post-booster, all subjects were seroprotected/seropositive for anti-diphtheria, anti-tetanus, anti-PT, anti-FHA and anti-poliovirus 1–3; 99.3% of dTpa-IPV and 60.4% of DTPa-IPV subjects were seropositive for anti-PRN; 98–100% of subjects were seropositive against MMRV antigens post-booster. Pain at the injection site (dTpa-IPV: 63.6%; DTPa-IPV: 63.2%) and fatigue (dTpa-IPV: 26.5%; DTPa-IPV: 23.7%) were the most commonly reported solicited local and general symptoms, during the 4-d follow-up period. No SAEs or fatalities were reported. Conclusions: The reduced-antigen-content dTpa-IPV vaccine was non-inferior to full-strength DTPa-IPV vaccine with respect to immunogenicity. The vaccine was well-tolerated and can be confidently used as a booster dose in pre-school children. PMID:22327497

  14. [Bordetella pertussis lipooligosaccharide-derived neoglycoconjugates - new components of pertussis vaccine].

    PubMed

    Koj, Sabina; Ługowski, Czesław; Niedziela, Tomasz

    2015-01-01

    Pertussis is a contagious respiratory tract disease caused by the Gram-negative bacterium Bordetella pertussis. Despite widespread vaccination, in recent years the pertussis incidence has increased. The whole-cell pertussis vaccine has been very effective but reactogenic. Therefore the improved vaccines contain only a few isolated and inactivated antigens of B. pertussis. However, a waning of the acellular vaccine-induced immunity indicates that these vaccines lack some important protective B. pertussis antigens. The vaccine containing an inactivated pertussis toxin induces the production of toxin-neutralizing antibodies, but it does not lead to destruction of bacteria. Since many virulence factors are involved in the pathogenesis of pertussis, beside the toxin-neutralizing activity, the direct bactericidal activity is essential in anti-pertussis immunity. Lipooligosaccharide is the main surface component of B. pertussis. It is a target for bactericidal antibodies during natural infection. The endotoxic activity of LOS makes it unacceptable for acellular vaccines against B. pertussis. However, the non-toxic moiety of the B. pertussis LOS-derived oligosaccharide coupled to a carrier protein forms an immunogenic glycoconjugate which has a potential application as a new component of a pertussis vaccine. In this paper, we present a review of current research and reasons for the increased pertussis incidence. The epidemiologic situation of pertussis in the past decades showing the ineffectiveness of contemporary, acellular pertussis vaccines is also discussed. The immune processes elicited by natural infection with B. pertussis were compared to the vaccine-induced immunity. The important role of bactericidal antibodies against lipooligosaccharide was indicated in effective immune defense. In a number of research papers the immunogenicity and protective properties of glycoconjugates containing the oligosaccharide component of B. pertussis have been described, and its

  15. Comparison of Three Whole-Cell Pertussis Vaccines in the Baboon Model of Pertussis

    PubMed Central

    Warfel, Jason M.; Zimmerman, Lindsey I.

    2015-01-01

    Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have escalated since the 1990s and reached a 50-year high of 48,000 cases in 2012. While this pertussis resurgence is not completely understood, we previously showed that the current acellular pertussis vaccines do not prevent colonization or transmission following challenge. In contrast, a whole-cell pertussis vaccine accelerated the rate of clearance compared to rates in unvaccinated animals and animals treated with the acellular vaccine. In order to understand if these results are generalizable, we used our baboon model to compare immunity from whole-cell vaccines from three different manufacturers that are approved outside the United States. We found that, compared to clearance rates with no vaccine and with an acellular pertussis vaccine, immunization with any of the three whole-cell vaccines significantly accelerated the clearance of B. pertussis following challenge. Whole-cell vaccination also significantly reduced the total nasopharyngeal B. pertussis burden, suggesting that these vaccines reduce the opportunity for pertussis transmission. Meanwhile, there was no difference in either the duration or in B. pertussis burden between unvaccinated and acellular-pertussis-vaccinated animals, while previously infected animals were not colonized following reinfection. We also determined that transcription of the gene encoding interleukin-17 (IL-17) was increased in whole-cell-vaccinated and previously infected animals but not in acellular-pertussis-vaccinated animals following challenge. Together with our previous findings, these data are consistent with a role for Th17 responses in the clearance of B. pertussis infection. PMID:26561389

  16. Immune responses to pertussis vaccines and disease.

    PubMed

    Edwards, Kathryn M; Berbers, Guy A M

    2014-04-01

    In this article we discuss the following: (1) acellular vaccines are immunogenic, but responses vary by vaccine; (2) pertussis antibody levels rapidly wane but promptly increase after vaccination; (3) whole-cell vaccines vary in immunogenicity and efficacy; (4) whole-cell vaccines and naturally occurring pertussis generate predominantly T-helper 1 (Th1) responses, whereas acellular vaccines generate mixed Th1/Th2 responses; (5) active transplacental transport of pertussis antibody is documented; (6) neonatal immunization with diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine has been associated with some suppression of pertussis antibody, but suppression has been seen less often with acellular vaccines; (7) memory B cells persist in both acellular vaccine- and whole cell vaccine-primed children; and (8) in acellular vaccine-primed children, T-cell responses remain elevated and do not increase with vaccine boosters, whereas in whole-cell vaccine-primed children, these responses can be increased by vaccine boosting and natural exposure. Despite these findings, challenges remain in understanding the immune response to pertussis vaccines. PMID:24158958

  17. The role of B. pertussis vaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development.

    PubMed

    Preston, Andrew

    2016-05-01

    Whooping cough, or pertussis, caused by Bordetella pertussis is considered resurgent in a number of countries world-wide, despite continued high level vaccine coverage. Among a number of causes for this that have been proposed, is the emergence of B. pertussis strains expressing variants of the antigens contained in acellular pertussis vaccines; i.e. the evolution of B. pertussis toward vaccine escape. This commentary highlights the contradictory nature of evidence for this but also discusses the importance of understanding the role of B. pertussis adaptation to vaccine-mediated immune selection pressures for vaccine-mediated pertussis control strategies. PMID:26889694

  18. Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX®) and a tetanus monovalent vaccine in healthy adults

    PubMed Central

    Laurichesse, Henri; Zimmermann, Ulrich; Galtier, Florence; Launay, Odile; Duval, Xavier; Richard, Patrick; Sadorge, Christine; Soubeyrand, Benoit

    2012-01-01

    In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur® or Tetavax®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5−10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ≥ 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: –1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed. ClinicalTrials.gov identifier: NCT00928785. Research sponsored by Sanofi Pasteur MSD. PMID:23032160

  19. Pertussis Outbreak, Southeastern Minnesota, 2012

    PubMed Central

    Theofiles, Alexander G.; Cunningham, Scott A.; Chia, Nicholas; Jeraldo, Patricio R.; Quest, Daniel J.; Mandrekar, Jayawant N.; Patel, Robin

    2015-01-01

    Objective To describe clinical and laboratory findings from the 2012 southeastern Minnesota pertussis outbreak. Patients and Methods Patients were selected for 2 parts of the study. In the first part, nasopharyngeal swabs from a convenience sample of 265 unique patients were used for both the clinician-requested polymerase chain reaction (PCR) test and culture. B pertussis isolates were tested for macrolide susceptibility and typed using whole genome sequencing and pulsed-field gel electrophoresis. Pertactin gene sequences were analyzed to identify pertactin-deficient B pertussis. In the second part, all patients seen at Mayo Clinic in Rochester, Minnesota, who had PCR results positive for Bordetella pertussis or Bordetella parapertussis between January 1, 2012, and December 31, 2012, were analyzed for patient demographic features and vaccination records. Results One hundred sixty patients had results positive for B pertussis, and 21 patients had results positive for B parapertussis. Among the 265 swabs cultured, B pertussis was detected by both culture and PCR in 11. One swab was positive for B pertussis by culture alone, and 13 were positive by PCR alone. Polymerase chain reaction detected B pertussis more frequently than did culture (P=.001). No macrolide resistance was detected. All 12 isolates tested had an altered pertactin gene, including 9 with a signal sequence deletion, 2 with insertion sequence disruptions, and 1 with a premature stop codon. Nine and 3 isolates were pertactin types prn1 and prn2, respectively. Whole genome sequencing and pulsed-field gel electrophoresis detected the presence of multiple B pertussis strains. The mean age of patients with pertussis was younger than that of those without pertussis (15.6 and 25.5 years, respectively; P=.002). Compared with those whose test results were negative for B pertussis, fewer patients with positive results had received whole-cell pertussis vaccine (P=.02). In the subgroup who had received acellular

  20. How to fight pertussis?

    PubMed

    Guiso, Nicole

    2013-07-01

    Universal pertussis vaccination has successfully decreased pertussis mortality and morbidity in childhood. However, despite intensive vaccination of young children, pertussis remains a major public health problem in both developing and industrialized regions. Recent epidemics in California and Australia demonstrated that the agent of the disease is still circulating. They also revealed several aspects that must not be neglected concerning vaccine-preventable diseases. Indeed, pertussis is one of the oldest vaccine-preventable bacterial diseases, so can provide a good illustration of all of the aspects associated with the need for surveillance after the introduction of vaccination. (i) The type of vaccine: two types of pertussis vaccine, whole cell and acellular, inducing different types of immunity are now used around the world. (ii) The vaccine strategy, the vaccine coverage and the duration of vaccine immunity: pertussis epidemics provide evidence that 90% of the infants must be vaccinated, vaccination must be sufficiently early and both vaccine-induced immunity and natural infection-induced immunity to pertussis wane with time indicating that pertussis is not only a pediatric disease. (iii) The agents of the disease, Bordetella pertussis and Bordetella parapertussis: the intensive vaccination of young infants modified the herd immunity, controlled bacteria similar to the vaccine strains but not all, revealing polymorphism of the agents of the disease evidencing the importance of continuing their isolation and their surveillance as well as monitoring their antibiotic resistance. (iv) The diagnosis of the disease: the epidemics showed the importance of specific diagnostic techniques that are easy to use by medical laboratories and the availability of the reagents required. (v) Communication with the public, the health authorities and the health providers: any changes of vaccine type, vaccine strategy, characteristics of the disease, and biological diagnosis must

  1. Pertussis Tests

    MedlinePlus

    ... as: Whooping Cough Tests Formal name: Bordetella pertussis Culture; Bordetella pertussis by PCR; Bordetella pertussis Antibodies (IgA, ... outbreak, at least one case be confirmed using culture. Culture – this test was the "gold standard" for ...

  2. The potential of adjuvants to improve immune responses against TdaP vaccines: A preclinical evaluation of MF59 and monophosphoryl lipid A.

    PubMed

    Agnolon, Valentina; Bruno, Cristina; Leuzzi, Rosanna; Galletti, Bruno; D'Oro, Ugo; Pizza, Mariagrazia; Seubert, Anja; O'Hagan, Derek T; Baudner, Barbara C

    2015-08-15

    The successful approach of combining diphtheria, tetanus and pertussis antigens into a single vaccine has become a cornerstone of immunization programs. Yet, even if vaccination coverage is high, a resurgence of pertussis has been reported in many countries suggesting current vaccines may not provide adequate protection. To induce better tailored and more durable immune responses against pertussis vaccines different approaches have been proposed, including the use of novel adjuvants. Licensed aP vaccines contain aluminum salts, which mainly stimulate humoral immune responses and might not be ideal for protecting against Bordetella pertussis infection. Adjuvants inducing more balanced T-helper profiles or even Th1-prone responses might be more adequate. In this study, two adjuvants already approved for human use have been tested: MF59 emulsion and the combination of aluminum hydroxide with the Toll-Like Receptor 4 agonist MPLA. Adjuvanticity was evaluated in a mouse model using a TdaP vaccine containing three B. pertussis antigens: genetically detoxified pertussis toxin (PT-9K/129G), filamentous hemagglutinin (FHA) and pertactin (PRN) The physico-chemical compatibility of TdaP antigens with the proposed adjuvants, together with a quicker onset and changed quality of the antibody responses, fully supports the replacement of aluminum salts with a new adjuvant to enhance aP vaccines immunogenicity. PMID:26149936

  3. Bordetella pertussis epidemiology and evolution in the light of pertussis resurgence.

    PubMed

    Sealey, Katie L; Belcher, Thomas; Preston, Andrew

    2016-06-01

    Whooping cough, or pertussis, is resurgent in many countries world-wide. This is linked to switching from the use of whole cell vaccines to acellular vaccines in developed countries. Current evidence suggests that this has resulted in the earlier waning of vaccine-induced immunity, an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetellapertussis variants that are better able to evade vaccine-mediated immunity than older isolates. This review discusses recent findings in B. pertussis epidemiology and evolution in the light of pertussis resurgence, and highlights the important role for genomics-based studies in monitoring B. pertussis adaptation. PMID:26932577

  4. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines

    PubMed Central

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela

    2016-01-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  5. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines.

    PubMed

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie

    2016-07-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  6. Protection Against Pertussis.

    PubMed

    Mehta, Parang N

    2016-08-01

    Though vaccines have been in use for over seventy years, we have been unable to eradicate or control pertussis. This disease is a worldwide problem, and recently has been occurring in outbreaks even in places with good immunization coverage. The debate about the use of acellular or whole cell vaccine has taken attention away from the other significant issues. The high rate of serious disease and death in young infants, and the repeated outbreaks of pertussis even in highly-vaccinated populations is a matter for grave concern. Finding strategies to protect the most vulnerable is a priority. Newer vaccines are under development, and will be welcome, but may be too expensive for mass use in resource-poor nations. It is important to adopt cost-effective strategies to deal with this disease. PMID:27567644

  7. Is Bordetella pertussis clonal?

    PubMed Central

    Khattak, M. N.; Matthews, R. C.; Burnie, J. P.

    1992-01-01

    OBJECTIVE--To establish whether Bordetella pertussis is essentially clonal. DESIGN--Analysis of restriction fragments of XbaI digests of DNA from clinical and control isolates of B pertussis by pulse field gel electrophoresis. MATERIALS--105 isolates of B pertussis: 67 clinical isolates from throughout the United Kingdom and 23 from Germany (collected during the previous 18 months); vaccine strains 2991 and 3700; and 13 control isolates from Manchester University's culture collection. MAIN OUTCOME MEASURES--Frequency of DNA types according to country of origin and classical serotyping. RESULTS--17 DNA types were identified on the basis of the variation in 11 fragments, banding at 200-412 kilobases; 15 types were found in the clinical and control isolates from the United Kingdom and seven in those from Germany. There was no correlation with serotype. DNA type 1 was the commonest overall (22/105 strains, 22%), predominating in serotypes 1,2 and 1,2,3 and including the vaccine strains but not the isolates from Germany. CONCLUSIONS--Current infections due to B pertussis are not caused by a clonal pathogen as multiple strains are circulating in a given population at one time. There is also considerable epidemiological variation in the pathogen population between countries. These findings may have implications for the design of acellular vaccines. Images FIG 1 FIG 2 FIG 3 PMID:1392709

  8. Roads to the development of improved pertussis vaccines paved by immunology

    PubMed Central

    Brummelman, Jolanda; Wilk, Mieszko M.; Han, Wanda G.H.; van Els, Cécile A.C.M.; Mills, Kingston H.G.

    2015-01-01

    Current acellular pertussis vaccines have various shortcomings, which may contribute to their suboptimal efficacy and waning immunity in vaccinated populations. This calls for the development of new pertussis vaccines capable of inducing long-lived protective immunity. Immunization with whole cell pertussis vaccines and natural infection with Bordetella pertussis induce distinct and more protective immune responses when compared with immunization with acellular pertussis vaccines. Therefore, the immune responses induced with whole cell vaccine or after infection can be used as a benchmark for the development of third-generation vaccines against pertussis. Here, we review the literature on the immunology of B. pertussis infection and vaccination and discuss the lessons learned that will help in the design of improved pertussis vaccines. PMID:26347400

  9. Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction.

    PubMed

    Patel, Mahendra K; Patel, Tejas K; Tripathi, C B

    2012-01-01

    A 5-month-old male patient developed recurrent seizures and acute encephalopathy possibly due to first dose of diphtheria, pertussis (whooping cough), and tetanus (DPT) vaccine used for routine immunization. Postreaction computed tomography (CT) scan of brain, magnetic resonance imaging (MRI) of brain, and electroencephalogram were normal. Pertussis fraction of DPT vaccine is responsible for this reaction. It is suggested that acellular pertussis vaccine should be used instead of whole cell vaccine because it is associated with lower frequency of neurological complications, such as seizures, encephalopathy, and hypotensive episodes. However, acellular pertussis-containing vaccines are currently not affordable in most developing countries. PMID:22368426

  10. Diphtheria, pertussis (whooping cough), and tetanus vaccine induced recurrent seizures and acute encephalopathy in a pediatric patient: Possibly due to pertussis fraction

    PubMed Central

    Patel, Mahendra K.; Patel, Tejas K.; Tripathi, C. B.

    2012-01-01

    A 5-month-old male patient developed recurrent seizures and acute encephalopathy possibly due to first dose of diphtheria, pertussis (whooping cough), and tetanus (DPT) vaccine used for routine immunization. Postreaction computed tomography (CT) scan of brain, magnetic resonance imaging (MRI) of brain, and electroencephalogram were normal. Pertussis fraction of DPT vaccine is responsible for this reaction. It is suggested that acellular pertussis vaccine should be used instead of whole cell vaccine because it is associated with lower frequency of neurological complications, such as seizures, encephalopathy, and hypotensive episodes. However, acellular pertussis-containing vaccines are currently not affordable in most developing countries. PMID:22368426

  11. Pertussis toxin

    SciTech Connect

    Sekura, R.D.; Moss, J.; Vaughan, M.

    1985-01-01

    This book contains 13 selections. Some of the titles are: Genetic and Functional Studies of Pertussis Toxin Substrates; Effect of Pertussis Toxin on the Hormonal Responsiveness of Different Tissues; Extracellular Adenylate Cyclase of Bordetella pertussis; and GTP-Regulatory Proteins are Introcellular Messagers: A Model for Hormone Action.

  12. [Pertussis (Whooping cough)--an update].

    PubMed

    Stock, Ingo

    2015-12-01

    Whooping cough is a highly contagious respiratory disease which is caused predominantly by the gram-negative bacterium Bordetella pertussis. Further Bordetella species such as B. parapertussis and the recently discovered species B. holmesii are also involved in whooping cough-like diseases. Depending on age, vaccination status and distance to pre-infection with B. pertussis, whooping cough shows a wide range of symptoms. The disease occurs at any age, leaving only short time immunity. During the last 15 years, in industrialized countries the number of reported pertussis cases has been increased markedly. The reason for this observation is still unclear Macrolides such as azithromycin and clarithromycin are regarded as antibiotics of first choice. In Germany, combination vaccines containing acellular pertussis vaccines is the most important strategy of prevention. To ensure the best possible protection against pertussis, booster doses at determined times should be given after primary vaccination in infancy. PMID:26837155

  13. Serospecific protection of mice against intranasal infection with Bordetella pertussis.

    PubMed

    Robinson, A; Gorringe, A R; Funnell, S G; Fernandez, M

    1989-08-01

    The ability of purified serospecific agglutinogens from Bordetella pertussis to protect mice against intranasal infection has been examined. Immunization with agglutinogen 2 protected mice against infection with 1.2.0 or 1.2.3 serotypes of B. pertussis, whereas immunization with agglutinogen 3 protected mice against infection with all serotypes. More importantly immunization with serospecific agglutinogen resulted in immune selection so that organisms recovered following infection did not express the immunizing antigen. The results are consistent with the suggestions that protection of children with whole cell pertussis vaccine is to some extent serospecific and that agglutinogens should be considered as constituents of acellular pertussis vaccines. PMID:2573215

  14. Tdap Booster Requirements for Secondary Schools

    MedlinePlus

    ... VISs Spanish-language VISs What's New: VISs Diseases & Vaccines Anthrax Pertussis Chickenpox (varicella) PCV Diphtheria PPSV H. influenzae (Hib) Polio Hepatitis A Rabies Hepatitis B Rotavirus HPV Rubella ... Adjuvants Religious Concerns Alternative Medicine Responding to Parents ...

  15. The changing age and seasonal profile of pertussis in Canada.

    PubMed

    Skowronski, Danuta M; De Serres, Gaston; MacDonald, Diane; Wu, Wrency; Shaw, Carol; Macnabb, Jane; Champagne, Sylvie; Patrick, David M; Halperin, Scott A

    2002-05-15

    During the postvaccine era in Canada, most cases of pertussis have been reported in children <5 years of age, with the highest incidence, morbidity, and mortality in infants <1 year old. Population-based data, with very high laboratory confirmation rates and hospital separation and mortality statistics, chronicle the changing age and seasonal profile associated with pertussis over recent successive outbreaks in British Columbia, Canada. A large outbreak during 2000 highlights 2 important changes to the postvaccine profile. For the first time in Canada, the incidence of pertussis among preteens and teens surpassed that of all other age groups. At the same time, a decreasing incidence of pertussis among infants and preschool children highlights reduced susceptibility in the very young. Recent changes in the childhood immunization program (including introduction of an acellular pertussis vaccine), waning immunity, and changes in laboratory methods are considered in explaining these 2 simultaneous but divergent trends in the pertussis profile. PMID:11992280

  16. Fed-batch cultivation of Bordetella pertussis: metabolism and Pertussis Toxin production.

    PubMed

    Thalen, Marcel; Venema, Marian; Dekker, Anita; Berwald, Luc; van den IJssel, Jan; Zomer, Bert; Beuvery, Coen; Martens, Dirk; Tramper, Johannes

    2006-12-01

    The production of acellular pertussis in comparison with whole cell pertussis vaccines demands 5-25 times the amount of Bordetella pertussis' virulence factors, such as Pertussis Toxin (PT), to produce the same number of vaccine doses. An increase in the volumetric productivity by employing fed-batch rather than the currently used batch cultivations of B. pertussis could reduce the cost price of acellular pertussis vaccines. This study defined the conditions that enable fed-batch cultivations at high specific PT production. A solution containing lactate and glutamate was fed to the cultures at various rates. The feed rate and whether or not the fed substrates were completely consumed, significantly influenced cellular metabolism. If lactate was detectable in the culture broth while glutamate was not, poly-hydroxy-butyrate (PHB) was formed. Any PHB present was metabolized when glutamate became detectable again in the culture liquid. At higher lactate and glutamate concentrations, free fatty acids were produced. Though toxic, free fatty acids were not the reason the cultures stopped growing. By choosing appropriate conditions, a cell density of 6.5 g/L dry weight was reached, i.e. a 7-fold increase compared to batch culture. The metabolic mechanisms behind the formation of PHB and fatty acids are discussed, as well as how to increase the cell density further. The PT production stopped at 12 mg/L, well before growth stopped, indicating that regulatory mechanisms of PT production may be involved. PMID:16500113

  17. Pertussis Frequently Asked Questions

    MedlinePlus

    ... Learn more about pertussis symptoms . Q: Are pertussis bacteria changing and causing an increase in pertussis cases? ... rates of pertussis, including changes in disease-causing bacteria types ("strains"). Unlike a foodborne illness where one ...

  18. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study

    PubMed Central

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-01-01

    abstract The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children <2 years of age (mean age: 15.8 months). During the 4-day follow-up period, pain (31.7%) and redness (27.3%) were the most frequent solicited local symptoms. Pain (2%) was also the most frequent grade 3 local symptom. One subject reported 2 serious adverse events that were not causally related to the study vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years. PMID:26337197

  19. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

    PubMed

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-03-01

    The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children <2 years of age (mean age: 15.8 months). During the 4-day follow-up period, pain (31.7%) and redness (27.3%) were the most frequent solicited local symptoms. Pain (2%) was also the most frequent grade 3 local symptom. One subject reported 2 serious adverse events that were not causally related to the study vaccine. DTPa-IPV/Hib conjugate vaccine was well tolerated as a booster dose in healthy Vietnamese children aged <2 years. PMID:26337197

  20. Pertussis: Where did we go wrong and what can we do about it?

    PubMed

    Locht, Camille

    2016-07-01

    Pertussis or whooping cough, mainly caused by the Gram-negative coccobacillus Bordetella pertussis, is a severe respiratory disease that can by life-threatening especially in young infants. It has recently made a spectacular come-back in high vaccination-coverage countries, such as the US, Australia and many European countries. Although a trend towards increased pertussis incidence was already visible before the switch from whole-cell to acellular vaccines, it was really since the introduction of the acellular vaccines that the number of cases reached record highs. Several hypotheses have been proposed to explain these observations. Unexpectedly fast waning of acellular vaccine-induced protection may be one of the major reasons. Furthermore, evidence from a recent non-human primate model suggests that acellular vaccines, although protective against pertussis disease, do not protect against B. pertussis infection, which may explain many of the current observations on the resurgence of pertussis. Optimized use of current vaccines has been explored, including cocoon vaccination of persons in close contact with newborn infants, neonatal vaccination and maternal immunization during pregnancy. All have their inherent limitations. New vaccines are therefore desperately needed, and current efforts have been geared towards the identification of novel antigens and adjuvants to prolong immunity and ameliorate protection. The most advanced vaccine candidate is live attenuated nasal BPZE1, a genetically modified B. pertussis derivative that has recently completed a first-in-man phase I trial and was shown to be safe in young male volunteers, able to transiently colonize the naso-pharynx and to induce antibody responses to B. pertussis antigens. This vaccine candidate is designed to protect against both pertussis disease and B. pertussis infection and may therefore be useful for long-term control of pertussis. PMID:27161992

  1. Construction of Bordetella pertussis strains that overproduce genetically inactivated pertussis toxin.

    PubMed Central

    Zealey, G R; Loosmore, S M; Yacoob, R K; Cockle, S A; Herbert, A B; Miller, L D; Mackay, N J; Klein, M H

    1992-01-01

    Nontoxic analogs of pertussis toxin (PT), produced by in vitro mutagenesis of the tox operon, are immunogenic and protective against infection by Bordetella pertussis. The moderate levels of PT production by B. pertussis, however, make it the limiting antigen in the formulation of multicomponent, acellular, recombinant whooping cough vaccines. To increase production of the highly detoxified Lys9Gly129 PT analog by B. pertussis, additional copies of the mutated tox operon were integrated into the bacterial chromosome at the tox or fha locus by unmarked allelic exchange. Recombinant strains produced in this way secreted elevated levels of the PT analog proportional to gene dosage. The strains were stable during 10-liter fermentations, and yields of up to 80 mg of PT analog per liter were obtained under production-scale conditions. The nontoxic analog was purified and shown to be indistinguishable from material obtained from a B. pertussis strain that contained only a single copy of the toxLys9Gly129 operon. Such strains are therefore suitable for large-scale, industrial production of an acellular whooping cough vaccine containing a genetically detoxified PT analog. Images PMID:1539974

  2. Epidemiology of whooping cough & typing of Bordetella pertussis.

    PubMed

    Hegerle, Nicolas; Guiso, Nicole

    2013-11-01

    Bordetella pertussis is a Gram-negative human-restricted bacterium that evolved from the broad-range mammalian pathogen, Bordetella bronchiseptica. It causes whooping cough or pertussis in humans, which is the most prevalent vaccine-preventable disease worldwide. The introduction of the pertussis whole-cell vaccination for young children, followed by the introduction of the pertussis acellular vaccination (along with booster vaccination) for older age groups, has affected the bacterial population and epidemiology of the disease. B. pertussis is relatively monomorphic worldwide, but nevertheless, different countries are facing different epidemiological evolutions of the disease. Although it is tempting to link vaccine-driven phenotypic and genotypic evolution of the bacterium to epidemiology, many other factors should be considered and surveillance needs to continue, in addition to studies investigating the impact of current clinical isolates on vaccine efficacy. PMID:24199799

  3. Whooping cough, twenty years from acellular vaccines introduction.

    PubMed

    Greco, D; Esposito, S; Tozzi, A; Pandolfi, E; Icardi, G; Giammanco, A

    2015-01-01

    Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years. PMID:26051141

  4. Which strategy for pertussis vaccination today?

    PubMed

    Girard, Dorota Z

    2002-01-01

    Pertussis (whooping cough) remains an epidemic disease responsible for infant and child morbidity and mortality, and is perceived as a serious public health problem. Since the widespread use of whole-cell pertussis vaccines in the 1940s, vaccination programs have varied greatly between countries. National specificity is a function of several factors. The most important are: vaccine efficacy and tolerability;vaccine coverage and distribution; and vaccine acceptance by parents and professionals. During the 1970s, Sweden, England, Wales and Japan provided contrasting examples of the attitude of health authorities to the use of whole-cell vaccines. The increase in pertussis incidence was noted as a consequence of active opposition to this vaccine. The re-emergence of pertussis in the 1990s, in countries with high vaccination coverage and increased incidence of disease in individuals >15 years and <6 months of age, has drawn attention to the role of booster doses of pertussis vaccines and their introduction into regular vaccination programs. The use of acellular vaccines for booster doses for adolescents and adults would seem unambiguous because of their decreased reactogenicity, although the exact schedule has yet to be established. The choice between the two kinds of vaccines is more difficult for primary courses, where safety and efficacy profiles are similar, and the attitude towards acellular vaccines varies from country to country. In this case, the strategy adopted results from the national history of pertussis infection and from the quality of the available whole-cell vaccine. Two contrasting examples are the US, where acellular vaccines were licensed for the primary series in the 1990s, and the UK, where whole-cell vaccines are exclusively used for primary immunization. The changing epidemiology of pertussis, and its local diversification, would suggest that at present it is difficult to define a single worldwide strategy with only one kind of vaccine and one

  5. Bordetella pertussis and Bordetella parapertussis: two immunologically distinct species.

    PubMed Central

    Khelef, N; Danve, B; Quentin-Millet, M J; Guiso, N

    1993-01-01

    Bordetella pertussis and Bordetella parapertussis are closely related species. Both are responsible for outbreaks of whooping cough in humans and produce similar virulence factors, with the exception of pertussis toxin, specific to B. pertussis. Current pertussis whole-cell vaccine will soon be replaced by acellular vaccines containing major adhesins (filamentous hemagglutinin and pertactin) and major toxin (pertussis toxin). All of these factors are antigens that stimulate a protective immune response in the murine respiratory model and in clinical assays. In the present study, we examined the protective efficacies of these factors, and that of adenylate cyclase-hemolysin, another B. pertussis toxin, against B. parapertussis infection in a murine respiratory model. As expected, pertussis toxin did not protect against B. parapertussis infection, since this bacterium did not express this protein, but the surprising result was that none of the other factors were protective against B. parapertussis infection. Furthermore, B. parapertussis adenylate cyclase-hemolysin, although it protected against B. parapertussis infection, did not protect against B. pertussis infection. Despite a high degree of homology between both B. pertussis and B. parapertussis species, no cross-protection was observed. Our results outline the fact that, as in other gram-negative bacteria, Bordetella surface proteins vary immunologically. Images PMID:8423077

  6. Seroprevalence of Antibodies to Pertussis Toxin among Different Age Groups in Thailand after 37 Years of Universal Whole-Cell Pertussis Vaccination

    PubMed Central

    Wanlapakorn, Nasamon; Ngaovithunvong, Varisara; Thongmee, Thanunrat; Vichaiwattana, Preeyaporn; Vongpunsawad, Sompong; Poovorawan, Yong

    2016-01-01

    Despite the high coverage of prophylactic vaccine against Bordetella pertussis infection in many countries for more than three decades, pertussis remains a common vaccine-preventable disease. Infections have been detected more commonly in countries using acellular pertussis vaccine in their Expanded Program of Immunization. Thailand implemented a routine infant immunization program with whole-cell pertussis vaccine in 1977, and since 1992, the national vaccine policy has offered a five-dose whole-cell pertussis vaccine for children given at the ages of 2, 4, 6, 18, and 48 months. This study aimed to investigate the seroprevalence of antibodies to pertussis toxin among healthy people across all ages to determine the level of whole-cell vaccine-induced immunity in the population, and to identify which age group should be targeted for a booster dose. The lowest seronegative rate and highest geometric mean concentrations were found in the 0–10 years age group, corresponding to their recent pertussis vaccination. The proportion of people with undetectable IgG level was prominent, starting after 11 years of age onwards. Now that a reduced-dose pertussis vaccine with fewer adverse effects is available, a booster dose during adolescence should be considered in order to reduce the incidence of pertussis disease. Further studies exploring how long the reduced-dose pertussis vaccine can provide protective immunity against pertussis disease when administered to adults and adolescents should also be performed. PMID:26837004

  7. Seroprevalence of Antibodies to Pertussis Toxin among Different Age Groups in Thailand after 37 Years of Universal Whole-Cell Pertussis Vaccination.

    PubMed

    Wanlapakorn, Nasamon; Ngaovithunvong, Varisara; Thongmee, Thanunrat; Vichaiwattana, Preeyaporn; Vongpunsawad, Sompong; Poovorawan, Yong

    2016-01-01

    Despite the high coverage of prophylactic vaccine against Bordetella pertussis infection in many countries for more than three decades, pertussis remains a common vaccine-preventable disease. Infections have been detected more commonly in countries using acellular pertussis vaccine in their Expanded Program of Immunization. Thailand implemented a routine infant immunization program with whole-cell pertussis vaccine in 1977, and since 1992, the national vaccine policy has offered a five-dose whole-cell pertussis vaccine for children given at the ages of 2, 4, 6, 18, and 48 months. This study aimed to investigate the seroprevalence of antibodies to pertussis toxin among healthy people across all ages to determine the level of whole-cell vaccine-induced immunity in the population, and to identify which age group should be targeted for a booster dose. The lowest seronegative rate and highest geometric mean concentrations were found in the 0-10 years age group, corresponding to their recent pertussis vaccination. The proportion of people with undetectable IgG level was prominent, starting after 11 years of age onwards. Now that a reduced-dose pertussis vaccine with fewer adverse effects is available, a booster dose during adolescence should be considered in order to reduce the incidence of pertussis disease. Further studies exploring how long the reduced-dose pertussis vaccine can provide protective immunity against pertussis disease when administered to adults and adolescents should also be performed. PMID:26837004

  8. A Murine Model in Which Protection Correlates with Pertussis Vaccine Efficacy in Children Reveals Complementary Roles for Humoral and Cell-Mediated Immunity in Protection against Bordetella pertussis

    PubMed Central

    Mills, Kingston H. G.; Ryan, Mark; Ryan, Elizabeth; Mahon, Bernard P.

    1998-01-01

    The results of phase 3 efficacy trials have shown that acellular and whole-cell pertussis vaccines can confer protection against whooping cough. However, despite the advances in vaccine development, clinical trials have not provided significant new information on the mechanism of protective immunity against Bordetella pertussis. Classical approaches based on measurement of antibody responses to individual antigens failed to define an immunological correlate of protection. A reliable animal model, predictive of acellular and whole-cell pertussis vaccine potency in children, would facilitate an elucidation of the mechanism of immune protection against B. pertussis and would assist in the regulatory control and future development of pertussis vaccines. In this study, we have shown that the rate of B. pertussis clearance following respiratory challenge of immunized mice correlated with vaccine efficacy in children. Using this model together with mice with targeted disruptions of the gamma interferon (IFN-γ) receptor, interleukin-4 or immunoglobulin heavy-chain genes, we have demonstrated an absolute requirement for B cells or their products in bacterial clearance and a role for IFN-γ in immunity generated by previous infection or immunization with the whole-cell pertussis vaccine. The results of passive immunization experiments suggested that protection early after immunization with acellular pertussis vaccines is mediated by antibody against multiple protective antigens. In contrast, more complete protection conferred by previous infection or immunization with whole-cell pertussis vaccines reflected the induction of Th1 cells. Our findings suggest that the mechanism of immunity against B. pertussis involves humoral and cellular immune responses which are not directed against a single protective antigen and thus provide an explanation for previous failures to define an immunological correlate of protection. PMID:9453614

  9. Immunogenicity of a Heptavalent Conjugate Pneumococcal Vaccine Administered Concurrently with a Combination Diphtheria, Tetanus, Five-Component Acellular Pertussis, Inactivated Polio, and Haemophilus influenzae Type b Vaccine and a Meningococcal Group C Conjugate Vaccine at 2, 3, and 4 Months of Age ▿

    PubMed Central

    Moss, S. J.; Fenton, A. C.; Toomey, J.; Grainger, A.; Borrow, R.; Balmer, P.; Smith, J.; Gennery, A. R.

    2010-01-01

    The immunogenicities of conjugate pneumococcal vaccines have been demonstrated when they are administered at 2, 3, and 4 months of age. There is a paucity of data on the immunogenicity of this vaccine when it is administered concurrently with other vaccines in the primary immunization schedule of the United Kingdom. We immunized 55 term infants at 2, 3, and 4 months of age with the seven-valent pneumococcal conjugate vaccine (PCV7), the meningococcal group C conjugate (MCC) vaccine, and the diphtheria, tetanus, five-component acellular pertussis, inactivated polio, and Haemophilus influenzae type b (DTaP5/IPV/Hib-TT) vaccine. The immune responses to the H. influenzae type b (Hib), MCC, and tetanus vaccines were measured at 2, 5, and 12 months of age; and the immune responses to PCV7 were measured at 2 and 5 months and then either at 12 months or following a 4th dose of PCV7. There were increases in the geometric mean concentrations (GMCs) of all antigens postimmunization. Greater than or equal to 90% of the infants achieved putatively protective levels postimmunization for all vaccine antigens except pneumococcal serotype 6B and Hib. The GMCs of the PCV7 serotypes increased following a 4th dose, although one infant had not reached putative levels of protection against serotype 6B. In conclusion, when infants were vaccinated according to the schedule described above, they had lower postprimary immunization responses to Hib, meningococcus group C capsular polysaccharide, and pneumococcal serotype 6B than the responses demonstrated by use of the other schedules. Despite this finding, there was a good response following a 4th dose of PCV7. PMID:20042517

  10. How to make sense of pertussis immunogenicity data.

    PubMed

    Olin, P; Hallander, H O; Gustafsson, L; Reizenstein, E; Storsaeter, J

    2001-12-15

    Studies on serologic correlates to protection in pertussis were reviewed. Trials in the 1950s showed that agglutinogen titers correlated to protection of whole-cell vaccines, but postvaccination antibodies against pertussis toxin (PT) and against filamentous hemagglutinin did not in a later trial of acellular vaccines. However, in household studies nested in 2 recent trials, preexposure antibody levels against pertactin and against fimbriae correlated with protection against typical and mild pertussis, and anti-PT correlated only with protection against typical pertussis. These findings could be used by regulatory agencies to license pertussis vaccines. A reference laboratory for pertussis should distribute panels to control interlaboratory variation in recommended assays, and a minimal response should be set for each pertussis antigen. We conclude that 2 studies have shown correlates between measurable anti-pertactin, anti-fimbriae, and anti-PT antibody levels at exposure and individual protection against pertussis. We suggest that postvaccination response rates may be used as surrogate markers of protection. PMID:11709761

  11. Pertussis vaccination and whooping cough: and now what?

    PubMed

    Guiso, Nicole

    2014-10-01

    Pertussis or whooping cough is a respiratory disease caused by Bordetella pertussis or Bordetella parapertussis that are only known to infect humans. This severe and acute respiratory disease presents epidemic cycles and became a vaccine-preventable disease in the 1940s/1950s when developed countries introduced vaccination. The first type of vaccine developed against this disease was a whole-cell pertussis (wP) vaccine containing inactivated B. pertussis bacteria. Most developed countries produced their own vaccine and given the pediatric nature of the disease at the time of licensure, infants and toddlers were the primary targets and were thus massively vaccinated. The characterization of few virulence factors produced by B. pertussis enabled the development of second-generation pertussis vaccines called the acellular pertussis (aP) vaccines. These only contain 1-5 purified, detoxified B. pertussis proteins and were first introduced in Japan around 30 years ago. Australia, Europe and North America introduced aP vaccines approximately 15 years later, which replaced wP vaccines since then. PMID:25020131

  12. Pertussis: History of the Disease and Current Prevention Failure.

    PubMed

    Kuchar, E; Karlikowska-Skwarnik, M; Han, S; Nitsch-Osuch, A

    2016-01-01

    Pertussis or whooping cough has been given many names over the centuries. It was first recognized in the Middle Ages and since then various epidemics have been described. Jules Bordet and Octave Gengou isolated Bordetella pertussis, a causative agent for whooping cough, in Paris more than 100 years ago, which created an excellent opportunity to invent a vaccine. In 1914 the whole-cell pertussis vaccine was invented, then in the 1940s it was combined with tetanus and diphtheria toxoids to become DTP and it became widely available. A successive decrease in the incidence of the disease has since been observed. The vaccine has been about 80 % effective in preventing serious disease and death from pertussis. The disadvantage is that the vaccine offers protection for 5-10 years after the last dose of the full vaccination course. The second issue is the question of how to prevent side effects of the whole-cell vaccine. In the 1990s, the acellular vaccine was introduced in the US and gradually replaced the whole-cell vaccine. About 10 years later, a possible failure with the new vaccine has been observed, that is a lack of long-term protection. Nowadays, both vaccines are used, with the acellular vaccine being vastly predominant in most developed countries. Pertussis incidence has increased since the 1980s, but new prevention strategies include booster doses for specific age groups. PMID:27256351

  13. The pertussis enigma: reconciling epidemiology, immunology and evolution

    PubMed Central

    Domenech de Cellès, Matthieu; Magpantay, Felicia M. G.; King, Aaron A.; Rohani, Pejman

    2016-01-01

    Pertussis, a highly contagious respiratory infection, remains a public health priority despite the availability of vaccines for 70 years. Still a leading cause of mortality in developing countries, pertussis has re-emerged in several developed countries with high vaccination coverage. Resurgence of pertussis in these countries has routinely been attributed to increased awareness of the disease, imperfect vaccinal protection or high infection rates in adults. In this review, we first present 1980–2012 incidence data from 63 countries and show that pertussis resurgence is not universal. We further argue that the large geographical variation in trends probably precludes a simple explanation, such as the transition from whole-cell to acellular pertussis vaccines. Reviewing available evidence, we then propose that prevailing views on pertussis epidemiology are inconsistent with both historical and contemporary data. Indeed, we summarize epidemiological evidence showing that natural infection and vaccination both appear to provide long-term protection against transmission and disease, so that previously infected or vaccinated adults contribute little to overall transmission at a population level. Finally, we identify several promising avenues that may lead to a consistent explanation of global pertussis epidemiology and to more effective control strategies. PMID:26763701

  14. The pertussis enigma: reconciling epidemiology, immunology and evolution.

    PubMed

    Domenech de Cellès, Matthieu; Magpantay, Felicia M G; King, Aaron A; Rohani, Pejman

    2016-01-13

    Pertussis, a highly contagious respiratory infection, remains a public health priority despite the availability of vaccines for 70 years. Still a leading cause of mortality in developing countries, pertussis has re-emerged in several developed countries with high vaccination coverage. Resurgence of pertussis in these countries has routinely been attributed to increased awareness of the disease, imperfect vaccinal protection or high infection rates in adults. In this review, we first present 1980-2012 incidence data from 63 countries and show that pertussis resurgence is not universal. We further argue that the large geographical variation in trends probably precludes a simple explanation, such as the transition from whole-cell to acellular pertussis vaccines. Reviewing available evidence, we then propose that prevailing views on pertussis epidemiology are inconsistent with both historical and contemporary data. Indeed, we summarize epidemiological evidence showing that natural infection and vaccination both appear to provide long-term protection against transmission and disease, so that previously infected or vaccinated adults contribute little to overall transmission at a population level. Finally, we identify several promising avenues that may lead to a consistent explanation of global pertussis epidemiology and to more effective control strategies. PMID:26763701

  15. Pertussis Signs & Symptoms

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... friendly Fact Sheet Pertussis Vaccination Pregnancy and Whooping Cough Clinicians Disease Specifics Treatment Clinical Features Clinical Complications ...

  16. Pertussis (Whooping Cough) Complications

    MedlinePlus

    ... CDC Cancel Submit Search The CDC Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... friendly Fact Sheet Pertussis Vaccination Pregnancy and Whooping Cough Clinicians Disease Specifics Treatment Clinical Features Clinical Complications ...

  17. Pertussis (Whooping Cough) Outbreaks

    MedlinePlus

    ... questions about pertussis outbreaks... Resources and Publications Find articles about pertussis outbreaks and resources for outbreak response... Postexposure Antimicrobial Prophylaxis The primary objective of PEP should be to prevent death ...

  18. Pertussis Diagnosis & Treatment

    MedlinePlus

    ... The CDC Cancel Submit Search The CDC Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... Kid-friendly Fact Sheet Pertussis Vaccination Pregnancy and Whooping Cough Clinicians Disease Specifics Treatment Clinical Features Clinical Complications ...

  19. Whooping Cough (Pertussis)

    MedlinePlus

    ... Whooping cough (pertussis) is an infection of the respiratory system caused by the bacterium Bordetella pertussis (or B. ... Immunizations Your Child's Immunizations Coughing Pneumonia Lungs and Respiratory System The Woes of Whooping Cough Contact Us Print ...

  20. T-cell immune responses to Bordetella pertussis infection and vaccination.

    PubMed

    Fedele, Giorgio; Cassone, Antonio; Ausiello, Clara Maria

    2015-10-01

    The recent immunological investigations, stemming from the studies performed in the nineties within the clinical trials of the acellular pertussis vaccines, have highlighted the important role played by T-cell immunity to pertussis in humans. These studies largely confirmed earlier investigations in the murine respiratory infection models that humoral immunity alone is not sufficient to confer protection against Bordetella pertussis infection and that T-cell immunity is required. Over the last years, knowledge of T-cell immune response to B. pertussis has expanded broadly, taking advantage of the general progress in the understanding of anti-bacterial immunity and of refinements in methods to approach immunological investigations. In particular, experimental models of B. pertussis infection highlighted the cooperative role played by T-helper (Th)1 and Th17 cells for protection. Furthermore, the new baboon experimental model suggested a plausible explanation for the differences observed in the strength and persistence of protective immunity induced by the acellular or whole-cell pertussis vaccines and natural infection in humans, contributing to explain the upsurge of recent pertussis outbreaks. Despite the progress, open questions remain, the answer to them will possibly provide better tools to fight one of the hardest-to-control vaccine preventable disease. PMID:26242279

  1. An ecological analysis of pertussis disease in Minnesota, 2009-2013.

    PubMed

    Iroh Tam, P Y; Menk, J S; Hughes, J; Kulasingam, S L

    2016-03-01

    The increase in pertussis cases in Minnesota in the last decade has been mainly attributed to the switch from whole cell to acellular pertussis [as part of the diphtheria, tetanus and acellular pertussis vaccine (DTaP)]. It is unclear, however, to what degree community-level risk factors also contribute. Understanding these factors can help inform public health policy-makers about where else to target resources. We performed an ecological analysis within Minnesota to identify risk factors at the county level using a Bayesian Poisson generalized linear areal model to account for spatial dependence. Univariate analyses suggested an association between increased pertussis rates at the county level and white maternal ethnicity, being US born, urban counties and average household size. In the multivariable analysis, the rate of pertussis was 1·79 times greater for urban vs. rural counties and 4·75 times greater for counties with a one-person larger average household size. Pertussis rates in counties with higher (i.e. 4+DTaP) receipt in children were 0·97 times lower. Examining county-level factors associated with varying levels of pertussis may help identify those counties that would most benefit from targeted interventions and increased resource allocation. PMID:26330135

  2. Bordetella pertussis transmission

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bordetella pertussis and Bordetella bronchiseptica are Gram negative bacterial respiratory pathogens. B. pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. B. pertussis and B. bronchiseptica share mechanisms of pathogenesis and are gene...

  3. Purification and immunological characterization of a GroEL-like protein from Bordetella pertussis.

    PubMed Central

    Burns, D L; Gould-Kostka, J L; Kessel, M; Arciniega, J L

    1991-01-01

    A GroEL-like protein from Bordetella pertussis was purified. This protein was found to have the tetradecameric subunit structure typical of the GroEL family of proteins and to contain epitopes similar to those of other members of this family, including a human GroEL-like protein. Active immunization of neonatal mice with the B. pertussis GroEL-like protein provided little protection against an aerosol challenge with B. pertussis. Antibodies to this protein were elicited in mice by a standard diphtheria-tetanus-pertussis (DTP) vaccine but not by an experimental acellular pertussis vaccine. Since the Bordetella GroEL-like protein was found to contain epitopes similar to those on the mammalian analog, the potential exists that vaccination with standard DTP vaccines may induce antibodies which react with the mammalian GroEL analog. Images PMID:2004820

  4. An improved whole cell pertussis vaccine with reduced content of endotoxin

    PubMed Central

    Dias, Waldely Oliveira; van der Ark, Arno A.J.; Sakauchi, Maria Aparecida; Kubrusly, Flávia Saldanha; Prestes, Ana Fabíola R.O.; Borges, Monamaris Marques; Furuyama, Noemi; Horton, Denise S.P.Q.; Quintilio, Wagner; Antoniazi, Marta; Kuipers, Betsy; van der Zeijst, Bernard A.M.; Raw, Isaias

    2013-01-01

    An improved whole cell pertussis vaccine, designated as Plow, which is low in endotoxicity due to a chemical extraction of lipo-oligosaccharide (LOS) from the outer membrane, was evaluated for safety, immunogenicity and potency, comparatively to a traditional whole cell pertussis vaccine. Current whole cell pertussis vaccines are effective but contain large quantities of endotoxin and consequently display local and systemic adverse reactions after administration. Endotoxin is highly inflammatory and contributes considerably to the reactogenicity as well as the potency of these vaccines. In contrast, acellular pertussis vaccines hardly contain endotoxin and are significantly less reactogenic, but their elevated costs limit their global use, especially in developing countries. In this paper, bulk products of Plow and a traditional whole cell vaccine, formulated as plain monocomponents or combined with diphtheria and tetanus toxoids (DTPlow or DTP, respectively) were compared by in vitro and in vivo assays. Chemical extraction of LOS resulted in a significant decrease in endotoxin content (20%) and a striking decline in endotoxin related toxicity (up to 97%), depending on the used in vitro or in vivo test. The LOS extraction did not affect the integrity of the product and, more importantly, did not affect the potency and/or stability of DTPlow. Moreover, hardly any differences in antibody and T-cell responses were observed. The development of Plow is a significant improvement regarding the endotoxicity of whole cell pertussis vaccines and therefore a promising and affordable alternative to currently available whole cell or acellular pertussis vaccines for developing countries. PMID:23291935

  5. Photos of Pertussis

    MedlinePlus

    ... for children. Viewing discretion is advised. Click on any image to enlarge it. Infant being treated for severe pertussis infection. She received extracorporeal membrane oxygenation (ECMO), a procedure ...

  6. Bordetella pertussis infection: pathogenesis, diagnosis, management, and the role of protective immunity.

    PubMed

    Kerr, J R; Matthews, R C

    2000-02-01

    Whooping cough is presently one of the ten most common causes of death from infectious disease worldwide. Despite a high vaccine uptake, resurgences of this disease have been observed in several countries. Virulence factors of Bordetella pertussis include agglutinogens, fimbriae, P.69/pertactin, pertussis toxin, filamentous haemagglutinin, adenylate cyclase, tracheal cytotoxin, dermonecrotic toxin, lipopolysaccharide, tracheal colonisation factor, serum resistance factor, and type III secretion. Virulence factor expression is regulated by the bvgAS locus, a two-component signal transduction system. The pathophysiologic sequence consists of attachment (fimbriae, P.69/pertactin, tracheal colonisation factor, pertussis toxin, filamentous haemagglutinin), evasion of host defence (adenylate cyclase, pertussis toxin, serum resistance factor), local effects (tracheal cytotoxin), and systemic effects (pertussis toxin). Bordetella pertussis is transmitted by respiratory droplets and causes disease only in humans. Various diagnostic methods are available, including culture, serological methods, and the polymerase chain reaction. Serotyping of isolates to detect agglutinogens 2 and 3 is useful because serotype 1,2 may be associated with higher mortality, and antibodies to these antigens (agglutinins) may be protective in both animals and humans. Immunisation using whole-cell vaccine is effective but is reactogenic. Acellular vaccines containing one to five components are being used increasingly in various countries. Protective immunity to pertussis correlates with high levels of antibody to each of pertactin, fimbriae, and pertussis toxin; however, doubt remains as to the relationship between agglutinogen 3 and fimbria 3, making results of trials investigating these virulence factors difficult to interpret. PMID:10746492

  7. The vaccine potential of Bordetella pertussis biofilm-derived membrane proteins.

    PubMed

    de Gouw, Daan; Serra, Diego O; de Jonge, Marien I; Hermans, Peter Wm; Wessels, Hans Jct; Zomer, Aldert; Yantorno, Osvaldo M; Diavatopoulos, Dimitri A; Mooi, Frits R

    2014-08-01

    Pertussis is an infectious respiratory disease of humans caused by the gram-negative pathogen Bordetella pertussis. The use of acellular pertussis vaccines (aPs) which induce immunity of relative short duration and the emergence of vaccine-adapted strains are thought to have contributed to the recent resurgence of pertussis in industrialized countries despite high vaccination coverage. Current pertussis vaccines consist of antigens derived from planktonic bacterial cultures. However, recent studies have shown that biofilm formation represents an important aspect of B. pertussis infection, and antigens expressed during this stage may therefore be potential targets for vaccination. Here we provide evidence that vaccination of mice with B. pertussis biofilm-derived membrane proteins protects against infection. Subsequent proteomic analysis of the protein content of biofilm and planktonic cultures yielded 11 proteins which were ≥three-fold more abundant in biofilms, of which Bordetella intermediate protein A (BipA) was the most abundant, surface-exposed protein. As proof of concept, mice were vaccinated with recombinantly produced BipA. Immunization significantly reduced colonization of the lungs and antibodies to BipA were found to efficiently opsonize bacteria. Finally, we confirmed that bipA is expressed during respiratory tract infection of mice, and that anti-BipA antibodies are present in the serum of convalescent whooping cough patients. Together, these data suggest that biofilm proteins and in particular BipA may be of interest for inclusion into future pertussis vaccines. PMID:26038752

  8. Pertussis Across the Globe: Recent Epidemiologic Trends From 2000 to 2013.

    PubMed

    Tan, Tina; Dalby, Tine; Forsyth, Kevin; Halperin, Scott A; Heininger, Ulrich; Hozbor, Daniela; Plotkin, Stanley; Ulloa-Gutierrez, Rolando; Wirsing von König, Carl Heinz

    2015-09-01

    Pertussis has reemerged as a problem across the world. To better understand the nature of the resurgence, we reviewed recent epidemiologic data and we report disease trends from across the world. Published epidemiologic data from January 2000 to July 2013 were obtained via PubMed searches and open-access websites. Data on vaccine coverage and reported pertussis cases from 2000 through 2012 from the 6 World Health Organization regions were also reviewed. Findings are confounded not only by the lack of systematic and comparable observations in many areas of the world but also by the cyclic nature of pertussis with peaks occurring every 3-5 years. It appears that pertussis incidence has increased in school-age children in North America and western Europe, where acellular pertussis vaccines are used, but an increase has also occurred in some countries that use whole-cell vaccines. Worldwide, pertussis remains a serious health concern, especially for infants, who bear the greatest disease burden. Factors that may contribute to the resurgence include lack of booster immunizations, low vaccine coverage, improved diagnostic methods, and genetic changes in the organism. To better understand the epidemiology of pertussis and optimize disease control, it is important to improve surveillance worldwide, irrespective of pertussis vaccine types and schedules used in each country. PMID:26376316

  9. [PERSISTENCE OF BORDETELLA PERTUSSIS BACTERIA AND A POSSIBLE MECHANISM OF ITS FORMATION].

    PubMed

    Karataev, G I; Sinyashina, L N; Medkova, A Yu; Semin, E G

    2015-01-01

    A growth of pertussis morbidity is observed in many countries of the world against the background of mass vaccindtion. Forms of the disease course have changed. Atypical forms of pertussis occur predominately in adolescents and adults. Asymptomatic carriage of the causative agent has been established. Infection of infants with. BordetelIa pertussis bacteria in more than 90% of cases occurs from parents and relatives. A prolonged persistence of the causative agent has been identified. Morbidity increase in developed countries is associated with the use of acellular vaccines, that do not protect from the infection, but reduce severity of the disease. A change of genotypes of the circulating bacteria strains is observed ubiquitously. Formation of a persistent form of B. pertussis is possible due to a reversible integration of IS-elements into bvgAS operon and other virulence genes. The results of studies of invasion and survival of B. pertussis bacteria in eukaryotic cells, a change in B. pertussis bacteria population after experimental infection of laboratory mice and monkeys are presented, accumulation of avirulent insertion Bvg mutants of B. pertussis was detected. The data obtained are in accordance with the results of analysis of causative agent population in patients with typical and atypical forms of pertussis in humans. More than 50% of the population of B. pertussis bacteria in practically healthy carriers was shown to be presented by avirulent insertion Bvg mutants. B. pertussis virulence reducing as a result of inactivation of single or several virulence genes probably provide long-term persistence of bacteria in host organism and formation of apparently healthy vehicles. Follow-up studies on that front would help to formulate new attitudes to preventive measures of pertussis and lead to development of fundamentally new pharmaceuticals (vaccines) preventing formation of bacterial persistence. PMID:26951000

  10. Agglutinogens and fimbriae of Bordetella pertussis.

    PubMed

    Ashworth, L A; Robinson, A; Funnell, S; Gorringe, A R; Irons, L I; Seabrook, R N

    1988-01-01

    Agglutinogen 2 (AGG2) of Bordetella pertussis is a fimbrial antigen and therefore a potential adhesin and acellular vaccine component. AGG2 was found to dissociate only under harsh conditions into the subunits of mol. wt. 22500 seen in SDS-PAGE. Results from studies of agglutinogen 3 (AGG3) are presented which confirm previous findings from this Laboratory that AGG3 is also a fimbrial protein but with a subunit mol. wt. of 22000. The amino acid sequence of AGG2, deduced from the nucleotide sequence of the gene encoding it, was used as a basis for synthesis of three peptides. Coupled to Keyhole Limpet Haemocyanin (KLH), the peptides were immunogenic in mice, inducing antibodies which bound well to homologous peptide in ELISA but poorly to intact fimbriae. Monoclonal and polyclonal serotype-specific antibodies failed to react significantly with the peptides or their KLH-conjugates. These results indicate that the synthetic peptides do not represent the serotype 2 epitope. Mice immunized with purified AGG2 or AGG3 were found to be protected against respiratory infection with B. pertussis. Results presented here indicate that this protection is, to a large extent, serotype-specific and that immunization of mice with AGG2 or AGG3 can lead to a change in serotype of the infecting strain. These results are analogous to findings from epidemiological studies of the protection induced in children by whole cell vaccines. They reaffirm the importance of both AGG2 and AGG3 as components of whole cell and acellular vaccines. PMID:2908520

  11. Expression, Purification and Characterization of Three Overlapping Immunodominant Recombinant Fragments from Bordetella pertussis Filamentous Hemagglutinin

    PubMed Central

    Asgarian-Omran, Hossein; Amirzargar, Ali Akbar; Arjmand, Mohammad; Eshraghian, Mohammadreza; Nikbin, Behrooz; Eshraghi, Saeid; Mahdavi, Marzieh; Khoshnoodi, Jalal; Jeddi-Tehrani, Mahmood; Rabbani, Hodjatallah; Shokri, Fazel

    2013-01-01

    Background Filamentous hemagglutinin (FHA) is one of the most important immunoprotective antigens of Bordetella pertussis (B. pertussis) and a major component of the acellular pertussis vaccine. In the present study, three overlapping recombinant fragments from the immunodominant region of FHA were produced and their immunogenicity was investigated. Methods Three overlapping coding sequences of FHA antigen were amplified from B. pertussis genomic DNA by PCR. Amplified fragments were expressed in Escherichia coli (E. coli) BL21(DE3) strain and purified through His-tag using Nickel-based chromatography. Purified fragments were characterized by SDS-PAGE and Western blotting techniques. In vitro peripheral blood mononuclear cells (PBMC) proliferation and IFN-γ production were assessed in a limited number of healthy adults vaccinated with a commercial acellular pertussis vaccine in response to all purified FHA fragments by H3-Thymidine incorporation and ELISA, respectively. Results Recombinant FHA segments were successfully cloned and produced at high levels in E. coli BL21(DE3). SDS-PAGE and Western blot analyses confirmed their purity and reactivity. All three recombinant fragments together with a commercial native FHA were able to induce in vitro PBMC proliferation and IFN-γ production. Conclusion Our preliminary results suggest that these overlapping recombinant FHA fragments are immunogenic and may prove to be immuno-protective. PMID:23626873

  12. Analysis of Bordetella pertussis clinical isolates circulating in European countries during the period 1998-2012.

    PubMed

    van Gent, M; Heuvelman, C J; van der Heide, H G; Hallander, H O; Advani, A; Guiso, N; Wirsing von Kőnig, C H; Vestrheim, D F; Dalby, T; Fry, N K; Pierard, D; Detemmerman, L; Zavadilova, J; Fabianova, K; Logan, C; Habington, A; Byrne, M; Lutyńska, A; Mosiej, E; Pelaz, C; Gröndahl-Yli-Hannuksela, K; Barkoff, A M; Mertsola, J; Economopoulou, A; He, Q; Mooi, F R

    2015-04-01

    Despite more than 50 years of vaccination, pertussis is still an endemic disease, with regular epidemic outbreaks. With the exception of Poland, European countries have replaced whole-cell vaccines (WCVs) by acellular vaccines (ACVs) in the 1990s. Worldwide, antigenic divergence in vaccine antigens has been found between vaccine strains and circulating strains. In this work, 466 Bordetella pertussis isolates collected in the period 1998-2012 from 13 European countries were characterised by multi-locus antigen sequence typing (MAST) of the pertussis toxin promoter (ptxP) and of the genes coding for proteins used in the ACVs: pertussis toxin (Ptx), pertactin (Prn), type 2 fimbriae (Fim2) and type 3 fimbriae (Fim3). Isolates were further characterised by fimbrial serotyping, multi-locus variable-number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). The results showed a very similar B. pertussis population for 12 countries using ACVs, while Poland, which uses a WCV, was quite distinct, suggesting that ACVs and WCVs select for different B. pertussis populations. This study forms a baseline for future studies on the effect of vaccination programmes on B. pertussis populations. PMID:25527446

  13. Quadracel: Vaccination Against Diphtheria, Tetanus, Pertussis, and Poliomyelitis in Children

    PubMed Central

    Mosley, Juan F.; Smith, Lillian L.; Parke, Crystal K.; Brown, Jamal A.; LaFrance, Justin M.; Clark, Patricia K.

    2016-01-01

    Introduction: Vaccinations in school-aged children are required by state and local law to maintain high vaccination coverage rates, as well as low rates of vaccine-preventable diseases. Diphtheria, tetanus, and pertussis are childhood diseases that can be life threatening; poliomyelitis, another childhood disease, can be disabling. In turn, vaccinations were developed to provide protection against these diseases. Today, several vaccinations are recommended for children, including but not limited to diphtheria, tetanus, and pertussis (DTaP) and poliomyelitis (IPV). DTaP requires five doses, and IPV requires four. Quadracel (diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine, Sanofi Pasteur Inc.) is a new vaccination developed to condense the last dose of both DTaP and IPV so they do not have to be given separately, thus reducing the total number of vaccinations required. Discussion: The Quadracel vaccine is an option for use in children who are completing the DTaP and IPV series. In a randomized, controlled, phase 3, pivotal trial, Quadracel proved to be as efficacious and safe as Daptacel (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed, Sanofi Pasteur Inc.) and IPOL (poliovirus vaccine inactivated, Sanofi Pasteur Inc.), given separately, to children between the ages of 4 and 6 years. Conclusion: Quadracel should be recommended to parents who have children between the ages of 4 and 6 years who meet the necessary administration criteria and need to finalize their DTaP and IPV series. Quadracel’s administration in the vaccination series replaces one additional injection, which may benefit children who are afraid of receiving shots and parents who need to schedule one less doctor’s appointment. PMID:27069343

  14. New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates

    PubMed Central

    Bouchez, Valérie; Hegerle, Nicolas; Strati, Francesco; Njamkepo, Elisabeth; Guiso, Nicole

    2015-01-01

    Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (PRN), were reported to reach high proportions of circulating isolates. More sporadic filamentous hemagglutinin (FHA) or pertussis toxin (PT) deficient isolates were also collected. The whole genome of some recent French isolates, deficient or non-deficient in vaccine antigens, were analyzed. Transcription profiles of the expression of the main virulence factors were also compared. The invasive phenotype in an in vitro human tracheal epithelial (HTE) cell model of infection was evaluated. Our genomic analysis focused on SNPs related to virulence genes known to be more likely to present allelic polymorphism. Transcriptomic data indicated that isolates circulating since the introduction of pertussis vaccines present lower transcription levels of the main virulence genes than the isolates of the pre-vaccine era. Furthermore, isolates not producing FHA present significantly higher expression levels of the entire set of genes tested. Finally, we observed that recent isolates are more invasive in HTE cells when compared to the reference strain, but no multiplication occurs within cells. PMID:26389958

  15. Comparative Epidemiologic Characteristics of Pertussis in 10 Central and Eastern European Countries, 2000-2013

    PubMed Central

    Heininger, Ulrich; André, Philippe; Chlibek, Roman; Kristufkova, Zuzana; Kutsar, Kuulo; Mangarov, Atanas; Mészner, Zsófia; Nitsch-Osuch, Aneta; Petrović, Vladimir; Prymula, Roman; Usonis, Vytautas; Zavadska, Dace

    2016-01-01

    We undertook an epidemiological survey of the annual incidence of pertussis reported from 2000 to 2013 in ten Central and Eastern European countries to ascertain whether increased pertussis reports in some countries share common underlying drivers or whether there are specific features in each country. The annual incidence of pertussis in the participating countries was obtained from relevant government institutions and/or national surveillance systems. We reviewed the changes in the pertussis incidence rates in each country to explore differences and/or similarities between countries in relation to pertussis surveillance; case definitions for detection and confirmation of pertussis; incidence and number of cases of pertussis by year, overall and by age group; population by year, overall and by age group; pertussis immunization schedule and coverage, and switch from whole-cell pertussis vaccines (wP) to acellular pertussis vaccines (aP). There was heterogeneity in the reported annual incidence rates and trends observed across countries. Reported pertussis incidence rates varied considerably, ranging from 0.01 to 96 per 100,000 population, with the highest rates generally reported in Estonia and the lowest in Hungary and Serbia. The greatest burden appears for the most part in infants (<1 year) in Bulgaria, Hungary, Latvia, Romania, and Serbia, but not in the other participating countries where the burden may have shifted to older children, though surveillance of adults may be inappropriate. There was no consistent pattern associated with the switch from wP to aP vaccines on reported pertussis incidence rates. The heterogeneity in reported data may be related to a number of factors including surveillance system characteristics or capabilities, different case definitions, type of pertussis confirmation tests used, public awareness of the disease, as well as real differences in the magnitude of the disease, or a combination of these factors. Our study highlights the

  16. Bordetella pertussis isolates in Finland: Serotype and fimbrial expression

    PubMed Central

    Heikkinen, Eriikka; Xing, Dorothy K; Ölander, Rose-Marie; Hytönen, Jukka; Viljanen, Matti K; Mertsola, Jussi; He, Qiushui

    2008-01-01

    Background Bordetella pertussis causes whooping cough or pertussis in humans. It produces several virulence factors, of which the fimbriae are considered adhesins and elicit immune responses in the host. B. pertussis has three distinct serotypes Fim2, Fim3 or Fim2,3. Generally, B. pertussis Fim2 strains predominate in unvaccinated populations, whereas Fim3 strains are often isolated in vaccinated populations. In Finland, pertussis vaccination was introduced in 1952. The whole-cell vaccine contained two strains, 18530 (Fim3) since 1962 and strain 1772 (Fim2,3) added in 1976. After that the vaccine has remained the same until 2005 when the whole-cell vaccine was replaced by the acellular vaccine containing pertussis toxin and filamentous hemagglutinin. Our aims were to study serotypes of Finnish B. pertussis isolates from 1974 to 2006 in a population with > 90% vaccination coverage and fimbrial expression of the isolates during infection. Serotyping was done by agglutination and serotype-specific antibody responses were determined by blocking ELISA. Results Altogether, 1,109 isolates were serotyped. Before 1976, serotype distributions of Fim2, Fim3 and Fim2,3 were 67%, 19% and 10%, respectively. From 1976 to 1998, 94% of the isolates were Fim2 serotype. Since 1999, the frequency of Fim3 strains started to increase and reached 83% during a nationwide epidemic in 2003. A significant increase in level of serum IgG antibodies against purified fimbriae was observed between paired sera of 37 patients. The patients infected by Fim3 strains had antibodies which blocked the binding of monoclonal antibodies to Fim3 but not to Fim2. Moreover, about one third of the Fim2 strain infected patients developed antibodies capable of blocking of binding of both anti-Fim2 and Fim3 monoclonal antibodies. Conclusion Despite extensive vaccinations in Finland, B. pertussis Fim2 strains were the most common serotype. Emergence of Fim3 strains started in 1999 and coincided with nationwide

  17. Filamentous hemagglutinin of Bordetella pertussis: nucleotide sequence and crucial role in adherence.

    PubMed Central

    Relman, D A; Domenighini, M; Tuomanen, E; Rappuoli, R; Falkow, S

    1989-01-01

    Filamentous hemagglutinin is a surface-associated adherence protein of Bordetella pertussis, which is a component of some new acellular pertussis vaccines. The nucleotide sequence of an open reading frame that encompasses the filamentous hemagglutinin structural gene, fhaB, suggests that proteolytic processing is necessary to generate the mature 220-kDa filamentous hemagglutinin product. An Arg-Gly-Asp (RGD) tripeptide is found within filamentous hemagglutinin that may be involved in its adherence properties. An internal in-frame deletion in fhaB, encompassing the RGD region, causes loss of B. pertussis-binding to ciliated eukaryotic cells, confirming a potential role for this protein in host-cell binding and infection. Images PMID:2539596

  18. Development of an IgY-based rocket-immunoelectrophoresis for identity monitoring of Pertussis vaccines.

    PubMed

    Matheis, Walter; Schade, Rüdiger

    2011-06-30

    An important step in vaccine production and quality control is the analysis of identity of different lots. For that purpose chicken was immunized with acellular Pertussis components (Pertussis toxoid, Filamenteous haemagglutinin, Pertactin, Fimbriae 2/3 antigen). The resulting antibodies (IgY) were non-invasive extracted from egg yolk and used for rocket immunoelectrophoresis (RIE). We demonstrated that the Ab reacted with characteristic peaks ("rockets") with the corresponding antigen. The shape of the peaks varied depending on the manufacturer and the nature of antigen (adsorbed or non-adsorbed). The coefficients of variation was about 20% during a year period. In summary, our data illustrate that an IgY-based RIE is not only a cost-effective method but also proficient for monitoring Pertussis vaccines. PMID:21586289

  19. Production and characterization of recombinant pertactin, fimbriae 2 and fimbriae 3 from Bordetella pertussis

    PubMed Central

    2009-01-01

    Background Bordetella pertussis is a causative agent of pertussis or whooping cough in humans. Pertactin (Prn), fimbriae 2 (Fim2) and fimbriae 3 (Fim3) of B. pertussis are important virulence factors and immunogens which have been included in some acellular pertussis vaccines. In this present study, we cloned, expressed and purified Prn, Fim2 and Fim3, respectively. The immunogenicity and protective efficacy of the three recombinant proteins (rPrn, rFim2 and rFim3) were investigated in mouse model. Results Three recombinant proteins with amount of 12 to 25 mg/L were produced. Compared to the control mice only immunized with adjuvant, serum IgG antibody responses were significantly induced in the mice immunized with rPrn, rFim2 or rFim3 (P < 0.001 for all three proteins). Furthermore, T cell responses characteristic of increased production of IL-2 and TNF-α (only for rPrn) were elicited in the mice immunized with the three proteins (P < 0.05 for all three proteins). Immunization with rPrn, but not with rFim2 or rFim3, significantly enhanced clearance of bacteria in the lungs of mice after intranasal challenge with B. pertussis (P < 0.05). When tested in a lethal intracerebral infection model, certain protection was observed in mice immunized with rPrn. Conclusions We have developed an efficient method to produce large amounts of rPrn, rFim2, and rFim3 from B. pertussis. The three recombinant proteins induced both humoral and cellular immune responses in mice. Immunization with rPrn also conferred protection against pertussis in mouse infection models. Our results indicated that the recombinant proteins still retain their immunological properties and highlighted the potential of the recombinant proteins for the future development of the B. pertussis vaccines. PMID:20040101

  20. The current epidemiology of pertussis in the developed world: UK and West Germany.

    PubMed

    Miller, E; Farrington, C P

    1988-01-01

    The existence of well established national reporting systems for monitoring pertussis incidence and vaccine uptake in the United Kingdom has allowed the epidemiology of whooping cough and the impact of vaccination to be studied in detail. The increase in pertussis morbidity that followed the decline in vaccine uptake in recent years confirms the continuing need for mass vaccination in a developed country. There is also evidence that pertussis may be responsible for many more deaths than official mortality statistics show. A national study of vaccine efficacy demonstrated over 80% protection against clinical disease during the first 5 years after vaccination. However, there is evidence that the current whole cell vaccine may protect less well against infection with agglutinogen serotype 3 than type 2 organisms which supports the view that both these antigens should be included in acellular vaccines to achieve good protection. In West Germany, unlike the UK, there are no national statistics on pertussis incidence, no national vaccination policy and no figures for vaccine uptake. Local studies have shown that vaccination rates are low and that pertussis is prevalent, particularly in the 2-4 year age-group, which is typical of a country with low uptake; similarly serotype 2 predominates. PMID:3273623

  1. Epidemiology of pertussis in Italy: disease trends over the last century.

    PubMed

    Gonfiantini, M V; Carloni, E; Gesualdo, F; Pandolfi, E; Agricola, E; Rizzuto, E; Iannazzo, S; Ciofi Degli Atti, M L; Villani, A; Tozzi, A E

    2014-01-01

    We reviewed the epidemiology of pertussis in Italy over the last 125 years to identify disease trends and factors that could have influenced these trends. We described mortality rates (1888-2012), case fatality rates (1925-2012), cumulative incidence rates (1925-2013) and age-specific incidence rates (1974-2013). We compared data from routine surveillance with data from a paediatric sentinel surveillance system to estimate under-notification. Pertussis mortality decreased from 42.5 per 100,000 population in 1890 to no reported pertussis-related death after 2002. Incidence decreased from 86.3 per 100,000 in 1927 to 1 per 100,000 after 2008. Vaccine coverage increased from 32.8% in 1993 to about 96% after 2006. As for under-notification, mean sentinel/routine surveillance incidence ratio increased with age (from 1.8 in <1 year-olds to 12.9 in 10-14 year-olds). Pertussis mortality decreased before the introduction of immunisation. Incidence has decreased only after the introduction of pertussis vaccine and in particular after the achievement of a high immunisation coverage with acellular vaccines. Routine surveillance does not show an increase in cumulative incidence nor in ≥ 15 year-olds as reported by other countries. Underrecognition because of atypical presentation and the infrequent use of laboratory tests may be responsible for under-notification, and therefore affect incidence reports and management of immunisation programmes. PMID:25323077

  2. Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model.

    PubMed

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2015-11-17

    Whooping cough or pertussis is a highly infectious respiratory disease in humans caused by Bordetella pertussis. The use of acellular vaccines (ACV) has been associated with the recent resurgence of pertussis in developed countries including Australia despite high vaccination coverage where B. pertussis strains that do not express pertactin (Prn), a key antigenic component of the ACV, have emerged and become prevalent. In this study, we used an in vivo competition assay in mice immunised with ACV and in naïve (control) mice to compare the proportion of colonisation with recent clinical Prn positive and Prn negative B. pertussis strains from Australia. The Prn negative strain colonised the respiratory tract more effectively than the Prn positive strain in immunised mice, out-competing the Prn positive strain by day 3 of infection. However, in control mice, the Prn positive strain out-competed the Prn negative strain. Our findings of greater ability of Prn negative strains to colonise ACV-immunised mice are consistent with reports of selective advantage for these strains in ACV-immunised humans. PMID:26432908

  3. Direct molecular typing of Bordetella pertussis from nasopharyngeal specimens in China in 2012-2013.

    PubMed

    Du, Q; Wang, X; Liu, Y; Luan, Y; Zhang, J; Li, Y; Liu, X; Ma, C; Li, H; Wang, Z; He, Q

    2016-07-01

    Data on the molecular epidemiology of Bordetella pertussis are limited in developing countries where whole-cell pertussis vaccines (WCVs) have been used. The aim of this study was to determine the genotypes of circulating B. pertussis in China by direct molecular typing of clinical specimens. DNA extracts of 122 nasopharyngeal swabs (NPs) positive for B. pertussis by polymerase chain reaction (PCR) (targeting IS481 and ptx-Pr) from 2012 to 2013 were used for typing using the multiple-locus variable number tandem repeat analysis (MLVA) and also by PCR-based multilocus sequence typing (MLST) of B. pertussis virulence genes (ptxP, prn, and fim3). One hundred and eight DNA extracts (89 %) generated a complete MLVA type (MT). Among the 18 MTs obtained, MT55 (52 %) and MT104 (13 %) were the most common. MT27, which is linked to the ptxP3 allele and is prevalent in many developed countries using acellular pertussis vaccines (ACVs), was only found in 7 (6 %) DNA extracts. Eighty-seven DNA extracts (71 %) produced a complete multiantigen sequence typing (MAST) type. Of them, 77 (89 %) had the ptxP1/prn1/fim3-1 allele profile. Four DNA extracts (5 %) had the ptxP3/prn2/fim3-2 profile and 3 (4 %) had the ptxP3/prn1/fim3-2 allele profile. These seven DNA extracts also harbored MT27. Our result shows that B. pertussis circulating in China was different from those found in countries where ACVs have been in use, supporting the notion that selection pressure induced by WCVs and ACVs on the bacterial population differs. PMID:27146879

  4. Prevalence and Molecular Characterization of Pertactin-Deficient Bordetella pertussis in the United States

    PubMed Central

    Queenan, A. M.; Cassiday, P. K.; Lynch, A. S.; Harrison, M. J.; Shang, W.; Williams, M. M.; Bowden, K. E.; Burgos-Rivera, B.; Qin, X.; Messonnier, N.; Tondella, M. L.

    2014-01-01

    Pertussis has shown a striking resurgence in the United States, with a return to record numbers of reported cases as last observed in the 1950s. Bordetella pertussis isolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting that B. pertussis is losing pertactin in response to vaccine immunity. Screening of 1,300 isolates from outbreak and surveillance studies (historical isolates collected from 1935 up to 2009, isolates from the 2010 California pertussis outbreak, U.S. isolates from routine surveillance between 2010-2012, and isolates from the 2012 Washington pertussis outbreak) by conventional PCR and later by Western blotting and prn sequencing analyses ultimately identified 306 pertactin-deficient isolates. Of these pertactin-deficient strains, 276 were identified as having an IS481 in the prn gene (prnIS481 positive). The first prnIS481-positive isolate was found in 1994, and the next prnIS481-positive isolates were not detected until 2010. The prevalence of pertactin-deficient isolates increased substantially to more than 50% of collected isolates in 2012. Sequence analysis of pertactin-deficient isolates revealed various types of mutations in the prn gene, including two deletions, single nucleotide substitutions resulting in a stop codon, an inversion in the promoter, and a single nucleotide insertion resulting in a frameshift mutation. All but one mutation type were found in prn2 alleles. CDC 013 was a predominant pulsed-field gel electrophoresis (PFGE) profile in the pertactin-positive isolates (203/994) but was found in only 5% (16/306) of the pertactin-deficient isolates. Interestingly, PFGE profiles CDC 002 and CDC 237 represented 55% (167/306) of the identified pertactin-deficient isolates. These results indicate that there has been a recent dramatic increase in pertactin-deficient B. pertussis isolates throughout the United States. PMID:24256623

  5. Lymphocyte receptors for pertussis toxin

    SciTech Connect

    Clark, C.G.; Armstrong, G.D. )

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  6. Subclass compositions of immunoglobulin G to pertussis toxin in patients with whooping cough, in healthy individuals, and in recipients of a pertussis toxoid vaccine.

    PubMed Central

    Zackrisson, G; Lagergård, T; Trollfors, B

    1989-01-01

    The subclass composition of serum immunoglobulin G (IgG) antibodies against pertussis toxin was studied in 108 serum samples obtained during various stages of disease from 75 patients with whooping cough. IgG1 and IgG3 antibodies were detected in 92 and 42% of the samples, respectively, while only a few contained IgG2 or IgG4 antibodies. Similarly, IgG1 antibodies were predominant in serum samples from healthy children and adults, many of whom had a history of whooping cough several years earlier. Of 85 children and 30 adults with detectable levels of total IgG, 65 and 14 had IgG1 antibodies, respectively, while only 9 of them had IgG3 antibodies. Again, very few sera contained IgG2 or IgG4 antibodies. In contrast, 13 children vaccinated with an acellular aluminum-adsorbed pertussis toxoid vaccine responded mainly with IgG1 and IgG4 antibodies. In conclusion, this study showed that the subclass composition of IgG antibodies to pertussis toxin after natural infection consists mainly of IgG1 and to a certain extent of IgG3, while an aluminum-adsorbed pertussis toxoid induces IgG1 and IgG4 antibodies. PMID:2768444

  7. Laboratory Maintenance of Bordetella pertussis.

    PubMed

    Hulbert, Robin R; Cotter, Peggy A

    2009-11-01

    The causative agent of the respiratory disease whooping cough, Bordetella pertussis, is a nutritionally fastidious microorganism but can be grown with relative ease in research laboratories. Stainer-Scholte synthetic broth medium and Bordet-Gengou blood agar both support growth of B. pertussis and are commonly used. B. pertussis prefers aerobic conditions and a temperature range of 35 degrees to 37 degrees C. Appropriate laboratory safety protocols are required to prevent the generation of aerosols, which could potentially spread this highly infectious agent. PMID:19885941

  8. Mouse and pig models for studies of natural and vaccine-induced immunity to Bordetella pertussis.

    PubMed

    Mills, Kingston H G; Gerdts, Volker

    2014-04-01

    The increasing incidence of whooping cough in many developed countries has been linked with waning immunity induced after immunization with acellular pertussis (aP) vaccines. The rational design of an improved aP vaccine requires a full understanding of the mechanism of protective immunity and preclinical studies in animal models. Infection of mice and pigs with Bordetella pertussis has many features of the infection seen in humans and has already provided valuable information on the roles of innate and adaptive immune responses in protection. Recent findings in these models have already indicated that it may be possible to develop an improved aP vaccine based on a formulation that includes a Toll-like receptor agonist as an adjuvant. PMID:24626866

  9. Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study.

    PubMed

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2016-07-25

    Molecular epidemiological data indicates that the resurgence of pertussis (whooping cough) in populations with high vaccine coverage is associated with genomic adaptation of Bordetella pertussis, the causative agent of the disease, to vaccine selection pressure. We have previously shown that in the period after the introduction of acellular pertussis vaccine (ACV), the majority of circulating strains in Australia switched to single nucleotide polymorphism (SNP) cluster I (carrying ptxP3/prn2), replacing SNP cluster II (carrying ptxP1/prn3). In this study, we carried out an in vivo competition assay using a mouse model infected with SNP cluster I and II B. pertussis strains from Australia. We found that the SNP cluster I strain colonised better than the SNP cluster II strain, in both naïve and immunised mice, suggesting that SNP cluster I strains had better fitness regardless of immunisation status of the host, consistent with SNP cluster I strains replacing SNP cluster II. Nevertheless, we found that ACV enhanced clearance of both SNP cluster I and II strains from the mouse respiratory tract. PMID:27346304

  10. Cellular pertussis vaccine containing a Bordetella pertussis strain that produces a nontoxic pertussis toxin molecule.

    PubMed Central

    Marsili, I; Pizza, M; Giovannoni, F; Volpini, G; Bartalini, M; Olivieri, R; Rappuoli, R; Nencioni, L

    1992-01-01

    Bordetella pertussis 165-9K/129G, which produces a nontoxic form of pertussis toxin (PT), was used to prepare a whole-cell diphtheria-tetanus-pertussis (DTP) vaccine. The in vivo potency and the serological response induced by this vaccine were comparable to those of the conventional DTP vaccine which contains active PT. The toxic activities induced by PT such as leukocytosis, histamine sensitivity, and potentiation of anaphylactic reactions, which are present in the conventional DTP vaccine, were absent in the new vaccine. These results suggest that the introduction of a whole-cell vaccine containing B. pertussis 165-9K/129G would induce the same immunity as the conventional vaccine and would avoid the administration of a harmful toxin to children. PMID:1541530

  11. Is Pertussis Infection Neglected in China? Evidence from a Seroepidemiology Survey in Zhejiang, an Eastern Province of China

    PubMed Central

    Zhou, Yang; Deng, Xuan; Pan, Jinren

    2016-01-01

    Background The resurgence of pertussis has occurred in many countries. However, the epidemiological profiles of pertussis cannot be well understood by the current surveillance system in China. This study was designed to investigate the age specific serologic evidence of antibodies against pertussis, and to offer information regarding the existence of pertussis infection in Zhejiang Province, China. Methods A cross-sectional serosurvey was carried out in 6 counties of Zhejiang Province during September and October of 2014. The immunoglobulin G-pertussis toxin (IgG-PT) levels were measured quantitatively with a commercially available enzyme-linked immunosorbent assay (ELISA). The antibody activities were expressed in the Food and Drug Administration (FDA)-U/ml and a level ≥30 FDA-U/ml was considered seropositive. An IgG-PT >80 FDA-U/ml indicated recent pertussis infection if the patient had not received immunization with the pertussis vaccine within the last year. Results The mean IgG-PT seropositivity rate among the 2107 subjects was 33.32% with a geometric mean concentration of 17.73 (95% confidence interval: 16.90–18.60) FDA-U/ml. The difference in the seropositivity rates reached significant means among the different age groups (waldχ2 = 198.41, P<0.0005), and children aged 3 years had the highest percentage (63.24%) of undetectable IgG-PT level. Of the 1707 subjects ≥3 years of age, 169 (9.90%) had evidence of a recent infection. The highest proportion of IgG-PT levels ≥80 FDA-U/ml was found in ≥60 years age group followed by 11–15 and 16–25 years age groups. Conclusions This study indicates the rather lower IgG-PT level sustained 1 year after the acellular pertussis vaccine booster dose, and substantial proportion of population susceptibility to pertussis in Zhejiang Province, China. Moreover, pertussis infection is not uncommon; it was estimated that 10% of subjects were recently infected approximately within the last 100 days. We highly suggest

  12. Whooping Cough (Pertussis) - Fact Sheet for Parents

    MedlinePlus

    ... this page: About CDC.gov . Redirect for the Pertussis fact sheet page. The current fact sheet can ... http://www.cdc.gov/vaccines/parents/diseases/child/pertussis.html Print page Share Compartir File Formats Help: ...

  13. Pertussis: Microbiology, Disease, Treatment, and Prevention.

    PubMed

    Kilgore, Paul E; Salim, Abdulbaset M; Zervos, Marcus J; Schmitt, Heinz-Josef

    2016-07-01

    Pertussis is a severe respiratory infection caused by Bordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. Sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution of B. pertussis strains. During the past 20 years, the scientific community has recognized pertussis among adults as well as infants and children. Increased recognition that older children and adolescents are at risk for disease and may transmit B. pertussis to younger siblings has underscored the need to better understand the role of innate, humoral, and cell-mediated immunity, including the role of waning immunity. Although recognition of adult pertussis has increased in tandem with a better understanding of B. pertussis pathogenesis, pertussis in neonates and adults can manifest with atypical clinical presentations. Such disease patterns make pertussis recognition difficult and lead to delays in treatment. Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology. Together, these advances provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines. PMID:27029594

  14. Tracking Pertussis and Evaluating Control Measures through Enhanced Pertussis Surveillance, Emerging Infections Program, United States.

    PubMed

    Skoff, Tami H; Baumbach, Joan; Cieslak, Paul R

    2015-09-01

    Despite high coverage with pertussis-containing vaccines, pertussis remains endemic to the United States. There have been increases in reported cases in recent years, punctuated by striking epidemics and shifting epidemiology, both of which raise questions about current policies regarding its prevention and control. Limited data on pertussis reported through the National Notifiable Disease Surveillance System have proved insufficient to answer these questions. To address shortcomings of national pertussis data, the Emerging Infections Program at the US Centers for Disease Control and Prevention launched Enhanced Pertussis Surveillance (EPS), which is characterized by systematic case ascertainment, augmented data collection, and collection of Bordetella pertussis isolates. Data collected through EPS have been instrumental in understanding the rapidly evolving epidemiology and molecular epidemiology of pertussis and have contributed essential information regarding pertussis vaccines. EPS also serves as a platform for conducting critical and timely evaluations of pertussis prevention and control strategies, including targeting of vaccinations and antimicrobial prophylaxis. PMID:26291475

  15. Tracking Pertussis and Evaluating Control Measures through Enhanced Pertussis Surveillance, Emerging Infections Program, United States

    PubMed Central

    Baumbach, Joan; Cieslak, Paul R.

    2015-01-01

    Despite high coverage with pertussis-containing vaccines, pertussis remains endemic to the United States. There have been increases in reported cases in recent years, punctuated by striking epidemics and shifting epidemiology, both of which raise questions about current policies regarding its prevention and control. Limited data on pertussis reported through the National Notifiable Disease Surveillance System have proved insufficient to answer these questions. To address shortcomings of national pertussis data, the Emerging Infections Program at the US Centers for Disease Control and Prevention launched Enhanced Pertussis Surveillance (EPS), which is characterized by systematic case ascertainment, augmented data collection, and collection of Bordetella pertussis isolates. Data collected through EPS have been instrumental in understanding the rapidly evolving epidemiology and molecular epidemiology of pertussis and have contributed essential information regarding pertussis vaccines. EPS also serves as a platform for conducting critical and timely evaluations of pertussis prevention and control strategies, including targeting of vaccinations and antimicrobial prophylaxis. PMID:26291475

  16. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    SciTech Connect

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J. )

    1989-11-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from (3H-nicotinamide)NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from (32P-adenylate)NAD (0.2 mol/mol of protein). Label from (3H-nicotinamide)NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with (3H-nicotinamide)NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

  17. Pertussis immunity and epidemiology: mode and duration of vaccine-induced immunity.

    PubMed

    Magpantay, F M G; Domenech DE Cellès, M; Rohani, P; King, A A

    2016-06-01

    The resurgence of pertussis in some countries that maintain high vaccination coverage has drawn attention to gaps in our understanding of the epidemiological effects of pertussis vaccines. In particular, major questions surround the nature, degree and durability of vaccine protection. To address these questions, we used mechanistic transmission models to examine regional time series incidence data from Italy in the period immediately following the introduction of acellular pertussis (aP) vaccine. Our results concur with recent animal-challenge experiments wherein infections in aP-vaccinated individuals proved as transmissible as those in naive individuals but much less symptomatic. On the other hand, the data provide evidence for vaccine-driven reduction in susceptibility, which we quantify via a synthetic measure of vaccine impact. As to the precise nature of vaccine failure, the data do not allow us to distinguish between leakiness and waning of vaccine immunity, or some combination of these. Across the range of well-supported models, the nature and duration of vaccine protection, the age profile of incidence and the range of projected epidemiological futures differ substantially, underscoring the importance of the remaining unknowns. We identify key data gaps: sources of data that can supply the information needed to eliminate these remaining uncertainties. PMID:26337864

  18. Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

    PubMed Central

    Mielcarek, Nathalie; Debrie, Anne-Sophie; Raze, Dominique; Bertout, Julie; Rouanet, Carine; Younes, Amena Ben; Creusy, Colette; Engle, Jacquelyn; Goldman, William E; Locht, Camille

    2006-01-01

    Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth. PMID:16839199

  19. Investigations into the emergence of pertactin-deficient Bordetella pertussis isolates in six European countries, 1996 to 2012.

    PubMed

    Zeddeman, A; van Gent, M; Heuvelman, C J; van der Heide, H G; Bart, M J; Advani, A; Hallander, H O; Wirsing von Konig, C H; Riffelman, M; Storsaeter, J; Vestrheim, D F; Dalby, T; Krogfelt, K A; Fry, N K; Barkoff, A M; Mertsola, J; He, Q; Mooi, F

    2014-01-01

    Pathogen adaptation has been proposed to contribute to the resurgence of pertussis. A striking recent example is the emergence of isolates deficient in the vaccine component pertactin (Prn). This study explores the emergence of such Prn-deficient isolates in six European countries. During 2007 to 2009, 0/83 isolates from the Netherlands, 0/18 from the United Kingdom, 0/17 Finland, 0/23 Denmark, 4/99 Sweden and 5/20 from Norway of the isolates collected were Prn-deficient. In the Netherlands and Sweden, respectively 4/146 and 1/8 were observed in a later period (2010–12). The Prn-deficient isolates were genetically diverse and different mutations were found to inactivate the prn gene. These are indications that Prn-deficiency is subject to positive selective pressure. We hypothesise that the switch from whole cell to acellular pertussis vaccines has affected the balance between ‘costs and benefits’ of Prn production by Bordetella pertussis to the extent that isolates that do not produce Prn are able to expand. The absence of Prn-deficient isolates in some countries may point to ways to prevent or delay the spread of Prn-deficient strains. In order to substantiate this hypothesis, trends in the European B. pertussis population should be monitored continuously. PMID:25166348

  20. Isotype and antigen specificity of pertussis agglutinins following whole-cell pertussis vaccination and infection with Bordetella pertussis.

    PubMed Central

    Mink, C M; O'Brien, C H; Wassilak, S; Deforest, A; Meade, B D

    1994-01-01

    Elevated agglutinin titers have been shown to correlate with protection from disease following whole-cell pertussis vaccination, but the isotype and antigen specificity of human agglutinating antibodies is unknown. In 13 immunoassays, immunoglobulin G antifimbria antibodies had the strongest correlation with agglutinin titers following culture-proven infection with Bordetella pertussis (R' = 0.79; P < 0.0001) and following whole-cell pertussis vaccination (R' = 0.87, P < 0.0001). PMID:7509316

  1. Conversion of Bordetella pertussis to Bordetella parapertussis.

    PubMed Central

    Kumazawa, N. H.; Yoshikawa, M.

    1978-01-01

    The epidemiological and drug susceptibility data on whooping cough suggested a possibility that Bordetella pertussis converts in some way to Bordetella parapertussis. To prove this, B. pertussis strain 75 was treated with N-methyl-N'-nitro-N-nitrosoguanidine and a mutant resistant to staphcillin v and eight mutants resistant to trimethoprim were isolated. The staphcillin V-resistant mutant of B. pertussis agreed with all of the criteria of B. parapertussis and the trimethoprim-resistant mutants also agreed with many of these criteria. Thus, a hypothesis is presented that B. parapertussis is a mutant of B. pertussis which appeared in nature probably by a selective pressure of antibiotics. PMID:211161

  2. Pertussis: the disease and new diagnostic methods.

    PubMed Central

    Friedman, R L

    1988-01-01

    Bordetella pertussis, the causative agent of whooping cough, produces an acute and chronic respiratory infection in infants and young children. B. pertussis is still a major health problem of young children throughout the world even though effective immunization against whooping cough is available. While predominantly a childhood disease, it has been reported also to be a cause of persistent cough in adults. This review discusses the numerous bacterial virulence factors that may play roles in the pathogenesis of pertussis and in immunity to infection. The present problems with pertussis diagnosis, recent advances, and future prospects for new and improved rapid diagnostics tests also are explored. PMID:2906814

  3. In vitro assessment of biodurability: acellular systems.

    PubMed Central

    de Meringo, A; Morscheidt, C; Thélohan, S; Tiesler, H

    1994-01-01

    The assessment of biodurability of man-made vitreous fibers is essential to the limitation of health hazards associated with human exposure to environments in which respirable fibers are present. In vitro acellular systems provide effective test methods of measuring fiber solubility provided care is taken to select the most suitable solvent and test conditions for the specific fiber type and dimension. PMID:7882955

  4. In vitro pyrogenicity of the diphtheria, tetanus and acellular pertussis components of a trivalent vaccine.

    PubMed

    Carlin, Gunnar; Viitanen, Eila

    2005-05-25

    We have earlier found that a trivalent vaccine, containing antigenic components from both Gram-positive and Gram-negative bacteria, induced secretion of the endogenous pyrogen interleukin 6 (IL-6) when added to fresh human blood in vitro. The results of the present study showed that the IL-6 secretion was induced by toxoids derived from the Gram-positive bacterium Corynebacterium diphtheriae. However, fresh whole blood from different donors reacted differently to the stimulation. The blood from some donors induced secretion of large concentrations of IL-6, while the blood from other donors induced essentially no IL-6 secretion as a response to stimulation with diphtheria toxoid or a mixture of diphtheria and tetanus toxoids. Repeated testing over several years using blood from the same donor confirmed a donor-dependency of the reaction. This donor-dependency was only found for the toxoid, since blood from all donors reacted with approximately similar IL-6 production to stimulation by endotoxin from the Gram-negative bacterium Escherichia coli, known to be mediated via the toll-like receptor (TLR) 4. Also, no donor-dependecy was found to highly purified lipoteichoic acid from the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, known to be mediated via TLR-2 and TLR-6. The receptors involved in stimulation by diphtheria toxoid are not known, but may differ from those used by endotoxin and lipoteichoic acid. PMID:15882532

  5. c-di-GMP Enhances Protective Innate Immunity in a Murine Model of Pertussis

    PubMed Central

    Elahi, Shokrollah; Van Kessel, Jill; Kiros, Tedele G.; Strom, Stacy; Hayakawa, Yoshihiro; Hyodo, Mamoru; Babiuk, Lorne A.; Gerdts, Volker

    2014-01-01

    Innate immunity represents the first line of defense against invading pathogens in the respiratory tract. Innate immune cells such as monocytes, macrophages, dendritic cells, NK cells, and granulocytes contain specific pathogen-recognition molecules which induce the production of cytokines and subsequently activate the adaptive immune response. c-di-GMP is a ubiquitous second messenger that stimulates innate immunity and regulates biofilm formation, motility and virulence in a diverse range of bacterial species with potent immunomodulatory properties. In the present study, c-di-GMP was used to enhance the innate immune response against pertussis, a respiratory infection mainly caused by Bordetella pertussis. Intranasal treatment with c-di-GMP resulted in the induction of robust innate immune responses to infection with B. pertussis characterized by enhanced recruitment of neutrophils, macrophages, natural killer cells and dendritic cells. The immune responses were associated with an earlier and more vigorous expression of Th1-type cytokines, as well as an increase in the induction of nitric oxide in the lungs of treated animals, resulting in significant reduction of bacterial numbers in the lungs of infected mice. These results demonstrate that c-di-GMP is a potent innate immune stimulatory molecule that can be used to enhance protection against bacterial respiratory infections. In addition, our data suggest that priming of the innate immune system by c-di-GMP could further skew the immune response towards a Th1 type phenotype during subsequent infection. Thus, our data suggest that c-di-GMP might be useful as an adjuvant for the next generation of acellular pertussis vaccine to mount a more protective Th1 phenotype immune response, and also in other systems where a Th1 type immune response is required. PMID:25333720

  6. Structure of Bordetella pertussis peptidoglycan

    SciTech Connect

    Folkening, W.J.; Nogami, W.; Martin, S.A.; Rosenthal, R.S.

    1987-09-01

    Bordetella pertussis Tohama phases I and III were grown to the late-exponential phase in liquid medium containing (/sup 3/H)diaminopimelic acid and treated by a hot (96/sup 0/C) sodium dodecyl sulfate extraction procedure. Washed sodium dodecyl sulfate-insoluble residue from phases I and III consisted of complexes containing protein (ca. 40%) and peptidoglycan (60/sup 6/). Subsequent treatment with proteinase K yielded purified peptidoglycan which contained N-acetylglucosamine, N-acetylmuramic acid, alanine, glutamic acid, and diaminopimelic acid in molar ratios of 1:1:2:1:1 and <2% protein. Radiochemical analyses indicated that /sup 3/H added in diaminopimelic acid was present in peptidoglycan-protein complexes and purified peptidoglycan as diaminopimelic acid exclusively and that pertussis peptidoglycan was not O acetylated, consistent with it being degraded completely by hen egg white lysozyme. Muramidase-derived disaccharide peptide monomers and peptide-cross-linked dimers and higher oligomers were isolated by molecular-sieve chromatography; from the distribution of these peptidoglycan fragments, the extent of peptide cross-linking of both phase I and III peptidoglycan was calculated to be ca. 48%. Unambiguous determination of the structure of muramidase-derived pepidoglycan fragments by fast atom bombardment-mass spectrometry and tandem mass spectrometry indicated that the pertussis peptidoglycan monomer fraction was surprisingly homogeneous, consisting of >95% N-acetylglucosaminyl-N-acetylmuramyl-alanyl-glutamyl-diaminopimelyl-alanine.

  7. [Evaluation of postvaccinal pertussis immunity by using immunoenzyme analysis].

    PubMed

    Khardina, A A; Lapaeva, I A; Amelina, I P; Rusakova, E V; Kuliakina, M N

    1989-01-01

    The effectiveness of adsorbed DPT vaccine manufactured in the USSR, evaluated by its capacity of inducing the formation of the main classes of immunoglobulins and by the duration of immune response to the acellular complex of protective antigens (pertussis toxin and agglutinogen-2), was studied with the use of modified EIA. Out of 273 children immunized with adsorbed DPT vaccine in the course of this study, 87.2% had IgG-antibodies, 14.1% had IgA-antibodies and 3.2% of the children had IgM-antibodies. The level of immunity in children having received the full course of immunization with adsorbed DPT vaccine was significantly higher in comparison with children given only the primary course of immunization and nonimmunized children of the same age. Antipertussis immunity was found to decrease two years after the completion of the course of immunization with adsorbed DPT vaccine and in children over 5-6 years of age. Adsorbed DPT vaccine prevented the disease, but not infection. The level of postinfection immunity was higher than that of postvaccinal immunity. PMID:2540600

  8. Pertussis toxin analog with reduced enzymatic and biological activities is a protective immunogen.

    PubMed Central

    Kimura, A; Mountzouros, K T; Schad, P A; Cieplak, W; Cowell, J L

    1990-01-01

    against a respiratory challenge with B. pertussis. Our studies with CRM3201 show that recombinant analogs of PTX have the potential to be developed into safe, protective immunogens for use in new acellular pertussis vaccines. PMID:2119344

  9. The preteen visit: an opportunity for prevention.

    PubMed

    Campos-Outcalt, Doug

    2006-12-01

    All early adolescents should visit a physician at age 11 or 12 years to receive a set of recommended vaccines. Two vaccines are recommended for boys in this age group-quadrivalent meningococcal conjugate vaccine (MCV4) and tetanus toxoid, reduced diphtheria, and acellular pertussis vaccine (Tdap). Three vaccines are recommended for girls--MCV4, Tdap, and human papilloma virus (HPV) vaccine. In addition, 2 doses of varicella vaccine are now recommended before age 5 years; both boys and girls at age 11 or 12 who have received only 1 dose should be given a second. PMID:17137541

  10. Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

    PubMed Central

    Cui, Wei-ling; Qiu, Long-hai; Lian, Jia-yan; Li, Jia-chun; Hu, Jun; Liu, Xiao-lin

    2016-01-01

    Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group) alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group). As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves. PMID:27127495

  11. Data from acellular human heart matrix.

    PubMed

    Sánchez, Pedro L; Fernández-Santos, M Eugenia; Espinosa, M Angeles; González-Nicolas, M Angeles; Acebes, Judith R; Costanza, Salvatore; Moscoso, Isabel; Rodríguez, Hugo; García, Julio; Romero, Jesús; Kren, Stefan M; Bermejo, Javier; Yotti, Raquel; Del Villar, Candelas Pérez; Sanz-Ruiz, Ricardo; Elizaga, Jaime; Taylor, Doris A; Fernández-Avilés, Francisco

    2016-09-01

    Perfusion decellularization of cadaveric hearts removes cells and generates a cell-free extracellular matrix scaffold containing acellular vascular conduits, which are theoretically sufficient to perfuse and support tissue-engineered heart constructs. This article contains additional data of our experience decellularizing and testing structural integrity and composition of a large series of human hearts, "Acellular human heart matrix: a critical step toward whole heat grafts" (Sanchez et al., 2015) [1]. Here we provide the information about the heart decellularization technique, the valve competence evaluation of the decellularized scaffolds, the integrity evaluation of epicardial and myocardial coronary circulation, the pressure volume measurements, the primers used to assess cardiac muscle gene expression and, the characteristics of donors, donor hearts, scaffolds and perfusion decellularization process. PMID:27331090

  12. Location of the three major agglutinogens of Bordetella pertussis by immuno-electronmicroscopy.

    PubMed

    Preston, N W; Zorgani, A A; Carter, E J

    1990-05-01

    When the three serotypes of Bordetella pertussis (types 1,2,3; 1,2 and 1,3) were labelled with agglutinins and protein-A gold, agglutinogen 1 was found on fimbriae and on the cell surface of types 1,2,3 and 1,2 but on the cell surface only of non-fimbriate type 1,3 organisms. In contrast, agglutinogen 2 was located on fimbriae only. Agglutinogen 3 was not labelled. When protein-A gold was replaced by immunoglobulin-G gold, agglutinogen 3 was found on the cell surface only, even of fimbriate bacteria of type 1,2,3. The implications of these findings for acellular vaccines are discussed. PMID:1971311

  13. Strategies to decrease pertussis transmission to infants.

    PubMed

    Forsyth, Kevin; Plotkin, Stanley; Tan, Tina; Wirsing von König, Carl Heinz

    2015-06-01

    The Global Pertussis Initiative (GPI) is an expert scientific forum addressing the worldwide burden of pertussis, which remains a serious health issue, especially in infants. This age cohort is at risk for developing pertussis by transmission from those in close proximity. Risk is increased in infants aged 0 to 6 weeks, as they are too young to be vaccinated. Older infants are at risk when their vaccination schedules are incomplete. Infants also bear the greatest disease burden owing to their high risk for pertussis-related complications and death; therefore, protecting them is a high priority. Two vaccine strategies have been proposed to protect infants. The first involves vaccinating pregnant women, which directly protects through the passive transfer of pertussis antibodies. The second strategy, cocooning, involves vaccinating parents, caregivers, and other close contacts, which indirectly protects infants from transmission by preventing disease in those in close proximity. The goal of this review was to present and discuss evidence on these 2 strategies. Based on available data, the GPI recommends vaccination during pregnancy as the primary strategy, given its efficacy, safety, and logistic advantages over a cocoon approach. If vaccination during pregnancy is not feasible, then all individuals having close contact with infants <6 months old should be immunized consistent with local health authority guidelines. These efforts are anticipated to minimize pertussis transmission to vulnerable infants, although real-world effectiveness data are limited. Countries should educate lay and medical communities on pertussis and introduce robust surveillance practices while implementing these protective strategies. PMID:25963002

  14. Bordetella pertussis filamentous hemagglutinin itself does not trigger anti-inflammatory interleukin-10 production by human dendritic cells.

    PubMed

    Villarino Romero, Rodrigo; Hasan, Shakir; Faé, Kellen; Holubova, Jana; Geurtsen, Jeroen; Schwarzer, Martin; Wiertsema, Selma; Osicka, Radim; Poolman, Jan; Sebo, Peter

    2016-01-01

    Filamentous hemagglutinin (FHA) is an important adhesin of the whooping cough agent Bordetella pertussis and is contained in most acellular pertussis vaccines. Recently, FHA was proposed to exert an immunomodulatory activity through induction of tolerogenic IL-10 secretion from dendritic cells. We have re-evaluated the cytokine-inducing activity of FHA, placing specific emphasis on the role of the residual endotoxin contamination of FHA preparations. We show that endotoxin depletion did not affect the capacity of FHA to bind primary human monocyte-derived dendritic cells, while it abrogated the capacity of FHA to elicit TNF-α and IL-10 secretion and strongly reduced its capacity to trigger IL-6 production. The levels of cytokines induced by the different FHA preparations correlated with their residual contents of B. pertussis endotoxin. Moreover, FHA failed to trigger cytokine secretion in the presence of antibodies that block TLR2 and/or TLR4 signaling. The TLR2 signaling capacity appeared to be linked to the presence of endotoxin-associated components in FHA preparations and not to the FHA protein itself. These results show that the endotoxin-depleted FHA protein does not induce cytokine release from human dendritic cells. PMID:26699834

  15. Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough.

    PubMed Central

    Nencioni, L; Pizza, M; Bugnoli, M; De Magistris, T; Di Tommaso, A; Giovannoni, F; Manetti, R; Marsili, I; Matteucci, G; Nucci, D

    1990-01-01

    the introduction of two amino acid substitutions within the enzymatically active subunit S1 of pertussis toxin (PT) abolishes its ADP-ribosyltransferase activity and toxicity on CHO cells (Pizza et al., Science 246:497-500, 1989). These genetically inactivated molecules are also devoid of other in vivo adverse reactions typical of PT, such as induction of leukocytosis, potentiation of anaphylaxis, stimulation of insulin secretion, and histamine sensitivity. However, the mutant PT molecules are indistinguishable from wild-type PT in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and maintain all the physical and chemical properties of PT, including affinity for toxin-neutralizing poly- and monoclonal antibodies. Either alone or stabilized with formaldehyde, PT mutants are able to induce high levels of neutralizing antibodies and to protect mice in a dose-dependent fashion against intracerebral challenge with virulent B. pertussis. These results clearly show that these genetically inactivated PT molecules are nontoxic but still immunogenic and justify their development as a component of a new, safer acellular vaccine against whooping cough. Images PMID:2323818

  16. Proliferative responses and gamma interferon and tumor necrosis factor production by lymphocytes isolated from tracheobroncheal lymph nodes and spleen of mice aerosol infected with Bordetella pertussis.

    PubMed Central

    Petersen, J W; Ibsen, P H; Hasløv, K; Heron, I

    1992-01-01

    A group of mice was aerosol infected with live, virulent Bordetella pertussis bacteria. During a period of 7 weeks following the infection, with intervals of 1 week, lymphocytes were isolated from the tracheobroncheal lymph nodes (TBL) and the spleens (SPL) of the infected mice. The in vitro proliferative responses as well as the gamma interferon and tumor necrosis factor production levels of the isolated lymphocytes in response to stimulation with whole killed B. pertussis bacteria were measured as parameters for cell-mediated immunity (CMI). The course of the infection was monitored by counting of CFU in the lungs of the mice. Moreover, antibody responses in serum against a range of B. pertussis antigens were assessed. The results showed that a vigorous proliferative response of the TBL and SPL to stimulation with whole killed B. pertussis bacteria was induced by the infection. The proliferative response of the TBL was significantly higher than the response of the SPL. The proliferative responses were maximal 3 to 4 weeks after the infection and were paralleled by in vitro gamma interferon and tumor necrosis factor production upon specific stimulation. The development of the CMI was observed simultaneously with the clearance of the infection from the lungs. Antibody responses became measurable in the sera only after the infection was cleared. A specific CMI against pertussis toxin, the filamentous hemagglutinin, the 69-kDa outer membrane protein, and the agglutinogens 2 and 3, antigens which are under consideration for inclusion in future acellular pertussis vaccines, was successfully demonstrated in mice 3 weeks after the infection. PMID:1398968

  17. Increase of pertussis incidence in 2010 to 2012 after 12 years of low circulation in Spain.

    PubMed

    Sizaire, V; Garrido-Estepa, M; Masa-Calles, J; Martinez de Aragon, M V

    2014-01-01

    In Spain, whole cell pertussis vaccination started in 1975, with three doses before the age of 6-7 months. Doses at 15-18 months and 4-6 years were introduced in 1996 and 2001, respectively. Spain switched to an acellular vaccine in 2005. From 1998 to 2009, pertussis incidence rates remained ≤1.5 cases/100,000 inhabitants but increased from 2010 to 7.5 cases/100,000 in 2012. Data from 1998 to 2012 were analysed to assess disease trends and susceptible populations. We defined four epidemic periods: 1998-2001 (reference), 2002-05, 2006-09 and 2010-12. In 2002-05, the incidence rate increased in individuals aged 15-49 years (IRR: 1.41 (95% CI: 1.11-1.78)) and ≥50 years (IRR: 2.78 (95% CI: 1.78-4.33)) and in 2006-09 increased also in infants aged <3 months (IRR: 1.83 (95% CI: 1.60-2.09)). In 2010-12, the incidence rate increased notably in all age groups, with IRRs ranging between 2.5 (95% CI: 2.3-2.8) in 5-9 year-olds and 36.0 (95% CI: 19.4-66.8) in 20-29 year-olds. These results, consistent with the country's vaccination history, suggest a progressive accumulation of susceptible individuals due to waning immunity after years of low incidence. Further vaccination strategies should be assessed and implemented to prevent pertussis in pre-vaccinated infants, in whom the disease is more severe. PMID:25139074

  18. Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine.

    PubMed

    Kraan, Heleen; Ten Have, Rimko; van der Maas, Larissa; Kersten, Gideon; Amorij, Jean-Pierre

    2016-08-31

    A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick injuries, and (iii) ensure better protection against pertussis as compared to vaccines containing acellular pertussis antigens. An approach to obtain a hexavalent vaccine might be reconstituting lyophilized polio vaccine (IPV-LYO) with liquid pentavalent vaccine just before intramuscular delivery. The potential limitations of this approach were investigated including thermostability of IPV as measured by D-antigen ELISA and rat potency, the compatibility of fluid and lyophilized IPV in combination with thimerosal and thimerosal containing hexavalent vaccine. The rat potency of polio type 3 in IPV-LYO was 2 to 3-fold lower than standardized on the D-antigen content, suggesting an alteration of the polio type 3 D-antigen particle by lyophilization. Type 1 and 2 had unaffected antigenicity/immunogenicity ratios. Alteration of type 3 D-antigen could be detected by showing reduced thermostability at 45°C compared to type 3 in non-lyophilized liquid controls. Reconstituting IPV-LYO in the presence of thimerosal (TM) resulted in a fast temperature dependent loss of polio type 1-3 D-antigen. The presence of 0.005% TM reduced the D-antigen content by ∼20% (polio type 2/3) and ∼60% (polio type 1) in 6h at 25°C, which are WHO open vial policy conditions. At 37°C, D-antigen was diminished even faster, suggesting that very fast, i.e., immediately after preparation, intramuscular delivery of the conceived hexavalent vaccine would not be a feasible option. Use of the TM-scavenger, l-cysteine, to bind TM (or mercury containing TM degradation products), resulted in a hexavalent vaccine mixture in which polio D-antigen was more stable. PMID:27470209

  19. Pertussis vaccination during pregnancy in Belgium: Follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age.

    PubMed

    Maertens, Kirsten; Caboré, Raïssa Nadège; Huygen, Kris; Vermeiren, Sandra; Hens, Niel; Van Damme, Pierre; Leuridan, Elke

    2016-06-30

    Vaccination of pregnant women with a pertussis containing vaccine is a recommended strategy in some industrialized countries, to protect young infants from severe disease. One of the effects of the presence of high titers of passively acquired maternal antibodies in young infants is blunting of immune responses to infant vaccination. We present infant immune responses to a fourth pertussis containing vaccine dose at 15 months of age, as a follow-up of previously presented data. In a prospective cohort study, women were either vaccinated with an acellular pertussis vaccine (Boostrix(®)) during pregnancy (vaccine group) or received no vaccine (control group). All infants were vaccinated with Infanrix Hexa(®) according to the standard Belgian vaccination schedule (8/12/16 weeks, 15 months). We report results from blood samples collected before and 1 month after the fourth vaccine dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT) and diphtheria toxoid (DT) were measured using commercially available ELISA tests. Antibody levels were expressed in International Units per milliliter. Demographic characteristics were similar in the vaccine and control group. Before the fourth vaccine dose, significantly lower antibody titers were measured in the vaccine group compared to the control group for anti-Prn IgG (p=0.003) and anti-DT IgG (p=0.023), with a steep decay of antibody titers since post-primary vaccination. One month after the fourth dose, antibody titers were only significantly lower in the vaccine group for anti-PT IgG (p=0.006). For all antigens, there was a rise in antibody titer after the fourth vaccine dose. The present results indicate still a minor blunting effect 1 month after a fourth vaccine dose for anti-PT antibodies. However, a good humoral immune response on all measured antigens was elicited in both groups of children. The clinical significance of such blunting

  20. Report of the Task Force on Pertussis and Pertussis Immunization--1988.

    ERIC Educational Resources Information Center

    American Academy of Pediatrics, Elk Grove Village, IL.

    Pertussis is a severe epidemic and endemic disease with significant morbidity and mortality. The use of whole-cell pertussis vaccines in the United States has been effective in controlling the disease but not in decreasing the circulation of the organism. Whole-cell vaccines commonly cause reactions in children, and in addition, they are often…

  1. Pertussis

    MedlinePlus

    ... develop about a week after exposure to the bacteria. Severe episodes of coughing start about 10 to 12 days later. In infants and young children, the coughing sometimes ends with a "whoop" noise. The sound is produced when the person tries to take ...

  2. Pertussis

    MedlinePlus

    ... weeks. Symptoms Initial symptoms are similar to the common cold . In most cases, they develop about a week ... 7, 2015. Read More Breathing - slowed or stopped Common cold Otitis Pneumonia - adults (community acquired) Seizures Update Date ...

  3. A Phase I Clinical Study of a Live Attenuated Bordetella pertussis Vaccine - BPZE1; A Single Centre, Double-Blind, Placebo-Controlled, Dose-Escalating Study of BPZE1 Given Intranasally to Healthy Adult Male Volunteers

    PubMed Central

    Thorstensson, Rigmor; Trollfors, Birger; Al-Tawil, Nabil; Jahnmatz, Maja; Bergström, Jakob; Ljungman, Margaretha; Törner, Anna; Wehlin, Lena; Van Broekhoven, Annie; Bosman, Fons; Debrie, Anne-Sophie; Mielcarek, Nathalie; Locht, Camille

    2014-01-01

    Background Acellular pertussis vaccines do not control pertussis. A new approach to offer protection to infants is necessary. BPZE1, a genetically modified Bordetella pertussis strain, was developed as a live attenuated nasal pertussis vaccine by genetically eliminating or detoxifying 3 toxins. Methods We performed a double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally for the first time to human volunteers, the first trial of a live attenuated bacterial vaccine specifically designed for the respiratory tract. 12 subjects per dose group received 103, 105 or 107 colony-forming units as droplets with half of the dose in each nostril. 12 controls received the diluent. Local and systemic safety and immune responses were assessed during 6 months, and nasopharyngeal colonization with BPZE1 was determined with repeated cultures during the first 4 weeks after vaccination. Results Colonization was seen in one subject in the low dose, one in the medium dose and five in the high dose group. Significant increases in immune responses against pertussis antigens were seen in all colonized subjects. There was one serious adverse event not related to the vaccine. Other adverse events were trivial and occurred with similar frequency in the placebo and vaccine groups. Conclusions BPZE1 is safe in healthy adults and able to transiently colonize the nasopharynx. It induces immune responses in all colonized individuals. BPZE1 can thus undergo further clinical development, including dose optimization and trials in younger age groups. Trial Registration ClinicalTrials.gov NCT01188512 PMID:24421886

  4. Acellular organ scaffolds for tumor tissue engineering

    NASA Astrophysics Data System (ADS)

    Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

    2015-12-01

    Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

  5. Are You 11-19 Years Old? Then You Need to Be Vaccinated against These Serious Diseases!

    MedlinePlus

    ... is usually given in childhood. Tetanus, diphtheria, and whooping cough (pertussis; Tdap) All preteens and teens (and adults!) ... vaccine that protects you from tetanus, diphtheria, and whooping cough (pertussis). After getting a dose of Tdap, you ...

  6. Bordetella pertussis Isolates from Argentinean Whooping Cough Patients Display Enhanced Biofilm Formation Capacity Compared to Tohama I Reference Strain.

    PubMed

    Arnal, Laura; Grunert, Tom; Cattelan, Natalia; de Gouw, Daan; Villalba, María I; Serra, Diego O; Mooi, Frits R; Ehling-Schulz, Monika; Yantorno, Osvaldo M

    2015-01-01

    Pertussis is a highly contagious disease mainly caused by Bordetella pertussis. Despite the massive use of vaccines, since the 1950s the disease has become re-emergent in 2000 with a shift in incidence from infants to adolescents and adults. Clearly, the efficacy of current cellular or acellular vaccines, formulated from bacteria grown in stirred bioreactors is limited, presenting a challenge for future vaccine development. For gaining insights into the role of B. pertussis biofilm development for host colonization and persistence within the host, we examined the biofilm forming capacity of eight argentinean clinical isolates recovered from 2001 to 2007. All clinical isolates showed an enhanced potential for biofilm formation compared to the reference strain Tohama I. We further selected the clinical isolate B. pertussis 2723, exhibiting the highest biofilm biomass production, for quantitative proteomic profiling by means of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry, which was accompanied by targeted transcriptional analysis. Results revealed an elevated expression of several virulence factors, including adhesins involved in biofilm development. In addition, we observed a higher expression of energy metabolism enzymes in the clinical isolate compared to the Tohama I strain. Furthermore, all clinical isolates carried a polymorphism in the bvgS gene. This mutation was associated to an increased sensitivity to modulation and a faster rate of adhesion to abiotic surfaces. Thus, the phenotypic biofilm characteristics shown by the clinical isolates might represent an important, hitherto underestimated, adaptive strategy for host colonization and long time persistence within the host. PMID:26696973

  7. Bordetella pertussis Isolates from Argentinean Whooping Cough Patients Display Enhanced Biofilm Formation Capacity Compared to Tohama I Reference Strain

    PubMed Central

    Arnal, Laura; Grunert, Tom; Cattelan, Natalia; de Gouw, Daan; Villalba, María I.; Serra, Diego O.; Mooi, Frits R.; Ehling-Schulz, Monika; Yantorno, Osvaldo M.

    2015-01-01

    Pertussis is a highly contagious disease mainly caused by Bordetella pertussis. Despite the massive use of vaccines, since the 1950s the disease has become re-emergent in 2000 with a shift in incidence from infants to adolescents and adults. Clearly, the efficacy of current cellular or acellular vaccines, formulated from bacteria grown in stirred bioreactors is limited, presenting a challenge for future vaccine development. For gaining insights into the role of B. pertussis biofilm development for host colonization and persistence within the host, we examined the biofilm forming capacity of eight argentinean clinical isolates recovered from 2001 to 2007. All clinical isolates showed an enhanced potential for biofilm formation compared to the reference strain Tohama I. We further selected the clinical isolate B. pertussis 2723, exhibiting the highest biofilm biomass production, for quantitative proteomic profiling by means of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry, which was accompanied by targeted transcriptional analysis. Results revealed an elevated expression of several virulence factors, including adhesins involved in biofilm development. In addition, we observed a higher expression of energy metabolism enzymes in the clinical isolate compared to the Tohama I strain. Furthermore, all clinical isolates carried a polymorphism in the bvgS gene. This mutation was associated to an increased sensitivity to modulation and a faster rate of adhesion to abiotic surfaces. Thus, the phenotypic biofilm characteristics shown by the clinical isolates might represent an important, hitherto underestimated, adaptive strategy for host colonization and long time persistence within the host. PMID:26696973

  8. Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP)

    MedlinePlus

    ... Things to Know About Zika & Pregnancy Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP) KidsHealth > For Parents > ... pertussis, and could pass it to vulnerable infants. Immunization Schedule DTaP immunizations are given as a series ...

  9. Pertussis toxins, other antigens become likely targets for genetic engineering

    SciTech Connect

    Marwick, C.

    1990-11-14

    Genetically engineered pertussis vaccines have yet to be fully tested clinically. But early human, animal, and in vitro studies indicate effectiveness in reducing toxic effects due to Bordetella pertussis. The licensed pertussis vaccines consists of inactivated whole cells of the organism. Although highly effective, they have been associated with neurologic complications. While the evidence continues to mount that these complications are extremely rare, if they occur at all, it has affected the public's acceptance of pertussis immunization.

  10. A cocooning project to protect newborns from pertussis.

    PubMed

    Rust, Christina

    2014-01-01

    The Pertussis Cocooning Project was created through a collaborative effort by a health care organization and a State Department for Public Health to decrease community pertussis rates and protect infants from the deadly effects of pertussis. Free pertussis immunizations are provided to all mothers who give birth at the health care organization and to all infants' family members and caregivers older than 18 years. PMID:24939197

  11. [Bordetella pertussis agglutinogens in cultivation dynamics].

    PubMed

    Basnak'ian, I A; Aleksakhina, N N; Shelemekh, O V; Miriasova, L V; Siundiukova, R A

    2007-01-01

    Bordetella pertussis growth phases during homogenous batch dynamic cultivation in the liquid medium as well as during the static cultivation on the solid medium were established. The maximal activity of agglutination reaction with antisera to B. pertussis agglutinogens 1, 2, and 3 was detected in bacterial culture at the end of exponential phase of growth. The activity of agglutination reaction decreased when cultures in stationary and death phases were used. During transition from exponential to death phase level of antibodies to agglutinogen 2 decreased by4 - 32 times. 2 - 4-fold decrease of antibodies level was observed when antiserum to agglutinogen 3 was used. Activity of agglutination reaction with antiserum to agglutinogen 1 was high and did not depend from phase of growth. When polyvalent antiserum to B. pertussis was used 4-fold decrease of antibody titers was observed in parallel with change of growth phases. Sera from rabbits immunized with B. pertussis cultures from the middle of exponential growth phase, the end of this phase, and begin of the death phase had high (maximal) level of agglutinating antibodies (6400), which was detected on 101 day after immunization with the former culture and on 31 day after immunization with either of the two latter cultures. To the end of experiment (292 day) titers decreased to 800, 3200, and 1600 respectively. These findings confirm an advisability of use of exponential growth culture for immunization of rabbits in order to obtain highly active diagnostic antisera to B. pertussis. PMID:17672129

  12. Infection of Newborn Piglets with Bordetella pertussis: a New Model for Pertussis

    PubMed Central

    Elahi, S.; Brownlie, R.; Korzeniowski, J.; Buchanan, R.; O'Connor, B.; Peppler, M. S.; Halperin, S. A.; Lee, S. F.; Babiuk, L. A.; Gerdts, V.

    2005-01-01

    Bordetella pertussis is the causative agent of pertussis or whooping cough. This bacterium is a human pathogen that under experimental conditions also infects selected rodents and primates. Here, we show for the first time that newborn piglets can be infected with B. pertussis when it is delivered intrapulmonarily. Infected piglets displayed fever and respiratory symptoms, such as nasal discharge, nonparoxysmal coughing, and breathing difficulties. Eventually, all infected animals developed severe bronchopneumonia, which in some cases was combined with a fibrinous pleuritits. Immunohistochemical staining revealed the presence of large numbers of B. pertussis cells within airways, adhering to the epithelial lining or phagocytosed by macrophages and neutrophils. Viable bacteria were reisolated from bronchoalveolar lavages and lung lesions for more than 10 days postinfection. The systemic presence of pertussis toxin was shown by hypoglycemia, lymphocytosis, and induction of a clustered pattern of CHO cells by serum and bronchoalveolar lavage samples. Thus, a large-animal model for pertussis was developed, which should complement existing rodent models for identifying the immune responses relevant to the design of new vaccines. In particular, this model should help researchers analyze the roles of both maternal and mucosal immunity in disease protection against pertussis and should ultimately assist in the design of new vaccines for early life protection. PMID:15908393

  13. Modulation of Bordetella pertussis by nicotinic acid.

    PubMed

    McPheat, W L; Wardlaw, A C; Novotny, P

    1983-08-01

    Growth of Bordetella pertussis in a high concentration of nicotinic acid (NA) had a modulating effect on several properties and activities of the bacteria. Compared with normally grown cells, those grown in a high concentration of NA had reduced capacity for taking up both NA and nicotinamide (ND); they had reduced adenylate cyclase activity and showed loss of agglutinogen factors 2 and 3, but an increase in factor 1. By contrast, cells grown in a high concentration of ND showed only a slightly decreased capacity for uptake of ND and none of the other changes. Modulation of B. pertussis by NA varied with the strain and culture conditions and appeared to be distinct from the antigenic modulation induced by high Mg2+ in the culture medium. Evidence is presented for the association of a small proportion of the extracytoplasmic adenylate cyclase with the outer membrane of B. pertussis. PMID:6307872

  14. Modulation of Bordetella pertussis by nicotinic acid.

    PubMed Central

    McPheat, W L; Wardlaw, A C; Novotny, P

    1983-01-01

    Growth of Bordetella pertussis in a high concentration of nicotinic acid (NA) had a modulating effect on several properties and activities of the bacteria. Compared with normally grown cells, those grown in a high concentration of NA had reduced capacity for taking up both NA and nicotinamide (ND); they had reduced adenylate cyclase activity and showed loss of agglutinogen factors 2 and 3, but an increase in factor 1. By contrast, cells grown in a high concentration of ND showed only a slightly decreased capacity for uptake of ND and none of the other changes. Modulation of B. pertussis by NA varied with the strain and culture conditions and appeared to be distinct from the antigenic modulation induced by high Mg2+ in the culture medium. Evidence is presented for the association of a small proportion of the extracytoplasmic adenylate cyclase with the outer membrane of B. pertussis. PMID:6307872

  15. Acellular Biomaterials: An Evolving Alternative to Cell-Based Therapies

    PubMed Central

    Burdick, Jason A.; Mauck, Robert L.; Gorman, Joseph H.; Gorman, Robert C.

    2014-01-01

    Acellular biomaterials can stimulate the local environment to repair tissues without the regulatory and scientific challenges of cell-based therapies. A greater understanding of the mechanisms of such endogenous tissue repair is furthering the design and application of these biomaterials. We discuss recent progress in acellular materials for tissue repair, using cartilage and cardiac tissues as examples of applications with substantial intrinsic hurdles, but where human translation is now occurring. PMID:23486777

  16. Reducing the endotoxic activity of pertussis vaccine.

    PubMed Central

    Bannatyne, R. M.; Cheung, R.

    1981-01-01

    Unadsorbed, regular production pertussis vaccine was treated with polymyxin B sulphate at concentrations of 25, 50 and 100 microgram/ml. The toxic activity of treated and untreated vaccines was compared using both the limulus amoebocyte lysate test and the mouse-weight-gain test. Protective efficacy was also assessed by the mouse protection test. No discernible effect on either toxicity or efficacy of the pertussis vaccine was observed. When the vaccine was treated with 5000 microgram/ml of polymyxin, endotoxic activity assessed by the limulus lysate test appeared to be abolished. PMID:7310121

  17. Crystallization of pertussigen from Bordetella pertussis.

    PubMed Central

    Arai, H; Munoz, J J

    1981-01-01

    A method is described for crystallizing pertussigen from Bordetella pertussis. The crystalline material induced histamine hypersensitivity in mice at a dose of 0.5 ng of protein and leukocytosis at a dose of 100 ng and was toxic at a dose of 429 microgram. The histamine-sensitizing activity and the toxicity were as high as ever reported. Images PMID:6260667

  18. Antibody titers and immune response to diphtheria-tetanus-pertussis and measles-mumps-rubella vaccination in children treated for acute lymphoblastic leukemia.

    PubMed

    Ercan, Tugba Erener; Soycan, Lebriz Yüksel; Apak, Hilmi; Celkan, Tiraje; Ozkan, Alp; Akdenizli, Emine; Kasapçopur, Ozgur; Yildiz, Inci

    2005-05-01

    The objective of this study was to investigate the diphtheria-tetanus-pertussis and/or measles-mumps antibody titers before and after vaccination at various time points of acute lymphoblastic leukemia (ALL) therapy and to suggest an appropriate vaccination approach for ALL patients. The authors studied 37 ALL patients and 14 healthy control subjects, divided into three groups. In group 1 (newly diagnosed patients), baseline anti-diphtheria, anti-tetanus, and anti-pertussis titers were determined. Patients in group 2 (on maintenance chemotherapy) and group 3 (patients not receiving therapy for 3-6 months) were vaccinated with diphtheria-tetanus with or without acellular pertussis; group 3 and control subjects were also given measles-mumps-rubella vaccine. Preimmunization and 1-month postimmunization titers were drawn. Preimmunization anti-diphtheria and anti-tetanus antibody titers between the groups and the controls were statistically similar. The seropositivity rate for anti-measles antibody in group 3 was significantly lower than controls. After vaccination, all of the patients developed protective anti-diphtheria and anti-tetanus antibody titers. The seroconversion rates of group 3 and controls for anti-measles and anti-mumps antibodies were statistically similar. The results showed that patients on maintenance therapy and after cessation of therapy made good antibody responses to diphtheria and tetanus toxoids, but response to measles and mumps vaccines was not as sufficient as toxoid vaccines. Children with ALL can receive the appropriate vaccines during and after maintenance treatment. PMID:15891564

  19. Bordetella pertussis: new concepts in pathogenesis and treatment

    PubMed Central

    Carbonetti, Nicholas H.

    2016-01-01

    Purpose of review The purpose of this review is to summarize and discuss recent findings and selected topics of interest in Bordetella pertussis virulence and pathogenesis and treatment of pertussis. It is not intended to cover issues on immune responses to B. pertussis infection or problems with currently used pertussis vaccines. Recent findings Studies on the activities of various B. pertussis virulence factors include the immunomodulatory activities of filamentous hemagglutinin, fimbriae, and adenylate cyclase toxin. Recently emerging B. pertussis strains show evidence of genetic selection for vaccine escape mutants, with changes in vaccine antigen-expressing genes, some of which may have increased the virulence of this pathogen. Severe and fatal pertussis in young infants continues to be a problem, with several studies highlighting predictors of fatality, including the extreme leukocytosis associated with this infection. Treatments for pertussis are extremely limited, though early antibiotic intervention may be beneficial. Neutralizing pertussis toxin activity may be an effective strategy, as well as targeting two host proteins, pendrin and sphingosine-1-phosphate receptors, as novel potential therapeutic interventions. Summary Pertussis is reemerging as a major public health problem and continued basic research is revealing information on bacterial virulence and disease pathogenesis, as well as potential novel strategies for vaccination and targets for therapeutic intervention. PMID:26906206

  20. Acellular Dermal Matrix in Rotator Cuff Surgery.

    PubMed

    Cooper, Joseph; Mirzayan, Raffy

    2016-01-01

    The success of rotator cuff repair (RCR) surgery can be measured clinically (validated outcome scores, range of motion) as well as structurally (re-tear rates using imaging studies). Regardless of repair type or technique, most studies have shown that patients do well clinically. However, multiple studies have also shown that structurally, the failure rate can be very high. A variety of factors, including poor tendon quality, age over 63 years, smoking, advanced fatty infiltration into the muscle, and the inability of the tendon to heal to bone, have been implicated as the cause of the high re-tear rate in RCRs. The suture-tendon interface is felt to be the weakest link in the RCR construct, and suture pullout through the tendon is believed to be the most common method of failure. This review of the published literature seeks to determine if there is support for augmentation of RCR with acellular dermal matrices to strengthen the suture-tendon interface and reduce the re-tear rate. PMID:27552454

  1. Antigenic Analysis of Bordetella pertussis Filamentous Hemagglutinin with Phage Display Libraries and Rabbit Anti-Filamentous Hemagglutinin Polyclonal Antibodies

    PubMed Central

    Wilson, Dan R.; Siebers, Annette; Finlay, B. Brett

    1998-01-01

    Although substantial advancements have been made in the development of efficacious acellular vaccines against Bordetella pertussis, continued progress requires better understanding of the antigenic makeup of B. pertussis virulence factors, including filamentous hemagglutinin (FHA). To identify antigenic regions of FHA, phage display libraries constructed by using random fragments of the 10-kbp EcoRI fragment of B. pertussis fhaB were affinity selected with rabbit anti-FHA polyclonal antibodies. Characterization of antibody-reactive clones displaying FHA-derived peptides identified 14 antigenic regions, each containing one or more epitopes. A number of clones mapped within regions containing known or putative FHA adhesin domains and may be relevant for the generation of protective antibodies. The immunogenic potential of the phage-displayed peptides was assessed indirectly by comparing their recognition by antibodies elicited by sodium dodecyl sulfate (SDS)-denatured and native FHA and by measuring the inhibition of this recognition by purified FHA. FHA residues 1929 to 2019 may contain the most dominant linear epitope of FHA. Clones mapping to this region accounted for ca. 20% of clones recovered from the initial library selection and screening procedures. They are strongly recognized by sera against both SDS-denatured and native FHA, and this recognition is readily inhibited by purified FHA. Given also that this region includes a factor X homolog (J. Sandros and E. Tuomanen, Trends Microbiol. 1:192–196, 1993) and that the single FHA epitope (residues 2001 to 2015) was unequivocally defined in a comparable study by E. Leininger et al. (J. Infect. Dis. 175:1423–1431, 1997), peptides derived from residues of 1929 to 2019 of FHA are strong candidates for future protection studies. PMID:9746593

  2. A change in vaccine efficacy and duration of protection explains recent rises in pertussis incidence in the United States.

    PubMed

    Gambhir, Manoj; Clark, Thomas A; Cauchemez, Simon; Tartof, Sara Y; Swerdlow, David L; Ferguson, Neil M

    2015-04-01

    Over the past ten years the incidence of pertussis in the United States (U.S.) has risen steadily, with 2012 seeing the highest case number since 1955. There has also been a shift over the same time period in the age group reporting the largest number of cases (aside from infants), from adolescents to 7-11 year olds. We use epidemiological modelling and a large case incidence dataset to explain the upsurge. We investigate several hypotheses for the upsurge in pertussis cases by fitting a suite of dynamic epidemiological models to incidence data from the National Notifiable Disease Surveillance System (NNDSS) between 1990-2009, as well as incidence data from a variety of sources from 1950-1989. We find that: the best-fitting model is one in which vaccine efficacy and duration of protection of the acellular pertussis (aP) vaccine is lower than that of the whole-cell (wP) vaccine, (efficacy of the first three doses 80% [95% CI: 78%, 82%] versus 90% [95% CI: 87%, 94%]), increasing the rate at which disease is reported to NNDSS is not sufficient to explain the upsurge and 3) 2010-2012 disease incidence is predicted well. In this study, we use all available U.S. surveillance data to: 1) fit a set of mathematical models and determine which best explains these data and 2) determine the epidemiological and vaccine-related parameter values of this model. We find evidence of a difference in efficacy and duration of protection between the two vaccine types, wP and aP (aP efficacy and duration lower than wP). Future refinement of the model presented here will allow for an exploration of alternative vaccination strategies such as different age-spacings, further booster doses, and cocooning. PMID:25906150

  3. Novel molecular biology approaches to acellular vaccines.

    PubMed

    Rappuoli, R; Pizza, M

    1996-01-01

    Bacterial toxins are commonly detoxified by chemical treatment in order to use them in human vaccines. We have used site-directed mutagenesis of toxin genes to obtain bacteria that produce naturally nontoxic mutants of bacterial toxins, such as pertussis toxin (PT), cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT). Genetically detoxified PT showed a superior safety and immunogenicity in animal models, phase I and phase II clinical trials, and a superior protective efficacy in the early and late stage of a phase III efficacy trial, proving in a definitive and extensive way that genetic detoxification of bacterial toxins can, and should, replace chemical treatment. The results obtained with genetically inactivated LT and CT indicate that genetic detoxification of bacterial toxins can be used not only to produce vaccines for systemic immunization that are superior to the ones produced by conventional technologies, but suggest that these type of molecules may be the prototype molecules for the design and construction of innovative vaccines with a totally new design, such as mucosally delivered preventive and therapeutic vaccines. PMID:9704103

  4. Genetic Variation of Bordetella pertussis in Austria.

    PubMed

    Wagner, Birgit; Melzer, Helen; Freymüller, Georg; Stumvoll, Sabine; Rendi-Wagner, Pamela; Paulke-Korinek, Maria; Repa, Andreas; Mooi, Frits R; Kollaritsch, Herwig; Mittermayer, Helmut; Kessler, Harald H; Stanek, Gerold; Steinborn, Ralf; Duchêne, Michael; Wiedermann, Ursula

    2015-01-01

    In Austria, vaccination coverage against Bordetella pertussis infections during infancy is estimated at around 90%. Within the last years, however, the number of pertussis cases has increased steadily, not only in children but also in adolescents and adults, indicating both insufficient herd immunity and vaccine coverage. Waning immunity in the host and/or adaptation of the bacterium to the immunised hosts could contribute to the observed re-emergence of pertussis. In this study we therefore addressed the genetic variability in B. pertussis strains from several Austrian cities. Between the years 2002 and 2008, 110 samples were collected from Vienna (n = 32), Linz (n = 63) and Graz (n = 15) by nasopharyngeal swabs. DNA was extracted from the swabs, and bacterial sequence polymorphisms were examined by MLVA (multiple-locus variable number of tandem repeat analysis) (n = 77), by PCR amplification and conventional Sanger sequencing of the polymorphic regions of the prn (pertactin) gene (n = 110), and by amplification refractory mutation system quantitative PCR (ARMS-qPCR) (n = 110) to directly address polymorphisms in the genes encoding two pertussis toxin subunits (ptxA and ptxB), a fimbrial adhesin (fimD), tracheal colonisation factor (tcfA), and the virulence sensor protein (bvgS). Finally, the ptxP promoter region was screened by ARMS-qPCR for the presence of the ptxP3 allele, which has been associated with elevated production of pertussis toxin. The MLVA analysis revealed the highest level of polymorphisms with an absence of MLVA Type 29, which is found outside Austria. Only Prn subtypes Prn1/7, Prn2 and Prn3 were found with a predominance of the non-vaccine type Prn2. The analysis of the ptxA, ptxB, fimD, tcfA and bvgS polymorphisms showed a genotype mixed between the vaccine strain Tohama I and a clinical isolate from 2006 (L517). The major part of the samples (93%) displayed the ptxP3 allele. The consequences for the vaccination strategy are discussed. PMID

  5. Clinical characteristics and outcomes of neonatal pertussis: a comparative study.

    PubMed

    Castagnini, Luis A; Munoz, Flor M

    2010-03-01

    We describe the features and outcomes of neonatal pertussis and compare these with neonates with non-pertussis acute respiratory illness from July 2000 through December 2007. Patients with pertussis had a more severe course of disease as evidenced by the clinical presentation, length of hospitalization, and oxygen requirement. Clinicians should have a high index of suspicion so that appropriate supportive care can be initiated promptly. PMID:20056236

  6. Challenges to acellular biological scaffold mediated skeletal muscle tissue regeneration.

    PubMed

    Corona, Benjamin T; Greising, Sarah M

    2016-10-01

    Volumetric muscle loss (VML) injuries present a complex and heterogeneous clinical problem that results in a chronic loss of muscle tissue and strength. The primary limitation to muscle tissue regeneration after VML injury is the frank loss of all native muscle constituents in the defect, especially satellite cells and the basal lamina. Recent advancements in regenerative medicine have set forth encouraging and emerging translational and therapeutic options for these devastating injuries including the surgical implantation of acellular biological scaffolds. While these biomaterials can modulate the wound environment, the existing data do not support their capacity to promote appreciable muscle fiber regeneration that can contribute to skeletal muscle tissue functional improvements. An apparent restriction of endogenous satellite cell (i.e., pax7(+)) migration to acellular biological scaffolds likely underlies this deficiency. This work critically evaluates the role of an acellular biological scaffold in orchestrating skeletal muscle tissue regeneration, specifically when used as a regenerative medicine approach for VML injury. PMID:27472161

  7. Clinical Definitions of Pertussis: Summary of a Global Pertussis Initiative Roundtable Meeting, February 2011

    PubMed Central

    Cherry, James D.; Tan, Tina; Wirsing von König, Carl-Heinz; Forsyth, Kevin D.; Thisyakorn, Usa; Greenberg, David; Johnson, David; Marchant, Colin; Plotkin, Stanley

    2012-01-01

    Existing clinical case definitions of pertussis are decades old and based largely on clinical presentation in infants and children, yet an increasing burden is borne by adolescents and adults who may manifest distinct signs/symptoms. Therefore, a “one-size-fits-all” clinical case definition is no longer appropriate. Seeking to improve pertussis diagnosis, the Global Pertussis Initiative (GPI) developed an algorithm that delineates the signs/symptoms of pertussis most common to 3 age groups: 0–3 months, 4 months to 9 years, and ≥10 years. These case definitions are based on clinical presentation alone, but do include recommendations on laboratory diagnostics. Until pertussis can be accurately diagnosed, its burden will remain underestimated, making the introduction of epidemiologically appropriate preventive strategies difficult. The proposed definitions are intended to be widely applicable and to encourage the expanded use of laboratory diagnostics. Determination of their utility and their sensitivity and/or specificity versus existing case definitions is required. PMID:22431797

  8. [Is it time to vaccine pregnant woman against pertussis?].

    PubMed

    Cofré, José

    2016-02-01

    Pertussis may cause death in neonates and very young infants. In these ages pertussis vaccine has not been administered yet or infants haven't received enough doses of vaccine to protect them. Cocoon strategy have been implemented in several countries and has limited efficacy because of low coverage among households. In vaccinated pregnant women transplacental transfer of pertussis antibodies starts at 32-34 weeks of pregnancy. United Kingdom, The United States of America and afterward other countries in Europe and America have adopted this strategy. Recent British research about security and effectiveness of pertussis vaccination in pregnant women to reduce pertussis incidence and fatality cases in neonate and very young infants infant support this strategy despite the fact that controlled studies about the efficacy and security in mothers and neonates have not been published. Several studies still not published or in progress are trying to answer these two questions and to evaluate possible interference between transplacentaly transferred pertussis antibodies and infants immune response to routine vaccines. Recently WHO has recommended pertussis vaccination during pregnancy in countries where neonatal pertussis is a public health problem. Nowadays, Chilean experts discuss if pertussis vaccination of pregnant women must be adopted in our country. PMID:26965878

  9. Critical Pertussis in a Young Infant Requiring Mechanical Ventilation

    PubMed Central

    Nataprawira, Heda Melinda; Somasetia, Dadang Hudaya; Sudarwati, Sri; Kadir, Minerva; Sekarwana, Nanan

    2013-01-01

    Pertussis may likely be misdiagnosed in its initial or catarrhal phase as a common respiratory infection. The earlier diagnosis of pertussis really depends on the capability of the medical professional especially in the first line public health services. The lack of awareness in diagnosis of severe pertussis as one of the causes of severe respiratory problems may likely misdiagnose pertussis as respiratory failure or even septic shock. In fact, pertussis may manifest as a critical pertussis which can be fatal due to the respiratory failure that require pediatric intensive care unit using mechanical ventilation. We reported a confirmed pertussis case of a 7-weeks-old female infant referred to our tertiary hospital with gasping leading to respiratory failure and septic shock requiring mechanical ventilation, aggressive fluid therapy, and antibiotics. Pertussis was diagnosed late during the course of illness when the patient was hospitalized. Improvement was noted after administering macrolide which gave a good response. Bordetella pertussis isolation from Bordet-Gengou media culture yielded positive result. PMID:23738154

  10. The resurgence of mumps and pertussis.

    PubMed

    Sabbe, Martine; Vandermeulen, Corinne

    2016-04-01

    Vaccines and extended vaccination programs have had an extensive impact on morbidity and mortality rates due to infectious diseases. Because of the continuous and extensive use of vaccines in industrialized countries, many infectious diseases such as poliomyelitis, diphtheria and measles have been reduced to near-extinction. However, in recent years, many countries including the United States of America, the United Kingdom and Belgium, have been confronted with a resurgence of mumps and pertussis, despite high vaccination coverage for both vaccines. In this commentary, possible causes of this resurgence will be discussed, such as the occurrence of adapted microbes, failure to vaccinate and primary and secondary vaccine failure. Additional research of the immunological mechanisms is clearly needed to support the development of possible new and more immunogenic vaccines against mumps and pertussis. Meanwhile, extensive vaccination campaigns with both vaccines remain necessary. PMID:26751186

  11. The resurgence of mumps and pertussis

    PubMed Central

    Sabbe, Martine; Vandermeulen, Corinne

    2016-01-01

    ABSTRACT Vaccines and extended vaccination programs have had an extensive impact on morbidity and mortality rates due to infectious diseases. Because of the continuous and extensive use of vaccines in industrialized countries, many infectious diseases such as poliomyelitis, diphtheria and measles have been reduced to near-extinction. However, in recent years, many countries including the United States of America, the United Kingdom and Belgium, have been confronted with a resurgence of mumps and pertussis, despite high vaccination coverage for both vaccines. In this commentary, possible causes of this resurgence will be discussed, such as the occurrence of adapted microbes, failure to vaccinate and primary and secondary vaccine failure. Additional research of the immunological mechanisms is clearly needed to support the development of possible new and more immunogenic vaccines against mumps and pertussis. Meanwhile, extensive vaccination campaigns with both vaccines remain necessary. PMID:26751186

  12. Efficacy of Pertussis Vaccines: A Brighter Horizon

    PubMed Central

    Preston, N. W.; Stanbridge, T. N.

    1972-01-01

    A study of pertussis infections in 186 children under 11 years of age in the Manchester region during 1969-71 suggests that recently-manufactured vaccines have been more effective than those made before 1967. The earlier vaccines were effective mainly against the serotypes of Bordetella pertussis possessing antigen 2, while those made from 1967 are more nearly equal in their effectiveness against thedi fferent serotypes. A booster dose of the earlier vaccines did not prevent infection with type 1,3 organisms, but we obtained a positive culture from only one child who had received four doses of recent vaccine. Simultaneous infection of a child with two or more serotypes was frequently seen. The predominant serotype in a patient was usually type 1,3; less often it was type 1,2,3 or type 1,2; it was never type 1. A change of serotype sometimes occurs during the course of the illness and is probably directed by the vaccination status of the patient in relation to the serotype of the initial infection. Our findings emphasize the need for vaccines to contain adequate amounts of all three pertussis agglutinogens, and for satisfactory immunization schedules to be used in their administration. PMID:4341645

  13. Evaluation of outbreak response immunization in the control of pertussis using agent-based modeling

    PubMed Central

    Qian, Weicheng; Osgood, Nathaniel D.

    2016-01-01

    Background Pertussis control remains a challenge due to recently observed effects of waning immunity to acellular vaccine and suboptimal vaccine coverage. Multiple outbreaks have been reported in different ages worldwide. For certain outbreaks, public health authorities can launch an outbreak response immunization (ORI) campaign to control pertussis spread. We investigated effects of an outbreak response immunization targeting young adolescents in averting pertussis cases. Methods We developed an agent-based model for pertussis transmission representing disease mechanism, waning immunity, vaccination schedule and pathogen transmission in a spatially-explicit 500,000-person contact network representing a typical Canadian Public Health district. Parameters were derived from literature and calibration. We used published cumulative incidence and dose-specific vaccine coverage to calibrate the model’s epidemiological curves. We endogenized outbreak response by defining thresholds to trigger simulated immunization campaigns in the 10–14 age group offering 80% coverage. We ran paired simulations with and without outbreak response immunization and included those resulting in a single ORI within a 10-year span. We calculated the number of cases averted attributable to outbreak immunization campaign in all ages, in the 10–14 age group and in infants. The count of cases averted were tested using Mann–Whitney U test to determine statistical significance. Numbers needed to vaccinate during immunization campaign to prevent a single case in respective age groups were derived from the model. We varied adult vaccine coverage, waning immunity parameters, immunization campaign eligibility and tested stronger vaccination boosting effect in sensitivity analyses. Results 189 qualified paired-runs were analyzed. On average, ORI was triggered every 26 years. On a per-run basis, there were an average of 124, 243 and 429 pertussis cases averted across all age groups within 1, 3 and

  14. Clinical presentation of pertussis in fully immunized children in Lithuania

    PubMed Central

    Narkeviciute, Irena; Kavaliunaite, Ema; Bernatoniene, Genovaite; Eidukevicius, Rimantas

    2005-01-01

    Background In Lithuania, the vaccination coverage against pertussis is high. Nevertheless, there is a significant increase in pertussis cases in fully immunized children. The aim of our study was to determine the frequency of classical symptoms of laboratory confirmed pertussis and describe its epidemiology in children fully vaccinated against pertussis. Methods From May to December 2001, 70 children aged 1 month to 15 years, suffering from prolonged cough were investigated in the Centre of Paediatrics, Vilnius University Children's Hospital. The collected information included personal data, vaccination history, clinical symptoms of the current illness, and treatment before hospitalization. At the admission to the hospital blood samples were taken from all studied children for Bordetella pertussis IgM and IgA. Results A total of 53 (75.7%) of the 70 recruited patients with prolonged cough showed laboratory evidence of pertussis. 32 of them were fully vaccinated with whole cell pertussis vaccine (DTP). The age of fully vaccinated patients varied from 4 to 15 years (average 10.9 ± 3.1; median 11). The time period between the last vaccination dose (fourth) and the clinical manifestation of pertussis was 2.6–13 years (average 8.9 ± 3.0; median 9). More than half of the children before the beginning of pertussis were in contact with persons suffering from long lasting cough illness in the family, school or day-care center. The mean duration from onset of pertussis symptoms until hospitalization was 61.4 ± 68.3 days (range, 7 to 270 days; median 30). For 11 patients who had had two episodes (waves) of coughing, the median duration of cough was 90 days, and for 21 with one episode 30 days (p < 0.0002). Most of the children (84.4%) had paroxysmal cough, 31.3% had post-tussive vomiting, 28.1% typical whoop, and 3.1% apnea. Only 15.6% children had atypical symptoms of pertussis. Conclusion Fully vaccinated children fell ill with pertussis at the median of 11 years old

  15. US hospital requirements for pertussis vaccination of healthcare personnel, 2011.

    PubMed

    Miller, Brady L; Ahmed, Faruque; Lindley, Megan C; Wortley, Pascale M

    2011-12-01

    In 2011, institutional requirements for pertussis vaccination of healthcare personnel were reported by nearly one-third of surveyed US hospitals. Requirements often applied to personnel with certain clinical responsibilities, such as those caring for infants. Healthcare personnel who were not on an institution's payroll were rarely subject to pertussis vaccination requirements. PMID:22080660

  16. Development of a rapid diagnostic test for pertussis: direct detection of pertussis toxin in respiratory secretions.

    PubMed Central

    Friedman, R L; Paulaitis, S; McMillan, J W

    1989-01-01

    Monoclonal antibodies (MAb) were produced against the specific Bordetella pertussis antigen pertussis toxin (PT). In preliminary studies, one MAb (IB12) was selected and used in an enzyme-linked dot blot immunoassay to evaluate the ability of the method to detect known amounts of PT in control experiments and to test its potential for direct detection of PT in nasopharyngeal secretion (NP) specimens from patients with confirmed cases of whooping cough. The dot blot assay was able to detect PT at levels as low as 10 ng per dot in either buffer or control NP specimens. The assay demonstrated specificity, reacting only with dot blots of whole B. pertussis and not Bordetella bronchiseptica, Bordetella parapertussis, or other bacterial strains. In preliminary studies, NP aspirate, swab, and wash specimens were compared. The specimen of choice was found to be the NP aspirate, for which 100% positive results were found in the assay. These initial studies suggest that the dot blot immunoassay in which a MAb is used for direct detection of PT in NP specimens may be useful as a rapid diagnostic test for pertussis. Images PMID:2808670

  17. Detecting Paroxysmal Coughing from Pertussis Cases Using Voice Recognition Technology

    PubMed Central

    Parker, Danny; Picone, Joseph; Harati, Amir; Lu, Shuang; Jenkyns, Marion H.; Polgreen, Philip M.

    2013-01-01

    Background Pertussis is highly contagious; thus, prompt identification of cases is essential to control outbreaks. Clinicians experienced with the disease can easily identify classic cases, where patients have bursts of rapid coughing followed by gasps, and a characteristic whooping sound. However, many clinicians have never seen a case, and thus may miss initial cases during an outbreak. The purpose of this project was to use voice-recognition software to distinguish pertussis coughs from croup and other coughs. Methods We collected a series of recordings representing pertussis, croup and miscellaneous coughing by children. We manually categorized coughs as either pertussis or non-pertussis, and extracted features for each category. We used Mel-frequency cepstral coefficients (MFCC), a sampling rate of 16 KHz, a frame Duration of 25 msec, and a frame rate of 10 msec. The coughs were filtered. Each cough was divided into 3 sections of proportion 3-4-3. The average of the 13 MFCCs for each section was computed and made into a 39-element feature vector used for the classification. We used the following machine learning algorithms: Neural Networks, K-Nearest Neighbor (KNN), and a 200 tree Random Forest (RF). Data were reserved for cross-validation of the KNN and RF. The Neural Network was trained 100 times, and the averaged results are presented. Results After categorization, we had 16 examples of non-pertussis coughs and 31 examples of pertussis coughs. Over 90% of all pertussis coughs were properly classified as pertussis. The error rates were: Type I errors of 7%, 12%, and 25% and Type II errors of 8%, 0%, and 0%, using the Neural Network, Random Forest, and KNN, respectively. Conclusion Our results suggest that we can build a robust classifier to assist clinicians and the public to help identify pertussis cases in children presenting with typical symptoms. PMID:24391730

  18. Pertussis Toxin Exacerbates and Prolongs Airway Inflammatory Responses during Bordetella pertussis Infection

    PubMed Central

    Connelly, Carey E.; Sun, Yezhou

    2012-01-01

    Throughout infection, pathogenic bacteria induce dramatic changes in host transcriptional repertoires. An understanding of how bacterial factors influence host reprogramming will provide insight into disease pathogenesis. In the human respiratory pathogen Bordetella pertussis, the causative agent of whooping cough, pertussis toxin (PT) is a key virulence factor that promotes colonization, suppresses innate immune responses during early infection, and causes systemic disease symptoms. To determine the full extent of PT-associated gene regulation in the airways through the peak of infection, we measured global transcriptional profiles in the lungs of BALB/c mice infected with wild-type (WT) or PT-deficient (ΔPT) B. pertussis. ΔPT bacteria were inoculated at a dose equivalent to the WT dose and at a high dose (ΔPThigh) to distinguish effects caused by higher bacterial loads achieved in WT infection from effects associated with PT. The results demonstrated that PT was associated with a significant upregulation of immune and inflammatory response genes as well as several other genes implicated in airway pathology. In contrast to the early, transient responses observed for ΔPThigh infection, WT infection induced a prolonged expression of inflammatory genes and increased the extent and duration of lung histopathology. In addition, the administration of purified PT to ΔPThigh-infected mice 1 day after bacterial inoculation exacerbated and prolonged inflammatory responses and airway pathology. These data indicate that PT not only is associated with exacerbated host airway responses during peak B. pertussis infection but also may inhibit host mechanisms of attenuating and resolving inflammation in the airways, suggesting possible links between PT and pertussis disease symptoms. PMID:23027529

  19. A comparative study of acellular nerve xenografts and allografts in repairing rat facial nerve defects.

    PubMed

    Huang, Haitao; Xiao, Hongxi; Liu, Huawei; Niu, Yu; Yan, Rongzeng; Hu, Min

    2015-10-01

    Acellular nerves are composed of a basal lamina tube, which retains sufficient bioactivity to promote axon regeneration, thereby repairing peripheral nerve gaps. However, the clinical application of acellular allografts has been restricted due to its limited availability. To investigate whether xenografts, a substitute to allograft acellular nerves in abundant supply, could efficiently promote nerve regeneration, rabbit and rat acellular nerve grafts were used to reconstruct 1 cm defects in Wistar rat facial nerves. Autologous peroneal nerve grafts served as a positive control group. A total of 12 weeks following the surgical procedure, the axon number, myelinated axon number, myelin sheath thickness, and nerve conduction velocity of the rabbit and rat‑derived acellular nerve grafts were similar, whereas the fiber diameter of the rabbit‑derived acellular xenografts decreased, as compared with those of rat‑derived acellular allografts. Autografts exerted superior effects on nerve regeneration; however, no significant difference was observed between the axon number in the autograft group, as compared with the two acellular groups. These results suggested that autografts perform better than acellular nerve grafts, and chemically extracted acellular allografts and xenografts have similar effects on the regeneration of short facial nerve defects. PMID:26239906

  20. A Cough-Based Algorithm for Automatic Diagnosis of Pertussis.

    PubMed

    Pramono, Renard Xaviero Adhi; Imtiaz, Syed Anas; Rodriguez-Villegas, Esther

    2016-01-01

    Pertussis is a contagious respiratory disease which mainly affects young children and can be fatal if left untreated. The World Health Organization estimates 16 million pertussis cases annually worldwide resulting in over 200,000 deaths. It is prevalent mainly in developing countries where it is difficult to diagnose due to the lack of healthcare facilities and medical professionals. Hence, a low-cost, quick and easily accessible solution is needed to provide pertussis diagnosis in such areas to contain an outbreak. In this paper we present an algorithm for automated diagnosis of pertussis using audio signals by analyzing cough and whoop sounds. The algorithm consists of three main blocks to perform automatic cough detection, cough classification and whooping sound detection. Each of these extract relevant features from the audio signal and subsequently classify them using a logistic regression model. The output from these blocks is collated to provide a pertussis likelihood diagnosis. The performance of the proposed algorithm is evaluated using audio recordings from 38 patients. The algorithm is able to diagnose all pertussis successfully from all audio recordings without any false diagnosis. It can also automatically detect individual cough sounds with 92% accuracy and PPV of 97%. The low complexity of the proposed algorithm coupled with its high accuracy demonstrates that it can be readily deployed using smartphones and can be extremely useful for quick identification or early screening of pertussis and for infection outbreaks control. PMID:27583523

  1. Pertussis vaccines: WHO position paper, August 2015--Recommendations.

    PubMed

    2016-03-14

    This article presents the World Health Organization's (WHO) recommendations for the use of vaccines against Bordetella pertussis from the WHO position paper on Pertussis vaccines: WHO position paper--August 2015, recently published in the Weekly Epidemiological Record (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2015;90(August(35)):433-60). This position paper summarizes the most recent developments in the field of pertussis disease and its prevention by vaccination. It includes the WHO position on the choice of Pertussis vaccine as well as on the use of additional strategies, particularly vaccination during pregnancy, for prevention of early infant mortality. This document replaces the first WHO position paper on vaccines against disease caused by Pertussis published in 2010 (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2010;85(October(40)):385-400) and incorporates the revised guidance on the choice of pertussis vaccines published in July 2014 (Pertussis vaccines: WHO position paper. Wkly Epidemiol Rec 2014;89(July(30)):337-44). Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2014 and April 2015 meetings. The evidence presented at the meetings can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. PMID:26562318

  2. [Booster vaccination against Bordella pertussis during pregnancy].

    PubMed

    Esteves-Jaramillo, Alejandra; Gómez Altamirano, César Misael; Esparza Aguilar, Marcelino; López-Collada, Vesta L Richardson

    2012-05-01

    During the last decades, the incidence of whopping cough, has been rising worldwide, despite the high coverage of the immunization programs. The highest mortality is found among children under 6 month of age, who are too young to have completed a primary vaccination series with three doses the pertussis vaccine, nevertheless this disease also affects adolescents and adults, who may only manifest mild symptomatology. Hence they do not get diagnosed or treated, becoming a potential community source of infection for young children. In order to prevent this transmission, the recommendation of vaccinating adolescents and adults, including of women in child bearing age, was issued. Nevertheless the immunization coverage among these populations was low. Postpartum vaccination was also recommended, but recent evidence have shown that the antibody levels in breast milk are detectable at least a week after immunization, allowing a window of opportunity for the infection in the newborn. Finally, it has been suggested that a booster dose against Bordetella pertussis, given to pregnant women is safe and immunogenic. Therefore, the antibody transferred across the placenta and through breast milk, could protect the product in the early stages of life. PMID:23301426

  3. Binding of NAD+ to pertussis toxin.

    PubMed

    Lobban, M D; Irons, L I; van Heyningen, S

    1991-06-24

    The equilibrium dissociation constant of NAD+ and pertussis toxin was determined by equilibrium dialysis and by the quenching of the protein's intrinsic fluorescence on titration with NAD+. A binding constant, Kd, of 24 +/- 2 microM at 30 degrees C was obtained from equilibrium dialysis, consistent with the previously determined value for the Michaelis constant, Km, of 30 +/- 5 microM for NAD+ (when the toxin is catalysing the ADP-ribosylation of water and of dithiothreitol). The intrinsic fluorescence of pertussis toxin was quenched by up to 60% on titration with NAD+, and after correction for dilution and inner filter effects, a Kd value of 27 microM at 30 degrees C was obtained, agreeing well with that found by equilibrium dialysis. The binding constants were measured at a number of temperatures using both techniques, and from this the enthalpy of binding of NAD+ to toxin was determined to be 30 kJ.mol-1, a typical value for a protein-ligand interaction. There is one binding site for NAD+ per toxin molecule. PMID:1648404

  4. Infection in the Nasal Tip Caused by Acellular Dermal Matrix.

    PubMed

    Lee, Kun Hee

    2015-12-01

    A 19-year-old female patient visited our clinic for rhinoplasty. She complained about her low take-off point, which was apparent in profile view, and wanted slight tip projection. She refused additional cartilage harvesting from ears or ribs but consented to the use of homologous tissue, including acellular dermal matrix, for her dorsum and tip. Septoturbinoplasty was performed, and only a very small amount of septal cartilage could be harvested. It was used as both the columellar strut and the alar rim graft. Nasal dorsum and tip were augmented with acellular dermal matrix. Three months postoperatively, she experienced a few episodes of edema and redness on her nasal tip, followed by pus exudation from the nasal skin. Six months postoperatively, she underwent revision rhinoplasty for removal of inflamed grafts, and onlay tip graft with homologous rib cartilage was performed. Nasal dorsum or tip grafts are an integral part of Asian rhinoplasty. Autogenous tissue is the gold standard for grafting materials. However, the limited availability of autogenous tissue and the preference of patients and surgeons for artificial surgical implants make Asian rhinoplasty challenging. Unavailability of autogenous cartilage and patient refusal of artificial implants led to the use of acellular dermal matrix (ADM) in the nasal dorsum and tip for this case. This is the first report of postoperative complication because of infection rather than absorption after ADM use. PMID:26894006

  5. Immunogenicity of specific Bordetella pertussis surface antigens in diphtheria-tetanus-pertussis (DTP) vaccines.

    PubMed Central

    Blaskett, A. C.; Cox, J. C.

    1988-01-01

    The predominant causative organism of whooping cough in Australia is of a serotype which has normally been associated overseas with unvaccinated communities. Australian DTP vaccines pass the statutory mouse test for Bordetella pertussis potency but this test is now believed to be relatively insensitive to certain factors, especially the major type-specific agglutinogens, which are presumably also important in the human host-parasite relationship. Because endemic B. bronchiseptica infections make some laboratory animals unsatisfactory for testing B. pertussis agglutinin responses, we have developed a test in which young farm sheep were immunized with vaccines. Type-specific agglutinins in their sera were assayed after absorption of non-specific agglutinins by suspensions of selected bordetella strains. Three well-reputed European DTP vaccines and two recent batches of Australian DTP vaccine were tested and compared thus. All evoked significant agglutinin responses to the main agglutinogens. PMID:2897927

  6. Genetic Analysis of Bordetella pertussis Isolates from the 2008–2010 Pertussis Epidemic in Japan

    PubMed Central

    Miyaji, Yusuke; Otsuka, Nao; Toyoizumi-Ajisaka, Hiromi; Shibayama, Keigo; Kamachi, Kazunari

    2013-01-01

    A large pertussis epidemic occurred between 2008 and 2010 in Japan. To investigate epidemic strains, we analyzed 33 Bordetella pertussis isolates from the epidemic period by sequencing virulence-associated genes (fim3, ptxP, ptxA, and prn) and performing multilocus variable-number tandem repeat analysis (MLVA), and compared these results with those of 101 isolates from non-epidemic, earlier and later time periods. DNA sequencing of the fim3 allele revealed that the frequency of fim3B was 4.3%, 12.8%, 30.3%, and 5.1% within isolates in 2002–2004, 2005–2007, 2008–2010, and 2011–2012, respectively. The isolation rate of the fim3B strain therefore temporarily increased during the epidemic period 2008–2010. In contrast, the frequencies of the virulence-associated allelic variants, ptxP3, ptxA1, and prn2, increased with time during overall study period, indicating that these variants were not directly involved in the occurrence of the 2008–2010 epidemic. MLVA genotyping in combination with analysis of allele types showed that the prevalence of an MT27d strain temporarily increased in the epidemic period, and that this strain carried virulence-associated allelic variants (fim3B, ptxP3, ptxA1, and prn2) also identified in recent epidemic strains of Australia, Europe, and the US. Phenotypic analyses revealed that the serotype Fim3 strain was predominant (≥87%) during all the periods studied, and that the frequency of adhesion pertactin (Prn) non-expressing B. pertussis decreased by half in the epidemic period. All MT27d strains expressed Prn and Fim3 proteins, suggesting that B. pertussis MT27d strains expressing Prn and Fim3B have the potential to cause large epidemics worldwide. PMID:24124606

  7. Infectious Disease Report: Bordetella pertussis Infection in Patients With Cancer.

    PubMed

    Yacoub, Abraham; Nanjappa, Sowmya; Janz, Tyler; Greene, John N

    2016-04-01

    We illustrate 2 cases of pneumonia associated with Bordetella pertussis infection in 72-year-old and 61-year-old patients with cancer receiving myelosuppressive therapy after hematopoietic stem cell transplantation. Bacterial infections are a significant cause of morbidity and mortality in patients with cancer, and those receiving hematopoietic stem cell transplant, solid organ transplant, or myelosuppressive therapy are at increased risk. The infection was detected and the 2 patients had good outcomes following azithromycin treatment. Pertussis, also known as whooping cough, is a contagious respiratory illness that has become a public health challenge due to decreased immunity of the pertussis vaccine. Therefore, it is critical to recognize pertussis early in the course of the disease. PMID:27218794

  8. Evaluation of the Specificity of BP3385 for Bordetella pertussis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BP3385 has been proposed as a diagnostic PCR target for discriminating between Bordetella pertussis and other Bordetella species that also infect humans. Our results demonstrate this gene is also present in some strains of Bordetella hinzii and Bordetella bronchiseptica....

  9. Geographic analysis of pertussis infection in an urban area: a tool for health services planning.

    PubMed Central

    Siegel, C; Davidson, A; Kafadar, K; Norris, J M; Todd, J; Steiner, J

    1997-01-01

    OBJECTIVE: This study examined whether incident cases of pertussis cluster in urban census tracts and identified community characteristics that predict high-incidence areas. METHODS: An ecological study design was used. The study population included all persons diagnosed with pertussis from January 1, 1986, through December 31, 1994. Maps of rates were constructed via a geographic information system and clustering was statistically confirmed. Associations between pertussis rates and community characteristics were tested. RESULTS: Mapping and statistical analysis revealed spatial clustering of pertussis. Higher age-adjusted rates of pertussis infection were associated with higher proportions of residents below poverty level. CONCLUSIONS: In urban areas pertussis infection clusters in areas of poverty. PMID:9431296

  10. Porcine acellular lung matrix for wound healing and abdominal wall reconstruction: A pilot study

    PubMed Central

    Fernandez-Moure, Joseph S; Van Eps, Jeffrey L; Rhudy, Jessica R; Cabrera, Fernando J; Acharya, Ghanashyam S; Tasciotti, Ennio; Sakamoto, Jason; Nichols, Joan E

    2016-01-01

    Surgical wound healing applications require bioprosthetics that promote cellular infiltration and vessel formation, metrics associated with increased mechanical strength and resistance to infection. Porcine acellular lung matrix is a novel tissue scaffold known to promote cell adherence while minimizing inflammatory reactions. In this study, we evaluate the capacity of porcine acellular lung matrix to sustain cellularization and neovascularization in a rat model of subcutaneous implantation and chronic hernia repair. We hypothesize that, compared to human acellular dermal matrix, porcine acellular lung matrix would promote greater cell infiltration and vessel formation. Following pneumonectomy, porcine lungs were processed and characterized histologically and by scanning electron microscopy to demonstrate efficacy of the decellularization. Using a rat model of subcutaneou implantation, porcine acellular lung matrices (n = 8) and human acellular dermal matrices (n = 8) were incubated in vivo for 6 weeks. To evaluate performance under mechanically stressed conditions, porcine acellular lung matrices (n = 7) and human acellular dermal matrices (n = 7) were implanted in a rat model of chronic ventral incisional hernia repair for 6 weeks. After 6 weeks, tissues were evaluated using hematoxylin and eosin and Masson’s trichrome staining to quantify cell infiltration and vessel formation. Porcine acellular lung matrices were shown to be successfully decellularized. Following subcutaneous implantation, macroscopic vessel formation was evident. Porcine acellular lung matrices demonstrated sufficient incorporation and showed no evidence of mechanical failure after ventral hernia repair. Porcine acellular lung matrices demonstrated significantly greater cellular density and vessel formation when compared to human acellular dermal matrix. Vessel sizes were similar across all groups. Cell infiltration and vessel formation are well-characterized metrics of incorporation

  11. Porcine acellular lung matrix for wound healing and abdominal wall reconstruction: A pilot study.

    PubMed

    Fernandez-Moure, Joseph S; Van Eps, Jeffrey L; Rhudy, Jessica R; Cabrera, Fernando J; Acharya, Ghanashyam S; Tasciotti, Ennio; Sakamoto, Jason; Nichols, Joan E

    2016-01-01

    Surgical wound healing applications require bioprosthetics that promote cellular infiltration and vessel formation, metrics associated with increased mechanical strength and resistance to infection. Porcine acellular lung matrix is a novel tissue scaffold known to promote cell adherence while minimizing inflammatory reactions. In this study, we evaluate the capacity of porcine acellular lung matrix to sustain cellularization and neovascularization in a rat model of subcutaneous implantation and chronic hernia repair. We hypothesize that, compared to human acellular dermal matrix, porcine acellular lung matrix would promote greater cell infiltration and vessel formation. Following pneumonectomy, porcine lungs were processed and characterized histologically and by scanning electron microscopy to demonstrate efficacy of the decellularization. Using a rat model of subcutaneou implantation, porcine acellular lung matrices (n = 8) and human acellular dermal matrices (n = 8) were incubated in vivo for 6 weeks. To evaluate performance under mechanically stressed conditions, porcine acellular lung matrices (n = 7) and human acellular dermal matrices (n = 7) were implanted in a rat model of chronic ventral incisional hernia repair for 6 weeks. After 6 weeks, tissues were evaluated using hematoxylin and eosin and Masson's trichrome staining to quantify cell infiltration and vessel formation. Porcine acellular lung matrices were shown to be successfully decellularized. Following subcutaneous implantation, macroscopic vessel formation was evident. Porcine acellular lung matrices demonstrated sufficient incorporation and showed no evidence of mechanical failure after ventral hernia repair. Porcine acellular lung matrices demonstrated significantly greater cellular density and vessel formation when compared to human acellular dermal matrix. Vessel sizes were similar across all groups. Cell infiltration and vessel formation are well-characterized metrics of incorporation

  12. Binding of ATP by pertussis toxin and isolated toxin subunits

    SciTech Connect

    Hausman, S.Z.; Manclark, C.R.; Burns, D.L. )

    1990-07-03

    The binding of ATP to pertussis toxin and its components, the A subunit and B oligomer, was investigated. Whereas, radiolabeled ATP bound to the B oligomer and pertussis toxin, no binding to the A subunit was observed. The binding of ({sup 3}H)ATP to pertussis toxin and the B oligomer was inhibited by nucleotides. The relative effectiveness of the nucleotides was shown to be ATP > GTP > CTP > TTP for pertussis toxin and ATP > GTP > TTP > CTP for the B oligomer. Phosphate ions inhibited the binding of ({sup 3}H)ATP to pertussis toxin in a competitive manner; however, the presence of phosphate ions was essential for binding of ATP to the B oligomer. The toxin substrate, NAD, did not affect the binding of ({sup 3}H)ATP to pertussis toxin, although the glycoprotein fetuin significantly decreased binding. These results suggest that the binding site for ATP is located on the B oligomer and is distinct from the enzymatically active site but may be located near the eukaryotic receptor binding site.

  13. Pertussis: the resurgence of a public health threat.

    PubMed

    Torre, Jackeline Aparecida Grando Della; Benevides, Gabriel Nuncio; de Melo, Ana Maria Andrello Gonçalves Pereira; Ferreira, Cristiane Rúbia

    2015-01-01

    Pertussis is an acute and very contagious pulmonary disease, clinically characterized by periods of coughing and paroxysms that may cause death. The disease afflicts mainly the pediatric population and is life threatening to children under the age of 1 year. Since the beginning of the second millennium, the number of cases of pertussis has increased, menacing public health, despite the availability of the pertussis vaccine. The resurgence of the disease among adults and older children creates a reservoir of infection that will afflict the unimmunized or incompletely immunized children. As newborns and infants show the highest mortality rate, immunization during pregnancy is a new strategy to reduce the burden of pertussis. The authors report the case of a newborn that presented respiratory distress accompanied by marked leukocytosis. Bronchiolitis was the initial diagnostic hypothesis, but the clinical picture became typical of pertussis when paroxysmal coughing ensued. Isolation of the Bordetella pertussis and antigenic demonstration by polymerase chain reaction were positive from respiratory secretion. Despite appropriate antibiotic therapy and intensive care management the child died and the autopsy showed characteristic diagnostic findings. The authors call attention to this diagnosis when facing respiratory failure among young children, mainly in the presence of marked leukocytosis. Thorough research on the immunization status of the patient's social environment is of crucial importance. PMID:26484329

  14. Clinical, laboratorial and radiographic predictors of Bordetella pertussis infection☆

    PubMed Central

    Bellettini, Camila Vieira; de Oliveira, Andressa Welter; Tusset, Cintia; Baethgen, Ludmila Fiorenzano; Amantéa, Sérgio Luís; Motta, Fabrizio; Gasparotto, Aline; Andreolla, Huander Felipe; Pasqualotto, Alessandro C.

    2014-01-01

    OBJECTIVE: To identify clinical, laboratorial and radiographic predictors for Bordetella pertussis infection. METHODS: This was a retrospective study, which analyzed medical records of all patients submitted to a molecular dignosis (qPCR) for B. pertussis from September 2011 to January 2013. Clinical and laboratorial data were reviewed, including information about age, sex, signs/symptoms, length of hospitalization, blood cell counts, imaging findings, coinfection with other respiratory pathogens and clinical outcome. RESULTS: 222 cases were revised. Of these, 72.5% had proven pertussis, and 60.9% were under 1 year old. In patients aging up to six months, independent predictors for B. pertussis infection were (OR 8.0, CI 95% 1.8-36.3; p=0.007) and lymphocyte count >104/µL (OR 10.0, CI 95% 1.8-54.5; p=0.008). No independent predictors of B. pertussis infection could be determined for patients older than six months. Co-infection was found in 21.4% of patients, of which 72.7% were up to six months of age. Adenovirus was the most common agent (40.9%). In these patients, we were not able to identify any clinical features to detect patients presenting with a respiratory co-infection, even though longer hospital stay was observed in patients with co-infections (12 vs. 6 days; p=0.009). CONCLUSIONS: Cyanosis and lymphocytosis are independent predictors for pertussis in children up to 6 months old. PMID:25510991

  15. Bordetella pertussis adenylate cyclase inactivation by the host cell.

    PubMed Central

    Gilboa-Ron, A; Rogel, A; Hanski, E

    1989-01-01

    Bordetella pertussis produces a calmodulin-dependent adenylate cyclase (AC) which acts as a toxin capable of penetrating eukaryotic cells and generating high levels of intracellular cyclic AMP. Transfer of target cells into B. pertussis AC-free medium leads to a rapid decay in the intracellular AC activity, implying that the invasive enzyme is unstable in the host cytoplasm. We report here that treatment of human lymphocytes with a glycolysis inhibitor and an uncoupler of oxidative phosphorylation completely blocked the intracellular inactivation of B. pertussis AC. Lymphocyte lysates inactivated all forms of B. pertussis AC in the presence of exogenous ATP. This inactivation was associated with degradation of an 125I-labelled 200 kDa form of B. pertussis AC. It appears that ATP is required for the proteolytic pathway, but not as an energy source, since non-hydrolysable ATP analogues supported inactivation and complete degradation of the enzyme. The possibility that binding of ATP to B. pertussis AC renders it susceptible to degradation by the host cell protease is discussed. Images Fig. 2. Fig. 4. PMID:2554887

  16. Bordetella pertussis modulates human macrophage defense gene expression.

    PubMed

    Valdez, Hugo Alberto; Oviedo, Juan Marcos; Gorgojo, Juan Pablo; Lamberti, Yanina; Rodriguez, Maria Eugenia

    2016-08-01

    Bordetella pertussis, the etiological agent of whooping cough, still causes outbreaks. We recently found evidence that B. pertussis can survive and even replicate inside human macrophages, indicating that this host cell might serve as a niche for persistence. In this work, we examined the interaction of B. pertussis with a human monocyte cell line (THP-1) that differentiates into macrophages in culture in order to investigate the host cell response to the infection and the mechanisms that promote that intracellular survival. To that end, we investigated the expression profile of a selected number of genes involved in cellular bactericidal activity and the inflammatory response during the early and late phases of infection. The bactericidal and inflammatory response of infected macrophages was progressively downregulated, while the number of THP-1 cells heavily loaded with live bacteria increased over time postinfection. Two of the main toxins of B. pertussis, pertussis toxin (Ptx) and adenylate cyclase (CyaA), were found to be involved in manipulating the host cell response. Therefore, failure to express either toxin proved detrimental to the development of intracellular infections by those bacteria. Taken together, these results support the relevance of host defense gene manipulation to the outcome of the interaction between B. pertussis and macrophages. PMID:27465637

  17. Construction and characterization in vivo of Bordetella pertussis aroA mutants.

    PubMed Central

    Roberts, M; Maskell, D; Novotny, P; Dougan, G

    1990-01-01

    A DNA fragment encoding a kanamycin resistance determinant was used to insertionally inactivate the cloned aroA gene of Bordetella pertussis in Escherichia coli K-12, and a conjugative shuttle vector system based on the suicide vector pRTP1 was used to deliver the mutations from E. coli back into B. pertussis CN2992FS and BP1. The aroA mutation was introduced by allelic exchange into the chromosome of B. pertussis, resulting in otherwise isogenic parental and aroA mutant pairs. The B. pertussis aroA mutants grew well on laboratory medium supplemented with aromatic compounds but failed to grow on unsupplemented medium. The B. pertussis aroA mutants expressed the normal B. pertussis extracellular, virulence-associated proteins; inactivated, whole-cell vaccines prepared from the mutants protected mice as efficiently as vaccines made from the parent strains against intracerebral challenge with the virulent B. pertussis 18323. Live B. pertussis aroA bacteria inefficiently colonized the lungs of NIH/S mice after they were challenged with aerosol, unlike the wild-type B. pertussis organism. Mice exposed to three separate aerosols of live B. pertussis aroA bacteria were protected against lung colonization after being exposed to an aerosol containing the virulent parental B. pertussis strain. High-level antibodies against B. pertussis rapidly appeared in the sera of mice immunized by aerosol with the B. pertussis aroA strains and challenged with the virulent parent. Images PMID:2407655

  18. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    PubMed Central

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  19. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair.

    PubMed

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-07-15

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  20. Use of an Acellular Regenerative Tissue Matrix Over Chronic Wounds

    PubMed Central

    Stacey, D. Heath

    2013-01-01

    Objectives: Bioengineered skin grafts, including acellular dermal matrices, may be effective in treating lower extremity and trunk wounds that are not responsive to traditional wound management. Acellular dermal wound matrix is derived from human acellular dermal wound matrix (HADWM) tissue and provides a scaffold that supports cellular repopulation and revascularization. The major structural components of the dermis are retained during processing, and a single application has been shown to help achieve wound closure. Methods: This patient case series examined the use of HADWM on lower extremity and trunk wounds in 11 patients (6 male and 5 female) with a mean age of 55 years (range: 31–83 years). Wounds were debrided 1 to 2 times, followed by placement of HADWM (range: 4–330 cm2) on wounds that varied from the dorsal surface of the foot, lower abdomen, and lower extremity to the Achilles flap. A nonadherent layer in conjunction with bacitracin was placed over HADWM. Negative pressure wound therapy (NPWT) was placed over the HADWM and initiated continuously at −125 mm Hg for 1 to 2 weeks. After the application of NPWT, HADWM was covered with various gauze dressings using mineral oil. Results: All patients completed their treatment successfully, and follow-up ranged from 1 week to 6 months. One patient experienced an infection, which resulted in partial graft loss that required replacement with HADWM and NPWT. No additional complications occurred in the other patients. Conclusions: This patient case series demonstrated successful use of HADWM and NPWT, which further supports published studies documenting HADWM success in chronic wounds. PMID:24324850

  1. Diphtheria, tetanus, and pertussis (DTaP) vaccines - what you need to know

    MedlinePlus

    ... taken in its entirety from the CDC Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine Information Statement (VIS): www. ... statements/dtap.html CDC review information for Diphtheria, Tetanus, and Pertussis (DTaP) VIS: Page last reviewed: June ...

  2. Diphtheria, Tetanus, and Pertussis (DTaP) Vaccines: What You Need to Know

    MedlinePlus

    ... STATEMENT DTaP Vaccine What You Need to Know (Diphtheria, Tetanus and Pertussis) Many Vaccine Information Statements are ... www. immunize. org/ vis 1 Why get vaccinated? Diphtheria, tetanus, and pertussis are serious diseases caused by ...

  3. Diphtheria, tetanus, and pertussis (DTaP) vaccines - what you need to know

    MedlinePlus

    ... is taken in its entirety from the CDC Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine Information Statement (VIS): ... vis-statements/dtap.html CDC review information for Diphtheria, Tetanus, and Pertussis (DTaP) VIS: Page last reviewed: ...

  4. Role of carbohydrate recognition domains of pertussis toxin in adherence of Bordetella pertussis to human macrophages.

    PubMed Central

    van't Wout, J; Burnette, W N; Mar, V L; Rozdzinski, E; Wright, S D; Tuomanen, E I

    1992-01-01

    Pertussis toxin (PT) and filamentous hemagglutinin can each mediate the association of Bordetella pertussis with human macrophages. Adherence via filamentous hemagglutinin leads to integrin-mediated entry and survival of the bacteria within the human cell. We determined the contribution of PT to bacterial adherence to human macrophages. Plating macrophages on wells coated with recombinant PT subunit 2 (S2) or S3 decreased PT-dependent bacterial binding by greater than 60%; S1, S4, and S5 were ineffective. S3-dependent adherence was reduced 63% +/- 8% by sialic acid, while S2-dependent adherence was reduced 53% +/- 11% by galactose. Loss of the carbohydrate recognition properties of S2 by deletion of residues 40 to 54 or site-specific mutations at Asn-93, His-47, or Arg-50 eliminated the ability of the subunit protein to competitively inhibit bacterial binding. Peptides corresponding to residues 28 to 45 of S2 and S3 competitively inhibited adherence. Treatment of macrophages with antibodies to Le(a) or Le(x) but not CD14, CD15, CD18, or HLA interfered with PT-mediated binding. Exposure of the macrophages to the B oligomer, S2, or S3 increased binding to the CD11b/CD18 integrin. These results indicate that the carbohydrate recognition domains of both S2 and S3 participate in adherence of B. pertussis to human macrophages. The PT receptor(s), as yet unidentified, appears to carry the Le(a) or Le(x) determinants and is functionally capable of modulating integrin-mediated binding to the macrophage. PMID:1353482

  5. Sources of pertussis infection in young babies from São Paulo State, Brazil.

    PubMed

    Berezin, Eitan Naaman; de Moraes, José Cassio; Leite, Daniela; Carvalhanas, Telma Regina M P; Yu, Ana Lucia Frugis; Blanco, Roberta Morozetti; Rodrigues, Marcela; Almeida, Flavia J; Bricks, Lucia Ferro

    2014-12-01

    Household contacts are important sources of Bordetella pertussis in infants. A total of 353 household contacts of 97 index cases were evaluated for pertussis by culture and polymerase chain reaction. Twenty eight contacts were positive (8.0%). The presence of symptoms did not influence the rate of diagnosed bacteriologic pertussis in communicants. We conclude that contacts with an index case can be positive for B. pertussis independently of the presence of symptoms. PMID:25386966

  6. Comparison of molecular detection methods for pertussis in children during a state-wide outbreak.

    PubMed

    Qin, X; Zerr, D M; Kronman, M P; Adler, A L; Berry, J E; Rich, S; Buccat, A M; Xu, M; Englund, J A

    2016-01-01

    A state-wide pertussis outbreak occurred in Washington during the winter-spring months of 2012, concurrent with respiratory viral season. We compared performance characteristics of a laboratory-developed pertussis PCR (LD-PCR for Bordetella pertussis, Bordetella parapertussis, and Bordetella holmesii) and rapid multiplex PCR (RM-PCR) for respiratory viruses (FilmArray™, BioFire, B. pertussis data unblinded following FDA approval post outbreak). We analyzed three cohorts of patients using physician testing orders as a proxy for clinical suspicion for pertussis or respiratory viruses: Cohort 1, tested by LD-PCR for pertussis pathogens only by nasopharyngeal swab; Cohort 2, by RM-PCR for respiratory viruses only by mid-nasal turbinate swab; and Cohort 3, by both methods. B. pertussis was detected in a total of 25 of the 490 patients in Cohort 3 in which LD-PCR detected 20/25 (80 %) cases and the RM-PCR detected 24/25 (96 %; p = 0.2). Pertussis pathogens were detected in 21/584 (3.6 %) of samples from Cohort 1 where clinicians had a relatively strong suspicion for pertussis. In contrast, B. pertussis was detected in only 4/3071 (0.1 %) specimens from Cohort 2 where suspicion for pertussis was lower (p < 0.001 for comparison with Cohort 1). In summary, the two laboratory methods were comparable for the detection of B. pertussis. PMID:27121506

  7. Association of Vitamin D Receptor Polymorphism with Susceptibility to Symptomatic Pertussis.

    PubMed

    Han, Wanda G H; Hodemaekers, Hennie M; Nagarajah, Bhawani; Poelen, Martien M C; Helm, Kina; Janssen, Riny; van Els, Cécile A C M

    2016-01-01

    Pertussis, caused by infection with the gram negative B. pertussis bacterium, is a serious respiratory illness that can last for months. While B. pertussis infection rates are estimated between 1-10% in the general population, notifications of symptomatic pertussis only comprise 0.01-0.1% indicating that most individuals clear B. pertussis infections without developing (severe) clinical symptoms. In this study we investigated whether genetic risk factors are involved in the development of symptomatic pertussis upon B. pertussis infection. Single-nucleotide polymorphisms (SNPs) in candidate genes, MBL2, IL17A, TNFα, VDR, and IL10 were genotyped in a unique Dutch cohort of symptomatic clinically confirmed (ex-)pertussis patients and in a Dutch population cohort. Of the seven investigated SNPs in five genes, a polymorphism in the Vitamin D receptor (VDR) gene (rs10735810) was associated with pertussis. The VDR major allele and its homozygous genotype were more present in the symptomatic pertussis patient cohort compared to the control population cohort. Interestingly, the VDR major allele correlated also with the duration of reported pertussis symptoms. Vitamin D3 (VD3) and VDR are important regulators of immune activation. Altogether, these findings suggest that polymorphisms in the VDR gene may affect immune activation and the clinical outcome of B. pertussis infection. PMID:26894582

  8. Association of Vitamin D Receptor Polymorphism with Susceptibility to Symptomatic Pertussis

    PubMed Central

    Han, Wanda G. H.; Hodemaekers, Hennie M.; Nagarajah, Bhawani; Poelen, Martien M. C.; Helm, Kina; Janssen, Riny; van Els, Cécile A. C. M.

    2016-01-01

    Pertussis, caused by infection with the gram negative B. pertussis bacterium, is a serious respiratory illness that can last for months. While B. pertussis infection rates are estimated between 1–10% in the general population, notifications of symptomatic pertussis only comprise 0.01–0.1% indicating that most individuals clear B. pertussis infections without developing (severe) clinical symptoms. In this study we investigated whether genetic risk factors are involved in the development of symptomatic pertussis upon B. pertussis infection. Single-nucleotide polymorphisms (SNPs) in candidate genes, MBL2, IL17A, TNFα, VDR, and IL10 were genotyped in a unique Dutch cohort of symptomatic clinically confirmed (ex-)pertussis patients and in a Dutch population cohort. Of the seven investigated SNPs in five genes, a polymorphism in the Vitamin D receptor (VDR) gene (rs10735810) was associated with pertussis. The VDR major allele and its homozygous genotype were more present in the symptomatic pertussis patient cohort compared to the control population cohort. Interestingly, the VDR major allele correlated also with the duration of reported pertussis symptoms. Vitamin D3 (VD3) and VDR are important regulators of immune activation. Altogether, these findings suggest that polymorphisms in the VDR gene may affect immune activation and the clinical outcome of B. pertussis infection. PMID:26894582

  9. Pertussis Serodiagnosis in Belgium from 1990 to 2009 ▿

    PubMed Central

    Vincent, Muriel; Rodeghiero, Caroline; Eylenbosch, Romain; Mans, Yvan; Swalus-Steenhouwer, Jeannine; Piérard, Denis; Huygen, Kris; Vanhoof, Raymond

    2011-01-01

    Diagnosis of pertussis by culture and PCR is most sensitive when performed on nasopharyngeal specimens collected <2 weeks and <3 weeks, respectively, after the onset of clinical disease. Conversely, serological testing allows the diagnosis of patients (mostly adults) with less typical whooping cough symptoms, for whom clinical samples are often collected at later time points. Here, we report on a 20-year serodiagnostic survey of pertussis in Belgium from 1990 to 2009. In total, 13,163 patients were analyzed for Bordetella pertussis-specific antibodies by agglutination, complement fixation, immunofluorescence, and ELISA. The number of positive pertussis cases detected by serodiagnosis ranged between 50 and 150 annually. The mean age of positive cases increased from 9.9 years in 1990 to 33.9 years in 2009. Whereas from 1990 to 2003, children and young adolescents made up the majority of cases, from 2004 onwards, cases were detected in all age groups and the distribution became bimodal, with a first peak at the age of 10 to 20 years and a second at the age of 35 to 50 years. In contrast, patients diagnosed since 2001 by PCR and/or culture were mostly children younger than 1 year of age. Despite extensive childhood vaccination campaigns, whooping cough is still present in Belgium. Our findings confirm the potential role of adults in the continued transmission of pertussis and strongly warrant booster or cocoon vaccinations in older age groups. PMID:21346057

  10. Review of the neutrophil response to Bordetella pertussis infection.

    PubMed

    Eby, Joshua C; Hoffman, Casandra L; Gonyar, Laura A; Hewlett, Erik L

    2015-12-01

    The nature and timing of the neutrophil response to infection with Bordetella pertussis is influenced by multiple virulence factors expressed by the bacterium. After inoculation of the host airway, the recruitment of neutrophils signaled by B. pertussis lipooligosaccharide (LOS) is suppressed by pertussis toxin (PTX). Over the next week, the combined activities of PTX, LOS and adenylate cyclase toxin (ACT) result in production of cytokines that generate an IL-17 response, promoting neutrophil recruitment which peaks at 10-14 days after inoculation in mice. Arriving at the site of infection, neutrophils encounter the powerful local inhibitory activity of ACT, in conjunction with filamentous hemagglutinin. With the help of antibodies, neutrophils contribute to clearance of B. pertussis, but only after 28-35 days in a naïve mouse. Studies of the lasting, antigen-specific IL-17 response to infection in mice and baboons has led to progress in vaccine development and understanding of pathogenesis. Questions remain about the mediators that coordinate neutrophil recruitment and the mechanisms by which neutrophils overcome B. pertussis virulence factors. PMID:26432818

  11. Acellular dermal matrices in breast reconstructions - a literature review.

    PubMed

    Skovsted Yde, Simon; Brunbjerg, Mette Eline; Damsgaard, Tine Engberg

    2016-08-01

    During the last two decades, acellular dermal matrices (ADM) have been more widely used in reconstructive procedures i.e. breast reconstructions. Several, both synthetic and biologic products derived from human, porcine and bovine tissue, have been introduced. Until this point postoperative complications for the acellular dermal matrices, as a group, have been the main focus. The purpose of this literature review is to summarize the current knowledge on the each biologic product used in breast reconstructions, including product specific complication frequencies. A systematic search of the literature was performed in the PubMed and EMBASE databases, identifying 55 relevant articles, mainly evidence level III. AlloDerm seems to be associated with severe complicating matters in the reconstructive process compared to other products. This could be due to the higher number of investigating studies relative to the others. The surgical area faces certain challenges comparing results, due to surgical variance, the data collection and follow-up. More well-defined guidelines and more high-evidence randomized studies could increase the overall level of evidence in this area. PMID:26881927

  12. Human acellular dermal wound matrix: evidence and experience.

    PubMed

    Kirsner, Robert S; Bohn, Greg; Driver, Vickie R; Mills, Joseph L; Nanney, Lillian B; Williams, Marie L; Wu, Stephanie C

    2015-12-01

    A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket(®) regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence-based and practical overview for treating chronic lower extremity wounds with this HADWM. PMID:24283346

  13. Pertussis antibodies in the sera of children exposed to Bordetella pertussis by vaccination or infection.

    PubMed

    Dolby, J M; Stephens, S

    1973-03-01

    Low agglutinin titres to pertussis suspensions were found in 99% of sera from a group comprising healthy adults and non-vaccinated, non-infected infants of 1-6 months of age. These are attributable to agglutinins to heat-stable antigens and/or heat labile agglutinogen 1, and cross-absorption tests must be done on the sera in order to distinguish between the two. Agglutinins to agglutinogens 2 and 3 were found in only about 20% of adult sera. Bactericidal antibody was low in titre or absent in all sera from non-exposed individuals.Raised bactericidal antibody titres and the presence of agglutinins 2 and 3 were attributed to exposure to Bordetella pertussis antigens, either as vaccine or as infection. The variation, amongst both vaccinated and infected children, was very great. A vaccinated child who became ill responded to the infection in much the same way as a non-vaccinated child. We were unable to relate the immunity of the child to the titres either of agglutinins or of the bactericidal antibody.The protective ability of sera from vaccinated or infected children measured in mice against small, lethal brain infections was also unrelated to the state of immunity in the children, but this protective ability was correlated with the complement-mediated bactericidal antibody titres of the sera.The distribution of agglutinins, bactericidal antibody, and anti-haemagglutinin in serum IgG and IgM was different in vaccinated and infected children. PMID:4348456

  14. Pertussis antibodies in the sera of children exposed to Bordetella pertussis by vaccination or infection

    PubMed Central

    Dolby, Jean M.; Stephens, Susan

    1973-01-01

    Low agglutinin titres to pertussis suspensions were found in 99% of sera from a group comprising healthy adults and non-vaccinated, non-infected infants of 1-6 months of age. These are attributable to agglutinins to heat-stable antigens and/or heat labile agglutinogen 1, and cross-absorption tests must be done on the sera in order to distinguish between the two. Agglutinins to agglutinogens 2 and 3 were found in only about 20% of adult sera. Bactericidal antibody was low in titre or absent in all sera from non-exposed individuals. Raised bactericidal antibody titres and the presence of agglutinins 2 and 3 were attributed to exposure to Bordetella pertussis antigens, either as vaccine or as infection. The variation, amongst both vaccinated and infected children, was very great. A vaccinated child who became ill responded to the infection in much the same way as a non-vaccinated child. We were unable to relate the immunity of the child to the titres either of agglutinins or of the bactericidal antibody. The protective ability of sera from vaccinated or infected children measured in mice against small, lethal brain infections was also unrelated to the state of immunity in the children, but this protective ability was correlated with the complement-mediated bactericidal antibody titres of the sera. The distribution of agglutinins, bactericidal antibody, and anti-haemagglutinin in serum IgG and IgM was different in vaccinated and infected children. PMID:4348456

  15. [Optimization of the pertussis vaccine production process].

    PubMed

    Germán Santiago, J; Zamora, N; de la Rosa, E; Alba Carrión, C; Padrón, P; Hernández, M; Betancourt, M; Moretti, N

    1995-01-01

    The production of Pertussis Vaccine was reevaluated at the Instituto Nacional de Higiene "Rafael Rangel" in order to optimise it in terms of vaccine yield, potency, specific toxicity and efficiency (cost per doses). Four different processes, using two culture media (Cohen-Wheeler and Fermentación Glutamato Prolina-1) and two types of bioreactors (25 L Fermentador Caracas and a 450 L industrial fermentor) were compared. Runs were started from freeze-dried strains (134 or 509) and continued until the obtention of the maximal yield. It was found that the combination Fermentación Glutamato Prolina-1/industrial fermentor, shortened the process to 40 hours while consistently yielding a vaccine of higher potency (7.91 +/- 2.56 IU/human dose) and lower specific toxicity in a mice bioassay. In addition, the physical aspect of the preparation was rather homogeneous and free of dark aggregates. Most importantly, the biomass yield more than doubled those of the Fermentador Caracas using the two different media and that in the industrial fermentor with the Cohen-Wheeler medium. Therefore, the cost per doses was substantially decreased. PMID:9279028

  16. Analysis of separate isolates of Bordetella pertussis repeated DNA sequences.

    PubMed

    McPheat, W L; Hanson, J H; Livey, I; Robertson, J S

    1989-06-01

    Two independent isolates of a Bordetella pertussis repeated DNA unit were sequenced and shown to be an insertion sequence element with five nucleotide differences between the two copies. The sequences were 1053 bp in length with near-perfect terminal inverted repeats of 28 bp, had three open reading frames, and were each flanked by short direct repeats. The two insertion sequences showed considerable homology to two other B. pertussis repeated DNA sequences reported recently: IS481 and a 530 bp repeated DNA unit. The B. pertussis insertion sequence would appear to comprise a group of closely related sequences differing mainly in flanking direct repeats and the terminal inverted repeats. The two isolates reported here, which were from the adenylate cyclase and agglutinogen 2 regions of the genome, were numbered IS48lvl and IS48lv2 respectively. PMID:2559151

  17. Pearl Kendrick, Grace Eldering, and the Pertussis Vaccine

    PubMed Central

    2010-01-01

    In light of the reemergence of pertussis (whooping cough), the pioneering research of Pearl Kendrick and Grace Eldering is worth revisiting. In the 1930s, working in the Michigan Department of Health laboratory in Grand Rapids, Michigan, USA, they began researching a pertussis vaccine. Their research offers an instructive case study of the creative public health research performed in state health department laboratories during the interwar years. State department of health laboratory directors actively promoted research by supporting advanced education; making facilities and funding available for individual projects; and, when possible, procuring new facilities. Using Michigan Department of Health resources and local and federal funding, Kendrick and Eldering developed standardized diagnostic tools; modified and improved extant vaccines; conducted the first successful, large-scale, controlled clinical trial of pertussis vaccine; and participated in international efforts to standardize and disseminate the vaccine. Their model may again offer a promising avenue for groundbreaking research. PMID:20678322

  18. Novel therapies for the treatment of pertussis disease.

    PubMed

    Scanlon, Karen M; Skerry, Ciaran; Carbonetti, Nicholas H

    2015-11-01

    Whooping cough, or pertussis, incidence has reached levels not seen since the 1950s. Previous studies have shown that antibiotics fail to improve the course of disease unless diagnosed early. Early diagnosis is complicated by the non-diagnostic presentation of disease early in infection. This review focuses on previous attempts at developing novel host-directed therapies for the treatment of pertussis. In addition, two novel approaches from our group are discussed. Manipulation of the signaling pathway of sphingosine-1-phosphate, a lipid involved in many immune processes, has shown great promise, but is in its infancy. Pendrin, a host epithelial anion exchanger upregulated in the airways with B. pertussis infection, appears to drive mucus production and dysregulation of airway surface liquid pH and salinity. In addition to detailing these potential new therapeutic targets, the need for greater focus on the neonatal model of disease is highlighted. PMID:26394802

  19. Helical structure of Bordetella pertussis fimbriae.

    PubMed Central

    Steven, A C; Bisher, M E; Trus, B L; Thomas, D; Zhang, J M; Cowell, J L

    1986-01-01

    The helical structures of Bordetella pertussis fimbriae of serotypes 2 and 6 were determined by optical diffraction analysis of electron micrographs of negatively stained paracrystalline bundles of purified fimbriae. The fimbrial structure is based on an axial repeat of 13 nm that contains five repeating units in two complete turns of a single-start helix. This structure was confirmed by direct measurements of mass per unit length for individual fimbriae performed by dark-field scanning transmission electron microscopy of unstained specimens. These data further established that the helically repeating unit is a monomer of fimbrial protein (Mr congruent to 22,000 for type 2 and Mr congruent to 21,500 for type 6). Radial density profiles calculated from the scanning transmission electron micrographs showed that the fimbria has peak density at its center, i.e., no axial channel, consistent with the results of conventional negative-staining electron microscopy. The radial profile gives an outermost diameter of approximately 7.5 nm, although the peripheral density is, on average, diffuse, allowing sufficient intercalation between adjacent fimbriae to give a center-to-center spacing of approximately 5.5 nm in the paracrystals. Despite serological and biochemical differences between type 2 and type 6 fimbriae, the packing arrangements of their fimbrial subunits are identical. From this observation, we infer that the respective subunits may have in common conserved regions whose packing dictates the helical geometry of the fimbria. It is plausible that a similar mechanism may underlie the phenomenon of phase variations in other systems of bacterial fimbriae. Images PMID:2875062

  20. Diphtheria Vaccination

    MedlinePlus

    ... and adults - Tetanus-diphtheria-acellular Pertussis vaccine Diphtheria Vaccination Pronounced (dif-THEER-ee-a) Recommend on Facebook ... Related Pages Pertussis Tetanus Feature Story: Adults Need Immunizations, Too Abbreviations DTaP=Pediatric - Diphtheria-Tetanus-acellular Pertussis ...

  1. Extended Eden model reproduces growth of an acellular slime mold

    NASA Astrophysics Data System (ADS)

    Wagner, Geri; Halvorsrud, Ragnhild; Meakin, Paul

    1999-11-01

    A stochastic growth model was used to simulate the growth of the acellular slime mold Physarum polycephalum on substrates where the nutrients were confined in separate drops. Growth of Physarum on such substrates was previously studied experimentally and found to produce a range of different growth patterns [Phys. Rev. E 57, 941 (1998)]. The model represented the aging of cluster sites and differed from the original Eden model in that the occupation probability of perimeter sites depended on the time of occupation of adjacent cluster sites. This feature led to a bias in the selection of growth directions. A moderate degree of persistence was found to be crucial to reproduce the biological growth patterns under various conditions. Persistence in growth combined quick propagation in heterogeneous environments with a high probability of locating sources of nutrients.

  2. Application of acellular dermis and autograft on burns and scars.

    PubMed

    Ramos Duron, L E; Martínez Pardo, M E; Olivera Zavaleta, V; Silva Diaz, T; Reyes Frías, M L; Luna Zaragoza, D

    1999-01-01

    The cases of two patients with burns treated with dermis allograft and of one patient for lip reconstructive aesthetic filling treated with less than one mm3 of radiosterilised acellular dermis are presented. This paper emphasizes the treatment with radiosterilised dermal grafts with a permanent character so far. Hospitals, therefore, can satisfy the demand for this kind of tissue in the case of disaster and patients with serious injuries. In the cases cited, histocompatibility analysis was not required, thus having the advantage of long-time storage of the radiosterilised dermis used on these patients. Neither inflammatory reaction nor acute phase re-absorption were observed. Moreover, shrink (contract) healing was diminished. After two years, the results are still satisfactory. PMID:10853787

  3. Fimbrial hemagglutinin in stationary and shake cultures of Bordetella pertussis.

    PubMed Central

    Arai, H; Munoz, J J

    1979-01-01

    Bordetella pertussis produced hemagglutinin in stationary cultures; in cultures kept under constant shaking, hemagglutinin was found only during the first 48 h of incubation but not after 3 to 5 days. The type of medium had a pronounced effect on production of hemagglutinin. Strain differences in ability to produce hemagglutinin were also detected. Images PMID:39897

  4. Pertussis: increasing disease as a consequence of reducing transmission.

    PubMed

    Aguas, Ricardo; Gonçalves, Guilherme; Gomes, M Gabriela M

    2006-02-01

    Since the 1980s, the occurrence of pertussis cases in developed countries has increased and shifted towards older age groups. This resurgence follows 30 years of intense mass vaccination, and has been attributed primarily to three factors: (1) more effective diagnosis of the disease, (2) waning of vaccine-induced immunity, and (3) loss of vaccine efficacy due to the emergence of new Bordetella pertussis strains. Here we develop and analyse a mathematical model to assess the plausibility of these hypotheses. We consider that exposure to B pertussis through natural infection or vaccination induces an immune response that prevents severe disease but does not fully prevent mild infections. We also assume that these protective effects are temporary due to waning of immunity. These assumptions, describing the mode of action of adaptive immunity, are combined with a standard transmission model. Two distinct epidemiological scenarios are detected: under low transmission, most infections lead to severe disease; under high transmission, mild infections are frequent, boosting clinical immunity and maintaining low levels of severe disease. The two behaviours are separated by a reinfection threshold in transmission. As a result, the highest incidence of severe disease is expected to occur at intermediate transmission intensities--near the reinfection threshold--suggesting that pertussis resurgence may be induced by a reduction in transmission, independently of vaccination. The model is extended to interpret the outcomes of current control measures and explore scenarios for future interventions. PMID:16439331

  5. Rational medium design for Bordetella pertussis: basic metabolism.

    PubMed

    Thalen, M; van den IJssel, J; Jiskoot, W; Zomer, B; Roholl, P; de Gooijer, C; Beuvery, C; Tramper, J

    1999-10-01

    In current Bordetella pertussis media ammonium accumulates because of an imbalance in the nitrogen:carbon ratio of the substrates used, which is one of the factors limiting cell density in fed-batch cultures. The aim of this study was to map B. pertussis catabolic and anabolic capabilities, in order to design a medium that avoids ammonium accumulation, while substrates are metabolised completely. Besides the known dysfunctional glycolysis, B. pertussis also possessed a partially dysfunctional citric-acid cycle. Although ammonium accumulation was avoided by adding various carbon sources to medium with glutamate, nuclear magnetic resonance (NMR) showed excretion of acetate, acetoacetate and beta-hydroxy-butyrate, thereby reducing the biomass yield. Acetoacetate and beta-hydroxy-butyrate were also formed in Verwey, B2 and modified Stainer-Scholte medium. Electron microscopy in combination with NMR showed that cells early on in these cultures contained poly-hydroxy-butyrate (PHB) globules, which disappeared later during the culture, coinciding with the appearance of beta-hydroxy-butyrate and/or acetoacetate. No globules nor metabolite excretion was detected when lactate in combination with glutamate were used as substrates. Thus, metabolite excretion and ammonium accumulation were avoided, while the yield of 8.8 g C-mol-1 compared favourably with literature values, averaging 6.5 g C-mol-1. Optimisation of this medium for pertussis toxin production will be reported in a separate article. PMID:10553654

  6. Modification of opiate agonist binding by pertussis toxin

    SciTech Connect

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  7. Bordetella pertussis, an agent not to forget: a case report

    PubMed Central

    2009-01-01

    Introduction In the past, pertussis affected particularly children under 6 years of age, but recent trends show that there is a shift toward the older age group. The clinical presentation can be atypical in the adolescent age group, and the disease is often misdiagnosed. Case presentation We present a case of an 11-year-old male patient oriented to our unit with anorexia, weight loss and persistent cough with nocturnal paroxysms for 4 weeks. He also reported occasional wheezing and chest tightness. He denied fever, chills, myalgia, sore throat, or rhinorrhea. The patient presented to his primary care physician 1 week prior with the same complaint and was treated with amoxicillin and ebastine. Facing the persistence of the complaints he was oriented to our unit in order to exclude tuberculosis. Further study confirmed Bordetella pertussis infection and he started clarithromycin (15 mg/kg/day for 14 days). The patient's symptoms resolved after two weeks. Two of the patient's family members have developed symptoms of Bordetella pertussis infection and were treated after convenient study. Conclusion Cough is one of the most common complaints among children and its causes are multiple. Active immunization and early diagnosis are crucial in the management of pertussis. PMID:19200362

  8. Vaccination against tetanus, diphtheria, pertussis and poliomyelitis in adult travellers.

    PubMed

    Gautret, Philippe; Wilder-Smith, Annelies

    2010-05-01

    This paper reviews the risk and vaccine recommendations for tetanus, diphtheria, pertussis and poliomyelitis for adult travellers. The travel clinic presents a unique opportunity to evaluate whether routine vaccinations are up-to-date. Tetanus, diphtheria and pertussis occur worldwide but are more common in low resource countries due to incomplete childhood vaccination coverage, environmental and socio-economic factors. Diphtheria has been reported in travellers without adequate protection. A booster against tetanus and diphtheria is recommended for all adult travellers, regardless of travel destination and duration. The incidence of pertussis in general adult travellers has been poorly studied. Extrapolating from the reported high incidence in travellers to the Hajj, the risk may be more substantial than thought. There are no universal recommendations for pertussis vaccination for adult travellers, and studies are needed to develop evidence based guidelines. Poliomyelitis is well controlled and now only occurs in a small number of countries. Travellers to and from endemic and re-infected countries should be fully vaccinated against poliomyelitis. PMID:20541135

  9. Dynamics of Pertussis Transmission in the United States.

    PubMed

    Magpantay, F M G; Rohani, P

    2015-06-15

    Past patterns of infectious disease transmission set the stage on which modern epidemiologic dynamics are played out. Here, we present a comprehensive account of pertussis (whooping cough) transmission in the United States during the early vaccine era. We analyzed recently digitized weekly incidence records from Morbidity and Mortality Weekly Reports from 1938 to 1955, when the whole-cell pertussis vaccine was rolled out, and related them to contemporary patterns of transmission and resurgence documented in monthly incidence data from the National Notifiable Diseases Surveillance System. We found that, during the early vaccine era, pertussis epidemics in US states could be categorized as 1) annual, 2) initially annual and later multiennial, or 3) multiennial. States with predominantly annual cycles tended to have higher per capita birth rates, more household crowding, more children per family, and lower rates of school attendance than the states with multiennial cycles. Additionally, states that exhibited annual epidemics during 1938-1955 have had the highest recent (2001-2010) incidence, while those states that transitioned from annual cycles to multiennial cycles have had relatively low recent incidence. Our study provides an extensive picture of pertussis epidemiology in the United States dating back to the onset of vaccination, a back-story that could aid epidemiologists in understanding contemporary transmission patterns. PMID:26022662

  10. Pertussis Epidemiology in Greece and Emerging Risk Groups during the Vaccination Era (1980–2008)

    PubMed Central

    Theodoridou, Maria; Dargenta, Georgia; Aptouramani, Maria; Papastergiou, Panagiotis; Katsiaflaka, Anna; Theodoridou, Kalliopi; Hadjichristodoulou, Christos

    2012-01-01

    To study the epidemiology of pertussis in Greece and epidemiologic changes throughout a period of twenty-nine years, we conducted a retrospective analysis of available data of pertussis cases for the past twenty-nine years (1980–2008) and a prospective analysis of hospitalized pertussis cases from a children's hospital in Athens for eight years (2001–2008). From 1980 through 2008, the incidence of pertussis in Greece declined from 11.2 to 0.05 cases per 100,000. Epidemic cycles occurring every 3 to 5 years were observed. Since pertussis circulation cannot be fully controlled by present immunization programs, efforts should be made to vaccinate infants at the recommended age, early diagnose, treatment as well as contact tracing of pertussis cases. Control of pertussis in social susceptible populations is necessary. A national program with adolescent and adult booster could decrease the circulation of B. pertussis. Despite an overall decrease for pertussis cases, pertussis is still a present and future challenge of public health service in Greece. PMID:23019527

  11. Pertussis Epidemiology in Greece and Emerging Risk Groups during the Vaccination Era (1980-2008).

    PubMed

    Theodoridou, Maria; Dargenta, Georgia; Aptouramani, Maria; Papastergiou, Panagiotis; Katsiaflaka, Anna; Theodoridou, Kalliopi; Hadjichristodoulou, Christos

    2012-01-01

    To study the epidemiology of pertussis in Greece and epidemiologic changes throughout a period of twenty-nine years, we conducted a retrospective analysis of available data of pertussis cases for the past twenty-nine years (1980-2008) and a prospective analysis of hospitalized pertussis cases from a children's hospital in Athens for eight years (2001-2008). From 1980 through 2008, the incidence of pertussis in Greece declined from 11.2 to 0.05 cases per 100,000. Epidemic cycles occurring every 3 to 5 years were observed. Since pertussis circulation cannot be fully controlled by present immunization programs, efforts should be made to vaccinate infants at the recommended age, early diagnose, treatment as well as contact tracing of pertussis cases. Control of pertussis in social susceptible populations is necessary. A national program with adolescent and adult booster could decrease the circulation of B. pertussis. Despite an overall decrease for pertussis cases, pertussis is still a present and future challenge of public health service in Greece. PMID:23019527

  12. Diagnostic value of symptoms and laboratory data for pertussis in adolescent and adult patients

    PubMed Central

    2013-01-01

    Background Several symptoms are classically thought to be suggestive of pertussis in children, but the diagnostic value of these symptoms in adolescent and adult patients is unclear. We evaluated the accuracy of the clinical findings for the early presumptive diagnosis of pertussis in adolescent and adult patients. Furthermore, we measured fractional exhaled nitric oxide (FeNO) with regard to whether we could distinguish eosinophilic inflammation of the airway and pertussis. FeNO is not expected to be associated with pertussis. Methods We compared 183 cases with laboratory-confirmed pertussis using serology and polymerase chain reaction and 1,132 cases without laboratory-confirmed pertussis. Results Among pertussis patients, paroxysmal cough was common with 90% sensitivity, but the specificity was low (25%). Posttussive vomiting and whoop were less common (sensitivity 25% and 19%, respectively), but both showed greater specificity for pertussis (80% and 86%, respectively). Posttussive gagging was observed with intermediate frequency and provided greater specificity (49% and 77%, respectively). Pertussis cases were most frequent between May and August with a peak in June. The mean FeNO value for the pertussis patients was 18.2 ± 9.2 ppb, which was significantly lower than that in asthma patients (56.9 ± 20.3 ppb, p <0.001). The most useful definition was posttussive vomiting and/or gagging, and a plus normal FeNO value, which had a sensitivity of 72% and a specificity of 70%. Conclusions Clinical symptoms and laboratory data are of limited value in making the diagnosis of pertussis, and it was clinically difficult to differentiate adolescent and adult patients with or without pertussis. However, pertussis should be considered if patients have posttussive vomiting and/or gagging and a normal FeNO concentration. PMID:23496900

  13. Seroprevalence study of B. pertussis infection in health care workers in Catalonia, Spain

    PubMed Central

    Urbiztondo, Luis; Broner, Sonia; Costa, Josep; Rocamora, Laura; Bayas, José M; Campins, Magda; Esteve, Maria; Borras, Eva; Domínguez, Angela; for the Study of the Immune Status in Health Care, the Working Group

    2014-01-01

    Pertussis is a re-emerging infection in countries with high infant immunization coverage. Healthcare workers (HCW) are exposed and can transmit the infection to especially-vulnerable patients. Therefore, pertussis vaccination of HCW is recommended. Between June 2008 and December 2010, 460 HCW from hospital and primary healthcare centers were recruited to determine susceptibility to pertussis. IgG antibodies against pertussis (anti-pertussis ab) were measured, using a routine technique that detects antibodies against pertussis including pertussis toxin (PT) and filamentous hemagglutinin (FHA). Positive results were confirmed with a more-specific technique that only assesses anti-PT IgG antibodies. The median age was 42 years (range, 21–65), 77.3% were female. 172 were nurses, 133 physicians, 60 other clinical workers and 95 non-clinical workers. None had received pertussis vaccination since childhood. The overall prevalence of anti-pertussis antibodies was 51.7%, (95% CI 47.1–56.4). Anti-PT antibodies were determined in the 220 HCW with positive anti-pertussis antibodies: 4 (1.8%) were negative and 33 (15%) had a high titer (≥ 45 IU/mL). No significant differences between the prevalence of anti-pertussis antibodies or anti-TP antibodies were found according to age, type of occupation or type of center. Our study confirms the need for vaccination of HCW because at least half are susceptible to pertussis. High anti-PT titers found in 15% of seropositive HCW showed that they had had recent contact with B. pertussis. PMID:25483549

  14. Whooping cough in Pakistan: Bordetella pertussis vs Bordetella parapertussis in 2005-2009.

    PubMed

    Bokhari, Habib; Said, Fahad; Syed, Muhammad A; Mughal, Amjad; Kazi, Yasmeen F; Heuvelman, Kees; Mooi, Frits R

    2011-10-01

    Pertussis, or whooping cough, is an acute respiratory disease mainly affecting infants and children and is caused by Bordetella pertussis and Bordetella parapertussis. The aim of this study was to investigate the share of Bordetella species from potential whooping cough cases during 2005-2009. Eight hundred and two samples from suspected pertussis cases were collected, mainly from 2 provinces of Pakistan. Bacterial culture, identification, DNA extraction and routinely used polymerase chain reaction (PCR) methods using IS1001, IS1002 and IS481 were used to identify the Bordetella species. The results were unexpected, because all of the isolates collected from the different cities were identified as B. parapertussis (7.4%); B. pertussis was not isolated from any sample. However, PCR results indicated the presence of a small percentage (0.6%) of B. pertussis among the total cases studied. This study suggests that vaccines to protect against both B. pertussis and B. parapertussis should be considered. PMID:21563881

  15. Th1/Th2 cell dichotomy in acquired immunity to Bordetella pertussis: variables in the in vivo priming and in vitro cytokine detection techniques affect the classification of T-cell subsets as Th1, Th2 or Th0.

    PubMed Central

    Barnard, A; Mahon, B P; Watkins, J; Redhead, K; Mills, K H

    1996-01-01

    In studies of the mechanism of immunity to Bordetella pertussis in a murine respiratory infection model, we have previously demonstrated that natural infection of immunization with a whole cell vaccine induces a potent protective immune response, which is mediated by T-helper type-1 (Th1) cells. In contrast an acellular vaccine generates Th2 cells and is associated with delayed bacterial clearance following respiratory challenge. In the present study we have investigated the apparent Th1/Th2 cell dichotomy in acquired immunity and have examined the factors that affect their induction or detection. The cytokine profiles of B. pertussis-specific T cells in immune animals were determined using antigen-stimulated ex vivo spleen cells or CD4+ T-cell lines and clones established in the presence of interleukin-2 (IL-2) or IL-4. Antigen-specific T cells derived from mice immunized with the acellular vaccine were almost exclusively of the Th2 cell type. In contrast, T-cell lines and clones established following respiratory infection or immunization with the whole cell vaccine were predominantly of the Th1 type. However, a proportion of T cells from convalescent mice, especially when cultured in the presence of IL-4, secreted IL-4 and IL-5 with or without detectable IL-2 and interferon-gamma (IFN-gamma), suggesting that Th0 or Th2 cells were also primed during natural infection in vivo. Furthermore, when mice were assessed 6 months after infection, spleen cells produced significant levels of IL-4 and IL-5, which were not evident at 6 weeks. The route of immunization and the genetic background of the mice were also found to influence the preferential priming of Th1 cells, and this was directly related to the level of protection against respiratory or intracerebral (i.c.) challenge. Our findings underline the critical role of CD4+ Th1 cells in immunity to B. pertussis, but also demonstrate that a number of factors in the in vivo priming and in vitro restimulation can skew the

  16. Investigation of the Regenerative Capacity of an Acellular Porcine Medial Meniscus for Tissue Engineering Applications

    PubMed Central

    Ingram, Joanne; Fisher, John; Ingham, Eileen

    2011-01-01

    Previously, we have described the development of an acellular porcine meniscal scaffold. The aims of this study were to determine the immunocompatibility of the scaffold and capacity for cellular attachment and infiltration to gain insight into its potential for meniscal repair and replacement. Porcine menisci were decellularized by exposing the tissue to freeze–thaw cycles, incubation in hypotonic tris buffer, 0.1% (w/v) sodium dodecyl sulfate in hypotonic buffer plus protease inhibitors, nucleases, hypertonic buffer followed by disinfection using 0.1% (v/v) peracetic, and final washing in phosphate-buffered saline. In vivo immunocompatibility was assessed after implantation of the acellular meniscal scaffold subcutaneously into galactosyltransferase knockout mice for 3 months in comparison to fresh and acellular tissue treated with α-galactosidase (negative control). The cellular infiltrates in the explants were assessed by histology and characterized using monoclonal antibodies against: CD3, CD4, CD34, F4/80, and C3c. Static culture was used to assess the potential of acellular porcine meniscal scaffold to support the attachment and infiltration of primary human dermal fibroblasts and primary porcine meniscal cells in vitro. The explants were surrounded by capsules that were more pronounced for the fresh meniscal tissue compared to the acellular tissues. Cellular infiltrates compromised mononuclear phagocytes, CD34-positive cells, and nonlabeled fibroblastic cells. T-lymphocytes were sparse in all explanted tissue types and there was no evidence of C3c deposition. The analysis revealed an absence of a specific immune response to all of the implanted tissues. Acellular porcine meniscus was shown to be capable of supporting the attachment and infiltration of primary human fibroblasts and primary porcine meniscal cells. In conclusion, acellular porcine meniscal tissue exhibits excellent immunocompatibility and potential for cellular regeneration in the longer

  17. Detection of antibodies against fimbria type 3 (Fim3) is useful diagnostic assay for pertussis.

    PubMed

    Oguchi, Kaoru; Miyata, Akiko; Kazuyama, Yukimasa; Noda, Atsuya; Suzuki, Eri; Watanabe, Mineo; Nakayama, Tetsuo

    2015-09-01

    Isolation of Bordetella pertussis and detection of the pertussis genome are not always successful because of low bacterial loads in adult patients with pertussis. Antibodies against pertussis toxin (PT) are measured but have low sensitivity in vaccinated subjects. There is no reliable diagnostic method at present. In this study, a fluorescent-EIA against several pertussis antigens and genome detection were investigated to establish clinical laboratory diagnostic methods for pertussis. The study was conducted in an outpatient clinic between September 2007 and 2013. Subjects consisted of 209 patients including adults suspected of pertussis and 35 staff members of the clinic. Loop-mediated isothermal amplification (LAMP) was performed to detect the pertussis genome in 5' UTR of the pertussis toxin (PT) gene. The catalytic region of the adenylate cyclase toxin (catACT), C-terminal of filamentous hemagglutinin (cFHA), and type 3 fimbria (Fim3) were selected, which are not pertussis vaccine component. Conventional PT and FHA antibodies were examined together with type 2 fimbria (Fim2) antibodies, and these are vaccine antigens. Pertussis DNA was detected in 23 (11%) out of 209. Detection sensitivity was high in young infants. Antibodies against Fim3 showed a higher positive rate in all age groups. Staff members at the pediatric outpatient clinic showed serological booster responses in Fim2 and Fim3 antibodies more sensitively than those in PT antibodies during outbreaks. LAMP was useful for detecting the pertussis genome in young infants, whereas a serological assay for fluorescent-EIA against Fim2 and Fim3 was preferable for adolescents and adults. PMID:26134278

  18. Serum Immunoglobulin G Analysis to Establish a Delayed Diagnosis of Chronic Cough due to Bordetella pertussis

    PubMed Central

    Bock, Jonathan M.; Burtis, Charles C.; Poetker, David M.; Blumin, Joel H.; Frank, Michael O.

    2014-01-01

    Objectives Incidence of Bordetella pertussis infection among adults has risen significantly throughout the United States, but pertussis is not often considered in the differential diagnosis of chronic cough in adults. The authors hypothesized that serum IgG testing can establish a diagnosis of pertussis infection late in disease presentation when cultures and polymerase chain reaction (PCR) testing are not reliable. Study Design Case series with chart review. Setting Tertiary care hospital. Subjects and Methods Institutional B pertussis serum IgG and PCR tests were reviewed since 2007. Clinical factors assessed included vaccination history, duration and severity of cough, and general medical history. Results Forty-eight patients had B pertussis fimbrial agglutinogen IgG levels tested since 2007, with a significant increase in positive IgG tests (>27 IU/mL, 3 times the upper limit of normal) since fall 2009. Nineteen patients (39.5%) met IgG criteria for likely recent pertussis infection. Six IgG-positive patients also had PCR swab testing performed, with 50% positive for B pertussis. IgG values were similar for patients with positive or negative B pertussis PCR testing with positive IgG titers. IgG-positive patients were much more likely to have posttussive syncope. Recent vaccination for pertussis within the 3 years prior to IgG testing did not significantly increase IgG levels. Conclusions One-time B pertussis serum IgG testing and patient history can establish a likely diagnosis of recent pertussis infection in the adult patient with chronic cough late in disease presentation when PCR testing is often negative. Pertussis should be considered in the differential diagnosis of all patients with chronic cough. PMID:21987649

  19. Recovery of Bordetella pertussis from PCR-Positive Nasopharyngeal Samples Is Dependent on Bacterial Load

    PubMed Central

    Steinbakk, Martin; Bjørnstad, Martha L.; Moghaddam, Amir; Reinton, Nils; Dahl, Mette L.; Grude, Nils; Sandven, Per

    2012-01-01

    Viable Bordetella pertussis isolates are essential for surveillance purposes. We performed culture of 223 PCR-positive nasopharyngeal samples. B. pertussis was recovered from 45 (20.2%) of the samples. Growth was associated with a high bacterial load, as determined by PCR. Culture from PCR-positive samples is a feasible approach to recover B. pertussis isolates, and culture can be limited to samples with a high bacterial load. PMID:23035189

  20. Recovery of Bordetella pertussis from PCR-positive nasopharyngeal samples is dependent on bacterial load.

    PubMed

    Vestrheim, Didrik F; Steinbakk, Martin; Bjørnstad, Martha L; Moghaddam, Amir; Reinton, Nils; Dahl, Mette L; Grude, Nils; Sandven, Per

    2012-12-01

    Viable Bordetella pertussis isolates are essential for surveillance purposes. We performed culture of 223 PCR-positive nasopharyngeal samples. B. pertussis was recovered from 45 (20.2%) of the samples. Growth was associated with a high bacterial load, as determined by PCR. Culture from PCR-positive samples is a feasible approach to recover B. pertussis isolates, and culture can be limited to samples with a high bacterial load. PMID:23035189

  1. Attitudes, knowledge and perceptions towards whooping cough and pertussis vaccine in hospitalized adults.

    PubMed

    Ridda, Iman; Gao, Zhanhai; Macintyre, C Raina

    2014-02-19

    Whooping cough or pertussis is a major cause of morbidity and mortality for adults and children around the world. There has been a rise in pertussis-related deaths in the elderly; pertussis vaccination is not currently routinely recommended in adults, excepting new parents and other adults household members including grandparents and care-givers of young children. Currently, there is lack of clear vaccine recommendations after the age of 50 years. Given the increase in adult pertussis, adult vaccine recommendations are a policy consideration. The study surveyed a convenience sample of patients previously recruited in a case control study designed to examine the burden of influenza with and without AMI in adults aged ≥ 40 years. Our findings showed that only 9.6% had received the pertussis vaccination within the past five years and 79.4% of participants had no knowledge of the pertussis adult booster vaccine, and 30.7% of participants who had regular contact with children under the age of two years in the past 12 months. The results showed that even though there is general acceptance of prevention by vaccines, there is low awareness about pertussis vaccination. This lack of knowledge presents a barrier against pertussis vaccination thus it is imperative that any future adult immunisation policy recommendations around pertussis vaccine include awareness programs in the target population. PMID:24370707

  2. The potential role of subclinical Bordetella Pertussis colonization in the etiology of multiple sclerosis.

    PubMed

    Rubin, Keith; Glazer, Steven

    2016-04-01

    It is established that (1) subclinical Bordetella pertussis colonization of the nasopharynx persists in highly vaccinated populations, and (2) B. pertussis toxin is a potent adjuvant that, when co-administered with neural antigens, induces neuropathology in experimental autoimmune encephalomyelitis, the principle animal model of multiple sclerosis. Building on these observations with supporting epidemiologic and biologic evidence, we propose that, contrary to conventional wisdom that subclinical pertussis infections are innocuous to hosts, B. pertussis colonization is an important cause of multiple sclerosis. PMID:26724970

  3. [Experimental, clinical and immunologic assessment of acellular staphylococcal vaccine "Staphylovac"].

    PubMed

    Egorova, N B; Efremova, V N; Kurbatova, E A; Gruber, I M

    2008-01-01

    Results of experimental, clinical and immunological effects of acellular dry staphylococcal vaccine "Staphylovac" developed in Mechnikov Research Institute of Vaccines and Sera are presented. Original mildly virulent strains of Staphylococcus aureus having high immunogenicity, and intra- and interspecies protective activity against different representatives of opportunistic microflora were used for construction of the preparation. Low-toxicity and weak anapylactogenicity of the vaccine were established. In experiments on mice, guinea pigs and rabbits significant protective, antigenic and immunomodulate activity of the preparation was revealed with low sensitization of animals. Clinical trials performed in different centers showed that inclusion of vaccinotherapy in complex treatment of chronic staphylococcal infections (chronic pyodermia, lung abscess etc.) resulted in prolonged pathologic locus, decrease of number and severity of exacerbations, prolongation of remission, and complete recovery in significant number of patients. Activation of innate and adaptive immunity was revealed in the same patients. It was shown on the large group of athletes that administration of the vaccine by aerosol route prevents disruption of immunologic adaptation occurring due to excess physical activity and stress situations during competitions. PMID:19186558

  4. Spherical indentation of free-standing acellular extracellular matrix membranes.

    PubMed

    Cloonan, Aidan J; O'Donnell, Michael R; Lee, William T; Walsh, Michael T; De Barra, Eamonn; McGloughlin, Tim M

    2012-01-01

    Numerous scaffold materials have been developed for tissue engineering and regenerative medicine applications to replace or repair damaged tissues and organs. Naturally occurring scaffold materials derived from acellular xenogeneic and autologous extracellular matrix (ECM) are currently in clinical use. These biological scaffold materials possess inherent variations in mechanical properties. Spherical indentation or ball burst testing has commonly been used to evaluate ECM and harvested tissue due to its ease of use and simulation of physiological biaxial loading, but has been limited by complex material deformation profiles. An analytical methodology has been developed and applied to experimental load-deflection data of a model hyperelastic material and lyophilized ECM scaffolds. An optimum rehydration protocol was developed based on water absorption, hydration relaxation and dynamic mechanical analysis. The analytical methodology was compared with finite element simulations of the tests and excellent correlation was seen between the computed biaxial stress resultants and geometry deformations. A minimum rehydration period of 5 min at 37°C was sufficient for the evaluated multilaminated ECM materials. The proposed approach may be implemented for convenient comparative analysis of ECM materials and source tissues, process optimization or during lot release testing. PMID:21864728

  5. Essential immunogens in human pertussis: the role of fimbriae.

    PubMed

    Preston, N W

    1985-01-01

    After the decline in pertussis vaccination in Britain from the mid-1970s, isolates possessing agglutinogen 2 (types 1.2.3 and 1.2) have replaced type 1.3 as the predominant serotypes. These agglutinogen-2 strains are fimbriate, and their predominance in non-vaccinated communities may result from enhanced attachment to mucosal cells. However, type 1.3 cells are not fimbriate; and, because agglutinogen 3 is essential in fully effective whole-cell vaccine, a subcellular vaccine prepared from fimbriae alone (agglutinogen 2) would probably be inadequate. The mouse can be killed with type 1 strains, devoid of agglutinogens 2 and 3, and is therefore not a suitable model for ensuring that pertussis vaccine contains these essential immunogens. PMID:2872099

  6. Perinatal management of fetal supraventricular tachycardia complicated by maternal pertussis.

    PubMed

    Dejong, Stephanie; Salmanian, Bahram; Shamshirsaz, Alireza A; Ruano, Rodrigo

    2015-01-01

    Prenatal pertussis has become a concern once again with the reappearance of the disease in the USA. A 30-year-old mother whose pregnancy was complicated with fetal arrhythmia was referred for further evaluation in the third trimester. After initial treatment with antiarrhythmic medications due to continued irregular rhythm, she was revisited for persistent hacking cough at 38 weeks gestational age. PCR examination confirmed pertussis diagnosis. Owing to increased risk of digoxin toxicity with concurrent antibiotic administration, antiarrhythmic medication was discontinued. Delivery was induced 2 days after the initiation of azithromycin therapy to prevent the transmission of the disease to the neonate. A well-planned delivery in a patient with prenatal diagnosis prevents neonatal infection while considering the obstetrical dilemma for concurrent management of the intrauterine arrhythmia and antibiotic administration. PMID:26153285

  7. Critical Pertussis Illness in Children, A Multicenter Prospective Cohort Study

    PubMed Central

    Berger, John T.; Carcillo, Joseph A.; Shanley, Thomas P.; Wessel, David L.; Clark, Amy; Holubkov, Richard; Meert, Kathleen L.; Newth, Christopher J.L.; Berg, Robert A.; Heidemann, Sabrina; Harrison, Rick; Pollack, Murray; Dalton, Heidi; Harvill, Eric; Karanikas, Alexia; Liu, Teresa; Burr, Jeri S.; Doctor, Allan; Dean, J. Michael; Jenkins, Tammara L.; Nicholson, Carol E.

    2013-01-01

    Objective Pertussis persists in the United States despite high immunization rates. The present report characterizes the presentation and acute course of critical pertussis by quantifying demographic data, laboratory findings, clinical complications, and critical care therapies required among children requiring admission to the pediatric intensive care unit (PICU). Design Prospective cohort study. Setting Eight PICUs comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 17 additional PICUs across the United States. Patients Eligible patients had laboratory confirmation of pertussis infection, were < 18 years of age, and died in the PICU or were admitted to the PICU for at least 24 hours between June 2008 and August 2011. Interventions None. Measurements and Main Results 127 patients were identified. Median age was 49 days, and 105 (83%) patients were < 3 months of age. Fifty-five (43%) required mechanical ventilation. Twelve (9.4%) died during initial hospitalization. Pulmonary hypertension was found in 16 patients (12.5%), and was present in 75% of patients who died, compared with 6% of survivors (p< 0.001). Median white blood cell count (WBC) was significantly higher in those requiring mechanical ventilation (p<0.001), those with pulmonary hypertension (p<0.001) and non-survivors (p<0.001). Age, sex and immunization status did not differ between survivors and non-survivors. Fourteen patients received leukoreduction therapy (exchange transfusion (12), leukopheresis (1) or both (1)). Survival benefit was not apparent. Conclusions Pulmonary hypertension may be associated with mortality in pertussis critical illness. Elevated WBC is associated with the need for mechanical ventilation, pulmonary hypertension, and mortality risk. Research is indicated to elucidate how pulmonary hypertension, immune responsiveness, and elevated WBC contribute to morbidity and mortality

  8. Laboratory-based surveillance of pertussis using multitarget real-time PCR in Japan: evidence for Bordetella pertussis infection in preteens and teens.

    PubMed

    Kamachi, K; Yoshino, S; Katsukawa, C; Otsuka, N; Hiramatsu, Y; Shibayama, K

    2015-11-01

    Between January 2013 and December 2014, we conducted laboratory-based surveillance of pertussis using multitarget real-time PCR, which discriminates among Bordetella pertussis, Bordetella parapertussis, Bordetella holmesii and Mycoplasma pneumoniae. Of 355 patients clinically diagnosed with pertussis in Japan, B. pertussis, B. parapertussis and M. pneumoniae were detected in 26% (n = 94), 1.1% (n = 4) and 0.6% (n = 2), respectively, whereas B. holmesii was not detected. It was confirmed that B. parapertussis and M. pneumoniae are also responsible for causing pertussis-like illness. The positive rates for B. pertussis ranged from 16% to 49%, depending on age. Infants aged ≤ 3 months had the highest rate (49%), and children aged 1 to 4 years had the lowest rate (16%, p < 0.01 vs. infants aged ≤ 3 months). Persons aged 10 to 14 and 15 to 19 years also showed high positive rates (29% each); the positive rates were not statistically significant compared with that of infants aged ≤ 3 months (p ≥ 0.06). Our observations indicate that similar to infants, preteens and teens are at high risk of B. pertussis infection. PMID:27076914

  9. Laboratory-based surveillance of pertussis using multitarget real-time PCR in Japan: evidence for Bordetella pertussis infection in preteens and teens

    PubMed Central

    Kamachi, K.; Yoshino, S.; Katsukawa, C.; Otsuka, N.; Hiramatsu, Y.; Shibayama, K.

    2015-01-01

    Between January 2013 and December 2014, we conducted laboratory-based surveillance of pertussis using multitarget real-time PCR, which discriminates among Bordetella pertussis, Bordetella parapertussis, Bordetella holmesii and Mycoplasma pneumoniae. Of 355 patients clinically diagnosed with pertussis in Japan, B. pertussis, B. parapertussis and M. pneumoniae were detected in 26% (n = 94), 1.1% (n = 4) and 0.6% (n = 2), respectively, whereas B. holmesii was not detected. It was confirmed that B. parapertussis and M. pneumoniae are also responsible for causing pertussis-like illness. The positive rates for B. pertussis ranged from 16% to 49%, depending on age. Infants aged ≤ 3 months had the highest rate (49%), and children aged 1 to 4 years had the lowest rate (16%, p < 0.01 vs. infants aged ≤ 3 months). Persons aged 10 to 14 and 15 to 19 years also showed high positive rates (29% each); the positive rates were not statistically significant compared with that of infants aged ≤ 3 months (p ≥ 0.06). Our observations indicate that similar to infants, preteens and teens are at high risk of B. pertussis infection. PMID:27076914

  10. Purification and characterization of fimbriae isolated from Bordetella pertussis.

    PubMed Central

    Zhang, J M; Cowell, J L; Steven, A C; Carter, P H; McGrath, P P; Manclark, C R

    1985-01-01

    Fimbriae were detached from Bordetella pertussis by mechanical shearing and purified by successive precipitations with ammonium sulfate, phosphate buffer (pH 6.0), and magnesium chloride. In each of these purification steps, the fimbriae aggregated into bundles as seen by electron microscopy. These aggregates could be disaggregated at pH 9.5. By electron microscopy, the purified fimbriae appeared as long filaments with a diameter of 5 nm. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified fimbriae showed a single protein subunit with a molecular weight of 22,000. The purified fimbriae did not have hemagglutinating activity when assayed with several types of erythrocytes, and they were antigenically, chemically, and structurally distinct from the filamentous hemagglutinin of B. pertussis. The purified fimbriae were also identified as serotype 2 agglutinogens, since antibody to the purified fimbriae agglutinated B. pertussis strains serotyped as 1.2.4, 1.2.3, or 1.2.3.6 but did not agglutinate those serotyped as 1.3.6. Images PMID:2859248

  11. Sustained Transmission of Pertussis in Vaccinated, 1–5-Year-Old Children in a Preschool, Florida, USA

    PubMed Central

    Pritchard, P. Scott; Martin, Stacey W.; Dusek, Cristina; Cathey, Erika; D’Alessio, Rebecca; Kirsch, Marjorie

    2016-01-01

    In September 2013, local county health officials in Tallahassee, Florida, USA, were notified of a laboratory-confirmed pertussis case in a 1-year-old preschool attendee. During a 5-month period, 26 (22%) students 1–5 years of age, 2 staff from the same preschool, and 11 family members met the national case definition for pertussis. Four persons during this outbreak were hospitalized for clinical management of pertussis symptoms. Only 5 students, including 2 students with pertussis, had not received the complete series of vaccinations for pertussis. Attack rates in 1 classroom for all students who received the complete series of vaccinations for pertussis approached 50%. This outbreak raises concerns about vaccine effectiveness in this preschool age group and reinforces the idea that recent pertussis vaccination should not dissuade physicians from diagnosing, testing, or treating persons with compatible illness for pertussis. PMID:26814429

  12. National and state vaccination coverage among adolescents aged 13-17 years--United States, 2012.

    PubMed

    2013-08-30

    At ages 11 through 12 years, the Advisory Committee on Immunization Practices (ACIP) recommends that preteens receive 1 dose of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine, 1 dose of meningococcal conjugate (MenACWY) vaccine, and 3 doses of human papillomavirus (HPV) vaccine. ACIP recommends administration of all age-appropriate vaccines during a single visit. ACIP also recommends that pre-teens and older adolescents receive an annual influenza vaccine as well as any overdue vaccines (e.g., varicella). To monitor vaccination coverage among persons aged 13-17 years, CDC analyzed data from the National Immunization Survey-Teen (NIS-Teen). This report highlights findings of that analysis. From 2011 to 2012, coverage increased for ≥1 Tdap vaccine dose (from 78.2% to 84.6%), ≥1 MenACWY vaccine dose (from 70.5% to 74.0%) and, among males, ≥1 HPV vaccine dose (from 8.3% to 20.8%). Among females, vaccination coverage estimates for each HPV vaccine series dose were similar in 2012 compared with 2011. Coverage varied substantially among states. Regarding Healthy People 2020 targets for adolescents, 36 states achieved targets for Tdap, 12 for MenACWY, and nine for varicella vaccine coverage. Large and increasing coverage differences between Tdap and other vaccines recommended for adolescents indicate that substantial missed opportunities remain for vaccinating teens, especially against HPV infection. Health-care providers should administer recommended HPV and meningococcal vaccinations to boys and girls during the same visits when Tdap vaccine is given. In addition, whether for health problems or well-checks, providers, parents, and adolescents should use every health-care visit as an opportunity to review adolescents' immunization histories and ensure that every adolescent is fully vaccinated. PMID:23985496

  13. Intention to Accept Pertussis Vaccination for Cocooning: A Qualitative Study of the Determinants

    PubMed Central

    Hautvast, Jeannine L. A.; van der Velden, Koos; Hulscher, Marlies E. J. L.

    2016-01-01

    Context Several countries have reported a resurgence of pertussis in the last decades. This puts infants (especially <6 months) at risk of severe complications, because they are too young to be fully protected by vaccination. The global pertussis initiative has proposed pertussis vaccination of young infants’ close contacts, in order to reduce pertussis transmission and the burden of the disease on infants. Our aim is to explore the perceived determinants (barriers and facilitators) of intention to accept vaccination among the possible target groups of pertussis vaccination for cocooning. Consideration of these determinants is necessary to optimise the uptake of the vaccination. Methods We conducted 13 focus groups and six individual semi-structured interviews with members of possible target groups for pertussis cocooning (i.e. parents, maternity assistants, midwives, and paediatric nurses) in the Netherlands. Here, both maternal pertussis vaccination as well as pertussis cocooning has not been implemented. The topic list was based on a literature review and a barrier framework. All interviews were transcribed verbatim and two researchers performed thematic content analysis. Findings The participants’ risk perception, outcome expectations, general vaccination beliefs, moral norms, opinion of others, perceived autonomy, anticipated regret, decisional uncertainty, and perceived organisational barriers were all factors that influenced the intention to accept pertussis vaccination for cocooning. Discussion This study has identified nine perceived determinants that influence the intention to accept pertussis cocooning vaccination. We add the following determinants to the literature: perceived cost-effectiveness (as a concept of outcome expectations), justice (as a concept of moral norms), anticipated regret, and decisional uncertainty. We recommend considering these determinants in vaccination programmes for pertussis cocooning vaccination. Experience, information

  14. ADP-ribosylation of transducin by pertussis toxin

    SciTech Connect

    Watkins, P.A.; Burns, D.L.; Kanaho, Y.; Liu, T.Y.; Hewlett, E.L.; Moss, J.

    1985-11-05

    Transducin, the guanyl nucleotide-binding regulatory protein of retinal rod outer segments that couples the photon receptor, rhodopsin, with the light-activated cGMP phosphodiesterase, can be resolved into two functional components, T alpha and T beta gamma. T alpha (39 kDa), which is (TSP)ADP-ribosylated by pertussis toxin and (TSP)NAD in rod outer segments and in purified transducin, was also labeled by the toxin after separation from T beta gamma (36 kDa and approximately 10 kDa); neither component of T beta gamma was a pertussis toxin substrate. Labeling of T alpha was enhanced by T beta gamma and was maximal at approximately 1:1 molar ratio of T alpha : T beta gamma. Limited proteolysis by trypsin of T alpha in the presence of guanyl-5'-yl imidodiphosphate (Gpp(NH)p) resulted in the sequential appearance of proteins of 38 and TS kDa. The amino terminus of both 38- and TS-kDa proteins was leucine, whereas that of T alpha could not be identified and was assumed to be blocked. The TS-kDa peptide was not a pertussis toxin substrate. Labeling of the 38-kDa protein was poor and was not enhanced by T beta gamma. Trypsin treatment of (TSP)ADP-ribosyl-T alpha produced a labeled 37-38-kDa doublet followed by appearance of radioactivity at the dye front. It appears, therefore, that, although the 38-kDa protein was poor toxin substrate, it contained the ADP-ribosylation site. Without rhodopsin, labeling of T alpha (in the presence of T beta gamma) was unaffected by Gpp(NH)p, guanosine 5'-O-(thiotriphosphate) (GTP gamma S), GTP, GDP, and guanosine 5'-O-(thiodiphosphate) (GDP beta S) but was increased by ATP. When photolyzed rhodopsin and T beta gamma were present, Gpp(NH)p and GTP gamma S decreased (TSP)ADP-ribosylation by pertussis toxin. Thus, pertussis toxin-catalyzed (TSP)ADP-ribosylation of T alpha was affected by nucleotides, rhodopsin and light in addition to T beta gamma.

  15. Synergistic binding of RNA polymerase and BvgA phosphate to the pertussis toxin promoter of Bordetella pertussis.

    PubMed Central

    Boucher, P E; Stibitz, S

    1995-01-01

    Regulation of virulence factor expression in Bordetella pertussis is mediated by the BvgAS two-component regulatory system. Although previous studies have demonstrated that the transcriptional regulation of the filamentous hemagglutinin gene (fhaB) involves binding of the BvgA activator directly to the fhaB promoter region, the mechanism of pertussis toxin operon (ptx) regulation by BvgA has remained unclear. We demonstrate in vitro the specific binding of BvgA to a region upstream of the ptx promoter that encompasses a 20-bp directly repeated sequence (positions -157 to -117) previously shown to be critical for BvgA-dependent activation. This binding is strictly dependent on the phosphorylation of BvgA, which can be obtained by incubation of BvgA with acetyl phosphate. By DNase I protection studies, we demonstrate the synergistic binding of BvgA-phosphate and purified Escherichia coli RNA polymerase to the ptx promoter. In the presence of the polymerase holoenzyme, a greatly extended footprint encompassing the region between -163 and the putative polymerase binding site was observed. The implications of these observations for pertussis toxin expression and regulation are discussed. PMID:7592424

  16. Temporal Expression of Pertussis Toxin and Ptl Secretion Proteins by Bordetella pertussis

    PubMed Central

    Rambow-Larsen, Amy A.; Weiss, Alison A.

    2004-01-01

    Pertussis toxin is an AB5 toxin comprised of protein subunits S1 through S5. The individual subunits are secreted by a Sec-dependent mechanism into the periplasm, where the toxin is assembled. The Ptl type IV secretion system mediates secretion of assembled toxin past the outer membrane. In this study, we examined the time course of protein expression, toxin assembly, and secretion as a function of the bacterial growth cycle. Logarithmic growth was observed after a 1-h lag phase. Secreted toxin was first observed at 3 h. Secretion continued throughout the logarithmic growth phase and decreased as the culture entered the stationary phase after about 24 h. On a per cell basis, toxin secretion occurred at a constant rate of 3 molecules/min/cell from 2 to 18 h. More of toxin subunits S1, S2, and S3 were produced than were secreted, resulting in periplasmic accumulation. Periplasmic S1, S2, and S3 were found to be soluble in the periplasm, as well as membrane associated. About one-half of the periplasmic S1, S2 and S3 subunits were incorporated into holotoxin. Secretion component PtlF was present at a low level at time zero, and the level increased between 2 and 24 h from 30 to 1,000 molecules per cell; however, the initial level of PtlF, 30 molecules per cell, supported maximal secretion. The accumulation of both periplasmic toxin and secretion components suggests that translation rates exceed the rate of secretion and that secretion, not toxin and Ptl complex assembly, is rate limiting. PMID:14679223

  17. Combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b vaccine; Infanrix™ hexa

    PubMed Central

    Baldo, Vincenzo; Bonanni, Paolo; Castro, Marcela; Gabutti, Giovanni; Franco, Elisabetta; Marchetti, Federico; Prato, Rosa; Vitale, Francesco

    2014-01-01

    Infant vaccination using 2-dose priming at 3 and 5 mo of age with a booster at 11–12 mo of age was pioneered in Italy. The 3-5-11 schedule is now used in a growing number of European countries. Infanrix™ hexa (DTPa-HBV-IPV/Hib, GlaxoSmithKline Vaccines) was first licensed for use in 2000 and has been the only pediatric hexavalent vaccine available since 2005. We reviewed available clinical trial data describing the immunogenicity of DTPa-HBV-IPV/Hib when administered at 3, 5, and 11 mo of age, and conducted an analysis of safety using global and Italian post-marketing surveillance data. In Italy, DTPa-HBV-IPV/Hib has a demonstrated safety record extending over a decade of use, it has been associated with record levels of vaccine coverage, and with sustained disease control in vaccinated cohorts. Hexavalent vaccines will continue to contribute to high vaccine coverage in Italy and across Europe. PMID:24004825

  18. Agglutinating monoclonal antibodies that specifically recognize lipooligosaccharide A of Bordetella pertussis.

    PubMed Central

    Li, Z M; Cowell, J L; Brennan, M J; Burns, D L; Manclark, C R

    1988-01-01

    Monoclonal antibodies that specifically agglutinate strains of Bordetella pertussis having serotype 1 agglutinogen were uniquely reactive with the electrophoretically slow-migrating A form of lipooligosaccharide. These monoclonal antibodies should be useful for the structural analysis of B. pertussis lipooligosaccharide and for the establishment of a better-defined serogroup for Bordetella species. Images PMID:2893776

  19. Agglutinating monoclonal antibodies that specifically recognize lipooligosaccharide A of Bordetella pertussis.

    PubMed

    Li, Z M; Cowell, J L; Brennan, M J; Burns, D L; Manclark, C R

    1988-03-01

    Monoclonal antibodies that specifically agglutinate strains of Bordetella pertussis having serotype 1 agglutinogen were uniquely reactive with the electrophoretically slow-migrating A form of lipooligosaccharide. These monoclonal antibodies should be useful for the structural analysis of B. pertussis lipooligosaccharide and for the establishment of a better-defined serogroup for Bordetella species. PMID:2893776

  20. Complete Genome Sequences of 11 Bordetella pertussis Strains Representing the Pandemic ptxP3 Lineage

    PubMed Central

    Bart, Marieke J.; van der Heide, Han G. J.; Zeddeman, Anne; Heuvelman, Kees; Mooi, Frits R.

    2015-01-01

    Pathogen adaptation has contributed to the resurgence of pertussis. To facilitate our understanding of this adaptation we report here 11 completely closed and annotated Bordetella pertussis genomes representing the pandemic ptxP3 lineage. Our analyses included six strains which do not produce the vaccine components pertactin and/or filamentous hemagglutinin. PMID:26607899

  1. Adaptive immune response to whole cell pertussis vaccine reflects vaccine quality: A possible complementation to the Pertussis Serological Potency test.

    PubMed

    Hoonakker, M E; Verhagen, L M; van der Maas, L; Metz, B; Uittenbogaard, J P; van de Waterbeemd, B; van Els, C A C M; van Eden, W; Hendriksen, C F M; Sloots, A; Han, W G H

    2016-08-17

    Whole cell Bordetella pertussis (wP) vaccines are still used in many countries to protect against the respiratory disease pertussis. The potency of whole-cell pertussis vaccine lots is determined by an intracerebral challenge test (the Kendrick test). This test is criticized due to lack of immunological relevance of the read-out after an intracerebral challenge with B. pertussis. The alternative in vivo test, which assesses specific antibody levels in serum after wP vaccination, is the Pertussis Serological Potency test (PSPT). Although the PSPT focuses on a parameter that contributes to protection, the protective immune mechanisms after wP vaccination includes more elements than specific antibody responses only. In this study, additional parameters were investigated, i.e. circulating pro-inflammatory cytokines, antibody specificity and T helper cell responses and it was evaluated whether they can be used as complementary readout parameters in the PSPT to assess wP lot quality. By deliberate manipulation of the vaccine preparation procedure, a panel of high, intermediate and low quality wP vaccines were made. The results revealed that these vaccines induced similar IL-6 and IP10 levels in serum 4h after vaccination (innate responses) and similar antibody levels directed against the entire bacterium. In contrast, the induced antibody specificity to distinct wP antigens differed after vaccination with high, intermediate and low quality wP vaccines. In addition, the magnitude of wP-induced Th cell responses (Th17, Th1 and Th2) was reduced after vaccination with a wP vaccine of low quality. T cell responses and antibody specificity are therefore correlates of qualitative differences in the investigated vaccines, while the current parameter of the PSPT alone was not sensitive enough to distinguish between vaccines of different qualities. This study demonstrates that assessment of the magnitude of Th cell responses and the antigen specificity of antibodies induced by w

  2. Pertussis toxin inhibits somatostatin-induced K/sup +/ conductance in human pituitary tumor cells

    SciTech Connect

    Yamashita, N.; Kojima, I.; Shibuya, N.; Ogata, E.

    1987-07-01

    The effect of pertussis toxin on somatostatin-induced K/sup +/ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K/sup +/ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma, 1, 0/10 in adenoma 2). Spontaneous action potentials, K/sup +/, Na/sup +/, and Ca/sup 2 +/ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with (/sup 32/P)NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.

  3. The contribution of PCR testing to influenza and pertussis notifications in Australia.

    PubMed

    Kaczmarek, M C; Ware, R S; Lambert, S B

    2016-01-01

    Influenza and pertussis are the two most common vaccine-preventable infections notified in Australia. We assessed the role of polymerase chain reaction (PCR) diagnosis in influenza and pertussis cases notified to the Australian National Notifiable Diseases Surveillance System (NNDSS). There were a total of 2 10 786 notified influenza cases (2001-2013) and 2 55 866 notified pertussis cases (1991-2013). After 1 January 2007, the majority of influenza and pertussis notifications were PCR-based (80·5% and 59·6%, respectively). Before 31 December 2006, PCR-based notifications were limited (29·1% and 11·7%, respectively). By 2013, PCR-based notifications had largely replaced all other diagnostic methods, with the exception of serology-based notifications in pertussis cases in adults aged ⩾ 25 years. PMID:26112983

  4. Genotypic Variation in the Bordetella pertussis Virulence Factors Pertactin and Pertussis Toxin in Historical and Recent Clinical Isolates in the United Kingdom

    PubMed Central

    Fry, Norman K.; Neal, Shona; Harrison, Timothy G.; Miller, Elizabeth; Matthews, Ruth; George, Robert C.

    2001-01-01

    The reemergence of pertussis has been reported in several countries despite high vaccination coverage. Studies in The Netherlands and Finland have investigated polymorphism in the genes coding for two important virulence factors of Bordetella pertussis, pertactin and pertussis toxin, and identified the emergence and subsequent dominance in circulating strains of pertactin and toxin variants not found in the whole-cell vaccine (WCV). The study described here investigated whether such variation had occurred in the United Kingdom, which presently has low levels of pertussis. Sequence analysis of the genes for pertactin (prnA) and the pertussis toxin S1 subunit (ptxA) among isolates of B. pertussis from 285 United Kingdom patients, from 1920 to 1999, revealed three prnA variants, prnA(1), prnA(2), and prnA(3), and two ptxA variants, ptxA(1) and ptxA(2), showing differences in nucleic acid sequence. The proportion of pertactin gene types not included in the United Kingdom WCV, i.e., prnA(2) and prnA(3), has increased in recent years and was found in 21 of 86 (24%) strains from the 1980s and 56 of 105 (53%) strains from the 1990s. To date, the presence of these nonvaccine prnA types has not been associated with a resurgence of pertussis in the United Kingdom. The distribution of prnA and ptxA types in The Netherlands, Finland, and the United Kingdom in the 1990s is distinct. The most striking difference in the United Kingdom isolates is that all 105 of the most recent circulating strains (from 1998 to 1999) are of a pertussis toxin type found in the United Kingdom WCV, i.e., ptxA(1). PMID:11500425

  5. Role of whole-cell pertussis vaccine in severe local reactions to the preschool (fifth) dose of diphtheria-pertussis-tetanus vaccine.

    PubMed Central

    Scheifele, D W; Bjornson, G; Halperin, S H; Mitchell, L; Boraston, S

    1994-01-01

    OBJECTIVE: To estimate the contribution of whole-cell pertussis vaccine to severe local reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine. DESIGN: Double-blind randomized controlled trial. SETTING: Urban community. PARTICIPANTS: Volunteer sample of 200 healthy children 4 to 6 years old who were eligible for the fifth dose of DPT vaccine. INTERVENTIONS: Children received, in both arms, either diphtheria toxoid-tetanus toxoid (DT) and monovalent pertussis vaccines (group A, 99 children) or DPT and meningococcal vaccines (group B, 101 children). All were licensed products from single lots. The children were assessed 24 hours later by a trained observer. Serum samples obtained before vaccination were tested for antibodies to tetanus and diphtheria toxins and five pertussis antigens by means of enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of severe local reactions (an area of redness or swelling or both of 50 mm or greater) 24 hours after vaccination. Relation between serum antibody levels before vaccination and rates of severe local reactions to corresponding vaccines. RESULTS: All of the subjects were followed up 24 hours after vaccination. Severe redness was present in 38% given DPT vaccine, 29% given intramuscular pertussis vaccine and 9% given DT vaccine (p < or = 0.002, three-way comparison). Severe swelling was common after vaccination with all three products. After intramuscular pertussis vaccination a relation was evident between the prevaccination levels of antibody to whole-cell pertussis bacteria and the rates of redness (p < 0.02) but not between the prevaccination subcellular antibody levels and the rates of redness. CONCLUSION: That pertussis vaccine resembled the DPT vaccine in causing severe redness suggests that it is the principal cause of such reactions after DPT vaccination. The DT vaccine was also reactogenic; thus, cumulative sensitization to one or more of

  6. Survey and Rapid Detection of Bordetella pertussis in Clinical Samples Targeting the BP485 in China

    PubMed Central

    Liu, Wei; Xu, Yinghua; Dong, Derong; Li, Huan; Zhao, Xiangna; Li, Lili; Zhang, Ying; Wei, Xiao; Wang, Xuesong; Huang, Simo; Zeng, Ming; Huang, Liuyu; Zhang, Shumin; Yuan, Jing

    2015-01-01

    Bordetella pertussis is an important human respiratory pathogen. Here, we describe a loop-mediated isothermal amplification (LAMP) method for the rapid detection of B. pertussis in clinical samples based on a visual test. The LAMP assay detected the BP485 target sequence within 60 min with a detection limit of 1.3 pg/μl, a 10-fold increase in sensitivity compared with conventional PCR. All 31 non-pertussis respiratory pathogens tested were negative for LAMP detection, indicating the high specificity of the primers for B. pertussis. To evaluate the application of the LAMP assay to clinical diagnosis, of 105 sputum and nasopharyngeal samples collected from the patients with suspected respiratory infections in China, a total of 12 B. pertussis isolates were identified from 33 positive samples detected by LAMP-based surveillance targeting BP485. Strikingly, a 4.5 months old baby and her mother were found to be infected with B. pertussis at the same time. All isolates belonged to different B. pertussis multilocus sequence typing groups with different alleles of the virulence-related genes including four alleles of ptxA, six of prn, four of tcfA, two of fim2, and three of fim3. The diversity of B. pertussis carrying toxin genes in clinical strains indicates a rapid and continuing evolution of B. pertussis. This combined with its high prevalence will make it difficult to control. In conclusion, we have developed a visual detection LAMP assay, which could be a useful tool for rapid B. pertussis detection, especially in situations where resources are poor and in point-of-care tests. PMID:25798436

  7. Pertussis after end of a mass vaccination project--end of the "vaccination honey-moon".

    PubMed

    Trollfors, Birger; Dotevall, Leif; Sundh, Valter; Welinder-Olsson, Christina

    2011-03-16

    After 16 years of no vaccination against pertussis in Sweden, mass vaccination of infants and catch-up vaccination of children up to 10 years with a monocomponent pertussis toxoid vaccine was performed in the Greater Gothenburg area of Sweden between 1995 and 1999. At the end of the project in February 1999, 56% of all 10 year old children born in the Greater Gothenburg area had received 3 doses of the pertussis toxoid. No booster doses were given. This led to a temporary almost complete elimination of the disease. The aim of the present study was to follow the incidence of pertussis after end of the mass vaccination project (1999-2009) as it is reflected by laboratory verified cases (cultures and/or PCR) and pertussis hospitalizations. A reemergence of pertussis was seen from the end of 1999 with a peak in 2004 followed by a decrease when booster doses to both 6 and 10 year old children were introduced in 2005-2006. From July 1, 1999 through December 31, 2009 a total of 1973 cases were diagnosed with culture or PCR. The disease was prevalent in all age groups. The highest documented incidence was seen in infants younger than 12 months. 450 patients with verified pertussis had received 3 doses of the pertussis toxoid vaccine in the mass vaccination project and some other trials (comprising a total of 69,423 children). The mean time from the last dose to the laboratory verification of pertussis was 5 years in these 450 cases. There were 128 hospitalizations, 106 of which were in infants. In conclusion, pertussis is still not eliminated from the area. Booster doses are needed but the numbers and optimal timing are not known. PMID:21292010

  8. Epithelial anion transporter pendrin contributes to inflammatory lung pathology in mouse models of Bordetella pertussis infection.

    PubMed

    Scanlon, Karen M; Gau, Yael; Zhu, Jingsong; Skerry, Ciaran; Wall, Susan M; Soleimani, Manoocher; Carbonetti, Nicholas H

    2014-10-01

    Pertussis disease, characterized by severe and prolonged coughing episodes, can progress to a critical stage with pulmonary inflammation and death in young infants. However, there are currently no effective treatments for pertussis. We previously studied the role of pertussis toxin (PT), an important Bordetella pertussis virulence factor, in lung transcriptional responses to B. pertussis infection in mouse models. One of the genes most highly upregulated in a PT-dependent manner encodes an epithelial transporter of bicarbonate, chloride, and thiocyanate, named pendrin, that contributes to asthma pathology. In this study, we found that pendrin expression is upregulated at both gene and protein levels in the lungs of B. pertussis-infected mice. Pendrin upregulation is associated with PT production by the bacteria and with interleukin-17A (IL-17A) production by the host. B. pertussis-infected pendrin knockout (KO) mice had higher lung bacterial loads than infected pendrin-expressing mice but had significantly reduced levels of lung inflammatory pathology. However, reduced pathology did not correlate with reduced inflammatory cytokine expression. Infected pendrin KO mice had higher levels of inflammatory cytokines and chemokines than infected pendrin-expressing mice, suggesting that these inflammatory mediators are less active in the airways in the absence of pendrin. In addition, treatment of B. pertussis-infected mice with the carbonic anhydrase inhibitor acetazolamide reduced lung inflammatory pathology without affecting pendrin synthesis or bacterial loads. Together these data suggest that PT contributes to pertussis pathology through the upregulation of pendrin, which promotes conditions favoring inflammatory pathology. Therefore, pendrin may represent a novel therapeutic target for treatment of pertussis disease. PMID:25069981

  9. Serological diagnosis of pertussis: evaluation of IgA against whole cell and specific Bordetella pertussis antigens as markers of recent infection.

    PubMed Central

    Poynten, M.; Hanlon, M.; Irwig, L.; Gilbert, G. L.

    2002-01-01

    In Australia, notification of pertussis cases in older children or adults has increased significantly in recent years. In most cases, laboratory diagnosis is based only on a positive serological test for IgA antibody against whole cell Bordetella pertussis. During a 3-month period, 318 consecutive sera submitted for diagnosis of pertussis were tested for IgA antibody against whole cell (WC) sonicated B. pertussis, pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). Results of one or more of these tests were positive in sera from 175 subjects and clinical information was obtained by telephone interview from 90 subjects. Using a clinical case definition as the reference standard, the sensitivities of the four IgA assays were variable but quite low (24-64%), but the specificities were high (93-98%). For diagnosis of pertussis in subjects with a compatible clinical illness, these and other findings support the use of serological testing for IgA antibody. PMID:12002533

  10. Incidence of pertussis in patients of general practitioners in Poland.

    PubMed

    Stefanoff, P; Paradowska-Stankiewicz, I A; Lipke, M; Karasek, E; Rastawicki, W; Zasada, A; Samuels, S; Czajka, H; Pebody, R G

    2014-04-01

    We estimated the incidence of pertussis in patients consulting general practitioners (GPs). Between July 2009 and April 2011, we conducted a prospective cohort study of patients attending 78 general practices (158 863 persons overall). We included patients aged ≥ 3 years, with cough lasting 2-15 weeks, who gave informed consent. GPs interviewed eligible patients, collected a blood specimen, and a nasopharyngeal swab. At follow-up 30-60 days after the initial visit, physicians collected a second blood specimen and conducted patient interview. Cases were confirmed by specific IgA and/or IgG antibody titre exceeding significantly the general population background level or detection of bacterial DNA by real-time PCR. During the study period, 3864 patients with prolonged cough consulted the participating GPs, of those 1852 met the inclusion criteria, 1232 were recruited, and 288 were confirmed as pertussis cases (4% by PCR, 96% by serology). The adjusted incidence rate was 201.1/100 000 person-years [95% confidence interval (CI) 133.9-302.0], ranging from 456.5 (95% CI 239.3-870.8) in the 15-19 years group to 94.0 (95% CI 33.4-264.5) in the 25-29 years group. The reporting ratio was 61, ranging from 4 in those aged 3-5 years, to 167 in those aged 65-69 years. The study confirmed high incidence of pertussis in all age groups in the general population, in particular in adults, not appropriately documented by the existing surveillance system. PMID:23870166

  11. Text4Health: Impact of Text Message Reminder–Recalls for Pediatric and Adolescent Immunizations

    PubMed Central

    Kharbanda, Elyse Olshen; Martinez, Raquel Andres; Lara, Marcos; Vawdrey, David; Natarajan, Karthik; Rickert, Vaughn I.

    2012-01-01

    Objectives. We conducted 2 studies to determine the impact of text message immunization reminder–recalls in an urban, low-income population. Methods. In 1 study, text message immunization reminders were sent to a random sample of parents (n = 195) whose children aged 11 to 18 years needed either or both meningococcal (MCV4) and tetanus–diphtheria–acellular pertussis (Tdap) immunizations. We compared receipt of MCV4 or Tdap at 4, 12, and 24 weeks with age- and gender-matched controls. In the other study, we compared attendance at a postshortage Haemophilus influenzae B (Hib) immunization recall session between parents who received text message and paper-mailed reminders (n = 87) and those who only received paper-mailed reminders (n = 87). Results. Significantly more adolescents with intervention parents received either or both MCV4 and Tdap at weeks 4 (15.4% vs 4.2%; P < .001), 12 (26.7% vs 13.9%; P < .005), and 24 (36.4% vs 18.1%; P < .001). Significantly more parents who received both Hib reminders attended a recall session compared with parents who only received a mailed reminder (21.8% vs 9.2%; P < .05). After controlling for age, gender, race/ethnicity, insurance status, and language, text messaging was still significantly associated with both studies’ outcomes. Conclusions. Text messaging for reminder–recalls improved immunization coverage in a low-income, urban population. PMID:22390457

  12. Design and Synthesis of an Artificial Pulmonary Pleura for High Throughput Studies in Acellular Human Lungs

    PubMed Central

    Wagner, Darcy E.; Fenn, Spencer L.; Bonenfant, Nicholas R.; Marks, Elliot R.; Borg, Zachary; Saunders, Patrick; Oldinski, Rachael A.; Weiss, Daniel J.

    2015-01-01

    Whole organ decellularization of complex organs, such as lungs, presents a unique opportunity for use of acellular scaffolds for ex vivo tissue engineering or for studying cell-extracellular matrix interactions ex vivo. A growing body of literature investigating decellularizing and recellularizing rodent lungs has provided important proof of concept models and rodent lungs are readily available for high throughput studies. In contrast, comparable progress in large animal and human lungs has been impeded owing to more limited availability and difficulties in handling larger tissue. While the use of smaller segments of acellular large animal or human lungs would maximize usage from a single lung, excision of small acellular segments compromises the integrity of the pleural layer, leaving the terminal ends of blood vessels and airways exposed. We have developed a novel pleural coating using non-toxic ionically crosslinked alginate or photocrosslinked methacrylated alginate which can be applied to excised acellular lung segments, permits inflation of small segments, and significantly enhances retention of cells inoculated through cannulated airways or blood vessels. Further, photocrosslinking methacrylated alginate, using eosin Y and triethanolamine (TEOA) at 530nm wavelength, results in a mechanically stable pleural coating that permits effective cyclic 3-dimensional stretch, i.e. mechanical ventilation, of individual segments. PMID:25750684

  13. Corneal Stroma Regeneration with Acellular Corneal Stroma Sheets and Keratocytes in a Rabbit Model

    PubMed Central

    Ma, Xiao Yun; Zhang, Yun; Zhu, Dan; Lu, Yang; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wen Jie

    2015-01-01

    Acellular corneal stroma matrix has been used for corneal stroma engineering. However, because of its compact tissue structure, regrowth of keratocytes into the scaffold is difficult. Previously, we developed a sandwich model for cartilage engineering using acellular cartilage sheets. In the present study, we tested this model for corneal stroma regeneration using acellular porcine corneal stroma (APCS) sheets and keratocytes. Porcine corneas were decellularized by NaCl treatment, and the APCS was cut into 20-μm-thick sheets. A rabbit corneal stroma defect model was created by lamellar keratoplasty and repaired by transplantation of five pieces of APCS sheets with keratocytes. Six months after transplantation, transparent corneas were present in the experimental group, which were confirmed by anterior segment optical coherence tomography examination and transmittance examination. The biomechanical properties in the experimental group were similar to those of normal cornea. Histological analyses showed an even distribution of keratocytes and well-oriented matrix in the stroma layer in the experimental group. Together, these results demonstrated that the sandwich model using acellular corneal stroma sheets and keratocytes could be potentially useful for corneal stroma regeneration. PMID:26167895

  14. Repair of a Gingival Fenestration Using an Acellular Dermal Matrix Allograft.

    PubMed

    Breault, Lawrence G; Brentson, Raquel C; Fowler, Edward B; Bisch, Frederick C

    2016-01-01

    A case report illustrating the successful treatment of a gingival fenestration with an acellular dermal matrix (ADM) allograft. After 2½ months of healing, the ADM was completely integrated into the soft tissues of the mandibular anterior gingiva with complete resolution of the gingival fenestration, resulting in excellent gingival esthetics. PMID:26874103

  15. Protective activities in mice of monoclonal antibodies against pertussis toxin.

    PubMed Central

    Sato, H; Sato, Y

    1990-01-01

    Pertussis toxin (PT) protein, which is the most important protective antigen of Bordetella pertussis, has a hexameric structure composed of five subunits, designated S1 through S5. Immunoprotective activity of 20 different mouse monoclonal antibodies (MAbs) against pertussis toxin, 10 anti-S1, 1 anti-S2, 2 anti-S3, 4 anti-S23, and 3 anti-S4 antibodies, were investigated by aerosol and intracerebral challenges with virulent B. pertussis organisms in mice. Four anti-S1, named 1B7, 1D7, 3F11, and 10D6, and three anti-S23 antibodies, named 11E6, 10B5, and 10C9, showed the highest, and almost complete, protectivity against the aerosol challenge. Mouse protectivity against the intracerebral challenge was significant for these four anti-S1 MAbs but not for any of the three anti-S23 MAbs. Four anti-S1 and two anti-S4 MAbs did not protect the mice against either challenge. The other seven MAbs also showed dose-dependent moderate but significant protection against the aerosol challenge. In the aerosol challenge system, bacterial numbers and amounts of PT detected in the lung and the number of peripheral leukocytes were lower in the mice given the protective MAbs. All mice surviving 5 weeks after the infection produced high titers of antibodies against PT, filamentous hemagglutinin (FHA), and agglutinogens from the challenge organisms. A combination of the protective MAbs 1B7 and 11E6 strongly suppressed the disease and mortality of the mice at smaller amounts than with the anti-PT polyclonal antibody. Although combinations of one of the protective MAb and anti-FHA or anti-agglutinogen 2 also showed extremely high mouse protection without development of symptoms of the disease, antibody titers of the survivors against PT, FHA, and agglutinogens were significantly low. The foregoing results suggest that some important protective epitopes should be in S1 and S2 and/or S3, although there are both differences and similarities in the protective roles between anti-S1 and anti-S23

  16. Protective activities in mice of monoclonal antibodies against pertussis toxin.

    PubMed

    Sato, H; Sato, Y

    1990-10-01

    Pertussis toxin (PT) protein, which is the most important protective antigen of Bordetella pertussis, has a hexameric structure composed of five subunits, designated S1 through S5. Immunoprotective activity of 20 different mouse monoclonal antibodies (MAbs) against pertussis toxin, 10 anti-S1, 1 anti-S2, 2 anti-S3, 4 anti-S23, and 3 anti-S4 antibodies, were investigated by aerosol and intracerebral challenges with virulent B. pertussis organisms in mice. Four anti-S1, named 1B7, 1D7, 3F11, and 10D6, and three anti-S23 antibodies, named 11E6, 10B5, and 10C9, showed the highest, and almost complete, protectivity against the aerosol challenge. Mouse protectivity against the intracerebral challenge was significant for these four anti-S1 MAbs but not for any of the three anti-S23 MAbs. Four anti-S1 and two anti-S4 MAbs did not protect the mice against either challenge. The other seven MAbs also showed dose-dependent moderate but significant protection against the aerosol challenge. In the aerosol challenge system, bacterial numbers and amounts of PT detected in the lung and the number of peripheral leukocytes were lower in the mice given the protective MAbs. All mice surviving 5 weeks after the infection produced high titers of antibodies against PT, filamentous hemagglutinin (FHA), and agglutinogens from the challenge organisms. A combination of the protective MAbs 1B7 and 11E6 strongly suppressed the disease and mortality of the mice at smaller amounts than with the anti-PT polyclonal antibody. Although combinations of one of the protective MAb and anti-FHA or anti-agglutinogen 2 also showed extremely high mouse protection without development of symptoms of the disease, antibody titers of the survivors against PT, FHA, and agglutinogens were significantly low. The foregoing results suggest that some important protective epitopes should be in S1 and S2 and/or S3, although there are both differences and similarities in the protective roles between anti-S1 and anti-S23

  17. Bordetella pertussis, B. parapertussis, vaccines and cycles of whooping cough.

    PubMed

    Bouchez, Valérie; Guiso, Nicole

    2015-10-01

    Whooping cough is a vaccine-preventable disease due to Bordetella pertussis and B. parapertussis. This highly contagious respiratory disease occurs through epidemic cycles every 3-5 years and vaccination did not change this frequency. Models suggest that the cyclic increase of susceptibles is linked to demographic differences and different vaccine coverage. However, differences in surveillance of the disease as well as adaptation of the agents of the disease to their human hosts and to vaccine pressure might also play an important role. These parameters are discussed in this review. PMID:26242280

  18. Acellular ostrich corneal stroma used as scaffold for construction of tissue-engineered cornea

    PubMed Central

    Liu, Xian-Ning; Zhu, Xiu-Ping; Wu, Jie; Wu, Zheng-Jie; Yin, Yong; Xiao, Xiang-Hua; Su, Xin; Kong, Bin; Pan, Shi-Yin; Yang, Hua; Cheng, Yan; An, Na; Mi, Sheng-Li

    2016-01-01

    AIM To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea. METHODS A hypertonic saline solution combined with a digestion method was used to decellularize the ostrich cornea. The microstructure of the acellular corneal matrix was observed by transmission electron microscopy (TEM) and hematoxylin and eosin (H&E) staining. The mechanical properties were detected by a rheometer and a tension machine. The acellular corneal matrix was also transplanted into a rabbit cornea and cytokeratin 3 was used to check the immune phenotype. RESULTS The microstructure and mechanical properties of the ostrich cornea were well preserved after the decellularization process. In vitro, the methyl thiazolyl tetrazolium results revealed that extracts of the acellular ostrich corneas (AOCs) had no inhibitory effects on the proliferation of the corneal epithelial or endothelial cells or on the keratocytes. The rabbit lamellar keratoplasty showed that the transplanted AOCs were transparent and completely incorporated into the host cornea while corneal turbidity and graft dissolution occurred in the acellular porcine cornea (APC) transplantation. The phenotype of the reconstructed cornea was similar to a normal rabbit cornea with a high expression of cytokeratin 3 in the superficial epithelial cell layer. CONCLUSION We first used AOCs as scaffolds to reconstruct damaged corneas. Compared with porcine corneas, the anatomical structures of ostrich corneas are closer to those of human corneas. In accordance with the principle that structure determines function, a xenograft lamellar keratoplasty also confirmed that the AOC transplantation generated a superior outcome compared to that of the APC graft. PMID:27158598

  19. Effects of the decellularization method on the local stiffness of acellular lungs.

    PubMed

    Melo, Esther; Garreta, Elena; Luque, Tomas; Cortiella, Joaquin; Nichols, Joan; Navajas, Daniel; Farré, Ramon

    2014-05-01

    Lung bioengineering, a novel approach to obtain organs potentially available for transplantation, is based on decellularizing donor lungs and seeding natural scaffolds with stem cells. Various physicochemical protocols have been used to decellularize lungs, and their performance has been evaluated in terms of efficient decellularization and matrix preservation. No data are available, however, on the effect of different decellularization procedures on the local stiffness of the acellular lung. This information is important since stem cells directly sense the rigidity of the local site they are engrafting to during recellularization, and it has been shown that substrate stiffness modulates cell fate into different phenotypes. The aim of this study was to assess the effects of the decellularization procedure on the inhomogeneous local stiffness of the acellular lung on five different sites: alveolar septa, alveolar junctions, pleura, and vessels' tunica intima and tunica adventitia. Local matrix stiffness was measured by computing Young's modulus with atomic force microscopy after decellularizing the lungs of 36 healthy rats (Sprague-Dawley, male, 250-300 g) with four different protocols with/without perfusion through the lung circulatory system and using two different detergents (sodium dodecyl sulfate [SDS] and 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate [CHAPS]). The local stiffness of the acellular lung matrix significantly depended on the site within the matrix (p<0.001), ranging from ∼ 15 kPa at the alveolar septum to ∼ 60 kPa at the tunica intima. Acellular lung stiffness (p=0.003) depended significantly, albeit modestly, on the decellularization process. Whereas perfusion did not induce any significant differences in stiffness, the use of CHAPS resulted in a ∼ 35% reduction compared with SDS, the influence of the detergent being more important in the tunica intima. In conclusion, lung matrix stiffness is considerably inhomogeneous, and

  20. Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering

    PubMed Central

    Korossis, Sotirios A.; Wilshaw, Stacy-Paul; Jennings, Louise M; Fisher, John; Ingham, Eileen

    2014-01-01

    Currently available replacement heart valves all have limitations. This study aimed to produce and characterize an acellular, biocompatible porcine pulmonary root conduit for reconstruction of the right ventricular outflow tract e.g., during Ross procedure. A process for the decellularization of porcine pulmonary roots was developed incorporating trypsin treatment of the adventitial surface of the scraped pulmonary artery and sequential treatment with hypotonic Tris buffer (HTB; 10 mM Tris pH 8.0, 0.1% (w/v) EDTA, and 10 KIU aprotinin), 0.1% (w/v) sodium dodecyl sulfate in HTB, two cycles of DNase and RNase, and sterilization with 0.1% (v/v) peracetic acid. Histology confirmed an absence of cells and retention of the gross histoarchitecture. Immunohistochemistry further confirmed cell removal and partial retention of the extracellular matrix, but a loss of collagen type IV. DNA levels were reduced by more than 96% throughout all regions of the acellular tissue and no functional genes were detected using polymerase chain reaction. Total collagen levels were retained but there was a significant loss of glycosaminoglycans following decellularization. The biomechanical, hydrodynamic, and leaflet kinematics properties were minimally affected by the process. Both immunohistochemical labeling and antibody absorption assay confirmed a lack of α-gal epitopes in the acellular porcine pulmonary roots and in vitro biocompatibility studies indicated that acellular leaflets and pulmonary arteries were not cytotoxic. Overall the acellular porcine pulmonary roots have excellent potential for development of a tissue substitute for right ventricular outflow tract reconstruction e.g., during the Ross procedure. PMID:24786313

  1. Invasion of HeLa 229 cells by virulent Bordetella pertussis.

    PubMed Central

    Ewanowich, C A; Melton, A R; Weiss, A A; Sherburne, R K; Peppler, M S

    1989-01-01

    Phase-dependent invasive behavior of Bordetella pertussis was demonstrated by recovery of viable organisms from gentamicin-treated HeLa cell monolayers and by transmission electron microscopy. Several mutants of B. pertussis with Tn5 or Tn5 lac inserted into various vir-regulated genes were evaluated for differences in their invasive abilities. Mutants lacking filamentous hemagglutinin, pertussis toxin, and two as yet uncharacterized vir-regulated products had levels of invasion significantly lower than that of the parent strain BP338. In contrast, invasion by mutants lacking adenylate cyclase toxin was significantly increased compared with that of wild-type B. pertussis. This increase in invasion was eliminated when concentrations of intracellular cyclic 3'-5' AMP were stimulated by treating HeLa cells with cholera toxin or forskolin. Entry of B. pertussis occurred through a microfilament-dependent phagocytic process, as evidenced by the marked reduction in uptake following treatment of HeLa cells with cytochalasin D. Invasion was inhibited with polyclonal anti-B. pertussis and anti-filamentous hemagglutinin antisera. In addition, a monoclonal antibody against lipooligosaccharide A reduced uptake by 65.5%. The preservation of HeLa cell integrity and the limited replication of intracellular bacteria suggest that invasion may represent a means by which B. pertussis evades an active host immune response. Images PMID:2547718

  2. Direct Detection of Erythromycin-Resistant Bordetella pertussis in Clinical Specimens by PCR.

    PubMed

    Wang, Zengguo; Han, Ruijun; Liu, Ying; Du, Quanli; Liu, Jifeng; Ma, Chaofeng; Li, Hengxin; He, Qiushui; Yan, Yongping

    2015-11-01

    Resistance of Bordetella pertussis to erythromycin has been increasingly reported. We developed an allele-specific PCR method for rapid detection of erythromycin-resistant B. pertussis directly from nasopharyngeal (NP) swab samples submitted for diagnostic PCR. Based on the proven association of erythromycin resistance with the A2047G mutation in the 23S rRNA of B. pertussis, four primers, two of which were designed to be specific for either the wild-type or the mutant allele, were used in two different versions of the allele-specific PCR assay. The methods were verified with results obtained by PCR-based sequencing of 16 recent B. pertussis isolates and 100 NP swab samples submitted for diagnostic PCR. The detection limits of the two PCR assays ranged from 10 to 100 fg per reaction for both erythromycin-susceptible and -resistant B. pertussis. Two amplified fragments of each PCR, of 286 and 112 bp, respectively, were obtained from a mutant allele of the isolates and/or NP swab samples containing B. pertussis DNAs. For the wild-type allele, only a 286-bp fragment was visible when the allele-specific PCR assay 1 was performed. No amplification was found when a number of non-Bordetella bacterial pathogens and NP swab samples that did not contain the DNAs of B. pertussis were examined. This assay can serve as an alternative for PCR-based sequencing, especially for local laboratories in resource-poor countries. PMID:26224847

  3. The First Report of Epidemic Pertussis by Bahaodowle Razi From the 15th Century Anno Domini

    PubMed Central

    Yarmohammadi, Hassan; Bahmani Kazeruni, Mohamad H.; Soofi, Amir; Zargaran, Arman

    2015-01-01

    Background: Pertussis or “whooping cough” is an acute, communicable infection of the respiratory tract caused by the Gram-negative bacterium Bordetella pertussis. It has been recorded in history of medicine that the first pertussis epidemic was reported in 1578 by a French scientist, Guillaume de Baillou, in Paris. Furthermore, the causative agent was first isolated in 1906 by Jules Jean Baptiste Vincent Bordet and his brother-in-law Octave Gengou. However, it seems that earlier reports can be found in history of medicine. Objectives: The aim of this study as to analyze the first Report of Epidemic Pertussis by Bahaodowle Razi From the 15th Century Anno Domini Materials and Methods: We investigated a copy (Persian lithograph) of the book named “a summary of experiences in medicine”, written by Bahaoddin-bin-Ghasem-Bahaoddin Razi (well known as Bahaodowle Razi) in 1502 to find the earliest existing report of epidemic pertussis in the history. Results: Bahaodowle Razi, a Persian physician from the 15th century Anno Domini (AD), reported two epidemics in Harat and one in Rey (inold Persia) for the first time, one century before Baillou. He named it as Sorfe-ie-Am (meaning public cough). Those occurred during his lifetime. Explaining about his observations and experiences about this epidemic, Bahaodowle Razi elaborated on prognosis, symptoms, etiology and predisposing factors of pertussis. Conclusions: This document shows that Bahaodowle Razi’s report was the first report of epidemic pertussis in the medical history. PMID:26413316

  4. Comparing Seasonal Pattern of Laboratory Confirmed Cases of Pertussis with Clinically Suspected Cases

    PubMed Central

    Ghorbani, Golam Reza; Zahraei, Seyed Mohsen; Moosazadeh, Mahmood; Afshari, Mahdi; Doosti, Fahimeh

    2016-01-01

    Objectives During recent decades, there has been limited attention on the seasonal pattern of pertussis within a high vaccine coverage population. This study aimed to compare the seasonal patterns of clinical suspected pertussis cases with those of laboratory confirmed cases in Iran. Methods The current study was conducted using time series methods. Time variables included months and seasons during 2011–2013. The effects of seasons and months on the incidence of pertussis were estimated using analysis of variance or Kruskal–Wallis. Results The maximum average incidence of clinically confirmed pertussis was 23.3 in July (p = 0.04), but the maximum incidence of clinical suspected pertussis was 115.7 in May (p = 0.6). The maximum seasonal incidences of confirmed and clinical pertussis cases were reported in summer (average: 12, p = 0.004), and winter (average: 108.1; p = 0.4), respectively. Conclusion The present study showed that the seasonal pattern of laboratory confirmed pertussis cases is highly definite and different from the pattern of clinical suspected cases. PMID:27169013

  5. The historical association between measles and pertussis: A case of immune suppression?

    PubMed Central

    Coleman, Stephen

    2015-01-01

    Objectives: According to historical medical reports, many children with measles subsequently contracted pertussis, often with fatal results. The likelihood of a child contracting pertussis after a measles infection is increased by its immune-suppressing effects. This research aims to verify the historical reports. Methods: The analysis examines statistically the historical relationship between average measles and pertussis incidence rates in the United States from 1938 to 1954 at the state level and in average weekly rates. Analysis of incidence rates is cross-sectional at the state level using public health data. Results: The results show that, on average and over time, states with higher measles rates have higher pertussis rates, and the peaks and nadirs of average weekly incidence rates of pertussis lag measles by a delay of about 3–4 weeks, well within the duration of immune suppression. Measles and pertussis have similar geographical distributions. Conclusion: The research tentatively supports the hypothesis that because of its immune-suppressing effects, measles causes an increase in pertussis, but other factors may be involved. Epidemic models should give more attention to the possibility of immune suppression for diseases such as measles where that might be a risk factor. The findings reemphasize the importance of measles vaccination for the prevention of other diseases. PMID:27092263

  6. The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

    PubMed Central

    Bibova, Ilona; Skopova, Karolina; Masin, Jiri; Cerny, Ondrej; Hot, David; Sebo, Peter

    2013-01-01

    Bordetella pertussis is a Gram-negative pathogen causing the human respiratory disease called pertussis or whooping cough. Here we examined the role of the RNA chaperone Hfq in B. pertussis virulence. Hfq mediates interactions between small regulatory RNAs and their mRNA targets and thus plays an important role in posttranscriptional regulation of many cellular processes in bacteria, including production of virulence factors. We characterized an hfq deletion mutant (Δhfq) of B. pertussis 18323 and show that the Δhfq strain produces decreased amounts of the adenylate cyclase toxin that plays a central role in B. pertussis virulence. Production of pertussis toxin and filamentous hemagglutinin was affected to a lesser extent. In vitro, the ability of the Δhfq strain to survive within macrophages was significantly reduced compared to that of the wild-type (wt) strain. The virulence of the Δhfq strain in the mouse respiratory model of infection was attenuated, with its capacity to colonize mouse lungs being strongly reduced and its 50% lethal dose value being increased by one order of magnitude over that of the wt strain. In mixed-infection experiments, the Δhfq strain was then clearly outcompeted by the wt strain. This requirement for Hfq suggests involvement of small noncoding RNA regulation in B. pertussis virulence. PMID:23980112

  7. Low pertussis toxin antibody levels in two regional cohorts of Canadian pregnant women.

    PubMed

    Bigham, Mark; Konrad, Stephanie; Van Buynder, Paul; Van Buynder, Jan; Isaac-Renton, Judy; ElSherif, May; Halperin, Scott A

    2014-11-12

    Infants under 6 months of age are at greatest risk of mortality and severe morbidity from pertussis disease. Interventions that increase pertussis protection in newborns are therefore a clear public health imperative. The objective of this study was to assess maternal pertussis toxin antibody (anti-PT) level as a potential source of mother-to-child transfer of pertussis-associated antibodies that may reduce neonatal risk of pertussis disease. Anti-PT level was assessed in a 2013 cohort of pregnant women from two regions in two Canadian provinces, British Columbia and Nova Scotia. Basic demographics, health, and pertussis immunization history were collected, along with blood specimens. Anti-PT levels were compared for self-reported vaccination status and prior pertussis disease. To assess secular trend, a parallel analysis was also undertaken, using anonymized residual sera from a 1996-1997 cohort of pregnant women in British Columbia. A total of 169 pregnant women participated in the study - 50 from Nova Scotia and 119 from British Columbia. The mean and median age of participants from both sites was 31 years of age (range 16-42 years). The lower limit of quantification of the anti-PT assay was 10 ELISA units per milliliter (EU/ml). Overall, 59% of women had anti-PT levels less than 10 EU/ml and anti-PT level did not differ with time since last self-reported pertussis vaccination (χ(2)(2)=3.166, p=0.205). Among a 1996-1997 cohort of pregnant women in British Columbia, 101 of 200 (51%) had anti-PT levels less than 10 EU/ml. Our study found that most pregnant women in two geographically disparate health regions in Canada have low residual anti-PT levels, may be vulnerable to pertussis infection themselves, and would unlikely be a source of passive ante- or postnatal transfer of anti-PT to their newborn. PMID:25269092

  8. Impact of a Pertussis Epidemic on Infant Vaccination in Washington State

    PubMed Central

    Opel, Douglas; DeHart, M. Patricia; Warren, Jodi; Rowhani-Rahbar, Ali

    2014-01-01

    BACKGROUND AND OBJECTIVES: Washington State experienced a pertussis epidemic from October 2011 to December 2012. There was wide variation in incidence by county. The objectives of this study were to determine how the pertussis epidemic affected infant vaccination in Washington State and whether the incidence in counties modified this effect. METHODS: We conducted an ecologic before–after study to compare the proportion of infants up to date (UTD) with a pertussis-containing vaccine at time points before (September 30, 2011), during (September 30, 2012), and after (September 30, 2013) the epidemic. Children aged 3 to 8 months enrolled in the Washington State Immunization Information System with documented county of residence were included. UTD status was determined as ≥1, ≥2, or ≥3 doses of a pertussis-containing vaccine at ages 3, 5, and 7 months, respectively. Generalized linear models with extension to the binomial family and clustered robust standard errors were used to examine differences in the proportion of UTD infants between preepidemic and either epidemic or postepidemic points. The potential modifying effect of pertussis incidence by county was examined. RESULTS: We found no significant difference in statewide UTD status with a pertussis-containing vaccine between preepidemic and either epidemic (absolute difference 2.1%; 95% confidence interval, −1.6 to 5.9) or postepidemic (absolute difference 0.2%; 95% confidence interval, −4.0 to 4.5) time points. There was no significant modification by county pertussis incidence. There was wide variation in the absolute difference in UTD status across counties. CONCLUSIONS: A statewide pertussis epidemic does not appear to have significantly changed the proportion of infants who were UTD with a pertussis-containing vaccine. PMID:25136046

  9. Genetic analysis of phase change in Bordetella pertussis.

    PubMed Central

    Weiss, A A; Falkow, S

    1984-01-01

    Avirulent-phase derivatives of Bordetella pertussis (those which have simultaneously lost the ability to synthesize several virulence-associated factors) and the genetic mechanism of the phase change were studied. Increased tolerance to erythromycin was shown to be an avirulent-phase marker. By the use of efficiency of plating on erythromycin, the proportion of avirulent-phase (Vir) variants in a virulent-phase (Vir+) population was determined to be between 10(-3) and 10(-6), depending on the strain. We showed that the phase shift is reversible and detected a complete Vir- to Vir+ to Vir- to cycle. In other experiments, hybridization studies with avirulent-phase mutants obtained by Tn5 mutagenesis suggested that a single region located at a unique site in the B. pertussis chromosome controls the phase change. One of the avirulent Tn5 mutants was used as a recipient in a conjugative cross with a virulent-phase donor. All recombinants which had reacquired the virulence-associated factors also lost Tn5, indicating the loss of Tn5 was required to restore the Vir+ phenotype. The Tn5 avirulent-phase mutants behave as if the insertion interrupted the function of a transacting gene product which is required for the expression of the other virulent-phase genes. A model of the molecular basis of the phase regulation is presented. Images PMID:6317569

  10. Environmental regulation of expression of virulence determinants in Bordetella pertussis.

    PubMed Central

    Melton, A R; Weiss, A A

    1989-01-01

    The trans-activator vir is required for expression of all virulence-associated genes in Bordetella pertussis. The nature of the global regulation of these factors by vir and environmental signals was examined by Northern blot analysis and with beta-galactosidase transcriptional fusions in five vir-regulated genes. Northern blots suggested that vir regulates at the level of transcription since Vir- organisms did not exhibit detectable mRNA from vir-regulated loci. Environmental signals such as high levels of salts, nicotinic acid, and 6-chloronicotinic acid or growth at low temperatures were examined. Of all of the cations and anions examined, only SO4 ions eliminated transcription of vir-regulated genes and reduced transcription of vir itself, suggesting that global regulation is obtained by modifying expression of the essential component, vir. Organisms grown on 6-chloronicotinic acid or quinaldic acid did not have detectable transcription from vir-regulated loci. Modulation by nicotinic acid, on the other hand, was strain dependent, acting at the level of transcription in strain 18-323 but not in Tohama I derivatives. Growth at lower temperatures reduced, but did not eliminate, transcription from vir-regulated loci. At 28 degrees C the ratio of pertussis toxin mRNA to recA mRNA (a non-vir-regulated factor) was equivalent to that at 37 degrees C, suggesting that transcription at low temperatures is reduced in a proportional manner and need not involve vir. Images PMID:2478524

  11. The multifaceted RisA regulon of Bordetella pertussis.

    PubMed

    Coutte, Loïc; Huot, Ludovic; Antoine, Rudy; Slupek, Stephanie; Merkel, Tod J; Chen, Qing; Stibitz, Scott; Hot, David; Locht, Camille

    2016-01-01

    The whooping cough agent Bordetella pertussis regulates the production of its virulence factors by the BvgA/S system. Phosphorylated BvgA activates the virulence-activated genes (vags) and represses the expression of the virulence-repressed genes (vrgs) via the activation of the bvgR gene. In modulating conditions, with MgSO4, the BvgA/S system is inactive, and the vrgs are expressed. Here, we show that the expression of almost all vrgs depends on RisA, another transcriptional regulator. We also show that some vags are surprisingly no longer modulated by MgSO4 in the risA(-) background. RisA also regulates the expression of other genes, including chemotaxis and flagellar operons, iron-regulated genes, and genes of unknown function, which may or may not be controlled by BvgA/S. We identified RisK as the likely cognate RisA kinase and found that it is important for expression of most, but not all RisA-regulated genes. This was confirmed using the phosphoablative RisAD(60)N and the phosphomimetic RisAD(60)E analogues. Thus the RisA regulon adds a new layer of complexity to B. pertussis virulence gene regulation. PMID:27620673

  12. Changing spatial epidemiology of pertussis in continental USA

    PubMed Central

    Choisy, Marc; Rohani, Pejman

    2012-01-01

    Prediction and control of the geographical spread of emerging pathogens has become a central public health issue. Because these infectious diseases are by definition novel, there are few data to characterize their dynamics. One possible solution to this problem is to apply lessons learnt from analyses of historical data on familiar and epidemiologically similar pathogens. However, the portability of the spatial ecology of an infectious disease in a different epoch to other infections remains unexamined. Here, we study this issue by taking advantage of the recent re-emergence of pertussis in the United States to compare its spatial transmission dynamics throughout the 1950s with the past decade. We report 4-year waves, sweeping across the continent in the 1950s. These waves are shown to emanate from highly synchronous foci in the northwest and northeast coasts. In contrast, the recent resurgence of the disease is characterized by 5.5-year epidemics with no particular spatial structure. We interpret this to be the result of dramatic changes in patterns of human movement over the second half of the last century, together with changing age distribution of pertussis. We conclude that extrapolation regarding the spatial spread of contemporaneous pathogens based on analyses of historical incidence may be potentially very misleading. PMID:23015623

  13. Enhancement of interleukin-4 production by pertussis toxin.

    PubMed Central

    Mu, H H; Sewell, W A

    1993-01-01

    Pertussis toxin (PT), a protein toxin of Bordetella pertussis, has many biological activities, including potent adjuvant capacity and the ability to up-regulate immunoglobulin E (IgE) production. Interleukin-4 (IL-4) is a cytokine which is essential for the IgE response. Accordingly, we examined the effect of PT on IL-4 production. Spleen and lymph node cell suspensions were prepared from immunized mice and cultured with antigen or polyclonal stimuli in vitro. IL-4 secretion was assessed by bioassay, and IL-4 mRNA expression was assessed by reverse transcription and polymerase chain reaction. Significantly larger amounts of IL-4 protein and mRNA were produced in vitro by cells from mice given PT at the time of immunization than by cells from mice given antigen alone, PT alone, or the combination of antigen with cyclophosphamide. Total and antigen-specific serum IgE levels were significantly elevated in immunized mice given PT, compared with the other groups. Thus, there was a relationship between serum IgE and IL-4 production. The administration of a single dose of an anti-IL-4 monoclonal antibody in vivo, at the time of immunization and treatment with PT, abolished the development of the IgE response. These results indicate that PT is a potent stimulus for the production of IL-4, which is required for the adjuvant effect of PT on IgE formation. Images PMID:8514386

  14. Comparative gene expression profiling in two congenic mouse strains following Bordetella pertussis infection

    PubMed Central

    Banus, Sander; Vandebriel, Rob J; Pennings, Jeroen LA; Gremmer, Eric R; Wester, Piet W; van Kranen, Henk J; Breit, Timo M; Demant, Peter; Mooi, Frits R; Hoebee, Barbara; Kimman, Tjeerd G

    2007-01-01

    Background Susceptibility to Bordetella pertussis infection varies widely. These differences can partly be explained by genetic host factors. HcB-28 mice are more resistant to B. pertussis infection than C3H mice, which could partially be ascribed to the B. pertussis susceptibility locus-1 (Bps1) on chromosome 12. The presence of C57BL/10 genome on this locus instead of C3H genome resulted in a decreased number of bacteria in the lung. To further elucidate the role of host genetic factors, in particular in the Bps1 locus, in B. pertussis infection, and to identify candidate genes within in this region, we compared expression profiles in the lungs of the C3H and HcB-28 mouse strains following B. pertussis inoculation. Twelve and a half percent of the genomes of these mice are from a different genetic background. Results Upon B. pertussis inoculation 2,353 genes were differentially expressed in the lungs of both mouse strains. Two hundred and six genes were differentially expressed between the two mouse strains, but, remarkably, none of these were up- or down-regulated upon B. pertussis infection. Of these 206 genes, 17 were located in the Bps1 region. Eight of these genes, which showed a strong difference in gene expression between the two mouse strains, map to the immunoglobulin heavy chain complex (Igh). Conclusion Gene expression changes upon B. pertussis infection are highly identical between the two mouse strains despite the differences in the course of B. pertussis infection. Because the genes that were differentially regulated between the mouse strains only showed differences in expression before infection, it appears likely that such intrinsic differences in gene regulation are involved in determining differences in susceptibility to B. pertussis infection. Alternatively, such genetic differences in susceptibility may be explained by genes that are not differentially regulated between these two mouse strains. Genes in the Igh complex, among which Igh-1a

  15. DNA topology affects transcriptional regulation of the pertussis toxin gene of Bordetella pertussis in Escherichia coli and in vitro.

    PubMed Central

    Scarlato, V; Aricò, B; Rappuoli, R

    1993-01-01

    The bvg locus of Bordetella pertussis encodes an environmentally inducible operon essential for the expression of virulence genes. We show that in Escherichia coli, the PTOX promoter cloned in cis of the bvg locus is activated and environmentally regulated. Cotransformation of E. coli with the bvg locus cloned in a low-copy-number plasmid and with the PTOX promoter cloned in a high-copy-number plasmid can give rise to two different results. If the PTOX promoter is cloned in the pGem-3 vector, transcription is absent. If the PTOX promoter is cloned in the plasmid pKK232, containing the PTOX promoter between two ribosomal gene terminators of transcription, transcription occurs, although regulation of transcription is abolished. Under these conditions, the intracellular amount of RNA transcripts is increased by adding to the culture medium novobiocin, an inhibitor of bacterial gyrases. In vitro, the transcription of the PTOX promoter is activated on E. coli RNA polymerase supplemented with cell extracts from wild-type B. pertussis. Addition of DNA gyrase to the mixture dramatically reduces the amount of RNA synthesized. Our data show that the products of the bvg locus, BvgA and BvgS, are directly involved in the regulation of the PTOX promoter in E. coli and that DNA topology may play a role in the induction of transcription. Images PMID:8393006

  16. Cross-reactions in IgM ELISA tests to Legionella pneumophila sg1 and Bordetella pertussis among children suspected of legionellosis; potential impact of vaccination against pertussis?

    PubMed Central

    2015-01-01

    The objective of this study was preliminary evaluation of IgM cross-reaction in sera collected from children hospitalized because of suspected legionellosis. Sera with positive IgM results to L. pneumophila sgs1-7, B. pertussis or with simultaneous detection of IgM antibodies to L. pneumophila sgs1-7 and B. pertussis, or IgM to L. pneumophila sgs1-7 and M. pneumoniae in routine tests, were selected. In total, an adapted pre-absorption test was used for the serological confirmation of legionellosis in the sera of 19 children suspected of legionellosis, and also in 3 adult persons with confirmed Legionnaires’ disease. Sera were pre-absorbed with antigens of L. pneumophila sg1, B. pertussis or both, and tested by ELISA tests. The reduction of IgM antibody level by pre-absorption with antigen/antigens was determined. Reduction of anti-Lpsgs1-7 IgM by pre-absorption with L.pneumophila sg1 antigen ranged from 1.5 to 80, and reduction of anti-Bp IgM by pre-absorption with B. pertussis ranged from 2.0 to 23.8. Reduction by both antigens varied depending on the age of the patients: among children <4 yrs.old, the reduction of anti-B. pertussis IgM by both antigens was higher than for B. pertussis antigen alone. Based on the high difference (≥ 2 times) between reduction by L.pneumophila sg1 and by B. pertussis antigen, legionellosis was confirmed in 8/19 children. The majority of them also indicated IgM positive/borderline results for B. pertussis or M.pneumoniae in routine ELISA tests. As a preliminary, we posed a hypothesis of a potential impact of an anti-pertussis vaccination on the results obtained in anti-L. pneumophila ELISA IgM tests among young children. PMID:26557032

  17. Serotype variation in Bordetella pertussis is governed by cis-acting elements.

    PubMed

    MacGregor, D; Coote, J G; Duggleby, C J; Parton, R

    1991-03-01

    Bordetella pertussis contains two genes encoding the serospecific fimbrial subunit proteins 2 and 3 which are assembled into completed fimbriae, which elicit the formation of agglutinating antibodies. Expression of these agglutinogens can vary independently of each other. A gene library from a B. pertussis strain (fimbrial serotype 0.3) was probed with an oligonucleotide probe specific for fimbrial subunit genes. Three homologous genetic loci were identified; an active fim 3 gene, an inactive fim 2 gene and an unknown fim-homologous region. The fim 3 gene carried on a cosmid produced agglutinating fimbrial structures in B. parapertussis and in variants of B. pertussis which had lost the capacity to produce the agglutinogen. This indicated that cis-acting factors are associated with serotype variation in B. pertussis rather than the production of trans-acting repressor molecules. PMID:2040439

  18. Surface proteins of Bordetella pertussis: comparison of virulent and avirulent strains and effects of phenotypic modulation.

    PubMed Central

    Armstrong, S K; Parker, C D

    1986-01-01

    The surface proteins of several Bordetella strains and their modulated derivatives were examined by surface radioiodination, cell fractionation, and Western blotting. A surface protein with a high Mr, missing in a mutant lacking the filamentous hemagglutinin, was identified in virulent Bordetella pertussis and Bordetella parapertussis cells and was absent in avirulent B. pertussis strains. The electrophoretic profiles of lipopolysaccharide and the 40,000-Mr anion-selective porin were not determinants which correlated with phase variation or phenotypic modulation. At least three envelope proteins (91,000, 32,000, and 30,000 molecular weight) were found only in virulent B. pertussis strains and were absent or diminished in the avirulent phase and most phenotypically modulated strains. Two transposon-induced mutants unable to produce hemolysin, dermonecrotic toxin, pertussis toxin, and filamentous hemagglutinin also lacked these three envelope proteins, confirming that virulence-associated envelope proteins were genetically regulated with other virulence-associated traits. Images PMID:2876957

  19. [Physico-chemical and serological study of agglutinogen 3 of B. pertussis].

    PubMed

    Amelina, I P

    1976-02-01

    Results of immunoelectrophoresis, gel-filtration and sedimentation analysis showed the preparation of agglutinogen 3 of B. pertussis to be homogenous. The principal physico-chemical characteristics of agglutinogen 3 (sedimentation constant, diffusion coefficient, molecular weight) were determined. PMID:178126

  20. Efficacy of enzyme-linked immunosorbent assay for rapid diagnosis of Bordetella pertussis infection.

    PubMed Central

    Lawrence, A J; Paton, J C

    1987-01-01

    We examined the diagnostic efficacy of an enzyme-linked immunosorbent assay (ELISA) for class-specific antibodies to Bordetella pertussis in acute-phase sera collected from 1,240 patients with suspected pertussis. A total of 833 serum specimens (67%) yielded positive results. The proportion of positive results increased to 77% if a second (convalescent-phase) serum was also tested. By comparison, a bacterial agglutination test for B. pertussis antibodies was positive in only 21% of acute-phase specimens and 50% of paired specimens. The high proportion of acute-phase sera which were ELISA positive indicates that a measurable serologic response has usually occurred by the time the diagnosis is suspected. Thus, the ELISA is potentially the most rapid means of laboratory confirmation of B. pertussis infection. PMID:2891724

  1. Prosthetic Breast Reconstruction With Acellular Dermal Matrices: Achieving Predictability and Reproducibility.

    PubMed

    Nahabedian, Maurice Y

    2016-05-01

    The use of acellular dermal matrices in the setting of prosthetic breast reconstruction has captured the attention of many plastic surgeons. The regenerative capacity of these materials has provided additional tissue support to the mastectomy skin flaps with the ultimate result of improving surgical and aesthetic outcomes. Despite the benefits, there remains a significant diversity with regard to outcomes with some surgeons reporting increased morbidity. The reasons for this are varied but ultimately related to differences in patient selection and surgical techniques. The purpose of this article is to provide strategies for using acellular dermal matrix to achieve success in a manner that is usually associated with outcomes that are predictable and reproducible. PMID:27579223

  2. Pioneering technique using Acellular Dermal Matrix in the rescue of a radiation ulcer

    PubMed Central

    NASEEM, S.; PATEL, A.D.; DEVALIA, H.

    2016-01-01

    Background Radiotherapy as an adjuvant to mastectomy is integral to the treatment of breast cancer, but can result in skin ulceration. Skin ulceration following radiotherapy is traditionally managed by removing the implant and allowing the skin to heal by secondary intention. Case report A 42-year-old woman underwent radiotherapy following a breast reconstruction. She developed a 2 x 3cm radiation ulcer. The ulcer was managed by removing the implant and performing capsulectomy. A Beckers 50 expander was placed and reinforced with acellular dermal matrix inferolaterally. At follow-up the patient had a good cosmetic outcome. Conclusion Post-radiation skin ulcers present a challenge to treat with no current standardised management. The use of acellular dermal matrix may present a new technique to promote healing in these testing cases. PMID:27142826

  3. Prosthetic Breast Reconstruction With Acellular Dermal Matrices: Achieving Predictability and Reproducibility

    PubMed Central

    2016-01-01

    Summary: The use of acellular dermal matrices in the setting of prosthetic breast reconstruction has captured the attention of many plastic surgeons. The regenerative capacity of these materials has provided additional tissue support to the mastectomy skin flaps with the ultimate result of improving surgical and aesthetic outcomes. Despite the benefits, there remains a significant diversity with regard to outcomes with some surgeons reporting increased morbidity. The reasons for this are varied but ultimately related to differences in patient selection and surgical techniques. The purpose of this article is to provide strategies for using acellular dermal matrix to achieve success in a manner that is usually associated with outcomes that are predictable and reproducible. PMID:27579223

  4. DermACELL: Human Acellular Dermal Matrix Allograft A Case Report.

    PubMed

    Cole, Windy E

    2016-03-01

    Diabetes often causes ulcers on the feet of diabetic patients. A 56-year-old, insulin-dependent, diabetic woman presented to the wound care center with a Wagner grade 3 ulcer of the right heel. She reported a 3-week history of ulceration with moderate drainage and odor and had a history of ulceration and osteomyelitis in the contralateral limb. Rigorous wound care, including hospitalization; surgical incision and drainage; intravenous antibiotic drug therapy; vacuum-assisted therapy; and a new room temperature, sterile, human acellular dermal matrix graft were used to heal the wound, save her limb, and restore her activities of daily living. This case presentation involves alternative treatment of a diabetic foot ulcer with this new acellular dermal matrix, DermACELL. PMID:27031550

  5. Long-term human serum antibody responses after immunization with whole-cell pertussis vaccine in France.

    PubMed

    Grimprel, E; Bégué, P; Anjak, I; Njamkepo, E; François, P; Guiso, N

    1996-01-01

    Three hundred sixty children were tested for pertussis serology 0.5 to 1.58 months after complete whole-cell pertussis vaccination. An immunoblot assay was used to detect serum antibodies to pertussis toxin, filamentous hemagglutinin, adenylate cyclase-hemolysin, and pertactin, and agglutination was used for detection of anti-agglutinogen antibodies. Antibodies against pertussis toxin, pertactin, and agglutinogens decreased rapidly after vaccination but increased secondarily, suggesting exposure to infected persons. In contrast, anti-filamentous hemagglutinin antibodies persisted and anti-adenylate cyclase-hemolysin antibodies increased continuously, suggesting either cross-reaction with non-Bordetella antigens or exposure to Bordetella isolates expressing these two antigens, including Bordetella pertussis. These data suggest that unrecognized pertussis is common in France despite massive and sustained immunization in infants and that vaccinated children become susceptible to infection more than 6 years after their last vaccination. PMID:8770511

  6. A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough.

    PubMed

    Nguyen, Annalee W; Wagner, Ellen K; Laber, Joshua R; Goodfield, Laura L; Smallridge, William E; Harvill, Eric T; Papin, James F; Wolf, Roman F; Padlan, Eduardo A; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A

    2015-12-01

    Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the Bordetella pertussis-induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. PMID:26631634

  7. Adenylate cyclase toxin is critical for colonization and pertussis toxin is critical for lethal infection by Bordetella pertussis in infant mice.

    PubMed Central

    Goodwin, M S; Weiss, A A

    1990-01-01

    Proliferation of Bordetella pertussis in the lungs of infant mice challenged by the intranasal route was examined. The bacteria rapidly proliferated in the lungs of mice challenged with a sublethal dose of a wild-type strain (BP338) or a filamentous hemagglutinin mutant (BPM409) from 500 at day 0 to 10(7) at day 15. The infection cleared in about 40 days. Pertussis toxin-deficient mutant BP357 gave a similar profile; however, the number of bacteria recovered was slightly reduced, suggesting that pertussis toxin is not essential for bacterial growth in the lungs. In contrast, adenylate cyclase toxin mutant BP348 was rapidly cleared from the lungs, with no viable bacteria remaining 10 days postchallenge, suggesting that the adenylate cyclase toxin is a colonization factor required for the bacteria to initiate infection. PMID:2401570

  8. Mouse or man? Which are pertussis vaccines to protect?

    PubMed

    Preston, N W; Stanbridge, T N

    1976-04-01

    Type 1 strains of Bordetella pertussis can infect mouse brain and have been recovered as type 1 organisms after death. When introduced into the naso-pharynx of the marmoset, they immediately acquired agglutinogen 2 or 3, and the resulting type 1,2 or 1,3 infection persisted for many weeks. As in the child, agglutinogens 2 and/or 3 appear to be essential for infection of the marmoset, whereas they are quite unnecessary in mouse brain. A vaccine (extract or whole cell) containing agglutinogen 1 may be sufficient to pass the mouse protection test but it may fail to immunize children. The mouse test is inadequate even for the screening of such extracts. PMID:177701

  9. Release and purification of fimbriae from Bordetella pertussis.

    PubMed

    Irons, L I; Ashworth, L A; Robinson, A

    1985-01-01

    A competitive ELISA has been used to monitor the release of fimbriae from 1.2.3 serotype of B. pertussis after treatment by different methods and fimbriae have been purified from homogenates or KSCN extracts by chromatography. Fimbriae purified from different serotypes have been studied by inhibition of bacterial agglutination, immunodiffusion and SDS-polyacrylamide gel electrophoresis. Fimbriae purified from a 1.2 serotype have been labelled in immunoelectron microscopy with a IgM monoclonal antibody to agglutinogen 2 and evidence is presented that fimbriae purified from a 1.3 serotype also carry the agglutinogen 3 specificity. A difference in subunit molecular weight has been found between fimbriae purified from 1.2 and 1.3 serotypes. PMID:2872101

  10. Association between Bordetella pertussis agglutinogen 2 and fimbriae.

    PubMed

    Carter, E J; Preston, N W

    1984-08-01

    Fimbriae have been demonstrated on strains of Bordetella pertussis that possess agglutinogen 2 (types 1, 2, 3 and 1, 2), but not on those that lack it (types 1,3 and 1). This correlation between fimbriation and the presence of agglutinogen 2 has been found with fresh isolates from children and with laboratory strains that are virulent for mice. If fimbriae enhance the attachment of bacteria to mucosal cells, these findings offer an explanation for the predominance of serotypes 1,2,3 and 1,2 in non-vaccinated communities. The findings also suggest that agglutinogen 3 is not a fimbrial antigen, and because this is an essential component of fully effective whole-cell vaccine, a subcellular vaccine prepared from fimbriae alone may be inadequate. PMID:6146723

  11. Evidence for a Role of the Polysaccharide Capsule Transport Proteins in Pertussis Pathogenesis

    PubMed Central

    Hoo, Regina; Lam, Jian Hang; Huot, Ludovic; Pant, Aakanksha; Li, Rui; Hot, David; Alonso, Sylvie

    2014-01-01

    Polysaccharide (PS) capsules are important virulence determinants for many bacterial pathogens. Bordetella pertussis, the agent of whooping cough, produces a surface associated microcapsule but its role in pertussis pathogenesis remained unknown. Here we showed that the B. pertussis capsule locus is expressed in vivo in murine lungs and that absence of the membrane-associated protein KpsT, involved in the transport of the PS polymers across the envelope, but not the surface-exposed PS capsule itself, affects drastically B. pertussis colonization efficacy in mice. Microarray analysis revealed that absence of KpsT in B. pertussis resulted in global down-regulation of gene expression including key virulence genes regulated by BvgA/S, the master two-component system. Using a BvgS phase-locked mutant, we demonstrated a functional link between KpsT and BvgA/S-mediated signal transduction. Whereas pull-down assays do not support physical interaction between BvgS sensor and any of the capsule locus encoded proteins, absence of KpsT impaired BvgS oligomerization, necessary for BvgS function. Furthermore, complementation studies indicated that instead of KpsT alone, the entire PS capsule transport machinery spanning the cell envelope likely plays a role in BvgS-mediated signal transduction. Our work thus provides the first experimental evidence of a role for a virulence-repressed gene in pertussis pathogenesis. PMID:25501560

  12. Diagnosis of Whooping Cough in Switzerland: Differentiating Bordetella pertussis from Bordetella holmesii by Polymerase Chain Reaction

    PubMed Central

    Pittet, Laure F.; Emonet, Stéphane; François, Patrice; Bonetti, Eve-Julie; Schrenzel, Jacques; Hug, Melanie; Altwegg, Martin; Siegrist, Claire-Anne; Posfay-Barbe, Klara M.

    2014-01-01

    Bordetella holmesii, an emerging pathogen, can be misidentified as Bordetella pertussis by routine polymerase chain reaction (PCR). In some reports, up to 29% of the patients diagnosed with pertussis have in fact B. holmesii infection and invasive, non-respiratory B. holmesii infections have been reported worldwide. This misdiagnosis undermines the knowledge of pertussis' epidemiology, and may lead to misconceptions on pertussis vaccine's efficacy. Recently, the number of whooping cough cases has increased significantly in several countries. The aim of this retrospective study was to determine whether B. holmesii was contributing to the increase in laboratory-confirmed cases of B. pertussis in Switzerland. A multiplex species-specific quantitative PCR assay was performed on 196 nasopharyngeal samples from Swiss patients with PCR-confirmed Bordetella infection (median age: 6 years-old, minimum 21 days-old, maximum 86 years-old), formerly diagnosed as Bordetella pertussis (IS481+). No B. holmesii (IS481+, IS1001−, hIS1001+) was identified. We discuss whether laboratories should implement specific PCR to recognize different Bordetella species. We conclude that in Switzerland B. holmesii seems to be circulating less than in neighboring countries and that specific diagnostic procedures are not necessary routinely. However, as the epidemiological situation may change rapidly, periodic reevaluation is suggested. PMID:24586447

  13. Diagnosis of whooping cough in Switzerland: differentiating Bordetella pertussis from Bordetella holmesii by polymerase chain reaction.

    PubMed

    Pittet, Laure F; Emonet, Stéphane; François, Patrice; Bonetti, Eve-Julie; Schrenzel, Jacques; Hug, Melanie; Altwegg, Martin; Siegrist, Claire-Anne; Posfay-Barbe, Klara M

    2014-01-01

    Bordetella holmesii, an emerging pathogen, can be misidentified as Bordetella pertussis by routine polymerase chain reaction (PCR). In some reports, up to 29% of the patients diagnosed with pertussis have in fact B. holmesii infection and invasive, non-respiratory B. holmesii infections have been reported worldwide. This misdiagnosis undermines the knowledge of pertussis' epidemiology, and may lead to misconceptions on pertussis vaccine's efficacy. Recently, the number of whooping cough cases has increased significantly in several countries. The aim of this retrospective study was to determine whether B. holmesii was contributing to the increase in laboratory-confirmed cases of B. pertussis in Switzerland. A multiplex species-specific quantitative PCR assay was performed on 196 nasopharyngeal samples from Swiss patients with PCR-confirmed Bordetella infection (median age: 6 years-old, minimum 21 days-old, maximum 86 years-old), formerly diagnosed as Bordetella pertussis (IS481+). No B. holmesii (IS481+, IS1001-, hIS1001+) was identified. We discuss whether laboratories should implement specific PCR to recognize different Bordetella species. We conclude that in Switzerland B. holmesii seems to be circulating less than in neighboring countries and that specific diagnostic procedures are not necessary routinely. However, as the epidemiological situation may change rapidly, periodic reevaluation is suggested. PMID:24586447

  14. Bayesian Correction of Misclassification of Pertussis in Vaccine Effectiveness Studies: How Much Does Underreporting Matter?

    PubMed

    Goldstein, Neal D; Burstyn, Igor; Newbern, E Claire; Tabb, Loni P; Gutowski, Jennifer; Welles, Seth L

    2016-06-01

    Diagnosis of pertussis remains a challenge, and consequently research on the risk of disease might be biased because of misclassification. We quantified this misclassification and corrected for it in a case-control study of children in Philadelphia, Pennsylvania, who were 3 months to 6 years of age and diagnosed with pertussis between 2011 and 2013. Vaccine effectiveness (VE; calculated as (1 - odds ratio) × 100) was used to describe the average reduction in reported pertussis incidence resulting from persons being up to date on pertussis-antigen containing vaccines. Bayesian techniques were used to correct for purported nondifferential misclassification by reclassifying the cases per the 2014 Council of State and Territorial Epidemiologists pertussis case definition. Naïve VE was 50% (95% confidence interval: 16%, 69%). After correcting for misclassification, VE ranged from 57% (95% credible interval: 30, 73) to 82% (95% credible interval: 43, 95), depending on the amount of underreporting of pertussis that was assumed to have occurred in the study period. Meaningful misclassification was observed in terms of false negatives detected after the incorporation of infant apnea to the 2014 case definition. Although specificity was nearly perfect, sensitivity of the case definition varied from 90% to 20%, depending on the assumption about missed cases. Knowing the degree of the underreporting is essential to the accurate evaluation of VE. PMID:27188939

  15. [Insertional Inactivation of Virulence Operon in Population of Persistent Bordetella pertussis Bacteria].

    PubMed

    Karataev, G I; Sinyashina, L N; Medkova, A Yu; Semin, E G; Shevtsova, Z V; Matua, A Z; Kondzariya, I G; Amichba, A A; Kubrava, D T; Mikvabia, Z Ya

    2016-04-01

    Avirulent B. pertussis bacteria containing IS elements in the bvgAS operon were detected during the study of whooping cough patients and bacilli carriers. The present work is devoted to the study of the accumulation dynamics and the mechanisms of generation of persistent forms of the B. pertussis bacteria in lower monkeys as the most adequate model for extrapolation ofthe experiment results to humans. By means of the real-time PCR method, it was established that the B. pertussis bacteria lived more than three months in the upper respiratory tract after a single intranasal monkey infection; the period was reduced to 14-28 days during repeated infection. An increase in the portion of B. pertussis Bvg mutants in the population to tens of percent from the total number of registered bacteria was registered. The experimental confirmation ofthe development and accumulation of avirulent B. pertussis Bvg mutants during the development of the infectious process was obtained. Further study of the composition of the B. pertussis persistent bacteria population at different stages of the disease will make it possible to formulate new approaches to the whooping cough diagnostics and prevention and creation of fundamentally new drugs. PMID:27529975

  16. Outcomes of allogenic acellular matrix therapy in treatment of diabetic foot wounds: an initial experience.

    PubMed

    Martin, Billy R; Sangalang, Melinda; Wu, Stephanie; Armstrong, David G

    2005-06-01

    The purpose of this study was to evaluate outcomes of persons with UT grade 2A neuropathic diabetic foot wounds treated with an acellular matrix. Data were abstracted for 17 consecutive patients with diabetes--76.5% males, aged 61.5 +/- 8.5 years with a mean glycated haemoglobin of 9.2 +/- 2.2% presenting for care at a large, multidisciplinary wound care centre. All patients received surgical debridement for their diabetic foot wounds and were placed on therapy consisting of a single application of an acellular matrix graft (GraftJacket; Wright Medical Technologies, Arlington, TN, USA) with dressing changes taking place weekly. Outcomes evaluated included time to complete wound closure and proportion of patients achieving wound closure in 20 weeks. Acellular matrix therapy was used as initial therapy and was sutured or stapled in place under a silicone-based non adherent dressing. Therapy was then followed by a moisture-retentive dressing until complete epithelialisation. In total, 82.4% of wounds measuring a mean 4.6 +/- 3.2 cm(2) healed in the 20-week evaluation period. For those that healed in this period, healing took place in a mean 8.9 +/- 2.7 weeks. We conclude that a regimen consisting of moist wound healing using an acellular matrix dressing may be a useful adjunct to appropriate diabetic foot ulcer care for deep, non-infected, non-ischaemic wounds. We await the completion of further trials in this area to confirm or refute this initial assessment. PMID:16722865

  17. Hertwig's epithelial root sheath cell behavior during initial acellular cementogenesis in rat molars.

    PubMed

    Yamamoto, Tsuneyuki; Yamamoto, Tomomaya; Yamada, Tamaki; Hasegawa, Tomoka; Hongo, Hiromi; Oda, Kimimitsu; Amizuka, Norio

    2014-11-01

    This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig's epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial-mesenchymal transition (EMT). Initial acellular cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle. PMID:24859538

  18. Prevalence, diagnosis, and disease course of pertussis in adults with acute cough: a prospective, observational study in primary care

    PubMed Central

    Teepe, Jolien; Broekhuizen, Berna DL; Ieven, Margareta; Loens, Katherine; Huygen, Kris; Kretzschmar, Mirjam; de Melker, Hester; Butler, Chris C; Little, Paul; Stuart, Beth; Coenen, Samuel; Goossens, Herman; Verheij, Theo JM

    2015-01-01

    Background Most cases of adult pertussis probably remain undiagnosed. Aim To explore the prevalence, diagnosis, and disease course of acute pertussis infection in adult patients presenting with acute cough. Design and setting Prospective observational study between 2007 and 2010 in primary care in 12 European countries. Method Adults presenting with acute cough (duration of ≤28 days) were included. Bordetella pertussis infection was determined by polymerase chain reaction (from nasopharyngeal flocked swabs and sputa) and by measurement of immunoglobulin G antibodies to pertussis toxin (PT) in venous blood at day 28. An antibody titre to PT of ≥125 IU/ml or PCR positive result in a respiratory sample defined recent infection. Patients completed a symptom diary for 28 days. Results Serum and/or respiratory samples were obtained in 3074 patients. Three per cent (93/3074) had recent B. pertussis infection. Prior cough duration >2 weeks discriminated to some extent between those with and without pertussis (adjusted odds ratio 1.89, 95% confidence interval = 1.17 to 3.07; P = 0.010). Median cough duration after presentation was 17 and 12 days in patients with and without pertussis, respectively (P = 0.008). Patients with pertussis had longer duration of phlegm production (P = 0.010), shortness of breath (P = 0.037), disturbed sleep (P = 0.013) and interference with normal activities or work (P = 0.033) after presentation. Conclusion Pertussis infection plays a limited role among adults presenting with acute cough in primary care, but GPs should acknowledge the possibility of pertussis in uncomplicated lower respiratory tract infection. As in children, pertussis also causes prolonged symptoms in adults. However, pertussis is difficult to discern from other acute cough syndromes in adults at first presentation. PMID:26412843

  19. Biomechanical evaluation of acellular collagen matrix augmented Achilles tendon repair in sheep.

    PubMed

    Song, Lin; Olsen, Raymond E; Spalazzi, Jeffrey P; Davisson, Twana

    2010-01-01

    The rate of rerupture of repaired Achilles tendon in young and athletic populations remains high despite improvement in surgical techniques, suture design, and postsurgical management. Acellular biological matrices can be used to enhance the immediate strength of repaired tendons and to serve as scaffolds for cell in-growth and constructive tissue remodeling. A number of commercially available matrices have been used clinically, albeit with varying degrees of success and failure. The disparity is likely attributable to the different physical and biochemical properties of individual matrices. In this study, we investigated the biomechanical characteristics of 2 different acellular collagen matrices, namely TissueMend and GraftJacket, using a sheep Achilles tendon repair model. Static and cyclic creep, cyclic and linear construct stiffness, maximum load to failure, and displacement at maximum load were determined at time zero. We found that the maximum load to failure, displacement, and ultimate failure mode were similar between tendons augmented with either acellular collagen matrix; however, TissueMend augmentation yielded lower creep and smaller construct elongation than did GraftJacket. The results indicated that the strength of TissueMend-augmented tendons and GraftJacket-augmented tendons was not statistically significantly different, although tendons augmented with TissueMend displayed greater stiffness, which may be clinically advantageous in the restoration of ruptured tendons. PMID:20797586

  20. Immunolocation of proteoglycans and bone-related noncollagenous glycoproteins in developing acellular cementum of rat molars.

    PubMed

    Yamamoto, T; Domon, T; Takahashi, S; Arambawatta, A K S; Wakita, M

    2004-09-01

    To elucidate the roles of proteoglycans of (PGs), bone sialoprotein (BSP), and osteopontin (OPN) in cementogenesis, their distribution was investigated in developing and established acellular cementum of rat molars by an immunoperoxidase method. To characterize PGs, antibodies against five species of glycosaminoglycans (GAGS), chondroitin-4-sulfate (C4S), chondroitin-6-sulfate (C6S), unsulfated chondroitin (C0S), dermatan sulfate (DS), and keratan sulfate (KS) were used. Routine histological staining was also applied. With onset of dentin mineralization, the initial cementum appeared on the dentin surface as a hematoxylin-stained fibril-poor layer. Subsequently, primitive principal fibers attached to the initial cementum. As the acellular cementum containing extrinsic fibers covered the initial cementum, the intal cementum formed the cemento-dentinal junction. Following immunohistochemistry at the earliest time of cementogenesis, the initial cementum was intensely immunoreactive for C4S, C6S, C0S, BSP, and OPN. After the initial cementum was embedded, neither the cemento-dentinal junction nor the cementum was immunoreactive for any GAG species. However, the cementum was immunoreactive for any GAG species. However, the cementum and cemento-dentinal were consistently immunoreactive for BSP. Although the cemento-dentinal junction was consistently immunoreactive for OPN, the remaining cementum showed no significant immunoreactivity. Thus, initial acellular cementogenesis requires a dense accumulation of PGs, BSP, and OPN, which may be associated with the mineralization process independently of collagen fibrils and initial principal fiber attachment. PMID:15278434

  1. Preparation and characterization of an acellular bovine pericardium intended for manufacture of valve bioprostheses.

    PubMed

    Goissis, Gilberto; Giglioti, Aparecida de Fátima; Braile, Domingo Marcolino

    2011-05-01

    Major problems with biological heart valves post-implantation are associated with progressive structural deterioration and calcification attributed to glutaraldehyde processing, dead cells, and cell fragments present in the native tissue. In spite of these problems, glutaraldehyde still is the reagent of choice. The results with acellular matrix xenograft usually prepared by detergent treatment in association with enzymes are rather conflicting because while preserving mechanical properties, tissue morphology and collagen structure are process dependent. This work describes a chemical approach for the preparation of an acellular bovine pericardium matrix intended for the manufacture of heart valve bioprostheses. Cell removal was performed by an alkaline extraction in the presence of calcium salts for periods ranging from 6 to 48 h. The results showed that cell removal was achieved after 12 h, with swelling and negative charge increasing with processing time. Nevertheless, collagen fibril structure, ability to form fibrils, and stability to collagenase were progressive after 24-h processing. There was no denaturation of the collagen matrix. A process is described for the preparation of acellular bovine pericardium matrices with preserved fibril structure and morphology for the manufacture of cardiac valve bioprostheses and may be used in other applications for tissue reconstruction. PMID:21595716

  2. Production of inflammatory cytokines in response to diphtheria-pertussis-tetanus (DPT), haemophilus influenzae type b (Hib), and 7-valent pneumococcal (PCV7) vaccines

    PubMed Central

    Kashiwagi, Yasuyo; Miyata, Akiko; Kumagai, Takuji; Maehara, Kouji; Suzuki, Eitarou; Nagai, Takao; Ozaki, Takao; Nishimura, Naoko; Okada, Kenji; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-01-01

    Haemophilus influenzae type b (Hib) and 7-valent pneumococcal (PCV7) vaccines both became recommended in Japan in 2010. In this study, cytokine production was investigated in peripheral blood mononuclear cells (PBMCs) cultures stimulated with diphtheria and tetanus toxoids combined with acellular pertussis vaccine (DPT), Hib, and PCV7 separately or concurrent different combinations, all as final off-the-shelf vaccines without the individual vaccine components as controls. Higher IL-1β levels were produced when cultures were stimulated with PCV than with DPT or Hib, and the concurrent stimulation including PCV7 enhanced the production of IL-1β. Although Hib induced higher levels of IL-6, no significant difference was observed in IL-6 production with the concurrent stimulation. The concurrent stimulation with Hib/PCV7 and DPT/Hib/PCV7 produced higher levels of TNF-α and human G-CSF. Cytokine profiles were examined in serum samples obtained from 61 vaccine recipients with febrile reactions and 18 recipients without febrile illness within 24 h of vaccination. No significant difference was observed in cytokine levels of IL-1β, IL-4, IL-6, IL-10, IL-12, IFN-γ, MIP-1, TNF-α, and prostaglandin E2 (PGE2) in sera between the two groups. However, significantly higher levels of human G-CSF were observed in recipients with febrile illness than in those without febrile reactions. Further investigations of the significance of elevated serum G-CSF levels are required in vaccine recipients with febrile illness. PMID:24589970

  3. Bordetella pertussis in infants hospitalized for acute respiratory symptoms remains a concern

    PubMed Central

    2013-01-01

    Background Preliminary results suggest that pertussis infection might be considered in infants during a seasonal respiratory syncytial virus (RSV) outbreak. Methods In order to analyze clinical features and laboratory findings in infants with pertussis hospitalized for acute respiratory symptoms during a seasonal RSV outbreak, we conducted a retrospective single-center study on 19 infants with pertussis (6 boys; median age 72 days) and 19 matched controls (RSV-bronchiolitis), hospitalized from October 2008 to April 2010. B. pertussis and RSV were detected from nasopharyngeal washes with Real Time-PCR. Results Infants with pertussis were less often breastfeed than infants with RSV bronchiolitis (63.2% vs 89.5%; p <0.06). Clinically, significantly fewer infants with pertussis than controls had more episodes of whooping cough (63.2% vs 0.0%; p < 0.001) and also less frequently fever at admission (15.8% vs 68.4%; p <0.01), apnea (52.6% vs 10.5%; p <0.006), and cyanosis (52.6% vs 10.5%; p < 0.006). Infants with pertussis had more often no abnormal chest sounds on auscultation than infants with RSV bronchiolitis (0% vs 42,1%; p < 0.005). The absolute blood lymphocyte and eosinophil counts were higher in infants with B. pertussis than in controls with bronchiolitis (23886 ± 16945 vs 10725 ± 4126 cells/mm3, p < 0.0001 and 13.653 ± 10.430 vs 4.730 ± 2.400 cells/mm3, p < 0.001). The molecular analysis of 2 B. pertussis isolates for ptxA1, ptxP3, and prn2 genes showed the presence of gene variants. Conclusions When infants are hospitalized for acute respiratory symptoms, physicians should suspect a pertussis infection, seek for specific clinical symptoms, investigate lymphocyte and eosinophil counts and thus diagnose infection early enough to allow treatment. PMID:24209790

  4. Serodiagnosis as Adjunct Assay for Pertussis Infection in São Paulo, Brazil

    PubMed Central

    Martin, Monte D.; Pawloski, Lucia C.; Leite, Daniela; Rocha, Karen C. P.; de Brito, Cyro A.; Vaz, Tânia M. I.; Martins, Luciano Moura; Alvarenga, Danielly P.; Ribeiro, Ana F.; Carvalhanas, Telma R. M. P.; Nakasaki, Rosa M. D.; Oliveira, Silvia S.; Waldman, Eliseu A.; Tondella, Maria Lucia

    2014-01-01

    Pertussis remains an important public health problem in many countries despite extensive immunization. Cultures and real-time PCR (RT-PCR) assays are the recommended pertussis diagnostic tests, but they lack sensitivity at the later stage of the disease. This study introduces the IgG anti-pertussis toxin enzyme-linked immunosorbent assay (PT ELISA) in our routine diagnosis to improve disease burden estimation. Serum samples and nasopharyngeal swabs (n = 503) were collected at the same time from patients presenting with cough illness suspected of being pertussis and tested by the PT ELISA and culture and/or RT-PCR, respectively. Patients were separated into three age groups: group 1, <1 year (n = 260; mean age, 3 months), group 2, 1 to 6 years (n = 81; mean age, 3 years), and group 3, ≥7 years (n = 162; mean age, 26 years). The times (means) from cough onset to specimen collection were 16, 24, and 26 days, respectively. In group 1, 83 (82.2%) of 101 positive cases were positive for pertussis by culture/RT-PCR, while 40 (39.6%) tested positive by PT ELISA. In group 2, 6 (19.4%) of 31 positive cases were culture/RT-PCR positive, and 29 (93.6%) were seropositive. In group 3, 13 (13.8%) of 94 positive cases were positive by culture/RT-PCR and 91 (96.8%) were positive by serology. Culture/RT-PCR detected more cases of pertussis in infants (P < 0.0001), whereas the PT ELISA detected more cases in adolescents and adults (P < 0.0001). The timing between cough onset and specimen collection or recent vaccination may have partially affected our results. Serology is a suitable, cost-effective, and complementary pertussis diagnostic tool, especially among older children, adolescents, and adults during the later disease phase. PMID:24599531

  5. Molecular Signatures of the Evolving Immune Response in Mice following a Bordetella pertussis Infection

    PubMed Central

    Raeven, René H. M.; Brummelman, Jolanda; Pennings, Jeroen L. A.; Nijst, Olaf E. M.; Kuipers, Betsy; Blok, Laura E. R.; Helm, Kina; van Riet, Elly; Jiskoot, Wim; van Els, Cecile A. C. M.; Han, Wanda G. H.; Kersten, Gideon F. A.; Metz, Bernard

    2014-01-01

    Worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. Since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. The purpose was to elucidate the kinetics of the protective immune response evolving after experimental Bordetella pertussis (B. pertussis) infection in mice. Data were collected from (i) individual analyses, i.e. microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii) twelve time points during the infection; and (iii) different tissues involved in the immune responses, i.e. lungs, spleen and blood. Combined data revealed detailed insight in molecular and cellular sequence of events connecting different phases (innate, bridging and adaptive) of the immune response following the infection. We detected a prolonged acute phase response, broad pathogen recognition, and early gene signatures of subsequent T-cell recruitment in the lungs. Activation of particular transcription factors and specific cell markers provided insight into the time course of the transition from innate towards adaptive immune responses, which resulted in a broad spectrum of systemic antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In addition, signatures preceding the local generation of Th1 and Th17 cells as well as IgA in the lungs, considered key elements in protection against B. pertussis, were established. In conclusion, molecular and cellular immunological processes in response to live B. pertussis infection were unraveled, which may provide guidance in selecting new vaccine candidates that should evoke local and prolonged protective immune responses. PMID:25137043

  6. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

    PubMed

    Becker, Simon; Steinmeyer, Jasmin; Avsar, Murat; Höffler, Klaus; Salman, Jawad; Haverich, Axel; Warnecke, Gregor; Ochs, Matthias; Schnapper, Anke

    2016-01-01

    Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition. PMID:26264867

  7. Maternal immunization

    PubMed Central

    Moniz, Michelle H; Beigi, Richard H

    2014-01-01

    Maternal immunization holds tremendous promise to improve maternal and neonatal health for a number of infectious conditions. The unique susceptibilities of pregnant women to infectious conditions, as well as the ability of maternally-derived antibody to offer vital neonatal protection (via placental transfer), together have produced the recent increased attention on maternal immunization. The Advisory Committee on Immunization Practices (ACIP) currently recommends 2 immunizations for all pregnant women lacking contraindication, inactivated Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Given ongoing research the number of vaccines recommended during pregnancy is likely to increase. Thus, achieving high vaccination coverage of pregnant women for all recommended immunizations is a key public health enterprise. This review will focus on the present state of vaccine acceptance in pregnancy, with attention to currently identified barriers and determinants of vaccine acceptance. Additionally, opportunities for improvement will be considered. PMID:25483490

  8. Development and Analytical Validation of an Immunoassay for Quantifying Serum Anti-Pertussis Toxin Antibodies Resulting from Bordetella pertussis Infection ▿

    PubMed Central

    Menzies, Sandra L.; Kadwad, Vijay; Pawloski, Lucia C.; Lin, Tsai-Lien; Baughman, Andrew L.; Martin, Monte; Tondella, Maria Lucia C.; Meade, Bruce D.

    2009-01-01

    Adequately sensitive and specific methods to diagnose pertussis in adolescents and adults are not widely available. Currently, no Food and Drug Administration-approved diagnostic assays are available for the serodiagnosis of Bordetella pertussis. Since concentrations of B. pertussis-specific antibodies tend to be high during the later phases of disease, a simple, rapid, easily transferable serodiagnostic test was developed. This article describes test development, initial evaluation of a prototype kit enzyme-linked immunosorbent assay (ELISA) in an interlaboratory collaborative study, and analytical validation. The data presented here demonstrate that the kit met all prespecified criteria for precision, linearity, and accuracy for samples with anti-pertussis toxin (PT) immunoglobulin G (IgG) antibody concentrations in the range of 50 to 150 ELISA units (EU)/ml, the range believed to be most relevant for serodiagnosis. The assay met the precision and linearity criteria for a wider range, namely, from 50 to 200 EU/ml; however, the accuracy criterion was not met at 200 EU/ml. When the newly adopted World Health Organization International Standard for pertussis antiserum (human) reference reagent was used to evaluate accuracy, the accuracy criteria were met from 50 to 200 international units/ml. In conclusion, the IgG anti-PT ELISA met all assay validation parameters within the range considered most relevant for serodiagnosis. This ELISA was developed and analytically validated as a user-friendly kit that can be used in both qualitative and quantitative formats. The technology for producing the kit is transferable to public health laboratories. PMID:19864485

  9. Whole-genome sequencing reveals the effect of vaccination on the evolution of Bordetella pertussis

    PubMed Central

    Xu, Yinghua; Liu, Bin; Gröndahl-Yli-Hannuksila, Kirsi; Tan, Yajun; Feng, Lu; Kallonen, Teemu; Wang, Lichan; Peng, Ding; He, Qiushui; Wang, Lei; Zhang, Shumin

    2015-01-01

    Herd immunity can potentially induce a change of circulating viruses. However, it remains largely unknown that how bacterial pathogens adapt to vaccination. In this study, Bordetella pertussis, the causative agent of whooping cough, was selected as an example to explore possible effect of vaccination on the bacterial pathogen. We sequenced and analysed the complete genomes of 40 B. pertussis strains from Finland and China, as well as 11 previously sequenced strains from the Netherlands, where different vaccination strategies have been used over the past 50 years. The results showed that the molecular clock moved at different rates in these countries and in distinct periods, which suggested that evolution of the B. pertussis population was closely associated with the country vaccination coverage. Comparative whole-genome analyses indicated that evolution in this human-restricted pathogen was mainly characterised by ongoing genetic shift and gene loss. Furthermore, 116 SNPs were specifically detected in currently circulating ptxP3-containing strains. The finding might explain the successful emergence of this lineage and its spread worldwide. Collectively, our results suggest that the immune pressure of vaccination is one major driving force for the evolution of B. pertussis, which facilitates further exploration of the pathogenicity of B. pertussis. PMID:26283022

  10. Local massage after vaccination enhances the immunogenicity of diphtheria-tetanus-pertussis vaccine.

    PubMed

    Hsu, C Y; Huang, L M; Lee, C Y; Lin, T Y; Lee, P I; Chen, J M

    1995-07-01

    The effect of local massage on adverse reactions and immunogenicity of diphtheria-tetanus-pertussis vaccine was investigated. After diphtheria-tetanus-pertussis vaccination 327 infants were either massaged or not, and adverse reactions were evaluated. Local pain and fever were more frequent in the massage group. The extra febrile episodes from massage were mild (38-39 degrees C). For evaluation of the antibody responses, 124 infants were recruited into massage or nonmassage cohorts and antibody production was measured at 2, 6, 7, 18 and 19 months of age, respectively. Subjects in the massage group developed significantly higher antibodies against filamentous hemagglutinin at 6 and 7 months of age, pertussis toxin at 6, 7, 18 and 19 months of age, pertussis agglutinogen at 18 and 19 months of age and those in the nonmassage group. Local massage after diphtheria-tetanus-pertussis vaccination was associated with better immunogenicity and more adverse reactions, including low grade fever and local pain, which were mild and not particularly disturbing. PMID:7567283

  11. Whole-genome sequencing reveals the effect of vaccination on the evolution of Bordetella pertussis.

    PubMed

    Xu, Yinghua; Liu, Bin; Gröndahl-Yli-Hannuksila, Kirsi; Tan, Yajun; Feng, Lu; Kallonen, Teemu; Wang, Lichan; Peng, Ding; He, Qiushui; Wang, Lei; Zhang, Shumin

    2015-01-01

    Herd immunity can potentially induce a change of circulating viruses. However, it remains largely unknown that how bacterial pathogens adapt to vaccination. In this study, Bordetella pertussis, the causative agent of whooping cough, was selected as an example to explore possible effect of vaccination on the bacterial pathogen. We sequenced and analysed the complete genomes of 40 B. pertussis strains from Finland and China, as well as 11 previously sequenced strains from the Netherlands, where different vaccination strategies have been used over the past 50 years. The results showed that the molecular clock moved at different rates in these countries and in distinct periods, which suggested that evolution of the B. pertussis population was closely associated with the country vaccination coverage. Comparative whole-genome analyses indicated that evolution in this human-restricted pathogen was mainly characterised by ongoing genetic shift and gene loss. Furthermore, 116 SNPs were specifically detected in currently circulating ptxP3-containing strains. The finding might explain the successful emergence of this lineage and its spread worldwide. Collectively, our results suggest that the immune pressure of vaccination is one major driving force for the evolution of B. pertussis, which facilitates further exploration of the pathogenicity of B. pertussis. PMID:26283022

  12. Mucosal immunization with filamentous hemagglutinin protects against Bordetella pertussis respiratory infection.

    PubMed Central

    Shahin, R D; Amsbaugh, D F; Leef, M F

    1992-01-01

    Mucosal immunization of mice with purified Bordetella pertussis filamentous hemagglutinin (FHA), by either the respiratory or the gut route, was found to protect against B. pertussis infection of the trachea and lungs. Intranasal immunization of BALB/c and (C57BL/6 x C3H/HeN)F1 adult female mice with FHA prior to B. pertussis aerosol challenge resulted in a 2 to 3 log reduction in number of bacteria recovered from the lungs and the tracheas of immunized mice in comparison to unimmunized controls. Intraduodenal immunization of adult mice with FHA before infection also resulted in approximately a 2 log reduction in the recovery of bacteria from the lungs and the tracheas of immunized mice in comparison to unimmunized controls. Immunoglobulin A and immunoglobulin G anti-FHA were both detected in bronchoalveolar lavage fluids of mucosally immunized mice. Limiting dilution analysis revealed a 60-fold increase in the frequency of FHA-specific B cells isolated from the lungs of mice immunized intranasally with FHA in comparison to unimmunized control mice. These data suggest that both gut and respiratory mucosal immunization with a major adhesin of B. pertussis generates a specific immune response in the respiratory tract that may serve as one means of mitigating subsequent B. pertussis respiratory infection. Images PMID:1548072

  13. Bordetella parapertussis and Bordetella bronchiseptica contain transcriptionally silent pertussis toxin genes.

    PubMed Central

    Aricò, B; Rappuoli, R

    1987-01-01

    Pertussis toxin, the major virulence factor of Bordetella pertussis, is not produced by the closely related species Bordetella parapertussis and Bordetella bronchiseptica. It is shown here that these two species possess but do not express the complete toxin operon. Nucleotide sequencing of an EcoRI fragment of 5 kilobases comprising the regions homologous to the pertussis toxin genes shows that in this region, B. parapertussis and B. bronchiseptica are 98.5% and 96% homologous, respectively, to B. pertussis. The changes (mostly base pair substitutions) in many cases are identical in B. parapertussis and B. bronchiseptica, suggesting that these two species derive from a common ancestor. Many of the mutations common to B. parapertussis and B. bronchiseptica involve the promoter region, which becomes very inefficient. The S1 subunits of both species, when expressed in Escherichia coli, have the same ADP-ribosylating activity as the S1 subunit from B. pertussis, indicating that the mutations in the S1 gene described here do not affect its function. Images PMID:3584073

  14. Geographic clustering of nonmedical exemptions to school immunization requirements and associations with geographic clustering of pertussis.

    PubMed

    Omer, Saad B; Enger, Kyle S; Moulton, Lawrence H; Halsey, Neal A; Stokley, Shannon; Salmon, Daniel A

    2008-12-15

    School immunization requirements are important in controlling vaccine-preventable diseases in the United States. Forty-eight states offer nonmedical exemptions to school immunization requirements. Children with exemptions are at increased risk of contracting and transmitting vaccine-preventable diseases. The clustering of nonmedical exemptions can affect community risk of vaccine-preventable diseases. The authors evaluated spatial clustering of nonmedical exemptions in Michigan and geographic overlap between exemptions clusters and clusters of reported pertussis cases. Kulldorf's scan statistic identified 23 statistically significant census tract clusters for exemption rates and 6 significant census tract clusters for reported pertussis cases between 1993 and 2004. The time frames for significant space-time pertussis clusters were August 1993-September 1993, August 1994-February 1995, May 1998-June 1998, April 2002, May 2003-July 2003, and June 2004-November 2004. Census tracts in exemptions clusters were more likely to be in pertussis clusters (odds ratio = 3.0, 95% confidence interval: 2.5, 3.6). The overlap of exemptions clusters and pertussis clusters remained significant after adjustment for population density, proportion of racial/ethnic minorities, proportion of children aged 5 years or younger, percentage of persons below the poverty level, and average family size (odds ratio = 2.7, 95% confidence interval: 2.2, 3.3). Geographic pockets of vaccine exemptors pose a risk to the whole community. In addition to monitoring state-level exemption rates, health authorities should be mindful of within-state heterogeneity. PMID:18922998

  15. Dose Response of Attenuated Bordetella pertussis BPZE1-Induced Protection in Mice▿

    PubMed Central

    Mielcarek, Nathalie; Debrie, Anne-Sophie; Mahieux, Severine; Locht, Camille

    2010-01-01

    Despite the availability of efficacious vaccines, the incidence of whooping cough is still high in many countries and is even increasing in countries with high vaccine coverage. Most severe and life-threatening pertussis cases occur in infants who are too young to be sufficiently protected by current vaccine regimens. As a potential solution to this problem, we have developed an attenuated live Bordetella pertussis vaccine strain, named BPZE1. Here, we show that after a single administration, BPZE1 induces dose-dependent protection against challenge with virulent B. pertussis in low-dose and in high-dose intranasal mouse lung colonization models. In addition, we observed BPZE1 dose-dependent antibody titers to B. pertussis antigens, as well as cell-mediated immunity, evidenced by the amounts of gamma interferon (IFN-γ) released from spleen cells upon stimulation with B. pertussis antigens. These two parameters may perhaps be used as readouts in clinical trials in humans that are currently being planned. PMID:20107007

  16. Single Amino Acid Polymorphisms of Pertussis Toxin Subunit S2 (PtxB) Affect Protein Function

    PubMed Central

    Millen, Scott H.; Watanabe, Mineo; Komatsu, Eiji; Yamaguchi, Fuminori; Nagasawa, Yuki; Suzuki, Eri; Monaco, Haleigh; Weiss, Alison A.

    2015-01-01

    Whooping cough due to Bordetella pertussis is increasing in incidence, in part due to accumulation of mutations which increase bacterial fitness in highly vaccinated populations. Polymorphisms in the pertussis toxin, ptxA and ptxB genes, and the pertactin, prn genes of clinical isolates of Bordetella pertussis collected in Cincinnati from 1989 through 2005 were examined. While the ptxA and prn genotypes were variable, all 48 strains had the ptxB2 genotype; ptxB1 encodes glycine at amino acid 18 of the S2 subunit of pertussis toxin, while ptxB2 encodes serine. We investigated antigenic and functional differences of PtxB1 and PtxB2. The S2 protein was not very immunogenic. Only a few vaccinated or individuals infected with B. pertussis developed antibody responses to the S2 subunit, and these sera recognized both polymorphic forms equally well. Amino acid 18 of S2 is in a glycan binding domain, and the PtxB forms displayed differences in receptor recognition and toxicity. PtxB1 bound better to the glycoprotein, fetuin, and Jurkat T cells in vitro, but the two forms were equally effective at promoting CHO cell clustering. To investigate in vivo activity of Ptx, one μg of Ptx was administered to DDY mice and blood was collected on 4 days after injection. PtxB2 was more effective at promoting lymphocytosis in mice. PMID:26375454

  17. The First Macrolide-Resistant Bordetella pertussis Strains Isolated From Iranian Patients

    PubMed Central

    Shahcheraghi, Fereshteh; Nakhost Lotfi, Masoumeh; Nikbin, Vajiheh Sadat; Shooraj, Fahimeh; Azizian, Reza; Parzadeh, Masoumeh; Allahyar Torkaman, Mohammad Reza; Zahraei, Seyed Mohsen

    2014-01-01

    Background: Whooping cough was considered as one of the major causes of childhood morbidity and mortality worldwide. Resistant isolates of Bordetella pertussis to macrolides in some countries have been recently reported. Objectives: Recent reports on macrolide-resistant B. pertussis isolates and lack of evidence for such resistance in clinical isolates of the Iranian patients led the authors of the current study to study antibiotic susceptibility of the collected isolates in the country. Susceptibility of the B. pertussis isolates to three antibiotics was studied. Relatedness of the strains recovered in this research was also examined. Materials and Methods: The antibacterial activities of erythromycin, azithromycin, and clarithromycin antibiotics against the recovered isolates of 779 nasopharyngeal swabs were examined using MIC (Minimum Inhibitory Concentration) method. Relationship of the strains was characterized by Pulsed-field Gel Electrophoresis (PFGE). Results: Among the specimens, 11 cases (1.4%) were culture-positive. Among these isolates, only two isolates had high MIC values for erythromycin and clarithromycin. Pulsed-field gel electrophoresis analysis of the isolates revealed 6 PFGE profiles (A-F) among which three and two isolates had the same patterns in profiles A and B, respectively. Conclusions: Azithromycin can be a good drug of choice to treat patients infected by B. pertussis in Iran. Clonal relationship of the isolates showed that the same B. pertussis strains were isolated from different patients in Iran. PMID:25371806

  18. Misidentification of Bordetella bronchiseptica as Bordetella pertussis using a Newly Described RT-PCR Targeting the Pertactin Gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently a real-time PCR (RT-PCT) assay based on sequence from the gene for pertactin was proposed for identification of Bordetella pertussis. Here we report that the B. pertussis pertactin gene sequence for the region encompassing the RT-PCR probe and primers is nearly identical to that of many B....

  19. [Accumulation of the bvg- Bordetella pertussis a virulent mutants in the process of experimental whooping cough in mice].

    PubMed

    Medkova, A Iu; Siniashina, L N; Rumiantseva, Iu P; Voronina, O L; Kunda, M S; Karataev, G I

    2013-01-01

    The duration of the persistence and dynamics of accumulation of insertion bvg- Bordetella pertussis mutants were studied in lungs of laboratory mice after intranasal and intravenous challenge by virulent bacteria of the causative agent of whooping cough. The capability of the virulent B. pertussis bacteria to long-term persistence in the body of mice was tested. Using the real-time PCR approximately hundred genome equivalents of the B. pertussis DNA were detected in lungs of mice in two months after infection regardless of the way of challenge. Using the bacterial test bacteria were identified during only four weeks after challenge. Bvg- B. pertussis avirulent mutants were accumulated for the infection time. The percentage of the avirulent bacteria in the B. pertussis population reached 50% in 7-9 weeks after challenge. The obtained results show that the laboratory mice can be used for study of the B. pertussis insertion mutant formation dynamics in vivo and confirm the hypothesis about insertional bvg- B. pertussis virulent mutants accumulation during development of pertussis infection in human. PMID:24645274

  20. Florid pustular dermatitis of breast: A case report on a unusual complication from acellular dermal matrix use

    PubMed Central

    James, Justin; Jackson, Lee; Saunders, Christobel

    2016-01-01

    Introduction Idiopathic erythematous reaction of the breast (Red breast syndrome) is a known complication following breast reconstruction with acellular dermal matrix. However pustular dermatitis like presentation is not previously known. Presentation of case We present a 42-year-old lady who developed bilateral pustular dermatitis like appearance following breast reconstruction with acellular dermal matrix slings. Though surgical washout was done, both expanders and flex HD could be preserved. Discussion Acellular dermal matrix use is the only possible explanation for such a presentation and this can be considered a variant of red breast syndrome. Conclusion Pustular dermatitis like presentation can be associated with acelluar dermal matrix use and should be considered in similar clinical presentations, since this can avoid unnecessary surgical procedures. PMID:27058152

  1. Purification and preliminary characterization of agglutinogen 3 from Bordetella pertussis.

    PubMed

    Fredriksen, J H; Frøholm, L O; Paulsen, B S

    1985-01-01

    One serotype antigen, agglutinogen 3, from Bordetella pertussis, (strain M2, serotype 1.3), has been purified. The purification procedure included acetone drying of cells harvested from shaking cultures. Agglutinogens were extracted in phosphate buffered saline. Crude extract was heat treated at 80 degrees C for 5 min and precipitated by ammonium sulphate between 25 and 60% saturation at 4 degrees C, providing 50% of the total activity and a five-fold purification. Further purification was attempted by gel filtration chromatography using a TSK-G3000 SW column. The ammonium sulphate precipitated fraction was also separated by anion exchange chromatography using a Mono Q HR 5/5 column. The purification work indicated that agglutinogen 3 is associated with several other substances and that this property can lead to purification difficulties. The isolation procedure was monitored by an agglutination-inhibition assay. The peak fraction from the ion exchange chromatography was purified up to 27-fold according to the specific activities (inhibition units per mg protein). The yield was only 1% due to severe loss of activity. In the gel filtration chromatography agglutinogen 3-activity eluted with a maximum activity corresponding to a molecular weight near 450,000. SDS-PAGE analysis indicated that agglutinogen 3 might have a subunit molecular weight of 20,800. PMID:2872104

  2. Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular Matrix for In Vitro Irritation Testing.

    PubMed

    Tsai, Pei-Chin; Zhang, Zheng; Florek, Charles; Michniak-Kohn, Bozena B

    2016-01-01

    The irritancy of topical products has to be investigated to ensure the safety and compliance. Although several reconstructed human epidermal models have been adopted by the Organization for Economic Cooperation and Development (OECD) to replace in vivo animal irritation testing, these models are based on a single cell type and lack dermal components, which may be insufficient to reflect all of the components of irritation. In our study, we investigated the use of acellular porcine peritoneum extracellular matrix as a substrate to construct full-thickness human skin equivalents (HSEs) for use as irritation screening tool. The acellular peritoneum matrix (APM) exhibited excellent skin cell attachment (>80%) and proliferation for human dermal fibroblasts (HDF) and immortalized human keratinocytes (HaCaT). APM-HSEs based on coculture of HDF and HaCaT were prepared. Increased HDF seeding density up to 5 × 10(4)/cm(2) resulted in APM-HSEs with a thicker and more organized epidermis. The epidermis of APM-HSEs expressed keratin 15, a keratinocyte proliferation marker, and involucrin, a differentiation marker, respectively. To assess the use of APM-HSEs for irritation testing, six proficiency chemicals, including three nonirritants (phosphate-buffered saline, polyethylene glycol 400, and isopropanol) and three irritants (1-bromohexane, heptanol, and sodium dodecyl sulfate) were applied. The APM-HSEs were able to discriminate nonirritants from irritants based on the viability. Levels of cytokines (interleukin [IL]-1α, IL-1ra, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor [GM-CSF]) in these treatment groups further assisted the irritancy ranking. In conclusion, we have developed partially differentiated full-thickness APM-HSEs based on acellular porcine peritoneum matrix, and these APM-HSEs demonstrated utility as an in vitro irritation screening tool. PMID:26415037

  3. The Human Umbilical Vein with Wharton's Jelly as an Allogeneic, Acellular Construct for Vocal Fold Restoration

    PubMed Central

    Rodriguez, Maritza L.; McFetridge, Peter S.

    2009-01-01

    This study investigated the potential of the decellularized human umbilical vein (HUV) as an allogeneic, acellular extracellular matrix (ECM) scaffold for engineering the vocal fold lamina propria in vitro. HUV specimens with Wharton's jelly on the abluminal surface were uniformly dissected from native umbilical cords using an automated procedure and subjected to a novel saline-based decellularization treatment for removal of potentially antigenic epitopes. Human vocal fold fibroblasts from primary culture were seeded onto the resulting acellular constructs and cultured for 21 days. The structures of decellularized and fibroblast-repopulated HUV constructs and the attachment, proliferation, and infiltration of fibroblasts were examined with light microscopy and scanning electron microscopy. Changes in the relative densities of collagen in the constructs associated with decellularization and recellularization were quantified using digital image analysis. In addition, fibroblasts infiltrating the scaffolds were released by cell recovery and quantified by counting. Viscoelastic properties of the scaffolds were measured using a linear, simple-shear rheometer at phonatory frequencies. Results showed that an acellular ECM construct with an intact three-dimensional structure of Wharton's jelly was fabricated. Vocal fold fibroblasts readily attached on the abluminal surface of the construct with high viability, with significant cellular infiltration up to approximately 600 μm deep into the construct. A significant increase in collagen expression was observed with recellularization. The elastic modulus and dynamic viscosity of the fibroblast-repopulated scaffolds were comparable to those of the human vocal fold lamina propria. These findings supported the potential of the construct as a possible surgical allograft for vocal fold restoration and reconstruction. PMID:19456236

  4. Current opinions on indications and algorithms for acellular dermal matrix use in primary prosthetic breast reconstruction.

    PubMed

    Vu, Michael M; Kim, John Y S

    2015-06-01

    Acellular dermal matrix (ADM) is widely used in primary prosthetic breast reconstruction. Many indications and contraindications to use ADM have been reported in the literature, and their use varies by institution and surgeon. Developing rational, tested algorithms to determine when ADM is appropriate can significantly improve surgical outcomes and reduce costs associated with ADM use. We review the important indications and contraindications, and discuss the algorithms that have been put forth so far. Further research into algorithmic decision-making for ADM use will allow optimized balancing of cost with risk and benefit. PMID:26161304

  5. Mechanisms by which acellular biologic scaffolds promote functional skeletal muscle restoration.

    PubMed

    Badylak, Stephen F; Dziki, Jenna L; Sicari, Brian M; Ambrosio, Fabrisia; Boninger, Michael L

    2016-10-01

    Acellular biologic scaffolds derived from extracellular matrix have been investigated in preclinical and clinical studies as a regenerative medicine approach for volumetric muscle loss treatment. The present manuscript provides a review of previous studies supporting the use of extracellular matrix derived biologic scaffolds for the promotion of functional skeletal muscle tissue formation that is contractile and innervated. The manuscript also identifies key mechanisms that have been associated with ECM-mediated skeletal muscle repair, and provides hypotheses as to why there have been variable outcomes, ranging from successful to unsatisfactory, associated with ECM bioscaffold implantation in the skeletal muscle injury microenvironment. PMID:27376561

  6. Biological activities of pertussigen from Bordetella pertussis strains of various agglutinogen types.

    PubMed

    Watanabe, M

    1984-01-01

    Pertussigen prepared from Bordetella pertussis strains of various agglutinogen types was found to have similar biological activities in mice, and to give precipitin lines of identity in agar diffusion tests. The doses required to induce histamine hypersensitivity ranged from 0.9 to 9.5 ng, and to induce leukocytosis from 124 to 190 ng. When pertussigen was detoxified by treatment with glutaraldehyde, it protected mice from intracerebral challenge with B. pertussis at doses of from 12.7 to 24.4 micrograms. The results showed that all smooth strains of B. pertussis produced pertussigen that was biologically and serologically similar, and that it was produced independently of fimbrial hemagglutinin. PMID:6088952

  7. ADP-ribosylation of membrane components by pertussis and cholera toxin

    SciTech Connect

    Ribeiro-Neto, F.A.P.; Mattera, F.; Hildebrandt, J.D.; Codina, J.; Field, J.B.; Birnbaumer, L.; Sekura, R.D.

    1985-01-01

    Pertussis and cholera toxins are important tools to investigate functional and structural aspects of the stimulatory (N/sub s/) and inhibitory (N/sub i/) regulatory components of adenylyl cyclase. Cholera toxin acts on N/sub s/ by ADP-ribosylating its ..cap alpha../sub s/ subunit; pertussis toxin acts on N/sub i/ by ADP-ribosylating its ..cap alpha..; subunit. By using (/sup 32/P)NAD/sup +/ and determining the transfer of its (/sup 32/P)ADP-ribose moiety to membrane components, it is possible to obtain information on N/sub s/ and N/sub i/. A set of protocols is presented that can be used to study simultaneously and comparatively the susceptibility of N/sub s/ and N/sub i/ to be ADP-ribosylated by cholera and pertussis toxin.

  8. Bordetella pertussis, the Causative Agent of Whooping Cough, Evolved from a Distinct, Human-Associated Lineage of B. bronchiseptica

    PubMed Central

    Diavatopoulos, Dimitri A; Cummings, Craig A; Schouls, Leo M; Brinig, Mary M; Relman, David A; Mooi, Frits R

    2005-01-01

    Bordetella pertussis, B. bronchiseptica, B. parapertussishu, and B. parapertussisov are closely related respiratory pathogens that infect mammalian species. B. pertussis and B. parapertussishu are exclusively human pathogens and cause whooping cough, or pertussis, a disease that has resurged despite vaccination. Although it most often infects animals, infrequently B. bronchiseptica is isolated from humans, and these infections are thought to be zoonotic. B. pertussis and B. parapertussishu are assumed to have evolved from a B. bronchiseptica–like ancestor independently. To determine the phylogenetic relationships among these species, housekeeping and virulence genes were sequenced, comparative genomic hybridizations were performed using DNA microarrays, and the distribution of insertion sequence elements was determined, using a collection of 132 strains. This multifaceted approach distinguished four complexes, representing B. pertussis, B. parapertussishu, and two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Of the two B. bronchiseptica complexes, complex IV was more closely related to B. pertussis. Of interest, while only 32% of the complex I strains were isolated from humans, 80% of the complex IV strains were human isolates. Comparative genomic hybridization analysis identified the absence of the pertussis toxin locus and dermonecrotic toxin gene, as well as a polymorphic lipopolysaccharide biosynthesis locus, as associated with adaptation of complex IV strains to the human host. Lipopolysaccharide structural diversity among these strains was confirmed by gel electrophoresis. Thus, complex IV strains may comprise a human-associated lineage of B. bronchiseptica from which B. pertussis evolved. These findings will facilitate the study of pathogen host-adaptation. Our results shed light on the origins of the disease pertussis and suggest that the association of B. pertussis with humans may be more ancient than previously assumed. PMID

  9. Identification of a 69-kilodalton nonfimbrial protein as an agglutinogen of Bordetella pertussis.

    PubMed

    Brennan, M J; Li, Z M; Cowell, J L; Bisher, M E; Steven, A C; Novotny, P; Manclark, C R

    1988-12-01

    Cells of Bordetella pertussis BP353, a nonfimbriated Eldering serotype 1.3 strain, were used as an immunogen to produce three monoclonal antibodies, BPE3, BPD8, and BPE8, that agglutinated the immunizing cells, as well as certain other nonfimbriated and fimbriated serotype 3-containing B. pertussis strains. The antibodies did not agglutinate serotype 1 or nontypable B. pertussis cells. These monoclonal antibodies specifically detected a 69-kilodalton (kDa) band on Western blots (immunoblots) containing whole B. pertussis cell lysates of Eldering agglutinogen serotypes 1.3, 1.3.6, 1.2.3.4, and 1.2.3.4.6. This 69-kDa antigen was released from the bacteria by cell incubation for 60 min at 60 degrees C, and it was purified by affinity chromatography with a BPE3-agarose affinity matrix. Purified material was used to produce a polyclonal antiserum that agglutinated all nonfimbriated and fimbriated B. pertussis cells containing serotype 3 agglutinogen. Immunogold electron microscopy and indirect immunofluorescence studies demonstrated that it is an outer membrane constituent but nonfimbrial in appearance. BPE3 did not detect purified fimbriae on Western blots, and antibodies to these fimbriae did not bind to the 69-kDa component. Although B. bronchiseptica and B. parapertussis cells were not agglutinated by the monoclonal antibodies, antigenically similar proteins were detected in extracts of the bacteria. These results identify the 69-kDa protein as a nonfimbrial agglutinogen present on all virulent strains of B. pertussis. The monoclonal antibodies described here should be useful for further studies on the structure and function of this protein. PMID:2903126

  10. Identification of a 69-kilodalton nonfimbrial protein as an agglutinogen of Bordetella pertussis.

    PubMed Central

    Brennan, M J; Li, Z M; Cowell, J L; Bisher, M E; Steven, A C; Novotny, P; Manclark, C R

    1988-01-01

    Cells of Bordetella pertussis BP353, a nonfimbriated Eldering serotype 1.3 strain, were used as an immunogen to produce three monoclonal antibodies, BPE3, BPD8, and BPE8, that agglutinated the immunizing cells, as well as certain other nonfimbriated and fimbriated serotype 3-containing B. pertussis strains. The antibodies did not agglutinate serotype 1 or nontypable B. pertussis cells. These monoclonal antibodies specifically detected a 69-kilodalton (kDa) band on Western blots (immunoblots) containing whole B. pertussis cell lysates of Eldering agglutinogen serotypes 1.3, 1.3.6, 1.2.3.4, and 1.2.3.4.6. This 69-kDa antigen was released from the bacteria by cell incubation for 60 min at 60 degrees C, and it was purified by affinity chromatography with a BPE3-agarose affinity matrix. Purified material was used to produce a polyclonal antiserum that agglutinated all nonfimbriated and fimbriated B. pertussis cells containing serotype 3 agglutinogen. Immunogold electron microscopy and indirect immunofluorescence studies demonstrated that it is an outer membrane constituent but nonfimbrial in appearance. BPE3 did not detect purified fimbriae on Western blots, and antibodies to these fimbriae did not bind to the 69-kDa component. Although B. bronchiseptica and B. parapertussis cells were not agglutinated by the monoclonal antibodies, antigenically similar proteins were detected in extracts of the bacteria. These results identify the 69-kDa protein as a nonfimbrial agglutinogen present on all virulent strains of B. pertussis. The monoclonal antibodies described here should be useful for further studies on the structure and function of this protein. Images PMID:2903126

  11. Reactions after pertussis vaccine: a manufacturer's experiences and difficulties since 1964

    PubMed Central

    Griffith, A H

    1978-01-01

    Pertussis vaccines vary in quality, safety, and efficacy according to the production strains of Bordetella pertussis, the method of manufacture, and quality control procedures. It is therefore not justifiable to combine information on the incidence, nature, and severity of reactions after all manufacturers' pertussis vaccines as if they were a single product. Attempts were made to collect information on all suspected cases of severe reactions that occurred after administration of about 15 million doses of Wellcome pertussis vaccines in the United Kingdom and Northern Ireland from 1964 to mid-1977. Altogether six deaths, six neurological reactions with sequelae, and 17 convulsions without sequelae were reported, but some were clearly not attributable to the vaccine, while, in other cases, the available information was inadequate for assessing the role of vaccination. Neurological disorders, similar to those reported in a few children after pertussis vaccination, occur unexpectedly in apparently healthy infants at the recommended age for immunisation, so chance association between vaccination and these events can be expected in some children. The Joint Committee on Vaccination and Immunisation has made several recommendations aimed at reducing severe reactions after pertussis vaccination. These include replacing plain vaccine with aluminium-adsorbed vaccine, but there is no clear evidence that the aluminium-adsorbed vaccine produces fewer reactions than the plain. There are difficulties enough in deciding the cause of events that occur after vaccination, since these reactions often occur naturally in children of vaccination age. The task is made even harder by the assumption that various manufacturers' vaccines are the same and the lack of information available to manufacturers about cases in which their vaccine has been implicated. Information on vaccines administered is entered on immunisation records cards; it should be used and referred to if reactions occur

  12. The Stimulated Innate Resistance Event in Bordetella pertussis Infection Is Dependent on Reactive Oxygen Species Production

    PubMed Central

    Zurita, E.; Moreno, G.; Errea, A.; Ormazabal, M.; Rumbo, M.

    2013-01-01

    The exacerbated induction of innate immune responses in airways can abrogate diverse lung infections by a phenomenon known as stimulated innate resistance (StIR). We recently demonstrated that the enhancement of innate response activation can efficiently impair Bordetella pertussis colonization in a Toll-like receptor 4 (TLR4)-dependent manner. The aim of this work was to further characterize the effect of lipopolysaccharide (LPS) on StIR and to identify the mechanisms that mediate this process. Our results showed that bacterial infection was completely abrogated in treated mice when the LPS of B. pertussis (1 μg) was added before (48 h or 24 h), after (24 h), or simultaneously with the B. pertussis challenge (107 CFU). Moreover, we detected that LPS completely cleared bacterial infection as soon as 2 h posttreatment. This timing suggests that the observed StIR phenomenon should be mediated by fast-acting antimicrobial mechanisms. Although neutrophil recruitment was already evident at this time point, depletion assays using an anti-GR1 antibody showed that B. pertussis clearance was achieved even in the absence of neutrophils. To evaluate the possible role of free radicals in StIR, we performed animal assays using the antioxidant N-acetyl cysteine (NAC), which is known to inactivate oxidant species. NAC administration blocked the B. pertussis clearance induced by LPS. Nitrite concentrations were also increased in the LPS-treated mice; however, the inhibition of nitric oxide synthetases did not suppress the LPS-induced bacterial clearance. Taken together, our results show that reactive oxygen species (ROS) play an essential role in the TLR4-dependent innate clearance of B. pertussis. PMID:23630952

  13. Bordetella pertussis Acquires Resistance to Complement-Mediated Killing In Vivo

    PubMed Central

    Pishko, Elizabeth J.; Betting, David J.; Hutter, Christina S.; Harvill, Eric T.

    2003-01-01

    In order to initially colonize a host, bacteria must avoid various components of the innate immune system, one of which is complement. The genus Bordetella includes three closely related species that differ in their ability to resist complement-mediated killing. Bordetella parapertussis and Bordetella bronchiseptica resist killing in naïve serum, a characteristic that may aid in efficient respiratory tract colonization and has been attributed to expression of O antigen. Bordetella pertussis lacks O antigen and is sensitive to naïve serum in vitro, yet it also efficiently colonizes the respiratory tract. Based on these observations, we hypothesized that B. pertussis may have an alternate mechanism to resist complement in vivo. While a number of reports on serum sensitivity of the bordetellae have been published, we show here that serum concentration and growth conditions can greatly alter the observed level of sensitivity to complement and that all but one strain of B. pertussis observed were sensitive to some level of naïve serum in vitro, particularly when there was excess complement. However, B. pertussis rapidly acquires increased resistance in vivo to naïve serum that is specific to the alternative pathway. Resistance is not efficiently acquired by B. parapertussis and B. bronchiseptica mutants lacking O antigen. This B. pertussis-specific mechanism of complement resistance does not appear to be dependent on either brkA or other genes expressed specifically in the Bvg+ phase. This in vivo acquisition of alternative pathway resistance suggests that there is a novel O antigen-independent method by which B. pertussis evades complement-mediated killing. PMID:12933835

  14. Bordetella pertussis acquires resistance to complement-mediated killing in vivo.

    PubMed

    Pishko, Elizabeth J; Betting, David J; Hutter, Christina S; Harvill, Eric T

    2003-09-01

    In order to initially colonize a host, bacteria must avoid various components of the innate immune system, one of which is complement. The genus Bordetella includes three closely related species that differ in their ability to resist complement-mediated killing. Bordetella parapertussis and Bordetella bronchiseptica resist killing in naïve serum, a characteristic that may aid in efficient respiratory tract colonization and has been attributed to expression of O antigen. Bordetella pertussis lacks O antigen and is sensitive to naïve serum in vitro, yet it also efficiently colonizes the respiratory tract. Based on these observations, we hypothesized that B. pertussis may have an alternate mechanism to resist complement in vivo. While a number of reports on serum sensitivity of the bordetellae have been published, we show here that serum concentration and growth conditions can greatly alter the observed level of sensitivity to complement and that all but one strain of B. pertussis observed were sensitive to some level of naïve serum in vitro, particularly when there was excess complement. However, B. pertussis rapidly acquires increased resistance in vivo to naïve serum that is specific to the alternative pathway. Resistance is not efficiently acquired by B. parapertussis and B. bronchiseptica mutants lacking O antigen. This B. pertussis-specific mechanism of complement resistance does not appear to be dependent on either brkA or other genes expressed specifically in the Bvg(+) phase. This in vivo acquisition of alternative pathway resistance suggests that there is a novel O antigen-independent method by which B. pertussis evades complement-mediated killing. PMID:12933835

  15. Specific immunoglobulin A to Bordetella pertussis antigens in mucosal secretion for rapid diagnosis of whooping cough.

    PubMed Central

    Granström, G; Askelöf, P; Granström, M

    1988-01-01

    Specific immunoglobulin A (IgA) to Bordetella pertussis filamentous hemagglutinin (FHA) and pertussis toxin (PT) was determined in mucosal secretions by an enzyme-linked immunosorbent assay (ELISA). It took 3 to 4 h to complete the ELISA. The upper limits of normal values for age were determined in nasopharyngeal (NPH) secretions from 23 patients with viral infections and in 10 healthy adults working with pertussis patients or cultures. A significant IgA response to FHA was found in 38 of 54 (70%) and to PT in 28 of 54 (52%) NPH secretions from patients with pertussis confirmed by culture, serology, or both. The rate of positive responses to either antigen (44 of 54 [81%]) was significantly higher than that by culture alone (29 of 54 [54%]; P less than 0.01). The rate of positive responses increased from 65% in patients with symptoms for 1 week or less to 87 to 92% in patients with symptoms for 2 or more weeks. The specific IgA response to PT was found in 100% of NPH samples from 17 unimmunized children less than 3 years of age and in only 30% of adults and immunized children greater than 3 years of age. A response to FHA was found in 65 to 73% of the NPH secretions in all age groups. Saliva samples were found to contain specific IgA to FHA and PT in all age groups, but these were of diagnostic value in 50% (11 of 22) of the adult patients. The specificity of the ELISA was 100% (10 of 10 negatives) in NPH secretions from patients with pertussis-like cough who had negative cultures and serology. The results indicate that determination of specific IgA to PT and FHA in NPH aspirates represents a sensitive and rapid diagnostic method for the detection of pertussis. Images PMID:2898484

  16. Isolation of High Level Macrolide Resistant Bordetella pertussis Without Transition Mutation at Domain V in Iran

    PubMed Central

    Mirzaei, Bahman; Bameri, Zakaria; Babaei, Ryhane; Shahcheraghi, Fereshteh

    2015-01-01

    Background: Bordetella pertussis, as a causative agent of whooping cough, due to the annual rise y of infection cases, failure of prophylaxis and treatment by macrolides, is considered as the new concern in the health care system. Objectives: The main objective of this study was the determination of single nucleotide polymorphisms (SNPs) at domain V, as the main binding site for macrolides, following the identification of high level macrolides resistant B. pertussis. Materials and Methods: Following the identification of 11 recovered B. pertussis isolates, from a total of 1084 nasopharyngeal swabs, by using the biochemical and molecular methods, the activities of erythromycin, azithromycin and clarithromycin antibiotics against the recovered isolates were examined. Subsequently, A-G transition mutations in domain V were analyzed by molecular techniques, such as Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and sequencing. Results: After susceptibility testing, one strain was detected as a high level macrolide resistant B. pertussis (Erythromycin = 128 μg/mL, Clarithromycin > 256 μg/mL). After sequencing and PCR-RFLP methods, transition mutations in positions 2047 and 2058 of the mentioned domain were not observed. Conclusions: Although previous studies have shown that A-G transition mutations in 23 SrRNA gene (domain V) are the main reason for the occurrence of high level macrolides resistance in B. pertussis, however, the mentioned single nucleotide polymorphisms (SNPs) have not been detected in our resistant strain. This is the first report of high level macrolide resistant B. pertussis, without SNPs in domain V, in Iran. PMID:26396713

  17. Quantification of the Adenylate Cyclase Toxin of Bordetella pertussis In Vitro and during Respiratory Infection

    PubMed Central

    Eby, Joshua C.; Gray, Mary C.; Warfel, Jason M.; Paddock, Christopher D.; Jones, Tara F.; Day, Shandra R.; Bowden, James; Poulter, Melinda D.; Donato, Gina M.; Merkel, Tod J.

    2013-01-01

    Whooping cough results from infection of the respiratory tract with Bordetella pertussis, and the secreted adenylate cyclase toxin (ACT) is essential for the bacterium to establish infection. Despite extensive study of the mechanism of ACT cytotoxicity and its effects over a range of concentrations in vitro, ACT has not been observed or quantified in vivo, and thus the concentration of ACT at the site of infection is unknown. The recently developed baboon model of infection mimics the prolonged cough and transmissibility of pertussis, and we hypothesized that measurement of ACT in nasopharyngeal washes (NPW) from baboons, combined with human and in vitro data, would provide an estimate of the ACT concentration in the airway during infection. NPW contained up to ∼108 CFU/ml B. pertussis and 1 to 5 ng/ml ACT at the peak of infection. Nasal aspirate specimens from two human infants with pertussis contained bacterial concentrations similar to those in the baboons, with 12 to 20 ng/ml ACT. When ∼108 CFU/ml of a laboratory strain of B. pertussis was cultured in vitro, ACT production was detected in 60 min and reached a plateau of ∼60 ng/ml in 6 h. Furthermore, when bacteria were brought into close proximity to target cells by centrifugation, intoxication was increased 4-fold. Collectively, these data suggest that at the bacterium-target cell interface during infection of the respiratory tract, the concentration of ACT can exceed 100 ng/ml, providing a reference point for future studies of ACT and pertussis pathogenesis. PMID:23429530

  18. Polymorphism of Repeated Regions of Pertactin in Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica

    PubMed Central

    Boursaux-Eude, Caroline; Guiso, Nicole

    2000-01-01

    Pertactin is an outer membrane protein expressed by Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica that induces protective immunity to Bordetella infections. The immunodominant and immunoprotective epitopes of pertactin include two repeated regions, I and II. Comparison of these two repeated regions showed that B. parapertussis pertactin is invariant, whereas B. pertussis pertactin varies mostly in region I and B. bronchiseptica pertactin varies in both repeated regions I and II, but mostly in region II. These differences may result from specific characteristics of these Bordetella species. PMID:10899896

  19. Update on Routine Childhood and Adolescent Immunizations.

    PubMed

    Ackerman, Lani K; Serrano, Jacquelyn L

    2015-09-15

    Recommendations for routine vaccinations in children and adolescents have changed multiple times in recent years, based on findings in clinical trials, licensure of new vaccines, and evidence of waning immunity. Despite the overwhelming success of vaccinations, vaccine delay and refusal are leading to pockets of vaccine-preventable diseases. Schedules for diphtheria and tetanus toxoids, and acellular pertussis (DTaP); hepatitis A and B; Haemophilus influenzae type b (Hib); inactivated poliovirus; varicella; and measles, mumps, and rubella are unchanged. However, since 2008, 13-valent pneumococcal conjugate vaccine has replaced the 7-valent vaccine; a new two-dose oral rotavirus vaccine has been approved; use of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine has been expanded to children seven to 10 years of age who received fewer than five doses of DTaP, as well as during each pregnancy; a booster dose of meningococcal vaccine is recommended in adolescents 16 to 18 years of age (unless the first dose was given after 16 years of age); new meningococcal vaccines have been approved for use in infants at high risk of meningococcal disease; influenza vaccine has been expanded to routine use in all children six months and older; and the human papillomavirus vaccine has been approved for routine immunization of adolescent boys and girls. For the 2015-2016 influenza season, either live attenuated or inactivated vaccine can be administered to healthy children two to eight years of age. PMID:26371731

  20. The use of acellular dermal matrix as a scaffold for periosteum replacement.

    PubMed

    Beniker, Dan; McQuillan, David; Livesey, Stephen; Urban, Robert M; Turner, Thomas M; Blum, Barbara; Hughes, Kim; Haggard, Warren O

    2003-05-01

    Three preclinical models were used to evaluate GraftJacket Acellular Periosteum Replacement Scaffold (Wright Medical Technology, Inc, Arlington, Tenn). The studies assessed the ability of the acellular dermal matrix to repopulate with cells, revascularize, provide a protected environment for bone defect restoration, and minimize fibrous tissue infiltration. An athymic nude rat muscle implantation study demonstrated a steady increase in cellular repopulation through days 2-21. The formation of blood vessels occurred between days 7-14 in this study. Results from a porcine femoral drill hole study indicated that the scaffold material was intact and adherent to surrounding bone and allowed cellular repopulation and vascular infiltration at a 5-week time period. A preliminary porcine segmental bone defect model at a 6-week time period demonstrated the ability of the scaffold material to protect the bone defect site as revealed by new bone formation within the margins of the defect and adjacent to the scaffold. The segmental model also indicated minimal to no soft tissue invasion into the defect site. The combined studies provided preliminary evidence that the dermal membrane material may be used as a scaffold for periosteum regeneration by allowing for cellular repopulation, revascularization, and bone defect restoration. PMID:12755232

  1. A preliminary study on the effects of acellular tissue graft augmentation in acute Achilles tendon ruptures.

    PubMed

    Lee, Daniel K

    2008-01-01

    Acute Achilles tendon rupture injuries present surgical challenges because of the mechanical forces placed on this tendon. The purpose of this study was to evaluate the effectiveness of an acellular human dermal tissue matrix, GraftJacket Matrix (Wright Medical Technology, Inc., Arlington, TN), as an augmentation material in acute Achilles tendon repair. Eleven consecutive patients with acute tendon ruptures were evaluated and followed up (20-31 months). Primary repair was followed by augmentation with the graft sutured circumferentially around the tendon. Patients were placed in an early functional rehabilitation program with postoperative evaluation at 3, 6, and 12 months. Outcome scores were calculated based on the American Orthopaedic Foot and Ankle Society ankle-hindfoot scoring system. At 20-month postoperative follow-up, there have been no cases of rerupture or recurrent pain. The average return-to-activity time was 11.8 +/- 0.75 weeks. These retrospective clinical results suggest that with an acellular human dermal tissue matrix to augment acute Achilles tendon, primary repair offers a desirable return-to-activity time without any rerupture or complications. ACFAS Level of Clinical Evidence: 2c. PMID:18156058

  2. Achilles tendon repair with acellular tissue graft augmentation in neglected ruptures.

    PubMed

    Lee, Daniel K

    2007-01-01

    Neglected Achilles tendon rupture injuries present surgical challenges because of the quality and quantity of tendon tissue during repair combined with the magnitude of mechanical forces placed on this tendon. The purpose of this study was to evaluate the effects of an acellular human dermal tissue matrix, GRAFTJACKET, as an augmentation material in neglected Achilles tendon repair. Nine patients with neglected Achilles tendon ruptures were evaluated and followed up for a minimum of 20 months. Primary repair was followed by augmentation with the graft and suturing circumferentially around the tendon. Patients were placed in an early, functional rehabilitation program with postoperative evaluation at 3, 6, and 12 months. Outcome scores were calculated based on the American Orthopaedic Foot and Ankle Society ankle-hindfoot scoring system. At 20 to 30 months postoperative follow-up range, there has been no incidence of re-rupture or recurrent pain. The average return-to-activity time was 15.2 +/- 1.7 weeks. The results from this retrospective clinical series suggest that using an acellular human dermal tissue matrix to augment neglected Achilles tendon rupture primary repair offers desirable return-to-activity time points and viable surgical alternative over previously reported surgical options. PMID:17980842

  3. Aseptic versus Sterile Acellular Dermal Matrices in Breast Reconstruction: An Updated Review

    PubMed Central

    Mendenhall, Shaun D.; Neumeister, Michael W.; Cederna, Paul S.; Momoh, Adeyiza O.

    2016-01-01

    Background: As the use of acellular dermal matrices in breast reconstruction has become more commonplace and efforts are made to improve on postoperative outcomes, the method of acellular dermal matrix (ADM) processing (aseptic versus sterile) has become a subject of interest. This article provides an updated overview of the critical aspects of ADM processing in addition to application of ADMs in single- and two-stage breast reconstruction, a review of the morbidity associated with ADM use, and alternatives. Methods: A literature review was performed in PubMed identifying recent systematic reviews, meta-analyses, and head-to-head comparisons on aseptically processed ADM and sterile-processed ADM in implant-based breast reconstruction. Results: Recent meta-analyses have shown a 2- to 3-fold increase in infections and tissue expander/implant explantation rates and a 3- to 4-fold increase in seroma formation compared with non-ADM reconstruction techniques. Comparisons of aseptic and sterile ADMs in multiple studies have shown no significant difference in infection rates and equivocal findings for other specific complications such as seroma formation. Conclusions: Current evidence on the impact of processing techniques that improve ADM sterility on postoperative morbidity in implant breast reconstruction is unclear. Deficiencies of the available data highlight the need for well-designed, multicenter, randomized controlled studies that will aid in optimizing outcomes in implant-based breast reconstruction. PMID:27536502

  4. Screening for Oxidative Stress Elicited by Engineered Nanomaterials: Evaluation of Acellular DCFH Assay

    PubMed Central

    Pal, Anoop K.; Bello, Dhimiter; Budhlall, Bridgette; Rogers, Eugene; Milton, Donald K.

    2012-01-01

    The DCFH assay is commonly used for measuring free radicals generated by engineered nanomaterials (ENM), a well-established mechanism of ENM toxicity. Concerns exist over susceptibility of the DCFH assay to: assay conditions, adsorption of DCFH onto ENM, fluorescence quenching and light scattering. These effects vary in magnitude depending on ENM physiochemical properties and concentration. A rigorous evaluation of this method is still lacking. The objective was to evaluate performance of the DCFH assay for measuring ENM-induced free radicals. A series of diverse and well-characterized ENM were tested in the acellular DCFH assay. We investigated the effect of sonication conditions, dispersion media, ENM concentration, and the use of horseradish peroxidase (HRP) on the DCFH results. The acellular DCFH assay suffers from high background signals resulting from dye auto-oxidation and lacks sensitivity and robustness. DCFH oxidation is further enhanced by HRP. The number of positive ENM in the assay and their relative ranking changed as a function of experimental conditions. An inverse dose relationship was observed for several Carbon-based ENM. Overall, these findings indicate the importance of having standardized assays for evaluating ENM toxicity and highlights limitations of the DCFH assay for measuring ENM-induced free radicals. PMID:22942866

  5. Deficiency in acellular cementum and periodontal attachment in bsp null mice.

    PubMed

    Foster, B L; Soenjaya, Y; Nociti, F H; Holm, E; Zerfas, P M; Wimer, H F; Holdsworth, D W; Aubin, J E; Hunter, G K; Goldberg, H A; Somerman, M J

    2013-02-01

    Bone sialoprotein (BSP) is an extracellular matrix protein found in mineralized tissues of the skeleton and dentition. BSP is multifunctional, affecting cell attachment and signaling through an RGD integrin-binding region, and acting as a positive regulator for mineral precipitation by nucleating hydroxyapatite crystals. BSP is present in cementum, the hard tissue covering the tooth root that anchors periodontal ligament (PDL) attachment. To test our hypothesis that BSP plays an important role in cementogenesis, we analyzed tooth development in a Bsp null ((-/-)) mouse model. Developmental analysis by histology, histochemistry, and SEM revealed a significant reduction in acellular cementum formation on Bsp (-/-) mouse molar and incisor roots, and the cementum deposited appeared hypomineralized. Structural defects in cementum-PDL interfaces in Bsp (-/-) mice caused PDL detachment, likely contributing to the high incidence of incisor malocclusion. Loss of BSP caused progressively disorganized PDL and significantly increased epithelial down-growth with aging. Bsp (-/-) mice displayed extensive root and alveolar bone resorption, mediated by increased RANKL and the presence of osteoclasts. Results collected here suggest that BSP plays a non-redundant role in acellular cementum formation, likely involved in initiating mineralization on the root surface. Through its importance to cementum integrity, BSP is essential for periodontal function. PMID:23183644

  6. Sterile acellular dermal collagen as a treatment for rippling deformity of breast.

    PubMed

    Busse, Brittany; Orbay, Hakan; Sahar, David E

    2014-01-01

    Prosthetic implants are frequently used for breast augmentation and breast reconstruction following mastectomy. Unfortunately, long-term aesthetic results of prosthetic breast restoration may be hindered by complications such as rippling, capsular contracture, and implant malposition. The advent of use of acellular dermal matrices has greatly improved the outcomes of prosthetic breast reconstruction. We describe a case of rippling deformity of breast that was treated using an acellular dermal matrix product, AlloMax. The patient presented with visible rippling of bilateral prosthetic breast implants as well as significant asymmetry of the breasts after multiple excisional biopsies for right breast ductal carcinoma in situ. A 6 × 10 cm piece of AlloMax was placed on the medial aspect of each breast between the implant and the skin flap. Follow-up was performed at 1 week, 3 months, and 1 year following the procedure. The patient recovered well from the surgery and there were no complications. At her first postoperative follow-up the patient was extremely satisfied with the result. At her 3-month and 1-year follow-up she had no recurrence of her previous deformity and no new deformity. PMID:25610697

  7. Repair of lacerated anterior tibial tendon with acellular tissue graft augmentation.

    PubMed

    DiDomenico, Lawrence A; Blasko, Gregory A; Cane, Laurence; Cross, Davina J

    2012-01-01

    In the present case report, we describe the surgical repair of a complete laceration of the anterior tibial tendon using acellular human dermal tissue matrix. A 17-year-old, elite league hockey player was injured in the locker room when a teammate still clad in ice skates stepped on his bare left foot. After evaluation at a local emergency department, the patient presented to our office the next day for additional evaluation. It was determined that surgery would be performed using acellular tissue graft augmentation, followed by physical therapy. Within 7 weeks of the injury, the athlete returned to his original level of activity. At 3 years of follow-up, he was playing Division 1 hockey at the university level. We believe that augmentation of the tendon repair with the grafting material enhanced the tendon tensile strength and promoted ingrowth through vascular channels. This, combined with the patient's dedication to physical therapy, led to excellent recovery in less time than anticipated. PMID:22762944

  8. Creation and implantation of acellular rat renal ECM-based scaffolds

    PubMed Central

    Peloso, Andrea; Ferrario, Jacopo; Maiga, Benedetta; Benzoni, Ilaria; Bianco, Carolina; Citro, Antonio; Currao, Manuela; Malara, Alessandro; Gaspari, Annalisa; Balduini, Alessandra; Abelli, Massimo; Piemonti, Lorenzo; Dionigi, Paolo; Orlando, Giuseppe; Maestri, Marcello

    2015-01-01

    Abstract Kidney transplantation is the only potentially curative treatment for patient facing end-stage renal disease, and it is now routinely used. Its use is mainly limited by the supply of transplantable donor organs, which far exceeds the demand. Regenerative medicine and tissue engineering offer promising means for overcoming this shortage. In the present study, we developed and validated a protocol for producing acellular rat renal scaffolds. Left kidneys were removed from 26 male Lewis rats (weights: 250–350 g) and decellularized by means of aortic anterograde perfusion with ionic and anionic detergents (Triton X-100 1% and SDS 1%, respectively). 19 scaffolds thus obtained (and contralateral native kidneys as controls) were deeply characterized in order to evaluate the decellularization quality, the preservation of extracellular matrix components and resultant micro-angioarchitecture structure. The other 7 were transplanted into 7 recipient rats that had undergone unilateral nephrectomy. Recipients were sacrificed on post-transplantation day 7 and the scaffolds subjected to histologic studies. The dual-detergent protocol showed, with only 5 h of perfusion per organ, to obtain thoroughly decellularized renal scaffolds consisting almost exclusively of extracellular matrix. Finally the macro- and the microarchitecture of the renal parenchyma were well preserved, and the grafts were implanted with ease. Seven days after transplant, the scaffolds were morphologically intact although all vascular structures were obstructed with thrombi. Production and implantation of acellular rat renal scaffolds is a suitable platform for further studies on regenerative medicine and tissue engineering. PMID:26186418

  9. Interposition Porcine Acellular Dermal Matrix Xenograft Successful Alternative in Treatment for Massive Rotator Cuff

    PubMed Central

    Neumann, Julie; Zgonis, Miltiadis H.; Reay, Kathleen Dolores; Mayer, Stephanie W.; Boggess, Blake; Toth, Alison P.

    2016-01-01

    Objectives: Despite advances in the surgical techniques of rotator cuff repair (RCR), the management of massive rotator cuff tears in shoulders without glenohumeral arthritis poses a difficult problem for surgeons. Failure of massive rotator cuff repairs range from 20-90% at one to two years postoperatively using arthrography, ultrasound, or magnetic resonance imaging. Additionally, there are inconsistent outcomes reported with debridement alone of massive rotator cuff tears as well as limitations seen with other current methods of operative intervention including arthroplasty and tendon transfers. The purpose of this prospective, comparative study was to determine if the repair of massive rotator cuff tears using an interposition porcine acellular dermal matrix xenograft improves subjective function, pain, range of motion, and strength at greater than two years follow-up. To our knowledge, this is the largest prospective series reporting outcomes of using porcine acellular dermal matrix xenograft as an interposition graft. Methods: Thirty-seven patients (37 shoulders) with an average age of 66 years (range 51-80 years) were prospectively followed for 33 months (range 23-48) following massive RCR using porcine acellular dermal matrix interposition xenograft. Subjective outcomes were measured using the Visual Analog Scale (VAS) pain score (0-10, 0 = no pain), Modified American Shoulder and Elbow Score (M-ASES), and Short-Form12 (SF-12) scores. Preoperative and postoperative objective outcome measures included active range of motion and supraspinatus and infraspinatus manual muscle strength. Postoperative outcome measures included quantitative muscle strength using a dynamometer and static and dynamic ultrasonography to assess the integrity of the repair. Results: Average VAS pain score decreased from 4.5 to 1.1 (P<0.001). Average postoperative M-ASES was 89.23. Average postoperative SF-12 was 52.6. Mean forward flexion, external and internal rotation significantly

  10. Under-recognized pertussis in adults from Asian countries: a cross-sectional seroprevalence study in Malaysia, Taiwan and Thailand.

    PubMed

    Koh, M T; Liu, C-S; Chiu, C-H; Boonsawat, W; Watanaveeradej, V; Abdullah, N; Zhang, Xh; Devadiga, R; Chen, J

    2016-04-01

    Surveillance data on the burden of pertussis in Asian adults are limited. This cross-sectional study evaluated the prevalence of serologically confirmed pertussis in adults with prolonged cough in Malaysia, Taiwan and Thailand. Adults (⩾19 years) with cough lasting for ⩾14 days without other known underlying cause were enrolled from outpatient clinics of seven public and/or private hospitals. Single blood samples for anti-pertussis toxin antibodies (anti-PT IgG) were analysed and economic impact and health-related quality of life (EQ-5D) questionnaires assessed. Sixteen (5·13%) of the 312 chronically coughing adults had serological evidence of pertussis infection within the previous 12 months (anti-PT IgG titre ⩾62·5 IU/ml). Three of them were teachers. Longer duration of cough, paroxysms (75% seroconfirmed, 48% non-seroconfirmed) and breathlessness/chest pain (63% seroconfirmed, 36% non-seroconfirmed) were associated with pertussis (P < 0·04). Of the seroconfirmed patients, the median total direct medical cost per pertussis episode in public hospitals (including physician consultations and/or emergency room visits) was US$13 in Malaysia, US$83 in Taiwan (n = 1) and US$26 in Thailand. The overall median EQ-5D index score of cases was 0·72 (range 0·42-1·00). Pertussis should be considered in the aetiology of adults with a prolonged or paroxysmal cough, and vaccination programmes considered. PMID:26468043

  11. High Seroprevalence of Bordetella pertussis in Patients with Chronic Obstructive Pulmonary Disease: A Case-Control Study

    PubMed Central

    Nadi, Ebrahim; Hajilooi, Mehrdad; Seif-Rabiei, Mohammad-Ali; Samaei, Atefeh

    2015-01-01

    Background: Bordetella pertussis has been suggested to take part in the acute exacerbation of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the association between B. pertussis and COPD. Materials and Methods: In this case-control study, 90 patients with COPD and 90 age- and sex- matched control subjects were included. Serum samples were tested for anti-B. pertussis IgG and IgA by ELISA. A physician completed a questionnaire including demographic characteristics, habitual history and spirometric findings for each patient. Results: Of 90 patients with chronic obstructive pulmonary disease, 66 (51%) had mild, 31 (34.4%) had moderate, and 13 (14.4%) had severe disease. There was no significant association between B. pertussis IgA seropositivity and COPD. Serum levels of anti- B. pertussis IgG were significantly higher in patients with COPD than in the control subjects (P < 0.001). No association was observed between B. pertussis infection and severity of COPD. Conclusion: The results suggest that there is an association between B. pertussis infection and COPD. Further studies should be planned to investigate the potential pathogenic mechanisms underlying these associations. PMID:26858762

  12. Antigenic relationship between serotype-specific agglutinogen and fimbriae of Bordetella pertussis.

    PubMed

    Ashworth, L A; Irons, L I; Dowsett, A B

    1982-09-01

    The widely held view that the filamentous hemagglutinin (FHA) of Bordetella pertussis is derived from fimbriae (pili) is not supported by studies of fimbriation and FHA content of the organism. Fimbriae do not label specifically with antibody to FHA in immuno-electron microscopy but do label with antibody to serotype-specific agglutinogen. PMID:6127315

  13. Identification of two bvg-repressed surface proteins of Bordetella pertussis.

    PubMed Central

    Stenson, T H; Peppler, M S

    1995-01-01

    Bordetella pertussis, the etiological agent of whooping cough, has the ability to modulate its phenotype in response to environmental conditions by using the BvgAS sensory transduction system which is encoded by the vir locus (now known as bvg). The BvgAS system is part of a large family of two-component sensory transduction systems which are common to a number of pathogenic bacteria. Although much is known about the proteins which exist in the B. pertussis virulent (X-mode or phase I) phenotype, relatively little is known about the proteins produced in the avirulent (C-mode or phase III) phenotype. We used sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing techniques to demonstrate the existence of at least 22 vir-repressed molecules which are increased in the avirulent phenotype. In addition, a series of monoclonal antibodies which are specific for the surface of avirulent B. pertussis were developed. Using immunological and protein techniques, we characterized two of these antigens as surface-exposed proteins. One of these antigens is expressed only in B. pertussis but not in the related species B. parapertussis and B. bronchiseptica. The other antigen is also present in B. parapertussis and B. bronchiseptica but is expressed at lower levels which are not regulated by bvg. The identification and characterization of vir-repressed proteins (and the genes which encode and regulate them) may help elucidate a physiological role for modulation of this obligate human pathogen. PMID:7558280

  14. [Conversion of Bordetella parapertussis serovar through lysogeny produced by pertussis phages].

    PubMed

    Mebel, S; Lapaeva, I

    1982-09-01

    Bacteriophages from Bordetella pertussis were titrated on the indicator strain B. parapertussis 17903 by using standard soft agar techniques. Secondary growth, occasionally observed in some phage plaques, was isolated and transferred onto selective media. Judging from growth on these special media and microscopic examination the isolated clones consisted entirely of Bordetellae. Determination of the agglutinogen pattern of 160 of these clones revealed that 88% contained agglutinogen 1; 87.5% agglutinogen 14, and 80.1% agglutinogen 12 (Table 3). However, none of the strains expressed the agglutinogen pattern of either the phage donor or the recipient strain. The isolated clones were lysogenic as demonstrated by phage production and immunity against superinfection (95% of the clones).--Absorption of the monospecific antisera with whole cells from lysogenic strains resulted in a drastic decrease or even complete loss of specific antibodies towards those antigens identified by slide agglutination reactions (Table 4). Cross absorption experiments with antisera against B. pertussis, B. parapertussis and strain 73 1/7 and various strains of the genus Bordetella and with a number of lysogenic strains showing various agglutination patterns allowed the conclusion that the latter ones were serologically related to B. pertussis. The lysogenic strains completely absorbed antibodies against B. bronchiseptica, and those strains that carried the agglutinogen 14 also absorbed antibodies against, B. parapertussis (Table 5). In conclusion, these results support the necessity to revise the subdivision of the genus Bordetella into three species. A change of B. parapertussis to B. pertussis within the epidemiological processes is considered. PMID:7180238

  15. Antibodies to Bordetella pertussis in human colostrum and their protective activity against aerosol infection of mice.

    PubMed Central

    Oda, M; Cowell, J L; Burstyn, D G; Thaib, S; Manclark, C R

    1985-01-01

    Colostrum samples from Indonesian mothers were assayed for antibodies which agglutinate Bordetella pertussis and for antibodies to the filamentous hemagglutinin and the lymphocytosis-promoting factor of B. pertussis. Agglutinins were assayed by a microtiter method, and 36 of 58 samples tested (62%) had titers above 1:10 (range, less than 1:10 to 1:160). An enzyme-linked immunosorbent assay detected anti-filamentous hemagglutinin in 39 of 60 samples (65%) and anti-lymphocytosis-promoting factor in 26 of 60 samples assayed (43%). A total of 52 samples (87%) were positive for at least one of these antibodies. Pooled colostrum samples were separated by affinity chromatography into fractions enriched secretory immunoglobulin A (sIgA) or IgG and examined for their ability to passively protect suckling mice from aerosol challenge with B. pertussis. Samples (160 micrograms of protein) were given intraperitoneally 90 min before challenge. Death, rate of gain in body weight, and leukocytosis were used as indicators of illness. Colostrum containing anti-lymphocytosis-promoting factor or agglutinins was protective, whereas colostrum lacking these but containing anti-filamentous hemagglutinin gave little protection. The sIgA-enriched and IgG-enriched fractions appeared to be equal in their ability to protect against respiratory challenge with B. pertussis. PMID:2857154

  16. Structure and biological properties of solubilized envelope proteins of Bordetella pertussis.

    PubMed Central

    Robinson, A; Hawkins, D C

    1983-01-01

    The structure and biological properties of solubilized envelope proteins of Bordetella pertussis have been examined. Several envelope proteins were found to be specific for phase I strains of B. pertussis and could be isolated by selective detergent extraction. These proteins had molecular weights of 90,000, 86,000, 81,000, 33,000, 31,000, and 30,000 and were reduced or absent in envelope preparations from Bordetella bronchiseptica, Bordetella parapertussis, or phase IV strains of B. pertussis. When the envelope preparations from phase I B. pertussis were assayed in the mouse intracerebral protection test they were found to be highly protective, and there was a strong correlation between the protective potency and the lymphocytosis-promoting factor (LPF) content of different preparations. Treatment with glutaraldehyde reduced the LPF activity, toxicity, and protective potency of the envelope extracts. Similarly affinity chromatography of envelope proteins on columns of haptoglobin coupled to Sepharose 4B reduced both the LPF content and the protective potency. The addition of a small amount of purified LPF to the haptoglobin-treated proteins restored the protective potency. The LPF by itself was nonprotective, indicating a potentiating role of LPF in the mouse intracerebral challenge test. Images PMID:6299946

  17. Induction of Bordetella pertussis-specific immune memory by DTPa vaccines.

    PubMed

    Morel, Sandra; Denoël, Philippe; Godfroid, Fabrice; Cortvrindt, Caroline; Vanderheyde, Nathalie; Poolman, Jan

    2011-04-18

    Several vaccines are available against pertussis, differing by the number of Bordetella pertussis antigens that they contain as well as their formulation. The GlaxoSmithKline Biologicals (GSK Bio) tricomponent DTPa vaccine (DTPa3, Infanrix™), and the Sanofi-Pasteur (SP) five-component formulation (DTPa5, Pediacel™) were shown to have comparable short-term efficacy in clinical trials. However, potential differences in long-term protection were recently suggested, which might reflect the elicitation of different specific immune memory by the two vaccines. Therefore, the purpose of the present study was to investigate in mice the immune responses against B. pertussis, and particularly the establishment of specific B cell memory after immunization with DTPa3 and DTPa5 vaccines. Whereas intranasal challenge experiments showed similar protection with both vaccines, DTPa3 induced higher antibody levels to FHA and PRN than DTPa5. Further, the frequency of memory B cells was investigated by B cell ELISPOT. Higher frequencies of PT- and PRN-specific memory B cells were evidenced after vaccination with DTPa3, compared with DTPa5. Although the origin of such difference is unclear, the use of two different adjuvants (aluminum phosphate versus hydroxide) is proposed as a possible explanation. In conclusion, this study proposes that the induction of higher levels of B. pertussis antigen-specific memory B cells with DTPa3 participate to the suggested longer persistence of protection observed with this vaccine, as compared with DTPa5. PMID:21382483

  18. Siderophore production and membrane alterations by Bordetella pertussis in response to iron starvation.

    PubMed Central

    Agiato, L A; Dyer, D W

    1992-01-01

    Bordetella pertussis was grown in iron (Fe)-free defined medium to limit the growth of the organism. Doubling times of the Fe-starved organism increased by approximately 1 h, and a 40% reduction in the final extent of growth in Fe-depleted medium was observed. Under these conditions, a hydroxamate siderophore named bordetellin was secreted by B. pertussis. Lactoferrin and transferrin supported growth of B. pertussis even when the protein was sequestered inside dialysis tubing. This suggested that binding of lactoferrin and transferrin to B. pertussis was not essential and that bordetellin production plays a major role in Fe uptake. Solid-phase dot blot assays indicated weak binding of lactoferrin to the cell surface, consistent with previous reports of a lactoferrin receptor. Three new proteins of 97, 77, and 63 kDa were synthesized in response to Fe starvation. Fe-inducible proteins of 103, 72, 24, 21, and 18 kDa were also observed. The synthesis of lipopolysaccharide was also altered by Fe availability. Images PMID:1309510

  19. [Whooping cough in Spain. Current epidemiology, prevention and control strategies. Recommendations by the Pertussis Working Group].

    PubMed

    Campins, Magda; Moreno-Pérez, David; Gil-de Miguel, Angel; González-Romo, Fernando; Moraga-Llop, Fernando A; Arístegui-Fernández, Javier; Goncé-Mellgren, Anna; Bayas, José M; Salleras-Sanmartí, Lluís

    2013-04-01

    A large increase of pertussis incidence has been observed in recent years in countries with high vaccination coverage. Outbreaks of pertussis are increasingly being reported. The age presentation has a bipolar distribution: infants younger 6months that have not initiated or completed a vaccination schedule, and adolescents and adults, due to the lost of natural or vaccine immunity over time. These epidemiological changes justify the need to adopt new vaccination strategies in order to protect young infants and to reduce pertussis incidence in all age groups. Adolescents and adults immunization must be a priority. In the first group, strategy is easy to implement, and with a very low additional cost (to replace dT vaccine by dTap one). Adult vaccination may be more difficult to implement; dT vaccine decennial booster should be replaced by dTap. The immunization of household contacts of newborn infants (cocooning) is the strategy that has a most important impact on infant pertussis. Recently, pregnant women vaccination (after 20weeks of gestation) has been recommended in some countries as the most effective way to protect the newborn. PMID:23411362

  20. Chao Yuanfang: Imperial Physician of the Sui Dynasty and an Early Pertussis Observer?

    PubMed Central

    Liang, Yan; Salim, Abdulbaset M.; Wu, Wendy; Kilgore, Paul E.

    2016-01-01

    Early Chinese texts contain extensive disease descriptions, including various texts that contain descriptions of modern-day conditions. During the Sui Dynasty, a leading scholar, Chao Yuanfang, may have authored a leading treatise 1400 years ago. Although these texts are the subject of ongoing research, evidence suggests that a clinical syndrome consistent with pertussis was observed in ancient China. PMID:26977422

  1. Effect of Basti (oil enema) therapy for the management of cough in pertussis.

    PubMed

    Gujarathi, Rahul H; Gokhale, Vivek M; Tongaonkar, Jayashree N

    2013-10-01

    Bordetella pertussis continues to circulate even in countries with good childhood vaccination coverage. Sporadic cases are still observed either due to no vaccination, incomplete vaccination or as a result of failure of vaccination. Though acute in nature it has a longer disease span with multiple life-threatening complications despite adequate management. This study was undertaken to study the effect of Sneha Basti (oil enema) in pertussis in relation to reduction in intensity of cough and complications of the disease when administered along with the conventional pharmacological therapy. Patients with the clinical picture mimicking pertussis were screened, investigated for pertussis and appropriate conventional pharmacological therapy of Erythromycin a preferred antimicrobial agent was started. Concurrently, Sneha Basti was administered to these two children. Both patients showed favourable results in terms of reduction of Kasa (cough) and the disease period with a faster recovery when compared to conventional therapy alone as has been observed routinely. No complications incurred during the complete disease span. It was concluded that if the pharmacological therapy is augmented with the complimentary systems of medicines, it can reduce the prolonged span and intensity of the disease and prevent other complications. PMID:24696577

  2. Pertussis infections and vaccinations in Bolivia, Brazil and Mexico from 1980 to 2009.

    PubMed

    McCormick, Colleen M; Czachor, John S

    2013-01-01

    Global coverage with three doses of the diphtheria, tetanus and pertussis vaccine (DTP3) increased from less than 5% in 1974 to 82% in 2009 due to worldwide focus on universal vaccination. Nonetheless, pertussis remains the fifth-leading cause of vaccine-preventable deaths. This study examines DTP3 vaccination from 1980 through 2009 in three countries within Latin America, Bolivia, Brazil and Mexico, selected for their distinct health care systems and vaccination strategies. Similar to global trends, these nations have achieved dramatic improvements in pertussis immunization. In Bolivia, immunization rates increased from 11% to 85%; in Brazil, rates increased from 37% to 97%; and in Mexico, the immunization rates increased from 44% to 72%. Pertussis infections have concomitantly decreased from 1980 to 2009. In Bolivia, cases decreased from 44.4 per 100,000 people to zero reported cases. In Brazil, the incidence decreased from 37.6 to 0.5 cases per 100,000. The incidence in Mexico decreased from 8.2 to 0.5 cases per 100,000. In order to increase vaccination rates further, health systems must continue to raise awareness about disease prevention, expand health surveillance systems, and improve access to health services. PMID:23623448

  3. Using the Health Belief Model to develop educational strategies to improve pertussis vaccination rates among preschool staff.

    PubMed

    Dardis, Melissa R; Koharchik, Linda S; Dukes, Shari

    2015-01-01

    The number of pertussis or "whooping cough" cases has steadily increased in the United States in the last 20 years. Many of the cases are adults who have not kept up with current vaccination recommendations. Adults are unknowingly exposing susceptible infants and unvaccinated children to this potentially deadly disease. Pertussis can spread rapidly, especially in household, daycare, and school settings. This pilot study examines how school nurses can be instrumental in improving staff immunization rates for pertussis by using the Health Belief Model as a framework for educational strategies. PMID:25626237

  4. Characterization of vir-activated TnphoA gene fusions in Bordetella pertussis.

    PubMed Central

    Finn, T M; Shahin, R; Mekalanos, J J

    1991-01-01

    The expression of many of the known virulence determinants of Bordetella pertussis is coordinately regulated by the vir regulatory locus and reduced in response to environmental signals called modulators. We have previously identified eight TnphoA gene fusions in B. pertussis in which the expression of alkaline phosphatase was maximal in the absence of the modulators nicotinic acid and MgSO4. We have termed the genes identified by these fusions vir-activated genes. Here we report the characterization of these TnphoA mutant strains. Four fusion strains were defective in known virulence determinants. For one of these, fusion strain SK39, Southern blot hybridization demonstrated that TnphoA was inserted in the S1 subunit gene of pertussis toxin. Hemagglutination assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblots identified three fusions strains, SK16, SK75, and SK91, that were defective in filamentous hemagglutinin. Whereas all three filamentous hemagglutinin-defective mutants showed either normal or enhanced colonization, the pertussis toxin-defective mutant showed a marked defect in pulmonary persistence. Of the four other fusion strains, two were deficient in outer membrane proteins. One of these, strain SK8, was defective in a major outer membrane protein of 95 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This strain colonized mouse lungs less well and did not induce lymphocytosis after aerosol challenge. The other strain, SK34, was defective in four outer membrane proteins, three of which were detectable only on a Western blot with polyclonal sera against B. pertussis. Two of our gene fusion strains did not show any defect in identifiable vir-regulated proteins. Images PMID:1652562

  5. Lethal infection by Bordetella pertussis mutants in the infant mouse model.

    PubMed Central

    Weiss, A A; Goodwin, M S

    1989-01-01

    Different aspects of lethal infection of infant mice with Bordetella pertussis were examined. Mutants deficient in vir-regulated genes were tested for the ability to cause a lethal infection in the infant mouse model. Adenylate cyclase toxin-hemolysin and pertussis toxin were required to cause a lethal infection at low doses. Mixed infection caused by challenging the mice with an equal number of pertussis toxin and adenylate cyclase toxin-hemolysin mutants at a dose at which neither alone was lethal was also unable to cause a lethal infection. Production of the filamentous hemagglutinin and the dermonecrotic toxin was not required to cause a lethal infection. Nine other mutants in vir-regulated genes whose phenotypes have yet to be determined were also tested. Only two of these mutants were impaired in the ability to cause a lethal infection. Expression of fimbriae does not appear to affect the dose required to cause a lethal infection; however, fimbrial expression was correlated with the later stages of a nonlethal, persistent infection. Growth of the bacteria in MgSO4, a condition which reversibly suppresses expression of the genes required for virulence, did not alter the ability of the bacteria to cause a lethal infection. Auxotrophic mutants deficient in leucine biosynthesis were as virulent as the parental strain; however, mutants deficient in methionine biosynthesis were less virulent. A B. parapertussis strain was much less effective in promoting a lethal infection than any of the wild-type B. pertussis strains examined. A persistent infection in the lungs was observed for weeks after challenge for mice given a sublethal dose of B. pertussis, and transmission from infected infants to the mother was never observed. PMID:2572561

  6. The major fimbrial subunit of Bordetella pertussis binds to sulfated sugars.

    PubMed Central

    Geuijen, C A; Willems, R J; Mooi, F R

    1996-01-01

    Bordetella pertussis fimbriae are composed of major and minor subunits, and recently it was shown that the minor fimbrial subunit binds to Vla-5, a receptor located on monocytes (W. Hazenbos, C. Geuijen, B. van den Berg, F. Mooi, and R. van Furth, J. Infect. Dis. 171:924-929, 1995). Here we present evidence that the major subunits bind to sulfated sugars, which are ubiquitous in the respiratory tract. Binding was observed to chondroitin sulfate, heparan sulfate, and dextran sulfate but not to dextran. Removal of the minor subunit from fimbriae did not significantly affect binding to sulfated sugars, indicating that the major subunit alone is sufficient for this binding. Fimbriae were also able to bind HEp-2 cells, which are known to display glycoconjugates on their surface. This binding was not dependent on the presence of the minor subunit. However, binding was dependent on the sulfation state of the glycoconjugates, since inhibition of the sulfation resulted in a significant reduction of fimbria binding. The specificity of fimbria binding was further characterized by using heparan sulfate-derived disaccharides in inhibition assays. Two disaccharides were highly effective inhibitors, and it was observed that both the degree of sulfation and the arrangement of the sulfate groups on the disaccharides were important for binding to fimbriae. B. pertussis bacteria also bound to sulfated sugars and HEp-2 cells, and analysis of B. pertussis mutants indicated that both filamentous hemagglutinin and fimbriae were required for this binding. A host protein present in the extracellular matrix, fibronectin, has binding activities similar to those of B. pertussis fimbriae, binding to both Vla-5 and sulfated sugars. Two regions in the major fimbrial subunit were identified which showed similarity with fibronectin peptides which bind to sulfated sugars. Thus, B. pertussis fimbriae exemplify molecular mimicry and may co-opt host processes by mimicking natural ligand

  7. Effects of Bordetella pertussis toxin pretreatment on the antiarrhythmic action of ischaemic preconditioning in anaesthetized rats.

    PubMed Central

    Piacentini, L; Wainwright, C L; Parratt, J R

    1995-01-01

    1. Bordetella pertussis toxin, which catalyses the ADP-ribosylation of certain guanine nucleotide binding proteins (G proteins), thus functionally uncoupling them from associated receptors, was examined to determine whether it modified the antiarrhythmic effect of ischaemic preconditioning in anaesthetized rats. 2. Pertussis toxin (25 micrograms kg-1, i.p., 48 h prior to heart isolation) attenuated the negative chronotropic effect of acetylcholine (ACh) in rat isolated Langendorff perfused hearts. ACh (10 microM) reduced heart rate by 4% in hearts taken from pertussis toxin-treated animals, compared to a reduction of 57% in hearts taken from animals treated only with vehicle. 3. In anaesthetized rats, ischaemic preconditioning (a single 3 min occlusion of the left main coronary artery followed by 10 min reperfusion) had a pronounced antiarrhythmic effect during a subsequent 30 min period of regional myocardial ischaemia. Compared to hearts receiving only a 30 min period of left coronary occlusion, there was a reduced mortality (67% and 0% for control and preconditioned groups, respectively; P < 0.01) and decreased incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF). Pretreatment with pertussis toxin (25 micrograms kg-1, i.p., 48 h previously) did not modify the arrhythmias associated with a 30 min period of regional myocardial ischaemia, neither did it modify the reduction in mortality (from 56% to 0%; P < 0.05) associated with preconditioning. Furthermore, the decrease in total ventricular premature beat count induced by preconditioning seen in controls (from 427 +/- 130 to 95 +/- 45) was also seen in pertussis toxin-treated rats (from 252 +/- 190 to 57 +/- 25).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7773535

  8. Cost-effectiveness of next-generation vaccines: The case of pertussis.

    PubMed

    Fitzpatrick, Meagan C; Wenzel, Natasha S; Scarpino, Samuel V; Althouse, Benjamin M; Atkins, Katherine E; Galvani, Alison P; Townsend, Jeffrey P

    2016-06-17

    Despite steady vaccination coverage rates, pertussis incidence in the United States has continued to rise. This public health challenge has motivated calls for the development of a new vaccine with greater efficacy and duration of protection. Any next-generation vaccine would likely come at a higher cost, and must provide sufficient health benefits beyond those provided by the current vaccine in order to be deemed cost-effective. Using an age-structured transmission model of pertussis, we quantified the health and economic benefits of a next-generation vaccine that would enhance either the efficacy or duration of protection of the childhood series, the duration of the adult booster, or a combination. We developed a metric, the maximum cost-effective price increase (MCPI), to compare the potential value of such improvements. The MCPI estimates the per-dose price increase that would maintain the cost-effectiveness of pertussis vaccination. We evaluated the MCPI across a range of potential single and combined improvements to the pertussis vaccine. As an upper bound, we found that a next-generation vaccine which could achieve perfect efficacy for the childhood series would permit an MCPI of $18 per dose (95% CI: $12-$31). Pertussis vaccine improvements that extend the duration of protection to an average of 75 years would allow for an MCPI of $22 per dose for the childhood series (CI: $10-$33) or $12 for the adult booster (CI: $4-$18). Despite the short duration of the adult booster, improvements to the childhood series could be more valuable than improvements to the adult booster. Combining improvements in both efficacy and duration, a childhood series with perfect efficacy and average duration of 75 years would permit an MCPI of $39 per dose, the highest of any scenario evaluated. Our results highlight the utility of the MCPI metric in evaluating potential vaccines or other interventions when prices are unknown. PMID:27087151

  9. Defining long-term drivers of pertussis resurgence, and optimal vaccine control strategies.

    PubMed

    Campbell, Patricia Therese; McCaw, James Matthew; McIntyre, Peter; McVernon, Jodie

    2015-10-26

    Pertussis resurgence has been reported from several developed countries with long-standing immunisation programs. Among these, Australia in 2003 discontinued an 18 months (fourth) booster dose in favour of an adolescent (fifth) dose. We developed a model to evaluate determinants of resurgence in Australia and alternative vaccine strategies for mitigation. Novel characteristics of our model included the use of seroepidemiologic data for calibration, and broad investigation of variables relevant to transmission of, and protection against, pertussis. We simulated multiple parameter combinations, retaining those consistent with observed data for subsequent use in predictive models comparing alternative vaccination schedules. Reproducing the early control of pertussis followed by late resurgence observed in Australia required natural immunity to last decades longer than vaccine-acquired immunity, with mean duration exceeding 50 years in almost 90% of simulations. Replacement of the dose at 18 months with an adolescent dose in 2003 resulted in a 40% increase in infections in the age group 18-47 months by 2013. A six dose strategy (2, 4, 6, 18 months, 4 and 15 years) yielded a reduction in infection incidence (pre-school 43%, infants 8%) greater than any alternative strategies considered for timing of five administered doses. Our finding that natural immunity drives long-term trends in pertussis cycles is relevant to a range of pertussis strategies and provides the necessary context in which to consider maternal vaccination. Comparatively short-lived vaccine-acquired immunity requires multiple boosters over the first two decades of life to maximise reduction in infections. PMID:26392008

  10. Native Hawaiian and Pacific Islander Health - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Tetanus and Diphtheria) Vaccine English Bakuna sa Td (Tetano at Dipterya) - Tagalog (Tagalog) PDF Immunization Action Coalition; ... Tetanus, Diphtheria, and Pertussis) Vaccine English Bakunang Tdap (Tetano, Dipterya at Tuspirina) - Tagalog (Tagalog) PDF Immunization Action ...

  11. Check-Ups and Immunizations | NIH MedlinePlus the Magazine

    MedlinePlus

    ... infect, cripple, or kill children. Which Vaccines Do Preteens and Teens Need, and When? Tdap: A booster ... tetanus, diphtheria, and pertussis (whooping cough). Recommended for preteens (11-12), as well as any teens (13- ...

  12. Childhood Vaccine Schedule

    MedlinePlus

    ... MMR, IPV, Var 11 – 12 Years Human papillomavirus vaccine— HPV In young girls, prevents most cases of genital warts and cervical cancer Tetanus, diphtheria and pertussis booster— Tdap Meningitis vaccine— MCV Protects against meningitis, an inflammation of the ...

  13. Healthy Family 2009: Protecting Toddlers and Teens

    MedlinePlus

    ... MMR, IPV, Var 11 – 12 Years Human papillomavirus vaccine— HPV In young girls, prevents most cases of genital warts and cervical cancer Tetanus, diphtheria and pertussis booster— Tdap Meningitis vaccine— MCV Protects against meningitis, an inflammation of the ...

  14. Effective management of major lower extremity wounds using an acellular regenerative tissue matrix: a pilot study.

    PubMed

    Brigido, Stephen A; Boc, Steven F; Lopez, Ramon C

    2004-01-01

    Wound healing is a significant problem in orthopedics. Graftjacket tissue matrix (Wright Medical Technology, Inc, Arlington, Tenn), a novel acellular regenerative tissue matrix, has been designed to aid wound closure. A prospective, randomized study was initiated to determine the efficacy of this tissue product in wound repair compared with conventional treatment. Lower extremity wounds are refractile to healing in patients with diabetes mellitus. Therefore, researchers used diabetic foot ulcers to evaluate the efficacy of GraftJacket tissue matrix in wound repair. Only a single administration of the tissue matrix was required. After 1 month of treatment, preliminary results demonstrate that this novel tissue matrix promotes faster healing at a statistically significant rate over conventional treatment. Because wounds in this series of patients are deep and circulation around the wound is poor, the preliminary results suggest that this tissue matrix will be applicable to other types of orthopedic wounds. PMID:14763548

  15. Confocal Laser Scanning Microscopy Evaluation of an Acellular Dermis Tissue Transplant (Epiflex®)

    PubMed Central

    Hohenberger, Peter

    2012-01-01

    The structure of a biological scaffold is a major determinant of its biological characteristics and its interaction with cells. An acellular dermis tissue transplant must undergo a series of processing steps, to remove cells and genetic material and provide the sterility required for surgical use. During manufacturing and sterilization the structure and composition of tissue transplants may change. The composition of the human cell-free dermis transplant Epiflex® was investigated with specific attention paid to its structure, matrix composition, cellular content and biomechanics. We demonstrated that after processing, the structure of Epiflex remains almost unchanged with an intact collagen network and extracellular matrix (ECM) protein composition providing natural cell interactions. Although the ready to use transplant does contain some cellular and DNA debris, the processing procedure results in a total destruction of cells and active DNA which is a requirement for an immunologically inert and biologically safe substrate. Its biomechanical parameters do not change significantly during the processing. PMID:23056225

  16. Tissue-engineered acellular small diameter long-bypass grafts with neointima-inducing activity.

    PubMed

    Mahara, Atsushi; Somekawa, Shota; Kobayashi, Naoki; Hirano, Yoshiaki; Kimura, Yoshiharu; Fujisato, Toshiya; Yamaoka, Tetsuji

    2015-07-01

    Researchers have attempted to develop efficient antithrombogenic surfaces, and yet small-caliber artificial vascular grafts are still unavailable. Here, we demonstrate the excellent patency of tissue-engineered small-caliber long-bypass grafts measuring 20-30 cm in length and having a 2-mm inner diameter. The inner surface of an acellular ostrich carotid artery was modified with a novel heterobifunctional peptide composed of a collagen-binding region and the integrin α4β1 ligand, REDV. Six grafts were transplanted in the femoral-femoral artery crossover bypass method. Animals were observed for 20 days and received no anticoagulant medication. No thrombogenesis was observed on the luminal surface and five cases were patent. In contrast, all unmodified grafts became occluded, and severe thrombosis was observed. The vascular grafts reported here are the first successful demonstrations of short-term patency at clinically applicable sizes. PMID:25941782

  17. Gravity related behavior of the acellular slime mold Physarum polycephalum (7-IML-1)

    NASA Technical Reports Server (NTRS)

    Block, I.

    1992-01-01

    The objective of the experiment is to investigate the effect of near weightlessness on a single cell. The test object is the acellular slime mold Physarum polycephalum. This cell is composed of a network of protoplastic strands which perform rhythmic contractions in the minute range. These contractions of the strands' ectoplastic walls generate the force to drive the vigorous shuttle streaming of fluid protoplasm inside the strands (hydrostatic pressure flow). A net transport of protoplasm in one direction determines the direction of the cell's locomotion itself. In this way, gravity modifies the contraction rhythm of the strands, the streaming velocity of protoplasm in the strands, and the direction of locomotion of the whole slime mold (geotaxis). The other parts of this experiment will address the major question of how this cell, which does not possess any specialized gravireceptors, gets the information about the direction of the gravity vector. Details of the experimental setup are given.

  18. Effects of a student pharmacist consultation on patient knowledge and attitudes about vaccines.

    PubMed

    Chou, Tony I-Fan; Lash, David Benjamin; Malcolm, Benjamin; Yousify, Layla; Quach, Julie Yennhi; Dong, Sandy; Yu, Junhua

    2014-01-01

    OBJECTIVE To measure the impact of student pharmacists' consultation on participant knowledge and attitudes about influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines. DESIGN Pre- and post-consultation surveys. SETTING Free health care service and immunization clinics in Vallejo and Martinez, CA. PARTICIPANTS Children and adults 13 years of age or older. INTERVENTION A convenience sample of participants completed a preintervention survey (PrIs) on basic vaccine knowledge and attitudes. Student pharmacists then delivered the intervention, which consisted of a 5-minute consultation on vaccines. A postintervention (PoIs) survey was administered immediately after the intervention. MAIN OUTCOME MEASURES Cumulative scores for eight knowledge-based questions and four attitude-based questions. RESULTS 198 participants completed both PrIs and PoIs. Compared with the PrI scores, the PoI scores showed significant improvement in basic vaccine knowledge and attitudes toward receiving vaccinations. Participants also were more likely to view pharmacists as a source of information about vaccines after the intervention. Student pharmacists administered 109 total vaccinations during the study, including 68 influenza vaccinations and 41 Tdap vaccinations. CONCLUSION A short, 5-minute consultation by a student pharmacist may increase vaccination rates and help serve as a vehicle to change the public's view of vaccines as well as pharmacists and their role in primary and preventive care. PMID:24632928

  19. Adolescent Vaccination Performance in South Carolina Compared to the United States.

    PubMed

    Roberts, James R; Naifeh, Monique; Jacobson, Robert M; Hinton, Erin; O'Brien, Elizabeth; Rogacki, Brianna; Thompson, David; Margolis, Benyamin; Darden, Paul M

    National data on vaccine up-to-date (UTD) suggest that insufficient numbers of adolescents receive needed vaccines. This study analyzed public use data of the National Immunization Survey-Teen (NIS-Teen) from 2010 through 2013 for South Carolina (SC) adolescents and compared immunization rates to those of United States (US) adolescents. We also examined trends for each vaccine recommended for adolescents for both SC and US adolescents. UTD rates in SC adolescents for the quadrivalent meningococcal conjugate vaccine (MCV4) and the tetanus- diphtheria, acellular pertussis (Tdap) vaccine lag those of US adolescents, despite demonstrating a trend of improvement in SC adolescents from 45% to 69% for MCV and from 48% to 72% for Tdap. Human papillomavirus (HPV) vaccine UTD rates for SC adolescents demonstrated improvement over a 4 year period. HPV vaccination for SC girls improved when compared to the US, however UTD rates for both the SC and US were still well below the Healthy People 2020 goal of 80%. For all three vaccines, parental recall for a provider recommendation to vaccinate their adolescent was around or below 50%, except for HPV in females where it reached 65% in SC and 69% in the US. Differences between state and national rates may help SC providers focus on specific interventions needed to improve UTD rates. PMID:27141702

  20. Ligament reconstruction with tendon interposition using an acellular dermal allograft for thumb carpometacarpal arthritis.

    PubMed

    Kokkalis, Zinon T; Zanaros, George; Sotereanos, Dean G

    2009-03-01

    Ligament reconstruction tendon interposition arthroplasty is currently the preferred technique for carpometacarpal joint arthritis of the thumb by most surgeons. Despite its efficacy, morbidity has been associated with the harvest of the flexor carpi radialis tendon. Using an allograft as material for arthroplasty, donor site morbidity is avoided. In this report, we present our surgical technique to perform ligament reconstruction tendon interposition arthroplasty using an acellular dermal matrix allograft (GraftJacket) in patients with Eaton stages II, III, and IV symptomatic first carpometacarpal arthritis.One hundred thumbs with trapeziometacarpal osteoarthritis underwent surgical treatment using GraftJacket allograft instead of the flexor carpi radialis tendon autograft. Each patient was followed for a minimum of 12 months. The surgical procedure included trapezial excision and identification of the flexor carpi radialis. The allograft was cut to create a 15-cm strip. The ligament reconstruction was performed by passing the strip around the flexor carpi radialis tendon and suturing it to the base of the thumb metacarpal base through an intramedullary drill hole. The remaining portion of the allograft was fashioned as an interposition mass (anchovy) and interposed between the scaphoid and the base of the first metacarpal.All but 1 patient experienced significant improvement in his or her pain scale rating and grip and pinch strengths. Outcomes from this study compare very favorably with those of other series. No patients experienced a foreign body reaction or infection in this series. We believe that the use of an acellular dermal allograft for both ligament reconstruction and tendon interposition provides a safe and an effective alternative technique for the treatment of advanced first carpometacarpal arthritis. PMID:19276927

  1. Physiological distal drift in rat molars contributes to acellular cementum formation.

    PubMed

    Tsuchiya, Shinobu; Tsuchiya, Masahiro; Nishioka, Takashi; Suzuki, Osamu; Sasano, Yasuyuki; Igarashi, Kaoru

    2013-08-01

    Occlusal forces may induce the physiological teeth migration in humans, but there is little direct evidence. Rat molars are known to migrate distally during aging, possibly caused by occlusal forces. The purpose of this study was to determine if a reduction in occlusion would decrease teeth migration and affect associated periodontal structures such as cementum. To reduce occlusal forces, the right upper first molar (M1) in juvenile rats was extracted. The transition of the position of upper second molar (M2) and formation of M2 cementum was followed during aging. From the cephalometric analyses, upper M2 was located more anterior compared with the original position with aging after M1 extraction. Associated with this "slowing-down" of the physiological drift, cementum thickness on distal surface, but not on mesial surface, of M2 root was significantly increased. The accumulation of alizarin red as vital stain indicative of calcification, was observed in the distal cementum of M2 root only on the side of M1 extraction. Extraction of M1 that results in less functional loading, distinctly attenuates the physiological drift only in the upper dentition. The decreased physiological drift appears to activate acellular cementum formation only on distal surface of M2 root, perhaps due to reduced mechanical stress associated with the attenuated distal drift. In conclusion, the physiological distal drift in rat molars appears to be largely driven by the occlusal force and also affects the formation of acellular cementum. These findings provide additional direct evidence for an important role of occlusal forces in tooth migration. PMID:23775928

  2. Is Sterile Better Than Aseptic? Comparing the Microbiology of Acellular Dermal Matrices

    PubMed Central

    Klein, Gabriel M.; Nasser, Ahmed E.; Phillips, Brett T.; Gersch, Robert P.; Fourman, Mitchell S.; Lilo, Sarit E.; Fritz, Jason R.; Khan, Sami U.; Dagum, Alexander B.

    2016-01-01

    Introduction: Postoperative infections are a major complication associated with tissue-expander-based breast reconstruction. The use of acellular dermal matrix (ADM) in this surgery has been identified as a potential reservoir of infection, prompting the development of sterile ADM. Although aseptic and sterile ADMs have been investigated, no study has focused on the occurrence and clinical outcome of bacterial colonization before implantation. Methods: Samples of aseptic AlloDerm, sterile Ready-To-Use AlloDerm, and AlloMax were taken before implantation. These samples were incubated in Tryptic soy broth overnight before being streaked on Trypticase soy agar, MacConkey agar, and 5% blood agar plates for culture and incubated for 48 hours. Culture results were cross-referenced with patient outcomes for 1 year postoperatively. Results: A total of 92 samples of ADM were collected from 63 patients. There were 15 cases of postoperative surgical site infection (16.3%). Only 1 sample of ADM (AlloMax) showed growth of Escherichia coli, which was likely a result of contamination. That patient did not develop any infectious sequelae. Patient outcomes showed no difference in the incidence of seroma or infection between sterile and aseptic ADMs. Conclusions: This study evaluates the microbiology of acellular dermal matrices before use in breast reconstruction. No difference was found in the preoperative bacterial load of either aseptic or sterile ADM. No significant difference was noted in infection or seroma formation. Given these results, we believe aseptic processing used on ADMs is equivalent to sterile processing in our patient cohort in terms of clinical infection and seroma occurrence postoperatively. PMID:27482500

  3. Changes in Predominance of Pulsed-Field Gel Electrophoresis Profiles of Bordetella pertussis Isolates, United States, 2000-2012.

    PubMed

    Cassiday, Pamela K; Skoff, Tami H; Jawahir, Selina; Tondella, M Lucia

    2016-03-01

    To clarify the characteristics of circulating Bordetella pertussis isolates, we used pulsed-field gel electrophoresis (PFGE) to analyze 5,262 isolates collected in the United States during 2000-2012. We found 199 PFGE profiles; 5 profiles accounted for 72% of isolates. The most common profile, CDC013, accounted for 35%-46% of isolates tested from 2000-2009; however, the proportion of isolates of this profile rapidly decreased in 2010. Profile CDC237, first seen in 2009, increased rapidly and accounted for 29% of 2012 isolates. No location bias was observed among profiles during 2000-2010, but differences were observed among isolates from different states during 2012. Predominant profiles match those observed in recent European PFGE studies. PFGE profile changes are concurrent with other recent molecular changes in B. pertussis and may be contributing to the reemergence of pertussis in the United States. Continued PFGE monitoring is critical for understanding the changing epidemiology of pertussis. PMID:26886905

  4. Changes in Predominance of Pulsed-Field Gel Electrophoresis Profiles of Bordetella pertussis Isolates, United States, 2000–2012

    PubMed Central

    Skoff, Tami H.; Jawahir, Selina; Tondella, M. Lucia

    2016-01-01

    To clarify the characteristics of circulating Bordetella pertussis isolates, we used pulsed-field gel electrophoresis (PFGE) to analyze 5,262 isolates collected in the United States during 2000–2012. We found 199 PFGE profiles; 5 profiles accounted for 72% of isolates. The most common profile, CDC013, accounted for 35%–46% of isolates tested from 2000–2009; however, the proportion of isolates of this profile rapidly decreased in 2010. Profile CDC237, first seen in 2009, increased rapidly and accounted for 29% of 2012 isolates. No location bias was observed among profiles during 2000–2010, but differences were observed among isolates from different states during 2012. Predominant profiles match those observed in recent European PFGE studies. PFGE profile changes are concurrent with other recent molecular changes in B. pertussis and may be contributing to the reemergence of pertussis in the United States. Continued PFGE monitoring is critical for understanding the changing epidemiology of pertussis. PMID:26886905

  5. Genome Structural Diversity among 31 Bordetella pertussis Isolates from Two Recent U.S. Whooping Cough Statewide Epidemics

    PubMed Central

    Bowden, Katherine E.; Weigand, Michael R.; Peng, Yanhui; Cassiday, Pamela K.; Sammons, Scott; Knipe, Kristen; Rowe, Lori A.; Loparev, Vladimir; Sheth, Mili; Weening, Keeley; Tondella, M. Lucia

    2016-01-01

    ABSTRACT During 2010 and 2012, California and Vermont, respectively, experienced statewide epidemics of pertussis with differences seen in the demographic affected, case clinical presentation, and molecular epidemiology of the circulating strains. To overcome limitations of the current molecular typing methods for pertussis, we utilized whole-genome sequencing to gain a broader understanding of how current circulating strains are causing large epidemics. Through the use of combined next-generation sequencing technologies, this study compared de novo, single-contig genome assemblies from 31 out of 33 Bordetella pertussis isolates collected during two separate pertussis statewide epidemics and 2 resequenced vaccine strains. Final genome architecture assemblies were verified with whole-genome optical mapping. Sixteen distinct genome rearrangement profiles were observed in epidemic isolate genomes, all of which were distinct from the genome structures of the two resequenced vaccine strains. These rearrangements appear to be mediated by repetitive sequence elements, such as high-copy-number mobile genetic elements and rRNA operons. Additionally, novel and previously identified single nucleotide polymorphisms were detected in 10 virulence-related genes in the epidemic isolates. Whole-genome variation analysis identified state-specific variants, and coding regions bearing nonsynonymous mutations were classified into functional annotated orthologous groups. Comprehensive studies on whole genomes are needed to understand the resurgence of pertussis and develop novel tools to better characterize the molecular epidemiology of evolving B. pertussis populations. IMPORTANCE Pertussis, or whooping cough, is the most poorly controlled vaccine-preventable bacterial disease in the United States, which has experienced a resurgence for more than a decade. Once viewed as a monomorphic pathogen, B. pertussis strains circulating during epidemics exhibit diversity visible on a genome

  6. Genome Structural Diversity among 31 Bordetella pertussis Isolates from Two Recent U.S. Whooping Cough Statewide Epidemics.

    PubMed

    Bowden, Katherine E; Weigand, Michael R; Peng, Yanhui; Cassiday, Pamela K; Sammons, Scott; Knipe, Kristen; Rowe, Lori A; Loparev, Vladimir; Sheth, Mili; Weening, Keeley; Tondella, M Lucia; Williams, Margaret M

    2016-01-01

    During 2010 and 2012, California and Vermont, respectively, experienced statewide epidemics of pertussis with differences seen in the demographic affected, case clinical presentation, and molecular epidemiology of the circulating strains. To overcome limitations of the current molecular typing methods for pertussis, we utilized whole-genome sequencing to gain a broader understanding of how current circulating strains are causing large epidemics. Through the use of combined next-generation sequencing technologies, this study compared de novo, single-contig genome assemblies from 31 out of 33 Bordetella pertussis isolates collected during two separate pertussis statewide epidemics and 2 resequenced vaccine strains. Final genome architecture assemblies were verified with whole-genome optical mapping. Sixteen distinct genome rearrangement profiles were observed in epidemic isolate genomes, all of which were distinct from the genome structures of the two resequenced vaccine strains. These rearrangements appear to be mediated by repetitive sequence elements, such as high-copy-number mobile genetic elements and rRNA operons. Additionally, novel and previously identified single nucleotide polymorphisms were detected in 10 virulence-related genes in the epidemic isolates. Whole-genome variation analysis identified state-specific variants, and coding regions bearing nonsynonymous mutations were classified into functional annotated orthologous groups. Comprehensive studies on whole genomes are needed to understand the resurgence of pertussis and develop novel tools to better characterize the molecular epidemiology of evolving B. pertussis populations. IMPORTANCE Pertussis, or whooping cough, is the most poorly controlled vaccine-preventable bacterial disease in the United States, which has experienced a resurgence for more than a decade. Once viewed as a monomorphic pathogen, B. pertussis strains circulating during epidemics exhibit diversity visible on a genome structural

  7. Acellularization-Induced Changes in Tensile Properties Are Organ Specific - An In-Vitro Mechanical and Structural Analysis of Porcine Soft Tissues

    PubMed Central

    Aust, Gabriela; Boldt, Andreas; Fritsch, Sebastian; Keil, Isabel; Koch, Holger; Möbius, Robert; Scheidt, Holger A.; Wagner, Martin F. X.; Hammer, Niels

    2016-01-01

    Introduction Though xenogeneic acellular scaffolds are frequently used for surgical reconstruction, knowledge of their mechanical properties is lacking. This study compared the mechanical, histological and ultrastructural properties of various native and acellular specimens. Materials and Methods Porcine esophagi, ureters and skin were tested mechanically in a native or acellular condition, focusing on the elastic modulus, ultimate tensile stress and maximum strain. The testing protocol for soft tissues was standardized, including the adaption of the tissue’s water content and partial plastination to minimize material slippage as well as templates for normed sample dimensions and precise cross-section measurements. The native and acellular tissues were compared at the microscopic and ultrastructural level with a focus on type I collagens. Results Increased elastic modulus and ultimate tensile stress values were quantified in acellular esophagi and ureters compared to the native condition. In contrast, these values were strongly decreased in the skin after acellularization. Acellularization-related decreases in maximum strain were found in all tissues. Type I collagens were well-preserved in these samples; however, clotting and a loss of cross-linking type I collagens was observed ultrastructurally. Elastins and fibronectins were preserved in the esophagi and ureters. A loss of the epidermal layer and decreased fibronectin content was present in the skin. Discussion Acellularization induces changes in the tensile properties of soft tissues. Some of these changes appear to be organ specific. Loss of cross-linking type I collagen may indicate increased mechanical strength due to decreasing transverse forces acting upon the scaffolds, whereas fibronectin loss may be related to decreased load-bearing capacity. Potentially, the alterations in tissue mechanics are linked to organ function and to the interplay of cells and the extracellular matrix, which is different in

  8. Filamentous hemagglutinin has a major role in mediating adherence of Bordetella pertussis to human WiDr cells.

    PubMed Central

    Urisu, A; Cowell, J L; Manclark, C R

    1986-01-01

    [35S]methionine-labeled Bordetella pertussis adhered to monolayers of WiDr cells, an epitheliumlike cell line from a human intestinal carcinoma. Adherence was proportional to the density of the WiDr cells and to the concentration of B. pertussis in the assay. Adherence of virulent phase I strains Tohama phase I, 114, and BP338 was much greater than adherence of avirulent strains Tohama phase III and 423 phase IV. Mutants deficient in the production of the filamentous hemagglutinin (FHA) were hemagglutination negative and adhered to WiDr cells much less efficiently than the parent strains. Preincubation of B. pertussis cells with FHA increased their hemagglutination activity and adherence to WiDr cells. Goat antibody to FHA inhibited, in a dose-dependent manner, the adherence of strain Tohama I but not the adherence of FHA-deficient mutant Tohama 325. At similar protein concentrations, normal goat antibody, goat antibody to pertussis toxin, or the Fab fragments of goat antibody to serotype 2 fimbriae had no effect on adherence. Also, an FHA-positive strain without fimbriae showed high adherence, while a fimbriated FHA-deficient mutant adhered poorly. Our data indicate that FHA plays a major role in adherence of B. pertussis to human WiDr cells. Fimbriae do not appear to mediate attachment of B. pertussis to WiDr cells. PMID:2872165

  9. A critical role for the TLR signaling adapter Mal in alveolar macrophage-mediated protection against Bordetella pertussis.

    PubMed

    Bernard, N J; Finlay, C M; Tannahill, G M; Cassidy, J P; O'Neill, L A; Mills, K H G

    2015-09-01

    Bordetella pertussis causes whooping cough, an infectious disease of the respiratory tract that is re-emerging despite high vaccine coverage. Here we examined the role of Toll-like receptor (TLR) adapter protein Mal in the control of B. pertussis infection in the lungs. We found that B. pertussis bacterial load in the lungs of Mal-defective (Mal(-/-)) mice exceeded that of wild-type (WT) mice by up to 100-fold and bacteria disseminated to the liver in Mal(-/-) mice and 50% of these mice died from the infection. Macrophages from Mal(-/-) mice were defective in an early burst of pro-inflammatory cytokine production and in their ability to kill or constrain intracellular growth of B. pertussis. Importantly, the B. pertussis bacterial load in the lungs inversely correlated with the number of alveolar macrophages. Despite the maintenance and expansion of other cell populations, alveolar macrophages were completely depleted from the lungs of infected Mal(-/-) mice, but not from infected WT mice. Our findings define for the first time a role for a microbial pattern-recognition pathway in the survival of alveolar macrophages and uncover a mechanism of macrophage-mediated immunity to B. pertussis in which Mal controls intracellular survival and dissemination of bacteria from the lungs. PMID:25515629

  10. Pertussis serological potency test as an alternatively to the intracerebral mouse protection test.

    PubMed

    van der Ark, A; van Straaten-van de Kappelle, I; Hendriksen, C; van de Donk, H

    1996-01-01

    The current potency test for pertussis vaccines, the intracerebral protection test (MPT), is still the only mandatory laboratory model available. This test, however, is a valid, but inhumane and imprecise test and therefore a good candidate for replacement. Recently we have developed the Pertussis Serological Potency Test (PSPT) as an alternative for the MPT. The PSPT is based on in vitro assessment of the humoral immune response against the whole range of surface -antigens of B. pertussis in mice after immunisation with Whole Cell Vaccine (WCV). We have demonstrated a relationship between the mean pertussis antibody concentration at the day of challenge and the proportion of surviving mice at each vaccine dose in the MPT (R = 0.91). The PSPT is a model in which mice (20-24 g) are immunised i.p. with graded doses of vaccine and bled after four weeks. Sera are titrated in a whole cell ELISA and potency based on the vaccine dose-dependent antibody response is estimated by means of a parallel line analysis. In an in-house validation study 13 WCVs were tested in the PSPT and MPT. Homogeneity of both tests was proven by means of the chi-square test; potencies were significantly similar (p = 0.95). Compared to the MPT, the PSPT is more reproducible as is indicated by its smaller 95% confidence intervals. Moreover, by using the PSPT the animal distress can be reduced to an acceptable level and the PSPT also results in a reduction of more than 25% in use of mice. Additional experiments showed that estimation of WCV-potency in the PSPT based on specific antibody responses against protective antigens (PT, FHA, 69- and 92-kDa OMPS) was not possible or did not correlate with protection in MPT. Sera obtained from the PSPT showed a correlation between pertussis antibody levels and complement-mediated killing by pertussis antibodies in in vitro assays. In conclusion, the PSPT is a promising substitute for the MPT though further validation and additional studies on functional

  11. Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration

    PubMed Central

    Wagner, Darcy E.; Bonenfant, Nicholas R.; Sokocevic, Dino; DeSarno, Michael; Borg, Zachary; Parsons, Charles; Brooks, Elice M.; Platz, Joseph; Khalpey, Zain; Hoganson, David M.; Deng, Bin; Lam, Ying Wai; Oldinski, Rachael A.; Ashikaga, Takamaru; Weiss, Daniel J.

    2014-01-01

    Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de- and recellularization of large animal and human lungs including techniques which allow multiple small segments (∼1–3cm3) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold. PMID:24411675

  12. National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years--United States, 2013.

    PubMed

    Elam-Evans, Laurie D; Yankey, David; Jeyarajah, Jenny; Singleton, James A; Curtis, Robinette C; MacNeil, Jessica; Hariri, Susan

    2014-07-25

    The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents routinely receive 1 dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine, 2 doses of meningococcal conjugate (MenACWY) vaccine, and 3 doses of human papillomavirus (HPV) vaccine.* ACIP also recommends administration of "catch-up"† vaccinations, such as measles, mumps, and rubella (MMR), hepatitis B, and varicella, and, for all persons aged ≥6 months, an annual influenza vaccination. ACIP recommends administration of all age-appropriate vaccines during a single visit. To assess vaccination coverage among adolescents aged 13-17 years, CDC analyzed data from the 2013 National Immunization Survey-Teen (NIS-Teen).§ This report summarizes the results of that analysis, which show that from 2012 to 2013, coverage increased for each of the vaccines routinely recommended for adolescents: from 84.6% to 86.0% for ≥1 Tdap dose; from 74.0% to 77.8% for ≥1 MenACWY dose; from 53.8% to 57.3% for ≥1 HPV dose among females, and from 20.8% to 34.6% for ≥1 HPV dose among males. Coverage varied by state and local jurisdictions and by U.S. Department of Health and Human Services (HHS) region. Healthy People 2020 vaccination targets for adolescents aged 13-15 years were reached in 42 states for ≥1 Tdap dose, 18 for ≥1 MenACWY dose, and 11 for ≥2 varicella doses. No state met the target for ≥3 HPV doses.¶ Use of patient reminder and recall systems, immunization information systems, coverage assessment and feedback to clinicians, clinician reminders, standing orders, and other interventions can help make use of every health care visit to ensure that adolescents are fully protected from vaccine-preventable infections and cancers (5), especially when such interventions are coupled with clinicians' vaccination recommendations. PMID:25055186

  13. School-Located Vaccination Clinics for Adolescents: Correlates of Acceptance Among Parents.

    PubMed

    Gargano, Lisa M; Weiss, Paul; Underwood, Natasha L; Seib, Katherine; Sales, Jessica M; Vogt, Tara M; Rask, Kimberly; Morfaw, Christopher; Murray, Dennis L; DiClemente, Ralph J; Hughes, James M

    2015-08-01

    Four vaccines are recommended by The Advisory Committee for Immunization Practices for adolescents: tetanus, diphtheria, acellular pertussis vaccine (Tdap), meningococcal conjugate vaccine (MCV4), human papillomavirus vaccine (HPV), and annual seasonal influenza vaccine. However, coverage among adolescents is suboptimal. School-located vaccination clinics (SLVCs) offer vaccines to students at school, increasing access. This study seeks to determine the relationship between attitudes of parents of middle- and high-school students and acceptance of SLVCs for all four adolescent recommended vaccines. We conducted a telephone and web-based survey among parents of students enrolled in six middle and five high schools in Georgia. Analyses were conducted to examine associations between parental attitudes and willingness to allow their child to be vaccinated at school. Tdap and influenza vaccine had the highest rates of parental SLVC acceptance while HPV vaccine had the lowest. Parents who accepted SLVCs had higher perceived severity of influenza, meningococcal, and HPV illnesses compared to parents who did not accept SLVC. Intention to vaccinate was associated with SLVC acceptance for Tdap [Adjusted OR (AOR) 7.38; 95% confidence interval (CI) 2.44-22.31], MCV4 (AOR 2.97; 95% CI 1.67-5.28), and HPV vaccines (AOR 7.61; 95% CI 3.43-16.89). Social norms were associated with acceptance of SLVCs for influenza vaccine (AOR 1.44; 95% CI 1.12-1.84). These findings suggest parents of adolescents are generally supportive of SLVCs for recommended adolescent vaccines. Perceived severity of illness and intention to get their adolescent vaccinated were the most consistent correlates of parental SLVC acceptance for all vaccines. Future SLVC planning should focus on perceptions of disease severity and benefits of vaccination. PMID:25528325

  14. Analysis of the chromosomal location of two copies of a Bordetella pertussis insertion sequence.

    PubMed

    McPheat, W L; Hanson, J H; Livey, I; Robertson, J S

    1989-07-01

    IS481v1 and IS481v2 are two copies of a Bordetella pertussis insertion sequence element. We have shown that IS481v1 is located within 3 kbp of the start of the adenylate cyclase gene whilst IS481v2 is immediately adjacent to the end of the agglutinogen 2 gene and provides the stop codon for that gene. In addition, IS481v1 and IS481v2 were present at these two specific sites in nine strains of B. pertussis, including two Phase IV strains which expressed neither adenylate cyclase nor agglutinogen 2 and three Phase I strains which did not express agglutinogen 2. The loss of expression in these strains is not the result of DNA rearrangements at the sites of IS481v1 or IS481v2. PMID:2552259

  15. Antigens of Bordetella pertussis V. Separation of Agglutinogen 1 and Mouse-Protective Antigen.

    PubMed

    Ross, R F; Munoz, J

    1971-02-01

    Agglutinogen 1 of Bordetella pertussis strain 353/Z (serotype 1) was separated from protective antigen and histamine-sensitizing factor by starch-block electrophoresis. Most of the agglutinogen 1 migrated towards the cathode in starch-block electrophoresis, although some remained near the origin. Fractions containing most of the agglutinogen 1 were free of detectable mouse-protecting or histamine-sensitizing activities. Agglutinogen 1 from a serotype 1, 3 B. pertussis strain (J20) migrated similarly to the agglutinogen 1 from strain 353/Z. All agglutinogen 3 activity was found at the point of application in the starch block. No clear relationship was found between agglutinogen 1 and mouse-protecting antigen or histamine-sensitizing factor. PMID:16557960

  16. Antigens of Bordetella pertussis V. Separation of Agglutinogen 1 and Mouse-Protective Antigen

    PubMed Central

    Ross, R. F.; Munoz, J.

    1971-01-01

    Agglutinogen 1 of Bordetella pertussis strain 353/Z (serotype 1) was separated from protective antigen and histamine-sensitizing factor by starch-block electrophoresis. Most of the agglutinogen 1 migrated towards the cathode in starch-block electrophoresis, although some remained near the origin. Fractions containing most of the agglutinogen 1 were free of detectable mouse-protecting or histamine-sensitizing activities. Agglutinogen 1 from a serotype 1, 3 B. pertussis strain (J20) migrated similarly to the agglutinogen 1 from strain 353/Z. All agglutinogen 3 activity was found at the point of application in the starch block. No clear relationship was found between agglutinogen 1 and mouse-protecting antigen or histamine-sensitizing factor. Images PMID:16557960

  17. Tolerance of initial diphtheria-tetanus-pertussis immunization in preterm infants.

    PubMed

    Topsis, J; Kandall, S; Weinstein, J; Wilets, I

    1996-01-01

    With the use of neurologic examinations, cranial sonograms, electroencephalograms, an cry analyses, we assessed neurologic function before and after an initial diphtheria-tetanus-pertussis immunization in 22 very low birth weight infants. Mean birth weight was 1036 +/- 137 gm; mean gestational age was 28.0 +/- 1.3 weeks. All 22 infants had recovered from respiratory distress syndrome, 10 infants had been treated for invasive bacterial or fungal infection, and 9 infants had had previous intraventricular hemorrhages. Initial immunization was administered at a mean age of 71 +/- 15 days (range 57 to 120 days) and a mean weight of 1895 +/- 245 gm (1370 to 2280 gm). Clinical reactions were mild and transient. No postimmunization changes in neurologic examinations or objective studies were noted compared with results of preimmunization studies. These findings support the safety of administering an initial diphtheria-tetanus-pertussis immunization to very low birth weight infants at the recommended age of 8 weeks. PMID:8732555

  18. [Cryofractographic study of intercellular junctions in the populations of agar-cultivated Bordetella pertussis].

    PubMed

    Vysotskiĭ, V V; Vaisman, I Sh; Efimova, O G; Chemurzieva, N V

    1985-09-01

    The characteristic feature of replicas obtained from the freeze-fractures of B. pertussis unfixed cultures developing on casein charcoal agar for 1-7 days is the associative growth of highly polymorphic cells, ensured by the ramified system of intercellular connections (IC) formed by the derivatives of the outer layers of the cell wall. This proves that the associative location of bacterial cells, linked by numerous IC, in the preparation is not the artefact appearing in the process of their chemical fixation. In replicas obtained from the freeze-fractures of B. pertussis cultures, previously fixed with glutaraldehyde, osmic acid and uranyl acetate, oval cells with the cytoplasm having a relatively homogeneous structure and with the smoothed-out three-layer cell wall prevail. As a rule, IC are limited to the sites of direct contacts between individual cells. PMID:2866645

  19. Pertussis immunisation in pregnancy: a summary of funded Australian state and territory programs.

    PubMed

    Beard, Frank H

    2015-09-01

    The Australian Immunisation Handbook, 10th edition now recommends pertussis vaccination during pregnancy as the preferred option for protecting vulnerable young infants. Jurisdictionally funded pertussis immunisation programs for pregnant women have been progressively introduced in all Australian states and territories between August 2014 and June 2015. A meeting convened by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases was held on 31 May 2015 to share information regarding jurisdictional policies and program implementation. This report of that meeting provides the first published comparison of these jurisdictional programs, which are of a broadly similar nature but with important differences. Monitoring and evaluation of the uptake, safety and impact of the current programs in Australia will be important to inform future policy decisions. PMID:26620346

  20. Human acellular dermal matrix for repair of abdominal wall defects: review of clinical experience and experimental data.

    PubMed

    Holton, Luther H; Kim, Daniel; Silverman, Ronald P; Rodriguez, Eduardo D; Singh, Navin; Goldberg, Nelson H

    2005-01-01

    The use of prosthetic mesh for the tension-free repair of incisional hernias has been shown to be more effective than primary suture repair. Unfortunately, prosthetic materials can be a suboptimal choice in a variety of clinical scenarios. In general, prosthetic materials should not be implanted into sites with known contamination or infection because they lack an endogenous vascular network and are thus incapable of clearing bacteria. This is of particular relevance to the repair of recurrent hernias, which are often refractory to repair because of indolent bacterial colonization that weakens the site and retards appropriate healing. Although fascia lata grafts and muscle flaps can be employed for tension-free hernia repairs, they carry the potential for significant donor site morbidity. Recently, a growing number of clinicians have used human acellular dermal matrix as a graft material for the tension-free repair of ventral hernias. This material has been shown to become revascularized in both animal and human subjects. Once repopulated with a vascular network, this graft material is theoretically capable of clearing bacteria, a property not found in prosthetic graft materials. Unlike autologous materials such as fascial grafts and muscle flaps, acellular dermal matrix can be used without subjecting the patient to additional morbidity in the form of donor site complications. This article presents a thorough review of the current literature, describing the properties of human acellular dermal matrix and discussing both animal and human studies of its clinical performance. In addition to the review of previously published clinical experiences, we discuss our own preliminary results with the use of acellular dermal matrix for ventral hernia repair in 46 patients. PMID:16218902

  1. Possible role of dentin matrix in region-specific deposition of cellular and acellular extrinsic fibre cementum.

    PubMed

    Takano, Yoshiro; Sakai, Hideo; Watanabe, Eiko; Ideguchi-Ohma, Noriko; Jayawardena, Chantha K; Arai, Kazumi; Asawa, Yukiyo; Nakano, Yukiko; Shuda, Yoko; Sakamoto, Yujiro; Terashima, Tatsuo

    2003-01-01

    The mechanism whereby a region-specific deposition of the two types of cementum (cellular cementum and acellular extrinsic fibre cementum) is regulated on the growing root surface was tested using bisphosphonate-affected teeth of young rats and guinea pigs. The animals were injected subcutaneously with 8 or 10 mg P x kg body weight(-1) x day(-1) of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) for 1 or 2 weeks. In rat molars, HEBP prevented mineralization of newly formed root dentin matrix and totally inhibited de novo deposition of acellular extrinsic fibre cementum. Instead, thick cellular cementum was induced on the non-mineralized root dentin surface, irrespective of the position of the root. In both animals, cellular cementum was also induced on the non-mineralized surface of root analogue dentin in HEBP-affected incisors, where only acellular extrinsic fibre cementum is deposited under normal conditions. In normal rat molars, dentin sialoprotein (DSP) was concentrated along the dentin-cellular cementum border, but not that of dentin and acellular extrinsic fibre cementum. In HEBP-affected rat incisors, DSP was shown to penetrate through the non-mineralized dentin into the surrounding tissues, but not through the mineralized portions. These data suggest that, at the site of cellular cementum formation, putative inducing factors for cellular cementum might diffuse into the periodontal space through the newly deposited mantle dentin matrix before it is mineralized. At earlier stages of root formation, mantle dentin might mineralize more promptly not to allow such diffusion. The timing of mineralization of mantle dentin matrix might be the key determinant of the types of the cementum deposited on the growing root surface. PMID:14756246

  2. Safety of pertussis vaccination in pregnant women in UK: observational study

    PubMed Central

    King, Bridget; Bryan, Phil

    2014-01-01

    Objective To examine the safety of pertussis vaccination in pregnancy. Design Observational cohort study. Setting The UK Clinical Practice Research Datalink. Participants 20 074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group. Main outcome measure Adverse events identified from clinical diagnoses during pregnancy, with additional data from the matched child record identified through mother-child linkage. The primary event of interest was stillbirth (intrauterine death after 24 weeks’ gestation). Results There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 0.69, 95% confidence interval 0.23 to 1.62) or later in pregnancy (0.85, 0.44 to 1.61) compared with historical national rates. Compared with a matched historical cohort of unvaccinated pregnant women, there was no evidence that vaccination accelerated the time to delivery (hazard ratio 1.00, 0.97 to 1.02). Furthermore, there was no evidence of an increased risk of stillbirth, maternal or neonatal death, pre-eclampsia or eclampsia, haemorrhage, fetal distress, uterine rupture, placenta or vasa praevia, caesarean delivery, low birth weight, or neonatal renal failure, all serious events that can occur naturally in pregnancy. Conclusion In women given pertussis vaccination in the third trimester, there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy. In particular, there was no evidence of an increased risk of stillbirth. Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates, these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making. PMID:25015137

  3. Deep Anterior Lamellar Keratoplasty Using Irradiated Acellular Cornea with Amniotic Membrane Transplantation for Intractable Ocular Surface Diseases

    PubMed Central

    Wee, Sung Wook; Choi, Sang Uk

    2015-01-01

    Purpose To report the clinical outcomes of deep anterior lamellar keratoplasty (DALK) when sterile gamma-irradiated acellular corneal tissues (VisionGraft) are used in combination with amniotic membrane transplantation (AMT) for intractable ocular surface diseases. Methods The medical records of fifteen patients who had DALK with AMT were retrospectively reviewed. Indications for surgery included ocular burn, bacterial keratitis, herpes simplex virus keratitis, corneal opacity with Stevens-Johnson syndrome, Mooren's ulcer, idiopathic myxoid degeneration of corneal stroma, and recurrent band keratopathy. DALK was performed using partial-thickness acellular corneal tissue and a temporary amniotic membrane patch was added at the end of the operation. Results All cases that underwent DALK with AMT became epithelialized within 2 postoperative weeks. Twelve patients showed favorable outcomes without graft rejection, corneal opacification, or neovascularization. The other three grafts developed corneal opacification and neovascularization, and required additional penetrating keratoplasty (PK). Unlike the results of previous PKs, there were no graft rejections and the graft clarity was well-maintained in these three cases for at least 8 months after PK. Conclusions DALK using sterile acellular corneal tissues in combination with AMT may be a good therapeutic strategy for treating intractable ocular surface diseases because of lowered immune rejection, fibroblast activation, and facilitation of epithelialization. Furthermore, DALK can help stabilize the ocular surface, prolong graft survival, and may allow better outcomes when combined with subsequent PK. PMID:25829823

  4. Management of failed and infected first metatarsophalangeal joint implant arthroplasty by reconstruction with an acellular dermal matrix: a case report.

    PubMed

    Khoury, Wissam E; Fahim, Ramy; Sciulli, Jessica M; Ehredt, Duane J

    2012-01-01

    Management of failed first metatarsophalangeal joint implant arthroplasty, especially in the face of infection, is an area of debate without a clear consensus. The purpose of the present report was to explore a new option of reconstructing the joint with an acellular dermal matrix substance in a single case study during a 12-month follow-up period. A staged approach that began with removal of the failed 2-component great toe implant, Koenig(®), excisional debridement of the wound with resection of the necrotic bone (proximal phalanx and distal portion of the first metatarsal bones), and culture-specific antibiosis therapy. The final stage included incorporating the acellular dermal matrix, Graftjacket(®) into the joint in an accordion-type fashion, and reconstruction of the joint capsule. Postoperative radiographs revealed a more rectus joint with some improvement in length. At 6 months postoperatively, magnetic resonance imaging revealed incorporation of the graft material into the joint. Finally, at the 1-year mark, the patient was pain free with satisfactory function at the first metatarsophalangeal joint during gait. This is the first reported case of salvaging failed and infected first metatarsophalangeal joint implant arthroplasty with incorporation of the acellular dermal matrix and provides a new option to consider in the future. PMID:22704789

  5. Development and Characterization of Acellular Extracellular Matrix Scaffolds from Porcine Menisci for Use in Cartilage Tissue Engineering

    PubMed Central

    Chen, Ying-Chen; Chen, Ray-Neng; Jhan, Hua-Jing; Liu, Der-Zen; Ho, Hsiu-O; Mao, Yong; Kohn, Joachim

    2015-01-01

    Given the growing number of arthritis patients and the limitations of current treatments, there is great urgency to explore cartilage substitutes by tissue engineering. In this study, we developed a novel decellularization method for menisci to prepare acellular extracellular matrix (ECM) scaffolds with minimal adverse effects on the ECM. Among all the acid treatments, formic acid treatment removed most of the cellular contents and preserved the highest ECM contents in the decellularized porcine menisci. Compared with fresh porcine menisci, the content of DNA decreased to 4.10%±0.03%, and there was no significant damage to glycosaminoglycan (GAG) or collagen. Histological staining also confirmed the presence of ECM and the absence of cellularity. In addition, a highly hydrophilic scaffold with three-dimensional interconnected porous structure was fabricated from decellularized menisci tissue. Human chondrocytes showed enhanced cell proliferation and synthesis of chondrocyte ECM including type II collagen and GAG when cultured in this acellular scaffold. Moreover, the scaffold effectively supported chondrogenesis of human bone marrow-derived mesenchymal stem cells. Finally, in vivo implantation was conducted in rats to assess the biocompatibility of the scaffolds. No significant inflammatory response was observed. The acellular ECM scaffold provided a native environment for cells with diverse physiological functions to promote cell proliferation and new tissue formation. This study reported a novel way to prepare decellularized meniscus tissue and demonstrated the potential as scaffolds to support cartilage repair. PMID:25919905

  6. Development and Characterization of Acellular Extracellular Matrix Scaffolds from Porcine Menisci for Use in Cartilage Tissue Engineering.

    PubMed

    Chen, Ying-Chen; Chen, Ray-Neng; Jhan, Hua-Jing; Liu, Der-Zen; Ho, Hsiu-O; Mao, Yong; Kohn, Joachim; Sheu, Ming-Thau

    2015-09-01

    Given the growing number of arthritis patients and the limitations of current treatments, there is great urgency to explore cartilage substitutes by tissue engineering. In this study, we developed a novel decellularization method for menisci to prepare acellular extracellular matrix (ECM) scaffolds with minimal adverse effects on the ECM. Among all the acid treatments, formic acid treatment removed most of the cellular contents and preserved the highest ECM contents in the decellularized porcine menisci. Compared with fresh porcine menisci, the content of DNA decreased to 4.10%±0.03%, and there was no significant damage to glycosaminoglycan (GAG) or collagen. Histological staining also confirmed the presence of ECM and the absence of cellularity. In addition, a highly hydrophilic scaffold with three-dimensional interconnected porous structure was fabricated from decellularized menisci tissue. Human chondrocytes showed enhanced cell proliferation and synthesis of chondrocyte ECM including type II collagen and GAG when cultured in this acellular scaffold. Moreover, the scaffold effectively supported chondrogenesis of human bone marrow-derived mesenchymal stem cells. Finally, in vivo implantation was conducted in rats to assess the biocompatibility of the scaffolds. No significant inflammatory response was observed. The acellular ECM scaffold provided a native environment for cells with diverse physiological functions to promote cell proliferation and new tissue formation. This study reported a novel way to prepare decellularized meniscus tissue and demonstrated the potential as scaffolds to support cartilage repair. PMID:25919905

  7. Comparison of type 2 and type 6 fimbriae of Bordetella pertussis by using agglutinating monoclonal antibodies.

    PubMed

    Li, Z M; Brennan, M J; David, J L; Carter, P H; Cowell, J L; Manclark, C R

    1988-12-01

    Two types of fimbriae have been identified on the pathogenic gram-negative organism Bordetella pertussis. Monoclonal antibodies to these fimbriae were produced to better understand the role of fimbriae as serotype-specific agglutinogens and to investigate the antigenic relationship between these fimbriae. Three monoclonal antibodies were identified that specifically agglutinated B. pertussis cells containing the U.S. Reference Factor 2 agglutinogen, and six monoclonal antibodies were produced that agglutinated only those strains containing the U.S. Reference Factor 6 agglutinogen. Indirect immunofluorescence studies and immunogold electron microscopy demonstrated that these monoclonal antibodies bind to an outer membrane component on serotype-specific strains of B. pertussis. All of the monoclonal antibodies reacted with native or partially assembled type-specific fimbriae but not with monomeric fimbrial subunits as indicated by Western blot (immunoblot) analysis. The fimbrial agglutinogens recognized by the monoclonal antibodies were also uniquely reactive with either U.S. Reference Factor 2 or 6 antiserum (Eldering agglutinogen 2 or 6 polyclonal antiserum) in an indirect ELISA. No cross-reactivity of the monoclonal antibodies with the unrelated fimbriae was observed in any of the comparative immunological studies. Some of the monoclonal antibodies agglutinated certain strains of B. bronchiseptica, suggesting that this closely related species can contain antigenically similar fimbriae. These monoclonal antibodies should prove useful for further structural and functional analysis of Bordetella fimbriae and for studies on the role that these antigens play in prevention of infection and disease. PMID:2903125

  8. Molecular cloning and characterization of protective outer membrane protein P.69 from Bordetella pertussis.

    PubMed Central

    Charles, I G; Dougan, G; Pickard, D; Chatfield, S; Smith, M; Novotny, P; Morrissey, P; Fairweather, N F

    1989-01-01

    Protein P.69 is localized on the outer membrane of Bordetella pertussis and is one of the virulence factors believed to contribute to the disease state of whooping cough. We demonstrate that protein synthesis of P.69 is under genetic control of the vir locus. Using oligonucleotide probes derived from the protein sequence of a cyanogen bromide fragment, we have cloned the gene for P.69 from B. pertussis CN2992. Analysis of the DNA sequence reveals a G + C-rich gene capable of encoding a protein of 910 amino acids with a Mr of 93,478, suggesting that P.69 is a processed form of a larger precursor. In common with some of the genes in the pertussis toxin operon, the sequence CCTGG was found 5' to the ATG initiation codon. At the 3' end, 29 bases after the TAA stop codon, the sequence GTTTTTCCT was found and may have some function in transcription termination. A full-length clone of the gene for P.69 carried by the cosmid pBPI69 was unable to direct the expression of P.69 protein in an Escherichia coli host. The generation of P.69-fusion products allowed the detection of P.69-specific protein products synthesized in E. coli. Images PMID:2542937

  9. Comparison of type 2 and type 6 fimbriae of Bordetella pertussis by using agglutinating monoclonal antibodies.

    PubMed Central

    Li, Z M; Brennan, M J; David, J L; Carter, P H; Cowell, J L; Manclark, C R

    1988-01-01

    Two types of fimbriae have been identified on the pathogenic gram-negative organism Bordetella pertussis. Monoclonal antibodies to these fimbriae were produced to better understand the role of fimbriae as serotype-specific agglutinogens and to investigate the antigenic relationship between these fimbriae. Three monoclonal antibodies were identified that specifically agglutinated B. pertussis cells containing the U.S. Reference Factor 2 agglutinogen, and six monoclonal antibodies were produced that agglutinated only those strains containing the U.S. Reference Factor 6 agglutinogen. Indirect immunofluorescence studies and immunogold electron microscopy demonstrated that these monoclonal antibodies bind to an outer membrane component on serotype-specific strains of B. pertussis. All of the monoclonal antibodies reacted with native or partially assembled type-specific fimbriae but not with monomeric fimbrial subunits as indicated by Western blot (immunoblot) analysis. The fimbrial agglutinogens recognized by the monoclonal antibodies were also uniquely reactive with either U.S. Reference Factor 2 or 6 antiserum (Eldering agglutinogen 2 or 6 polyclonal antiserum) in an indirect ELISA. No cross-reactivity of the monoclonal antibodies with the unrelated fimbriae was observed in any of the comparative immunological studies. Some of the monoclonal antibodies agglutinated certain strains of B. bronchiseptica, suggesting that this closely related species can contain antigenically similar fimbriae. These monoclonal antibodies should prove useful for further structural and functional analysis of Bordetella fimbriae and for studies on the role that these antigens play in prevention of infection and disease. Images PMID:2903125

  10. The location of surface antigens of Bordetella pertussis by immuno-electron microscopy.

    PubMed

    Ashworth, L A; Dowsett, A B; Irons, L I; Robinson, A

    1985-01-01

    Immuno-electron microscopy using colloidal gold-tagged monoclonal antibodies (McAbs) has been used to detect antigens on the surface of Bordetella pertussis cells. McAbs to serotype-specific agglutinogens 2 and 3 labelled fimbriae in a serotype-specific manner. An attempt was made to determine whether individual fimbriae of serotype 1.2.3 cells bear both antigens 2 and 3. In double labelling experiments, individual cells were found to label with McAbs to antigen 2 (3 nm gold) and to antigen 3 (15 nm gold). Many fimbriae labelled with only one of these reagents, but there were instances where both labels could have been attached to the same fimbria. No fimbrial labelling was obtained with McAb to agglutinogen 1. Gold-tagged McAbs to filamentous haemagglutinin (FHA) labelled neither the fimbriae nor the surface of B. pertussis cells. Unfixed cells on electron microscope grids appeared to shed FHA readily. After fixation, a small proportion of cells bore aggregates of FHA which labelled specifically with anti-FHA McAb-gold. Results with one McAb to lymphocytosis promoting factor indicated that this antigen may be more intimately associated with the surface of B. pertussis than is FHA. PMID:2872100

  11. Pertussis toxin: the cause of the harmful effects and prolonged immunity of whooping cough. A hypothesis.

    PubMed

    Pittman, M

    1979-01-01

    The nature of the pathogenesis and of the prolonged immunity of whooping cough has not been clearly defined. The literature of Bordetella pertussis indicated that only the antigen that induces histamine sensitization, lymphocytosis, and other biological reactions in mice is the cause of the harmful effects and prolonged immunity of whooping cough. This antigen has the general characteristics of bacterial protein exotoxins that cause the harmful effects of infectious diseases such as diphtheria and tetanus. It is proposed that this antigen, which is histamine-sensitizing, lymphocyte-leukocyte-promoting, and islets-activating (HSF-LPF-IAP), be designated pertussis toxin. Agglutinogen, hemagglutinin, and heat-labile (at 56 C) and heat-stable (at 100 C) toxins are no doubt interrelated with the immunologic and/or toxic reactions of whooping cough. It appears that the first defense against the disease is the antibody that prevents adhesion of the bacteria to the cilia of the respiratory epithelium and that the second defense is the antitoxin against pertussis toxin (HSF-LPF-IAP). PMID:233166

  12. Purification of serotype 2 fimbriae of Bordetella pertussis and their identification as a mouse protective antigen.

    PubMed

    Zhang, J M; Cowell, J L; Steven, A C; Manclark, C R

    1985-01-01

    Fimbriae were removed from Bordetella pertussis by mechanical shearing and purified by successive precipitations with ammonium sulfate, pH 6.0 phosphate buffer, and magnesium chloride. Electron microscopy showed the purified fimbriae to be long filamentous structures (5 nm in diameter) which aggregated into bundles at pH 6.0. Sodium dodecyl sulfate gel electrophoresis of the purified fimbriae gave a single protein subunit with a molecular weight of 22,000. The purified fimbriae did not have hemagglutinating activity when assayed with a variety of erythrocytes and were shown to be antigenically and structurally distinct from the filamentous hemagglutinin of B. pertussis. The purified fimbriae were identified as serotype 2 agglutinogens as antibody to the purified fimbriae agglutinated B. pertussis strains serotyped as 1.2.4, 1.2.3, or 1.2.3.6, but did not agglutinate serotypes 1.3.6. Immunization of mice with the purified fimbriae (14 micrograms) protected them from a lethal respiratory infection with strain 18323 (agglutinogen serotype 1.2.3.4.6) or with strain 432 (serotype 1.3.6). Immunization of mice with purified fimbriae containing 0.02% LPF also protected them from a lethal intracerebral infection with 18323. The ED50 was about 13 micrograms. Fimbriae containing less than 0.005% LPF did not protect mice from intracerebral challenge. PMID:2872103

  13. Pertussis Toxin B-Pentamer Mediates Intercellular Transfer of Membrane Proteins and Lipids

    PubMed Central

    Millen, Scott H.; Schneider, Olivia D.; Miller, William E.; Monaco, John J.; Weiss, Alison A.

    2013-01-01

    Pertussis toxin (PTx) is the major virulence factor of Bordetella pertussis. The enzymatic or active (A) subunit inactivates host G protein coupled receptor (GPCR) signaling pathways. The non-enzymatic binding (B) subunit also mediates biological effects due to lectin-like binding characteristics, including the induction of T cell receptor (TCR) signaling and subsequent down-regulation of chemokine receptor expression. Here we report another activity attributable to PTxB, facilitating transfer of membrane material between mammalian cells. This activity does not require the TCR, and does not require cell-to-cell contact or cellular aggregation. Rather, membrane vesicles are transferred from donor to recipient cells in a toxin-dependent fashion. Membrane transfer occurs in different cell types, including cultured human T cells, CHO cells, and human primary peripheral blood mononuclear cells. Transfer involves both lipid and integral membrane proteins, as evidenced by the transfer of T and B cell-specific receptor molecules to other PBMCs. Interestingly, membrane transfer activity is a property that PTx shares with some, but not all, cell-aggregating lectins that are mitogenic for human T cells, and appears to be related to the ability to bind certain host cell glycolipids. This phenomenon may represent another mechanism by which pertussis toxin disrupts mammalian intra- and inter-cellular signaling. PMID:24019885

  14. Detection of Bordetella pertussis in Infants Suspected to have Whooping Cough

    PubMed Central

    Hajia, Massoud; Rahbar, Mohammad; Fallah, Fatemeh; Safadel, Nooshafarin

    2012-01-01

    Background: Even with high coverage of vaccination programs, Bordetella pertussis is still reported in various countries. It causes a high rate of mortality and morbidity in infants while it could be asymptomatic in adults. At the present study, we are going to evaluate the frequency of B. pertussis among received specimens. Methods: This cross-sectional study was performed on 138 children under one year who were suspected to have whooping cough from October 2008 to March in 2011. Nasopharyngeal dacron and rayon swabs and sera were used for PCR and serology respectively. Results: The mean age of the subjects was 1.9± 0.9 months. PCR was positive in 12 cases; ELISA was in agreement with PCR results except in one case that showed the specific antibody at borderline limit. Conclusion: The rate of reported positive results showed that pertussis not only is still present in the community, but the number of the asymptomatic cases who are able to transmit the disease may be considerable. PMID:22754598

  15. Combined diphtheria, tetanus, pertussis, and Haemophilus influenzae type b vaccines for primary immunisation.

    PubMed Central

    Bell, F; Martin, A; Blondeau, C; Thornton, C; Chaplais, J; Finn, A

    1996-01-01

    A total of 146 infants were immunised at ages 2, 3, and 4 months with a combined diphtheria, tetanus, pertussis (DTP)--Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) vaccine (Pasteur Merieux) to assess the antibody response and adverse events associated with immunisation. Adverse events, including fever, were recorded by parents in a diary for three days following each injection. Blood was taken before the first immunisation and four weeks after the third immunisation to assess antibody response. Data were compared with those from historical controls who had received DTP and PRP-T vaccines by separate injection. The combined vaccine was well tolerated. Rates of local and general reactions were similar to those reported for infants immunised by separate injection. All infants achieved protective antibody titres (> 0.01 IU/ml) for diphtheria and tetanus; 98% acquired Hib (PRP) antibody > 0.15 microgram/ml and 82.5% > 1.0 microgram/ml. Pertussis antibody titres (pertussis toxin, filamentous haemagglutinin, total agglutinins, and agglutinins 2 and 3) showed appreciable rise following immunisation. DTP and PRP-T vaccines provide similar antibody responses and adverse effects whether mixed in the same syringe or administered by separate injection. The vaccines could be combined for use in the United Kingdom primary immunisation schedule. PMID:8984914

  16. Cost-Effectiveness of Pertussis Vaccination During Pregnancy in the United States.

    PubMed

    Atkins, Katherine E; Fitzpatrick, Meagan C; Galvani, Alison P; Townsend, Jeffrey P

    2016-06-15

    Vaccination against pertussis has reduced the disease burden dramatically, but the most severe cases and almost all fatalities occur in infants too young to be vaccinated. Recent epidemiologic evidence suggests that targeted vaccination of mothers during pregnancy can reduce pertussis incidence in their infants. To evaluate the cost-effectiveness of antepartum maternal vaccination in the United States, we created an age-stratified transmission model, incorporating empirical data on US contact patterns and explicitly modeling parent-infant exposure. Antepartum maternal vaccination incurs costs of $114,000 (95% prediction interval: 82,000, 183,000) per quality-adjusted life-year, in comparison with the strategy of no adult vaccination, and is cost-effective in the United States according to World Health Organization criteria. By contrast, vaccinating a second parent is not cost-effective, and vaccination of either parent postpartum is strongly dominated by antepartum maternal vaccination. Nonetheless, postpartum vaccination of mothers who were not vaccinated antepartum improves upon the current recommendation of untargeted adult vaccination. Additionally, the temporary direct protection of the infant due to maternal antibody transfer has efficacy for infants comparable to that conferred to toddlers by the full primary vaccination series. Efficient protection against pertussis for infants begins before birth. We highly recommend antepartum vaccination for as many US mothers as possible. PMID:27188951

  17. Healing rates for challenging rotator cuff tears utilizing an acellular human dermal reinforcement graft

    PubMed Central

    Agrawal, Vivek

    2012-01-01

    Purpose: This study presents a retrospective case series of the clinical and structural outcomes (1.5 T MRI) of arthroscopic rotator cuff repair with acellular human dermal graft reinforcement performed by a single surgeon in patients with large, massive, and previously repaired rotator cuff tears. Materials and Methods: Fourteen patients with mean anterior to posterior tear size 3.87 ± 0.99 cm (median 4 cm, range 2.5–6 cm) were enrolled in the study and were evaluated for structural integrity using a high-field (1.5 T) MRI at an average of 16.8 months after surgery. The Constant-Murley scores, the Flexilevel Scale of Shoulder Function (Flex SF), scapular plane abduction, and strength were analyzed. Results: MRI results showed that the rotator cuff repair was intact in 85.7% (12/14) of the patients studied. Two patients had a Sugaya Type IV recurrent tear (2 of 14; 14.3%), which were both less than 1 cm. The Constant score increased from a preoperative mean of 49.72 (range 13–74) to a postoperative mean of 81.07 (range 45–92) (P value = 0.009). Flexilevel Scale of Shoulder Function (Flex SF) Score normalized to a 100-point scale improved from a preoperative mean of 53.69 to a postoperative mean of 79.71 (P value = 0.003). The Pain Score improved from a preoperative mean of 7.73 to a postoperative mean of 13.57 (P value = 0.008). Scapular plane abduction improved from a preoperative mean of 113.64° to a postoperative mean of 166.43° (P value = 0.010). The strength subset score improved from a preoperative mean of 1.73 kg to a postoperative mean of 7.52 kg (P value = 0.006). Conclusions: This study presents a safe and effective technique that may help improve the healing rates of large, massive, and revision rotator cuff tears with the use of an acellular human dermal allograft. This technique demonstrated favorable structural healing rates and statistically improved functional outcomes in the near term. Level of Evidence: 4. Retrospective case series. PMID

  18. Pertussis toxin-sensitive G-protein mediates the alpha 2-adrenergic receptor inhibition of melatonin release in photoreceptive chick pineal cell cultures

    SciTech Connect

    Pratt, B.L.; Takahashi, J.S.

    1988-07-01

    The avian pineal gland is a photoreceptive organ that has been shown to contain postjunctional alpha 2-adrenoceptors that inhibit melatonin synthesis and/or release upon receptor activation. Physiological response and (32P)ADP ribosylation experiments were performed to investigate whether pertussis toxin-sensitive guanine nucleotide-binding proteins (G-proteins) were involved in the transduction of the alpha 2-adrenergic signal. For physiological response studies, the effects of pertussis toxin on melatonin release in dissociated cell cultures exposed to norepinephrine were assessed. Pertussis toxin blocked alpha 2-adrenergic receptor-mediated inhibition in a dose-dependent manner. Pertussis toxin-induced blockade appeared to be noncompetitive. One and 10 ng/ml doses of pertussis toxin partially blocked and a 100 ng/ml dose completely blocked norepinephrine-induced inhibition. Pertussis toxin-catalyzed (32P)ADP ribosylation of G-proteins in chick pineal cell membranes was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Membranes were prepared from cells that had been pretreated with 0, 1, 10, or 100 ng/ml pertussis toxin. In the absence of pertussis toxin pretreatment, two major proteins of 40K and 41K mol wt (Mr) were labeled by (32P)NAD. Pertussis toxin pretreatment of pineal cells abolished (32P) radiolabeling of the 40K Mr G-protein in a dose-dependent manner. The norepinephrine-induced inhibition of both cAMP efflux and melatonin release, as assessed by RIA of medium samples collected before membrane preparation, was also blocked in a dose-dependent manner by pertussis toxin. Collectively, these results suggest that a pertussis toxin-sensitive 40K Mr G-protein labeled by (32P)NAD may be functionally associated with alpha 2-adrenergic signal transduction in chick pineal cells.

  19. Permanent brain damage and pertussis vaccination: is the end of the saga in sight?

    PubMed

    Griffith, A H

    1989-06-01

    The development and widespread uptake of a safe and efficacious aluminium adsorbed diphtheria-tetanus-pertussis vaccine (DTP) in the United States between 1933 and 1944 led to a gradual decline in whooping cough morbidity and instilled confidence in a vaccination programme which has been effectively maintained for over 40 years. T his contrasts with the turbulent history of pertussis vaccination in the United Kingdom where doubts as to the efficacy of available vaccines delayed their active national promotion until 1957, after which various reports resulted in further doubts over efficacy and safety. In 1974, the mass media became involved in the safety issue when the National Hospital for Sick Children case series of neurological events, which had occurred after DTP vaccination was made core material for a television documentary. The Department of Health and Social Security (DHSS) responded by establishing two retrospective studies of case records of post vaccination adverse events and two prospective studies. One of the latter, the National Childhood Encephalopathy Study (NCES) was regarded as the definitive case control study. A claim for damages, Loveday v Renton and The Wellcome Foundation, heard in the High Court of Justice in London, from early October 1987 until late February 1988 dealt with the general issue of whether, on the balance of probabilities, pertussis vaccine could cause permanent brain damage. The cornerstone of the claim that pertussis vaccine can cause permanent brain damage has always been the apparent clustering of onset of neurological disorders within the first 24-48 h after vaccination. One of the main finds of the NCES, however, which was not divulged in any published report but emerged in the course of the hearing, was that permanent brain damage did not occur within 48 h of DTP vaccination in any child in England, Scotland and Wales from mid-1976 to mid-1979 when 2 million doses of vaccine were used. The NCES, in this respect

  20. [Serological evaluation of Bordetella pertussis infection in adults with prolonged cough].

    PubMed

    Sönmez, Cemile; Çöplü, Nilay; Gözalan, Ayşegül; Yılmaz, Ülkü; Bilekli, Selen; Demirci, Nilgün Yılmaz; Biber, Çiğdem; Erdoğan, Yurdanur; Esen, Berrin; Çöplü, Lütfi

    2016-07-01

    Pertussis is a vaccine-preventable disease that is transmitted from infected to susceptible individuals by respiratory route. Bordetella pertussis infection may occur at any age as neither vaccine nor natural infection induced immunity lasts life-long. This study was planned to demonstrate the serological evidence of infection among adults, to raise awareness among clinicians and to provide data for the development of strategies to protect vulnerable infants. A total of 538 patients (345 female, 193 male) ages between 18-87 years who had a complain of prolonged cough for more than two weeks were included in the study. Anti-pertussis toxin (PT) IgG and anti-filamentous hemagglutinin (FH) IgG levels from single serum samples were measured by an in-house ELISA test which was standardized and shown to be efficient previously. Anti-PT IgG antibody levels of ≥ 100 EU/ml were considered as acute/recent infection with B.pertussis. In our study, 9.7% (52/538) of the patients had high levels of anti-PT IgG (≥ 100 EU/ml) and among those patients 43 (43/52; 82.7%) also had high (≥ 100 EU/ml) anti-FHA IgG levels. There were no statistically significant differences in terms of age, gender, education level, DPT (diphtheria-pertussis-tetanus) vaccination history, smoking history or average daily cigarette consumption (p> 0.05) between the cases with high antibody levels (n= 52). When the symptoms and the presence of cases with high antibody levels were evaluated, it was detected that no one parameter was significantly different from others, except that 24.1% of the cases with inspiratory whooping had high anti-PT levels. There was also no statistically significant difference between high anti-PT levels ≥ 100 EU/ml and the patients with risk factors [smoking (21/200; 10.5%), presence of disease that cause chronic cough and/or drug usage (19/171; %11.1), and whole factors which cause chronic cough (32/306; %10.5)] and without risk factors (p= 0.581; p= 0.357; p= 0

  1. Human keratinocyte growth and differentiation on acellular porcine dermal matrix in relation to wound healing potential.

    PubMed

    Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Königova, Radana; Matouskova, Eva

    2012-01-01

    A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7-10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing. PMID:22629190

  2. Cellular Response to a Novel Fetal Acellular Collagen Matrix: Implications for Tissue Regeneration

    PubMed Central

    Rennert, Robert C.; Garg, Ravi K.; Gurtner, Geoffrey C.

    2013-01-01

    Introduction. PriMatrix (TEI Biosciences Inc., Boston, MA, USA) is a novel acellular collagen matrix derived from fetal bovine dermis that is designed for use in partial- and full-thickness wounds. This study analyzes the cellular response to PriMatrix in vivo, as well as the ability of this matrix to facilitate normal tissue regeneration. Methods. Five by five mm squares of rehydrated PriMatrix were implanted in a subcutaneous fashion on the dorsum of wild-type mice. Implant site tissue was harvested for histology, immunohistochemistry (IHC), and flow cytometric analyses at multiple time points until day 28. Results. PriMatrix implants were found to go through a biological progression initiated by a transient infiltrate of inflammatory cells, followed by mesenchymal cell recruitment and vascular development. IHC analysis revealed that the majority of the implanted fetal dermal collagen fibers persisted through day 28 but underwent remodeling and cellular repopulation to form tissue with a density and morphology consistent with healthy dermis. Conclusions. PriMatrix implants undergo progressive in vivo remodeling, facilitating the regeneration of histologically normal tissue through a mild inflammatory and progenitor cell response. Regeneration of normal tissue is especially important in a wound environment, and these findings warrant further investigation of PriMatrix in this setting. PMID:23970899

  3. Treatment of severe burn with DermACELL®, an acellular dermal matrix

    PubMed Central

    Chen, Shyi-Gen; Tzeng, Yuan-Sheng; Wang, Chih-Hsin

    2012-01-01

    For treatment of skin burn injuries, there exist several methods of treatment related to tissue regeneration, including the use of autograft skin and cryopreserved skin. However, each method has drawbacks. An alternative method for tissue regeneration is allograft acellular dermal matrix, with potential as a biocompatible scaffold for new tissue growth. One recently produced material of this type is DermACELL®, which was used in this case presentation for treating a scar resulting from second- and third-degree burns in a 33-year-old female patient. The patient presented with significant hypertrophic scarring from the elbow to the hand and with limited wrist and elbow motion. The scarring was removed, and the patient was treated with a 1:3 mesh of DermACELL. The wound was resurfaced with a split thickness skin graft, and postoperative care included application of pressure garment and silicone sheet, as well as range of motion exercise and massage. At 30 days after DermACELL application, the wound appeared well-healed with little scar formation. At 180 days post-application, the wound continued to appear healed well without significant scar formation. Additionally, the wound was supple, and the patient experienced significant improvement in range of motion. In the case presented, DermACELL appears to have been a successful method of treatment for scarring due to severe burns by preventing further scar formation and improving range of motion. PMID:23071908

  4. Effect of dynamic seeding methods on the distribution of fibroblasts within human acellular dermis.

    PubMed

    Vitacolonna, Mario; Belharazem, Djeda; Hohenberger, Peter; Roessner, Eric D

    2015-12-01

    The purpose of this investigation was to compare different dynamic cell seeding methods regarding their seeding efficiency, homogeneity, infiltration depth and proliferation within a human acellular dermis. In addition, the growth behaviour was observed during a 12-day static in vitro culture. The dynamic methods included orbital-shaker seeding and the use of a plate centrifuge with different rotational speeds, combinations of low-pressure for matrix degassing and centrifugal seeding. Scaffolds were incubated for up to 12 days statically. Cell distribution and infiltration depth were analysed histologically at days 0, 4, 8 and 12. Seeding efficiency and cell proliferation were quantified with the MTT-assay at the same time points. Centrifugal seeding with 300g for 5 × 1 min combined with matrix degassing significantly increased the seeding efficiency and homogeneity compared to the other methods. However, following static culture, no cells were detectable after 4 days in the inner matrix zones. Furthermore, none of the degassing+centrifugation groups reached a significantly higher proliferation at day 8 compared to the reference. The use of a single dynamic method resulted in an inefficient cell seeding. We archived the highest seeding efficiency, homogeneity and infiltration depth using a combination of degassing+centrifugation at 300g for 5 × 1 min. PMID:25795264

  5. Calcification resistance for photooxidatively crosslinked acellular bovine jugular vein conduits in right-side heart implantation.

    PubMed

    Lü, Wei-Dong; Wang, An-Ping; Wu, Zhong-Shi; Zhang, Ming; Hu, Tie-Hui; Lei, Guang-Yan; Hu, Ye-Rong

    2012-10-01

    This study aimed to investigate the effect of decellularization plus photooxidative crosslinking and ethanol pretreatment on bioprosthetic tissue calcification. Photooxidatively crosslinked acellular (PCA) bovine jugular vein conduits (BJVCs) and their photooxidized controls (n = 5 each) were sterilized in a graded concentration of ethanol solutions for 4 h, and used to reconstruct dog right ventricular outflow tracts. At 1-year implantation, echocardiography showed similar hemodynamic performance, but obvious calcification for the photooxidized BJVC walls. Further histological examination showed intense calcium deposition colocalized with slightly degraded elastic fibers in the photooxidized BJVC walls, with sparsely distributed punctate calcification in the valves and other areas of walls. But PCA BJVCs had apparent degradation of elastic fibers in the walls, with only sparsely distributed punctate calcification in the walls and valves. Content assay demonstrated comparable calcium content for the two groups at preimplantation, whereas less calcium for the PCA group in the walls and similar calcium in the valvular leaflets compared with the photooxidized group at 1-year retrieval. Elastin content assay presented the conduit walls of PCA group had less elastin content at preimplantation, but similar content at 1-year retrieval compared with the photooxidized group. Phospholipid analysis showed phospholipid extraction by ethanol for the PCA group was more efficacious than the photooxidized group. These results indicate that PCA BJVCs resist calcification in right-side heart implantation owing to decellularization, further photooxidative crosslinking, and subsequent phospholipid extraction by ethanol at preimplantation. PMID:22615255

  6. Brainless but Multi-Headed: Decision Making by the Acellular Slime Mould Physarum polycephalum.

    PubMed

    Beekman, Madeleine; Latty, Tanya

    2015-11-20

    Because of its peculiar biology and the ease with which it can be cultured, the acellular slime mould Physarum polycephalum has long been a model organism in a range of disciplines. Due to its macroscopic, syncytial nature, it is no surprise that it has been a favourite amongst cell biologists. Its inclusion in the experimental tool kit of behavioural ecologists is much more recent. These recent studies have certainly paid off. They have shown that, for an organism that lacks a brain or central nervous system, P. polycephalum shows rather complex behaviour. For example, it is capable of finding the shortest path through a maze, it can construct networks as efficient as those designed by humans, it can solve computationally difficult puzzles, it makes multi-objective foraging decisions, it balances its nutrient intake and it even behaves irrationally. Are the slime mould's achievements simply "cute", worthy of mentioning in passing but nothing to take too seriously? Or do they hint at the fundamental processes underlying all decision making? We will address this question after reviewing the decision-making abilities of the slime mould. PMID:26189159

  7. Glycerolized Reticular Dermis as a New Human Acellular Dermal Matrix: An Exploratory Study.

    PubMed

    Ferrando, Pietro Maria; Balmativola, Davide; Cambieri, Irene; Scalzo, Maria Stella; Bergallo, Massimiliano; Annaratone, Laura; Casarin, Stefania; Fumagalli, Mara; Stella, Maurizio; Sapino, Anna; Castagnoli, Carlotta

    2016-01-01

    Human Acellular Dermal Matrices (HADM) are employed in various reconstructive surgery procedures as scaffolds for autologous tissue regeneration. The aim of this project was to develop a new type of HADM for clinical use, composed of glycerolized reticular dermis decellularized through incubation and tilting in Dulbecco's Modified Eagle's Medium (DMEM). This manufacturing method was compared with a decellularization procedure already described in the literature, based on the use of sodium hydroxide (NaOH), on samples from 28 donors. Cell viability was assessed using an MTT assay and microbiological monitoring was performed on all samples processed after each step. Two surgeons evaluated the biomechanical characteristics of grafts of increasing thickness. The effects of the different decellularization protocols were assessed by means of histological examination and immunohistochemistry, and residual DNA after decellularization was quantified using a real-time TaqMan MGB probe. Finally, we compared the results of DMEM based decellularization protocol on reticular dermis derived samples with the results of the same protocol applied on papillary dermis derived grafts. Our experimental results indicated that the use of glycerolized reticular dermis after 5 weeks of treatment with DMEM results in an HADM with good handling and biocompatibility properties. PMID:26918526

  8. Glycerolized Reticular Dermis as a New Human Acellular Dermal Matrix: An Exploratory Study

    PubMed Central

    Ferrando, Pietro Maria; Balmativola, Davide; Cambieri, Irene; Scalzo, Maria Stella; Bergallo, Massimiliano; Annaratone, Laura; Casarin, Stefania; Fumagalli, Mara; Stella, Maurizio; Sapino, Anna; Castagnoli, Carlotta

    2016-01-01

    Human Acellular Dermal Matrices (HADM) are employed in various reconstructive surgery procedures as scaffolds for autologous tissue regeneration. The aim of this project was to develop a new type of HADM for clinical use, composed of glycerolized reticular dermis decellularized through incubation and tilting in Dulbecco’s Modified Eagle’s Medium (DMEM). This manufacturing method was compared with a decellularization procedure already described in the literature, based on th