Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection with the intracellular parasite Toxoplasma gondii renders cells resistant to multiple pro-apoptotic signals, but underlying mechanisms have not been delineated. The phosphoinositide 3-kinase (PI 3-kinase) pathway and the immediate downstream effector protein kinase B (PKB/Akt) play important roles in cell survival and apoptosis inhibition. Here, we show that Toxoplasma infection of mouse macrophages activates PKB/Akt in vivo and in vitro. In a mixed population of infected and non-infected macrophages, activation is only observed in parasite-infected cells. The PI 3-kinase inhibitors wortmannin and LY294002 block parasite-induced PKB phosphorylation. PKB activation occurs independently of Toll-like receptor adaptor protein MyD88 but uncoupling of Gi-protein-mediated signaling with pertussis toxin prevents PKB phosphorylation. Moreover, in the presence of PI 3-kinase inhibitors or pertussis toxin, not only PKB activation but also ERK1/2 activation during T. gondii infection is defective. Most importantly, the parasite's ability to induce macrophage resistance to pro-apoptotic signaling is prevented by incubation with PI 3-kinase inhibitors. This study demonstrates that T. gondii exploits host Gi-protein-dependent PI 3-kinase signaling to prevent induction of apoptosis in infected macrophages.
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PMID:Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis. 1663 8

On June 10, 2005, a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) formulated for use in adults and adolescents was licensed in the United States for persons aged 11-64 years (ADACEL, manufactured by sanofi pasteur, Toronto, Ontario, Canada). Prelicensure studies demonstrated safety and efficacy, inferred through immunogenicity, against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adults. To reduce pertussis morbidity among adults and maintain the standard of care for tetanus and diphtheria prevention and to reduce the transmission of pertussis to infants and in health-care settings, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adults aged 19-64 years should receive a single dose of Tdap to replace tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they received their last dose of Td >or=10 years earlier and they have not previously received Tdap; 2) intervals shorter than 10 years since the last Td may be used for booster protection against pertussis; 3) adults who have or who anticipate having close contact with an infant aged <12 months (e.g., parents, grandparents aged <65 years, child-care providers, and health-care personnel) should receive a single dose of Tdap to reduce the risk for transmitting pertussis. An interval as short as 2 years from the last Td is suggested; shorter intervals can be used. When possible, women should receive Tdap before becoming pregnant. Women who have not previously received Tdap should receive a dose of Tdap in the immediate postpartum period; 4) health-care personnel who work in hospitals or ambulatory care settings and have direct patient contact should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap. An interval as short as 2 years from the last dose of Td is recommended; shorter intervals may be used. These recommendations for use of Tdap in health-care personnel are supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC). This statement 1) reviews pertussis, tetanus and diphtheria vaccination policy in the United States; 2) describes the clinical features and epidemiology of pertussis among adults; 3) summarizes the immunogenicity, efficacy, and safety data of Tdap; and 4) presents recommendations for the use of Tdap among adults aged 19-64 years.
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PMID:Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. 1716 97

Infections represent a significant threat in solid-organ recipients. However, a certain number of infections can be prevented by immunizing patients before their transplantation. The aim of this study is to determine the level of immunity of children undergoing liver transplantation and to assess their capacity to maintain protective levels after surgery. Charts of 44 children transplanted with deceased donation livers between 1990 and 2002 at the Children's Hospital of Geneva were reviewed. Vaccine antibody responses were established pre- and post-transplantation. Only 43% of patients were up to date for diphtheria, tetanus, acellular pertussis, and polio vaccines at the pretransplantation visit, while 44% of children older than 12 months had received their required measles-mumps-rubella vaccines. Six of 44 children had received at least one dose of hepatitis B vaccine, while only two patients had received at least one dose of hepatitis A vaccine. After immunization, and one yr after transplantation, only 14 of 44 patients had detectable anti-HBs antibodies and seven of 18 had anti-HAV antibodies. Varicella antibodies were undetectable in 15 of 19 patients immunized prior to transplantation. This study highlights the need to enforce vaccination before transplantation, follow-up on vaccine- induced immunity, and adapt vaccination schedules after liver transplantation in children, especially for non-live vaccines, which are universally recommended in this population.
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PMID:Vaccine-induced immunity in children after orthotopic liver transplantation: a 12-yr review of the Swiss national reference center. 1723 21

Pertussis is not a notifiable disease in France. In addition to a paediatric hospital sentinel surveillance system, pertussis epidemiological data have, since 1996, been gathered through the voluntary notification of community clusters by general practitioners, and since 2001 by the statutory notification of nosocomial infection to the relevant local health authority. The local health authority forwards the information to the French National Institute for Surveillance (InVS). The objective of this study was to analyse pertussis data outside the routine paediatric hospital sentinel surveillance system. We gathered all the information concerning healthcare-associated infections and community clusters of pertussis (specific forms, investigation reports, emails etc.) reported to the InVS between 2000 and 2005. The InVS received and analysed 67 reports with a total of 595 cases. Almost half of the reports (n=31) came from hospitals, and healthcare workers were usually first affected. Control measures were put in place in 22 healthcare facilities and the average duration of an outbreak episode was 48 days. Outside healthcare facilities, clusters were reported also from 17 daycare facilities or schools and five workplaces. Among the 595 cases, six deaths occurred in children under seven months of age. Pertussis is still occurring in France and affects those who are not or who are no longer protected by the vaccine. Infection of infants within the household could be prevented if their parents and siblings were immunised. The number and size of pertussis clusters in hospitals could be reduced through immunisation of health staff, and timely and adequate outbreak management.
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PMID:Nosocomial infections and community clusters of pertussis in France, 2000-2005. 1800 52

Infection control has a particularly important role in paediatric hospitals and must take into account the specificity of the needs and environment of the paediatric patient. Children are susceptible to infections that are prevented in older patients by vaccination or previous natural exposure. Consequently, the nosocomial pathogens and most common health-care-associated infection sites in children differ from those observed among adults. The immunological naivety of young children, especially neonates, translates into an enhanced susceptibility to many infections with important health consequences as well as higher rates and longer duration of microorganism shedding. In particular, respiratory virus infections, rotavirus, varicella zoster virus, and pertussis represent persistent challenges in children's hospitals. Specific factors such as the use of breastmilk, toys, or therapy animals are associated with an increased risk for health-care-associated infections. We review the emergence of antimicrobial-resistant organisms and strategies to prevent health-care-associated infections in the paediatric setting.
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PMID:Infection control in paediatrics. 1815 87

African trypanosomes of the Trypanosoma brucei species are extra-cellular parasites that cause human African trypanosomiasis (HAT) as well as infections in game animals and livestock. Trypanosomes are known to evade the immune response of their mammalian host by continuous antigenic variation of their surface coat. Here, we aim to demonstrate that in addition, trypanosomes (i) cause the loss of various B cell populations, (ii) disable the hosts' capacity to raise a long-lasting specific protective anti-parasite antibody response, and (iii) abrogate vaccine-induced protective response to a non-related human pathogen such as Bordetella pertussis. Using a mouse model for T. brucei, various B cell populations were analyzed by FACS at different time points of infection. The results show that during early onset of a T. brucei infection, spleen remodeling results in the rapid loss of the IgM(+) marginal zone (IgM(+)MZ) B cell population characterized as B220(+)IgM(High)IgD(Int) CD21(High)CD23(Low)CD1d(+)CD138(-). These cells, when isolated during the first peak of infection, stained positive for Annexin V and had increased caspase-3 enzyme activity. Elevated caspase-3 mRNA levels coincided with decreased mRNA levels of the anti-apoptotic Bcl-2 protein and BAFF receptor (BAFF-R), indicating the onset of apoptosis. Moreover, affected B cells became unresponsive to stimulation by BCR cross-linking with anti-IgM Fab fragments. In vivo, infection-induced loss of IgM(+) B cells coincided with the disappearance of protective variant-specific T-independent IgM responses, rendering the host rapidly susceptible to re-challenge with previously encountered parasites. Finally, using the well-established human diphtheria, tetanus, and B. pertussis (DTPa) vaccination model in mice, we show that T. brucei infections abrogate vaccine-induced protective responses to a non-related pathogen such as B. pertussis. Infections with T. brucei parasites result in the rapid loss of T-cell independent IgM(+)MZ B cells that are normally functioning as the primary immune barrier against blood-borne pathogens. In addition, ongoing trypanosome infections results in the rapid loss of B cell responsiveness and prevent the induction of protective memory responses. Finally, trypanosome infections disable the host's capacity to recall vaccine-induced memory responses against non-related pathogens. In particular, these last results call for detailed studies of the effect of HAT on memory recall responses in humans, prior to the planning of any mass vaccination campaign in HAT endemic areas.
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PMID:Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses. 1851

On July 10, 2004, staff members at a children's hospital in Texas noted that six infants with pertussis diagnosed by clinical symptoms and confirmed by polymerase chain reaction (PCR) testing had all been born during June 4-16 at the same area general hospital. The infants had symptoms consistent with pertussis, including cough, congestion, cyanosis, emesis, or apnea. Infection-control personnel at the general hospital (general hospital A), children's hospital (children's hospital A), and the county health department investigated and determined that an outbreak of pertussis among 11 newborns at general hospital A had occurred after direct exposure to a health-care worker (HCW) with pertussis. This report describes the outbreak investigation and highlights the importance of following recommendations to administer tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine to HCWs to prevent transmission of pertussis to patients.
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PMID:Hospital-acquired pertussis among newborns--Texas, 2004. 1852 16

The African economy will only be able to develop significantly if several public health issues are first addressed. The infantile mortality rate is an excellent index of a population's overall health status. Infections being responsible for more than 60% of deaths, vaccination is crucial. The Expanded Program of Immunization (EPI) (Programme Elargi de Vaccination) launched in 1974 has avoided countless deaths. Until the early 1990s, vaccine coverage of the program's target diseases (tuberculosis, diphtheria, tetanus, pertussis, poliomyelitis, measles, yellow fever and hepatitis B) increased rapidly. It then began to decline, however, owing to financial, sociopolitical and vaccine supply problems. Since 2000, this downward trend has been partially reversed, notably through the creation of GAVI and the development of vaccines industries in poor countries. The outlook is brighter now than it has been for some time.
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PMID:[Vaccination and development in sub-Saharian Africa]. 1866 58

Infections represent an important risk for pediatric transplant recipients. Many infections are preventable through immunization, and ongoing studies are working on increasing the number of available vaccines for these children either before or after transplantation. We examine new immunization schedules (such as pertussis vaccines in teenagers) and newly available vaccines (such as human papillomavirus vaccine), and suggest how to deliver them in pediatric transplant candidates or recipients. We also review less common vaccines (such as encephalitis vaccines), and possible vaccines of the future that could have an important clinical impact in these children, such as CMV or EBV vaccines.
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PMID:Immunization and transplantation--what is new and what is coming? 1903 8

Infection of macrophages with Leishmania parasites does not result in the production of IL-12. In addition, infection with Leishmania suppresses IL-12 production elicited by otherwise potent activators of IL-12. We provide evidence that engagement of phosphatidyl inositol-3 kinase (PI3K) signaling during Leishmania amazonensis infection leads to the prevention of IL-12 p70 production at the level of transcription of its p40 subunit in bone marrow derived macrophages (BMDMPhi). Inhibition of PI3K signaling with specific inhibitors of PI3K or the downstream kinase Akt, reverses the IL-12 blockade. Although the MAP kinase ERK (p44 and p42) was transiently activated by infection with L. amazonensis, inhibition of MEK, the kinase upstream of ERK, with PD98059, did not reverse the blockade of IL-12. Furthermore, inhibition of the other MAP kinases JNK and p38 as well as treatment of cells with pertussis toxin that blocks G protein mediated signaling, did not reverse the prevention of IL-12 production by Leishmania infection. Interestingly, activation of PI3K/Akt signaling had differential effects on ERK and p38 activation. Taken together we propose that infection of BMDMPhi with Leishmania promastigotes activates both positive and negative signaling pathways that control IL-12 production. PI3K signaling activated by the infection is the negative signaling pathway that prevents IL-12 production.
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PMID:Activation of PI3K/Akt signaling has a dominant negative effect on IL-12 production by macrophages infected with Leishmania amazonensis promastigotes. 1918 78


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