Targeted immunization to protect infants against pertussis in the United States

Pertussis is an infectious disease caused by the bacteria Bordetella pertussis, and is associated with a serious respiratory infection, a prolonged cough, and can require hospitalization. A vaccine for adolescents and adults has been available since 2005. This paper examines one recommended immunization strategy to prevent pertussis among infants, called “cocooning.” The strategy focuses on creating immunity among adult caregivers so they serve as a protective cocoon to the newborns, who are too young to be vaccinated. This paper looks at relevant studies summarizing implementation of cocooning strategies and addresses the question – Does the research literature support the view of using cocooning as an effective strategy to prevent pertussis in infants? After exclusions, 8 studies remained for synthesis. The evidence shows that cocooning is complex strategy and the evidence is mixed when it comes to ensuring an increase in immunization of caregivers. ^

Spatial analysis of pertussis cases in Harris County from 2005-2010

Objective: This study examined the recent trends and characteristics of reported pertussis in Harris County from 2005-2010. ^ Methods: The study population included surveillance data from all reported pertussis cases from January 1, 2005 to December 31, 2010 to Harris County Public Health and Environmental Services (HCPHES). We calculated incidence and attack rates for varying age groups, race/ethnicity, and gender. Spatial analyses were conducted of hot spot and cluster of incident cases in Harris County census tracts. Maps were constructed using geographic information system. ^ Results: Age-specific incidence rates of reported cases of pertussis were highest among infants under a year of age and lowest among adults age 20 and older. Hispanics represented the most cases reported compared to any other race or ethnic group (42% of 483 cases). Age-adjusted rates were highest in 2009 at 9.81 cases per 100,000 population. Only 31.2% of people received at least four of the recommended five doses of vaccine. Spatial analyses revealed statistically significant clusters within the northeast region of Harris County. ^ Conclusions: Hispanic infants are the most at risk group for pertussis. Although 70% of cases had a history of immunization, 41.8% of infants were appropriately vaccinated for their age. Increased vaccination coverage may decrease the incidence of pertussis.^

An investigation of pertussis cases in a Texas county from 2008 through 2012

Background: Once thought to be eradicated, pertussis is now making a steady comeback throughout Texas and the United States. Pertussis can have an effect on all demographics, but infants have the greatest health concern as they suffer the highest case-fatality rate. The objective of this study was to create and report a comprehensive summary of confirmed or probable pertussis cases in a Texas County during the 2008 through 2012 time period.^ Methods: A cross-sectional study design was used to show at risk populations in a Texas county using descriptive statistics of data from probable and confirmed pertussis cases in this Texas County from 2008-2012. Data was collected during routine pertussis investigations conducted by the local health department of this Texas County.^ Results: There was a sharp increase in pertussis cases seen in this county in 2012. Hispanics made up the majority of cases (74.9%) as compared to 12.8% of cases among Whites, 3.1% of cases among Blacks and 9.2% of cases among unknown/other. The population of Hispanics within this county was 58.9%. Almost a quarter of cases (24.2%) in this study were hospitalized. There was no difference identified in the proportion of male sources of exposure (48.9%) as compared to female (51.1%). Household contacts were the main sources of exposure: siblings (29.2%), fathers (14.5%), children (14.6%), and mothers (12.5%).^ Conclusion: Prevention intervention needs to be designed to target vulnerable populations and reduce the effect of this sometimes fatal disease. These results show pertussis proportionally has a greater effect on Hispanics. Additional research needs to be conducted on risk factors such as household crowding and immunization status among Hispanics to identify if ethnicity plays a role in risk of transmission of pertussis. The results were limited due to the large amount of missing data in vaccination history and identification of source of exposure.^

Toxina botulínica para la secreción descontrolada de saliva : presentación de un caso

La neurotoxina botulínica es producida por la bacteria anaerobia Clostridium botulinum (NTBo). Bloquea la transmisión neuromuscular por lo cual es utilizada para el tratamiento de enfermedades con hiperactividad muscular, bloqueando la liberación de acetilcolina y así la transmisión sináptica en la unión neuromuscular, lo que lleva al debilitamiento y atrofia de los músculos. Este mecanismo de acción motivó el uso de la toxina botulínica en las enfermedades con elevado tono muscular, como la distonía y la espasticidad, por lo cual también ha revolucionado la opción de tratamiento de los trastornos autónomos de hipersecreción. La sialorrea es un síntoma común en diversas enfermedades neurológicas. Las inyecciones de toxina botulínica, guiadas por ultrasonidos en las glándulas salivales, produce una disminución de la salivación excesiva en niños con deficiencias neurológicas como parálisis cerebral. La utilización de la toxina botulínica tipo A ha sido sugerida como tratamiento de la sialorrea en pacientes con parálisis cerebral (PC). Esta recomendación ha sido hecha por el efecto anticolinérgico de esta sustancia, principalmente por su capacidad para bloquear la liberación de acetilcolina a nivel de las membranas pre-sinápticas Aunque la respuesta al tratamrento es distinta en cada niño, en general se ha observado que cuanto más a menudo se utiliza la toxlna botulínica y más alta es la dosis utilizada, los resultados son mejores. Los expertos consideran conveniente el procedimiento porque muchos de estos pacientes están utilizando la toxina botulínica para sus problemas musculares y las distrntas condiciones pueden ser tratadas al mismo tiempo Se reporta la descripción de la aplicación de toxina botulínica en una paciente niña que concurre al Instituto de Rehabilitación Infantil TELETON de la ciudad de Valparaíso, Chile, con un trastorno motor severo y con salivación incontrolada persistente que provoca enfermedades respiratorias a repetición

Charge-dependent translocation of Bordetella pertussis adenylate cyclase toxin into eukaryotic cells: Implication for the in vivo delivery of CD8+ T cell epitopes into antigen-presenting cells

Bordetella pertussis secretes a calmodulin-activated adenylate cyclase toxin, CyaA, that is able to deliver its N-terminal catalytic domain (400-aa residues) into the cytosol of eukaryotic target cells, directly through the cytoplasmic membrane. We have previously shown that CyaA can be used as a vehicle to deliver T cell epitopes, inserted within the catalytic domain of the toxin, into antigen-presenting cells and can trigger specific class I-restricted CD8+ cytotoxic T cell responses in vivo. Here, we constructed a series of recombinant toxins harboring at the same insertion site various peptide sequences of 11–25 amino acids, corresponding to defined CD8+ T cell epitopes and differing in the charge of the inserted sequence. We show that inserted peptide sequences containing net negative charges (−1 or −2) decreased or completely blocked (charge of −4) the internalization of the toxin into target cells in vitro and abolished the induction of cytotoxic T cell responses in vivo. The blocking of translocation due to the inserted acidic sequences can be relieved by appropriate mutations in the flanking region of CyaA that counterbalance the inserted charges. Our data indicate that (i) the electrostatic charge of the peptides inserted within the catalytic domain of CyaA is critical for its translocation into eukaryotic cells and (ii) the delivery of T cell epitopes into the cytosol of antigen-presenting cells by recombinant CyaA toxins is essential for the in vivo stimulation of specific cytotoxic T cells. These findings will help to engineer improved recombinant CyaA vectors able to stimulate more efficiently cellular immunity.

The role of members of the pertussis toxin-sensitive family of G proteins in coupling receptors to the activation of the G protein-gated inwardly rectifying potassium channel

Inwardly rectifying potassium (K+) channels gated by G proteins (Kir3.x family) are widely distributed in neuronal, atrial, and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials, slowing the heart rate and modulating hormone release. They are directly activated by Gβγ subunits released from G protein heterotrimers of the Gi/o family upon appropriate receptor stimulation. Here we examine the role of isoforms of pertussis toxin (PTx)-sensitive G protein α subunits (Giα1–3 and GoαA) in mediating coupling between various receptor systems (A1, α2A, D2S, M4, GABAB1a+2, and GABAB1b+2) and the cloned counterpart of the neuronal channel (Kir3.1+3.2A). The expression of mutant PTx-resistant Gi/oα subunits in PTx-treated HEK293 cells stably expressing Kir3.1+3.2A allows us to selectively investigate that coupling. We find that, for those receptors (A1, α2A) known to interact with all isoforms, Giα1–3 and GoαA can all support a significant degree of coupling to Kir3.1+3.2A. The M4 receptor appears to preferentially couple to Giα2 while another group of receptors (D2S, GABAB1a+2, GABAB1b+2) activates the channel predominantly through Gβγ liberated from GoA heterotrimers. Interestingly, we have also found a distinct difference in G protein coupling between the two splice variants of GABAB1. Our data reveal selective pathways of receptor activation through different Gi/oα isoforms for stimulation of the G protein-gated inwardly rectifying K+ channel.

Induction of mucosal immune responses against a heterologous antigen fused to filamentous hemagglutinin after intranasal immunization with recombinant Bordetella pertussis.

Live vaccine vectors are usually very effective and generally elicit immune responses of higher magnitude and longer duration than nonliving vectors. Consequently, much attention has been turned to the engineering of oral pathogens for the delivery of foreign antigens to the gut-associated lymphoid tissues. However, no bacterial vector has yet been designed to specifically take advantage of the nasal route of mucosal vaccination. Herein we describe a genetic system for the expression of heterologous antigens fused to the filamentous hemagglutinin (FHA) in Bordetella pertussis. The Schistosoma mansoni glutathione S-transferase (Sm28GST) fused to FHA was detected at the cell surface and in the culture supernatants of recombinant B. pertussis. The mouse colonization capacity and autoagglutination of the recombinant microorganism were indistinguishable from those of the wild-type strain. In addition, and in contrast to the wild-type strain, a single intranasal administration of the recombinant strain induced both IgA and IgG antibodies against Sm28GST and against FHA in the bronchoalveolar lavage fluids. No anti-Sm28GST antibodies were detected in the serum, strongly suggesting that the observed immune response was of mucosal origin. This demonstrates, to our knowledge, for the first time that recombinant respiratory pathogens can induce mucosal immune responses against heterologous antigens, and this may constitute a first step toward the development of combined live vaccines administrable via the respiratory route.

A trace component of ginseng that inhibits Ca2+ channels through a pertussis toxin-sensitive G protein.

A crude extract from ginseng root inhibits high-threshold, voltage-dependent Ca2+ channels through an unknown receptor linked to a pertussis toxin-sensitive G protein. We now have found the particular compound that seems responsible for the effect: it is a saponin, called ginsenoside Rf (Rf), that is present in only trace amounts within ginseng. At saturating concentrations, Rf rapidly and reversibly inhibits N-type, and other high-threshold, Ca2+ channels in rat sensory neurons to the same degree as a maximal dose of opioids. The effect is dose-dependent (half-maximal inhibition: 40 microM) and it is virtually eliminated by pretreatment of the neurons with pertussis toxin, an inhibitor of G(o) and Gi GTP-binding proteins. Other ginseng saponins--ginsenosides Rb1, Rc, Re, and Rg1--caused relatively little inhibition of Ca2+ channels, and lipophilic components of ginseng root had no effect. Antagonists of a variety of neurotransmitter receptors that inhibit Ca2+ channels fail to alter the effect of Rf, raising the possibility that Rf acts through another G protein-linked receptor. Rf also inhibits Ca2+ channels in the hybrid F-11 cell line, which might, therefore, be useful for molecular characterization of the putative receptor for Rf. Because it is not a peptide and it shares important cellular and molecular targets with opioids, Rf might be useful in itself or as a template for designing additional modulators of neuronal Ca2+ channels.

Síndrome hemolítica urémica provocada por Escherichia coli produtora de toxina Shiga : a propósito de um caso clinico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Bexiga hiperactiva e utilização de toxina botulínica na hiperactividade do detrusor : resultados obtidos pelo Serviço de Urologia do HSM-CHLN

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Abordagem terapêutica da toxina botulínica em patologias das glândulas salivares

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Immunization with a circumsporozoite epitope fused to Bordetella pertussis adenylate cyclase in conjunction with cytotoxic T-lymphocyte-associated antigen 4 blockade confers protection against Plasmodium berghei liver-stage malaria

The adenylate cyclase toxoid (ACT) of Bordetella pertussis is capable of delivering its N-terminal catalytic domain into the cytosol of CD11b-expressing professional antigen-presenting cells such as myeloid dendritic cells. This allows delivery of CD8+ T-cell epitopes to the major histocompatibility complex (MHC) class I presentation pathway. Recombinant detoxified ACT containing an epitope of the Plasmodium berghei circumsporozoite protein (CSP), indeed, induced a specific CD8+ T-cell response in immunized mice after a single application, as detected by MHC multimer staining and gamma interferon (IFN-gamma) ELISPOT assay. This CSP-specific response could be significantly enhanced by prime-boost immunization with recombinant ACT in combination with anti-CTLA-4 during the boost immunization. This increased response was accompanied by complete protection in a number of mice after a challenge with P. berghei sporozoites. Transient blockade of CTLA-4 may overcome negative regulation and hence provide a strategy to enhance the efficacy of a vaccine by amplifying the number of responding T cells.

Parents guide to childhood immunization : diphtheria, tetanus (lockjaw), pertussis (whooping cough), polio, measles, mumps, rubella (German measles), haemophilus influenzae type B (hib).

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