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The present work confirmed that B. pertussis infection or pertussis toxin produce hypoglycaemia in mice. The hypoglycaemia was associated with hyperinsulinaemia, and both were abolished by destruction of the pancreatic β cells with alloxan. Impaired glucose counterregulatory mechanisms may also contribute to pertussis-induced hypoglycaemia, as the hypoglycaemic action of insulin was prolonged in pertussis infected mice. On the other hand, impaired responsiveness to lower doses of insulin was found. Pertussis-induced hyperinsulinaemia had two components. First, the increase in serum insulin in response to food intake was both greater and more prolonged in pertussis-infected mice. Second, infected or pertussis toxin-treated animals, unlike controls, showed a marked increase in serum insulin in response to certain stresses, such as ether, histamine, anoxia and 2-deoxyglucose. However, other stresses (LPS, cold and hypoxia) did not cause hyperinsulinaemia in pertussis infected mice. Stress-induced hyperinsulinaemia was also seen in normal mice receiving the a2- adrenoceptor blocking drug idazoxan. Stress-induced hyperinsulinaemia in a2 adrenoceptor blocked mice, but not in pertussis-treated mice, was prevented by β adrenoceptor blockade using propranolol. Adrenal demedullation or ganglionic blockade (using hexamethonium) in normal mice also allowed stress induced hyperinsulinaemia. Thus, adrenal medullary catecholamines may normally serve to prevent stress induced hyperinsulinaemia, which becomes unmasked when they are absent or when their action is prevented. Stress-induced hyperinsulinaemia in pertussis treated mice was unlikely to involve autonomic, cholinergic oropioid mechanisms as it was not blocked by hexamethonium, atropine or naloxone. Human infants with pertussis showed no hypoglycaemia compared with non-pertussis controls, although their plasma insulin concentrations were slightly but significantly raised. It remains possible that hyperinsulinaemia with resultant profound hypoglycaemia might occur in susceptible patients following exposure to pertussis-toxin (either during the disease or following vaccination).

published_or_final_version / Community Medicine / Master / Master of Public Health

No description available.

Introduction: Bordetella pertussis is an important human pathogen that causes whooping cough (pertussis), an endemic illness responsible of significant morbidity and mortality, especially in infants and children. Worldwide, there are an estimated of 16 million cases of pertussis, resulting in about 195,000 child deaths per year. In Peru, pertussis is a major health problem that has been on the increase despite immunization efforts. The objective of this study was to determine the prevalence of B. pertussis among children under five years of age suspected to have whopping cough in Cajamarca, Peru. Methodology: Children diagnosed with whooping cough admitted to the Hospital Regional de Cajamarca from August 2010 to July 2013 were included. Nasopharyngeal samples were obtained for B. pertussis culture and polymerase chain reaction (PCR) detection. Results: In 133 children, the pertussis toxin and IS481 gene were detected in 38.35% (51/133) of the cases by PCR, while only 9.02% (12/133) of the Bordetella cultures were positive. The most frequent symptoms in patients with positive B. pertussis were paroxysm of coughing 68.63% (35/51), cyanosis 56.86% (29/51), respiratory distress 43.14% (22/51), and fever 39.22% (20/51). Pneumonia and acute bronchial obstructive syndrome were present in 17.65% (9/51) and 13.72% (7/51) of the cases, respectively. Conclusions: B. pertussis is responsible for an important proportion of whooping cough in hospitalized children in Cajamarca. Epidemiologic surveillance programs for B. pertussis are essential in Peru, especially in children who could most benefit from the vaccine.

Objectives To report the incidence, epidemiology, and clinical features of Bordetella pertussis in Peruvian infants under 1 year old. Patients and methods A prospective cross-sectional study was conducted in five hospitals in Peru from January 2010 to July 2012. A total of 392 infants under 1 year old were admitted with a clinical diagnosis of whooping cough and tested for B. pertussis by PCR. Results The pertussis toxin and IS481 genes were detected in 39.54% (155/392) of the cases. Infants aged less than 3 months were the most affected, with a prevalence of 73.55% (114/155). The most common household contact was the mother, identified in 20% (31/155) of cases. Paroxysm of coughing (89.03%, 138/155), cyanosis (68.39%, 106/155), respiratory distress (67.09%, 104/155), and breastfeeding difficulties (39.35%, 61/155) were the most frequent symptoms reported. Conclusion An increase in pertussis cases has been reported in recent years in Peru, despite national immunization efforts. Surveillance with PCR for B. pertussis is essential, especially in infants less than 1 year old, in whom a higher rate of disease-related complications and higher mortality have been reported. / This 312 work was supported by Sanofi Aventis del Peru. Conflict 313 of interest: On behalf of all authors, the corresponding author 314 states that there are no conflicts of interest or funding related 315 to this study

No description available.

Objective: Describe the prevalence of Bordetella pertussis via PCR in children under 5 years old hospitalized as probable cases of pertussis and report the most common clinical features among them. Results: A positive PCR result for B. pertussis was observed in 20.5% of our samples (18/88), one-third of them were from infants between 2 and 3 months old. The most common symptoms were paroxysms of coughing (88.9%), difficulty breathing (72.2%), cyanosis (77.8%) and fever (50%). The mother was the most common symptomatic carrier (27.8%), followed by uncles/aunts (22.2%) among children with pertussis. / This work was supported by fourth research incentive of the Universidad Peruana de Ciencias Aplicadas (UPC), Lima‑Peru. / Revisión por pares

Orientador: Maria Marluce dos Santos Vilela / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T01:20:12Z (GMT). No. of bitstreams: 1 Zorzeto_TatianeQueiroz_M.pdf: 1695884 bytes, checksum: 267f0534bc256440762ad9d78bc6402d (MD5) Previous issue date: 2008 / Resumo: A associação temporal de eventos adversos de variada gravidade à imunização com pertussis celular total (DTP) tem estimulado o desenvolvimento de vacinas antipertussis menos reatogênicas. Este ensaio clínico fase I visou à avaliação da imunogenicidade da vacina pertussis celular modificada pela extração do lipopolissacarídeo (DTPm) em comparação com a vacina convencional (DTP). Um total de 234 lactentes foi imunizado aos dois, quatro e seis meses de idade com DTPm ou DTP. Os títulos de anticorpos para os componentes pertussis, tétano, difteria e hepatite B foram determinados um mês após a terceira dose de vacina. A proliferação de células T CD3+ foi avaliada por citometria de fluxo após seis dias de cultivo de células mononucleares de sangue periférico estimuladas com células inativadas de B. pertussis ou com fitohemaglutinina (PHA). Células CD4+, CD8+ e TCR ?d+ foram identificadas no gate de blastos. Os níveis de IFN-?, TNF-a, IL-4 e IL-10 no sobrenadante de cultura foram quantificados por ensaio imunoenzimático (ELISA). A vacina modificada DTPm mostrou-se inferior à DTP quanto ao título de anticorpos antipertussis, mas não houve diferença de resposta aos outros componentes vacinais avaliados. A porcentagem líquida de blastos sob estímulo da B. pertussis foi menor no grupo que recebeu três doses de DTPm (mediana de 3,9% para DTPm e 6,2% para DTP, p=0,029), mas as freqüências de células CD4+, CD8+ e ?d+ em proliferação e as concentrações de citocinas não diferiram entre os grupos. A vacina DTPm não apresentou, portanto, imunogenicidade similar à da vacina DTP convencional nos ensaios laboratoriais / Abstract: Concerns about systemic reactions after immunization with whole-cell pertussis (wP) have stimulated efforts to produce less reactogenic vaccines. This phase I comparative trial aimed the efficacy evaluation of a cellular pertussis vaccine with low lipopolysaccharide (LPS) content (wPlow) in comparison to conventional wP vaccine. A total of 234 infants was vaccinated at 2, 4, and 6 months with conventional wP or wPlow. Serum antibody titers to pertussis, diphtheria, tetanus and hepatitis B were measured 1 month after the third dose of vaccine. Proliferation of CD3+ T cells was evaluated by flow cytometry after 6 days of peripheral blood mononuclear cells culture, with heat-killed B. pertussis or phytohemagglutinin (PHA) stimulation. CD4+, CD8+ and TCR ?d+ cells were identified in the gate of blast lymphocytes. IFN-?, TNF-a, IL-4 and IL-10 levels in supernatants were determined by ELISA. wPlow was inferior to wP in terms of anti-pertussis titers, but there was no diference in other serum antibody evaluations. Net percent blasts in cultures with B. pertussis was lower in the group vaccinated with wPlow (medians of 3.9% and for wPlow and 6.2% for wP; p=0.029), but the frequency of proliferating CD4+, CD8+ and ?d+ cells and the cytokine concentrations in supernatants were similar between vaccination groups. Therefore, wPlow wasn't as imunogenic as conventional wP in experimental evaluations / Mestrado / Saude da Criança e do Adolescente / Mestre em Saude da Criança e do Adolescente

This thesis is concerned with quantifying the dynamical role of stochasticity in models of recurrent epidemics. Although the simulation of stochastic models can accurately capture the qualitative epidemic patterns of childhood diseases, there is still considerable discussion concerning the basic mechanisms generating these patterns. The novel aspect of this thesis is the use of analytic methods to quantify the results from simulations. All the models are formulated as continuous time Markov processes, the temporal evolutions of which is described by a master equation. This is expanded in the inverse system size, which decomposes the full stochastic dynamics into a macroscopic part, described by deterministic equations, plus a stochastic fluctuating part. The first part examines the inclusion of non-exponential latent and infectious periods into the the standard susceptible-infectious-recovered model. The method of stages is used to formulate the problem as a Markov process and thus derive a power spectrum for the stochastic oscillations. This model is used to understand the dynamics of whooping cough, which we show to be the mixture of an annual limit cycle plus resonant stochastic oscillations. This limit cycle is generated by the time-dependent external forcing, but we show that the spectrum is close to that predicted by the unforced model. It is demonstrated that adding distributed infectious periods only changes the frequency and amplitude of the stochastic oscillations---the basic mechanisms remain the same. In the final part of this thesis, the effect of seasonal forcing is studied with an analysis of the full time-dependent master equation. The comprehensive nature of this approach allows us to give a coherent picture of the dynamics which unifies past work, but which also provides a systematic method for predicting the periods of oscillations seen in measles epidemics. In the pre-vaccination regime the dynamics are dominated by a period doubling bifurcation, which leads to large biennial oscillations in the deterministic dynamics. Vaccination is shown to move the system away from the biennial limit cycle and into a region where there is an annual limit cycle and stochastic oscillations, similar to whooping cough. Finite size effects are investigated and found to be of considerable importance for measles dynamics, especially in the biennial regime.