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

Pertussis, once a serious respiratory disease in children, has recently been identified as a common cause of chronic cough in adults. Military personnel are known to be vulnerable to this disease. After a training barracks exposure to pertussis, routine arrangements for contact prophylaxis with erythromycin failed. This experience is reported here as well as that of our subsequent aggressive attempts using directly observed prophylaxis (DOP) with standard erythromycin regimens. No secondary cases occurred. However, many contacts (35%) could not finish a 14-day course despite DOP, mostly because of nausea (85%) or diarrhea (72%). Seventeen (18%) soldiers missed classes because of erythromycin side effects; five required emergency department visits or hospital admission for the same. Sixteen (17%) soldiers were switched to azithromycin because of side effects; all were able to complete a 14-day course without symptoms. High adherence rates with erythromycin administration using DOP are attainable but may trigger unacceptable toxicities; alternative prophylactic regimens should be considered for active duty personnel.
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PMID:Experience with directly observed prophylaxis using erythromycin in military trainees exposed to pertussis. 1528 68

Respiratory disease caused by atypical bacteria remains an important cause of morbidity and mortality for adults and children, despite the widespread use of effective antimicrobials agents. Culture remains the "gold standard" for the detection of these agents. However, culture is labor-intensive, takes several days to weeks for growth, and can be very insensitive for the detection of some of these organisms. Newer singleplex PCR diagnostic tests are sensitive and specific, but multiple assays would be needed to detect all of the common pathogens. Therefore, we developed the Pneumoplex assays, a multiplex PCR-enzyme hybridization assay (the standard assay) and a multiplex real-time assay to detect the most common atypical pathogens in a single test. Primer and probe sequences were designed from conserved regions of specific genes for each of these organisms. The limits of detection were as follows: for Bordetella pertussis, 2 CFU/ml; for Legionella pneumophila (serotypes 1 to 15) and Legionella micdadei, 9 and 80 CFU/ml, respectively; for Mycoplasma pneumoniae, 5 CFU/ml; and for Chlamydia (Chlamydophila) pneumoniae, 0.01 50% tissue culture infective doses. Recombinant DNA controls for each of these organisms were constructed, and the number of copies for each DNA control was calculated. The Pneumoplex could detect each DNA control down to 10 copies/ml. The analytical specificity demonstrated no cross-reactivity between 23 common respiratory pathogens. One hundred twenty-five clinical bronchoalveolar lavage fluid samples tested by the standard assay demonstrated that the Pneumoplex yielded a sensitivity and a specificity of 100 and 98.5%, respectively. This test has the potential to assist clinicians in establishing a specific etiologic diagnosis before initiating therapy, to decrease hospital costs, and to prevent inappropriate antimicrobial therapy.
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PMID:The pneumoplex assays, a multiplex PCR-enzyme hybridization assay that allows simultaneous detection of five organisms, Mycoplasma pneumoniae, Chlamydia (Chlamydophila) pneumoniae, Legionella pneumophila, Legionella micdadei, and Bordetella pertussis, and its real-time counterpart. 1569 46

Bordetella pertussis, B. parapertussis, and B. bronchiseptica are closely related species associated with respiratory disease in humans and other mammals. While B. bronchiseptica has a wide host range, B. pertussis and B. parapertussis evolved separately from a B. bronchiseptica-like progenitor to naturally infect only humans. Despite very different doubling times in vitro, all three establish similar levels of infection in the mouse lung within 72 h. Recent work has revealed separate roles for Toll-like receptor 4 (TLR4) in immunity to B. pertussis and B. bronchiseptica, while no role for TLR4 during B. parapertussis infection has been described. Here we compared the requirement for TLR4 in innate host defense to these organisms using the same mouse infection model. While B. bronchiseptica causes lethal disease in TLR4-deficient mice, B. pertussis and B. parapertussis do not. Correspondingly, TLR4 is critical in limiting B. bronchiseptica but not B. pertussis or B. parapertussis bacterial numbers during the first 72 h. Interestingly, B. bronchiseptica induces a TLR4-dependent cytokine response that is considerably larger than that induced by B. pertussis or B. parapertussis. Analysis of their endotoxins using RAW cells suggests that B. bronchiseptica lipopolysaccharide (LPS) is 10- and 100-fold more stimulatory than B. pertussis or B. parapertussis LPS, respectively. The difference in LPS stimulus is more pronounced when using HEK293 cells expressing human TLR4. Thus, it appears that in adapting to infect humans, B. pertussis and B. parapertussis independently modified their LPS to reduce TLR4-mediated responses, which may compensate for slower growth rates and facilitate host colonization.
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PMID:Comparative toll-like receptor 4-mediated innate host defense to Bordetella infection. 1629 9

Pertussis is an infectious respiratory disease for which mass vaccination is an effective preventive strategy. In many developed countries, where high vaccination coverage has been maintained for approximately 50 years, re-emergence of the disease has been observed in all age groups. In the municipality of Rio de Janeiro (RJ), where vaccination started in the 1980s, surveillance data show no sign of disease re-emergence. We developed a mathematical model that incorporates the major demographic aspects of a large urban centre in a developing nation, in addition to the most important epidemiological aspects of disease transmission. Parameter values were estimated based on RJ demographic and vaccine coverage data. Overall, all vaccination strategies determined a major decrease (over 95% decrease when compared to the pre-vaccine era) in the incidence of primary infections (occurring in individuals who have never been immunized through infection or vaccine). On the other hand, the strategies (a) three doses at age 2-11 months, (b) three doses plus booster at age 12-23 months, (c) three doses plus booster at age 4-5 years, and (d) three doses plus both boosters, differently affected the incidence of secondary infections (occurring in previously infected/vaccinated individuals). Given that the immunity against pertussis wanes with time and that the infectious agent has not been eliminated from the population, it is expected that pertussis will continue to be a problem in RJ. Actually, since immunity acquired from vaccine wanes faster than disease-acquired immunity and the possibility of natural boosters has decreased with mass vaccination, an increase in the incidence of secondary infections among older age groups is expected (and predicted by the model). Possible explanations as to why this dynamics is not captured by the RJ surveillance system are discussed. A poorly effective surveillance system and a lack of awareness regarding loss of immunity and the possibility of pertussis infection in older age groups are among them. Finally, we bring attention to the need of (i) field studies for the measurement of pertussis incidence in adolescents and adults; (ii) better understanding of the transmission dynamics currently occurring in RJ, and (iii) re-evaluation of vaccination strategies with the possible introduction of acellular vaccines for the vaccination of older individuals.
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PMID:A modelling analysis of pertussis transmission and vaccination in Rio de Janeiro, Brazil. 1631 89

Bordetella pertussis, the causative agent of the acute childhood respiratory disease whooping cough, is a human-adapted variant of Bordetella bronchiseptica, which displays a broad host range and typically causes chronic, asymptomatic infections. These pathogens express a similar but not identical surface-exposed and secreted protein called filamentous hemagglutinin (FHA) that has been proposed to function as both a primary adhesin and an immunomodulator. To test the hypothesis that FHA plays an important role in determining host specificity and/or the propensity to cause acute versus chronic disease, we constructed a B. bronchiseptica strain expressing FHA from B. pertussis (FHA(Bp)) and compared it with wild-type B. bronchiseptica in several natural-host infection models. FHA(Bp) was able to substitute for FHA from B. bronchiseptica (FHA(Bb)) with regard to its ability to mediate adherence to several epithelial and macrophage-like cell lines in vitro, but it was unable to substitute for FHA(Bb) in vivo. Specifically, FHA(Bb), but not FHA(Bp), allowed B. bronchiseptica to colonize the lower respiratory tracts of rats, to modulate the inflammatory response in the lungs of immunocompetent mice, resulting in decreased lung damage and increased bacterial persistence, to induce a robust anti-Bordetella antibody response in these immunocompetent mice, and to overcome innate immunity and cause a lethal infection in immunodeficient mice. These results indicate a critical role for FHA in B. bronchiseptica-mediated immunomodulation, and they suggest a role for FHA in host specificity.
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PMID:Bordetella filamentous hemagglutinin plays a critical role in immunomodulation, suggesting a mechanism for host specificity. 1633 99

Innate immunity plays an important role in protection against respiratory infections in humans and animals. Host defense peptides such as beta-defensins represent major components of innate immunity. We recently developed a novel porcine model of pertussis, an important respiratory disease of young children and infants worldwide. Here, we investigated the role of porcine beta-defensin 1 (pBD-1), a porcine defensin homologue of human beta-defensin 2, in conferring protection against respiratory infection with Bordetella pertussis. In this model, newborn piglets were fully susceptible to infection and developed severe bronchopneumonia. In contrast, piglets older than 4 weeks of age were protected against infection with B. pertussis. Protection was associated with the expression of pBD-1 in the upper respiratory tract. In fact, pBD-1 expression was developmentally regulated, and the absence of pBD-1 was thought to contribute to the increased susceptibility of newborn piglets to infection with B. pertussis. Bronchoalveolar lavage specimens collected from older animals as well as chemically synthesized pBD-1 displayed strong antimicrobial activity against B. pertussis in vitro. Furthermore, in vivo treatment of newborn piglets with only 500 mug pBD-1 at the time of challenge conferred protection against infection with B. pertussis. Interestingly, pBD-1 displayed no bactericidal activity in vitro against Bordetella bronchiseptica, a closely related natural pathogen of pigs. Our results demonstrate that host defense peptides play an important role in protection against pertussis and are essential in modulating innate immune responses against respiratory infections.
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PMID:The host defense peptide beta-defensin 1 confers protection against Bordetella pertussis in newborn piglets. 1655 64

The incidence of B pertussis has increased by 50% from the 1980s to the 1990s, primarily among those aged 4 months and younger. Worldwide, pertussis is a significant cause of infectious mortality with 40 million cases and 400.000 deaths. Most of these cases and deaths occur in infancy. Symptoms vary from common cold in adults to respiratory distress in infants. Non immune babies with respiratory disease and significant lymphocytosis should be considered to have pertussis until proven otherwise. The onset of severe pulmonary hypertension during B pertussis pneumonia is frequenly rapid and relentless. Exchange-transfusion can be life-saving by reducing the leucocyte mass. Classic vaccination or boosters given to adults and adolescents would reduce the spread from parents tho infants, but a new vaccination schedule is under investigation at Vanderbilt Children's Hospital to give baby's first pertussis vaccination at birth?
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PMID:[Clinical case of the month. Fatal pertussis infection in a 2 month old infant]. 1668 Sep 98

Pertussis, or whooping cough, is a highly infectious, nationally notifiable respiratory disease associated with prolonged cough illness and paroxysms of coughing, inspiratory "whoop," or posttussive vomiting. Reported pertussis cases have tripled in the United States since 2001, with 25,616 probable or confirmed cases reported in 2005. This increase has been attributed to increased circulation of Bordetella pertussis, waning vaccine-induced immunity among adults and adolescents, heightened awareness of pertussis among health-care providers, increased public health reporting, and increased use of polymerase chain reaction (PCR) testing for diagnosis. To minimize the spread of pertussis, control measures must be implemented early in the course of illness when the risk for transmission is highest. However, diagnosis of pertussis is complicated by nonspecific signs and symptoms, particularly in the early catarrhal stage of disease. In addition, the lack of rapid, sensitive, and specific laboratory tests makes early and accurate identification of pertussis challenging. This report describes two hospital outbreaks and one community outbreak of respiratory illness during 2004-2006 in New Hampshire, Massachusetts, and Tennessee that were attributed initially to pertussis. However, subsequent investigations revealed negative or equivocal laboratory results and epidemiologic and clinical features atypical of pertussis, suggesting that pertussis was not the cause of these outbreaks. The findings in this report underscore the need for thorough epidemiologic and laboratory investigation of suspected pertussis outbreaks when considering extensive control measures.
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PMID:Outbreaks of respiratory illness mistakenly attributed to pertussis--New Hampshire, Massachusetts, and Tennessee, 2004-2006. 1771 12

Pertussis, a respiratory disease caused by infection with Bordetella pertussis, represents one of the most devastating diseases in infants and young children worldwide. Significant research efforts over the last five decades have led to the introduction of two types of vaccines, which are now available worldwide and which have significantly reduced the global incidence of pertussis. The use of animal models and, in particular, the mouse model has benefited in the development of these vaccines tremendously. However, open questions regarding the duration of immunity, the type of immune response needed for protection and the role of mucosal and innate immunity in disease protection still remain. Here, we review the various animal models available currently and their benefits for studying this important disease.
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PMID:The benefits of using diverse animal models for studying pertussis. 1792 Feb 73

Bordetella pertussis causes whooping cough, an endemic respiratory disease that is increasing in prevalence despite vaccination efforts. Although host immunity is modulated by virulence factors of this pathogen, it is unclear what host factors are required to overcome their effects. Here, we investigate an apparent relationship between the effects of pertussis toxin and tumor necrosis factor (TNF)- alpha . B. pertussis grew efficiently and caused moderate pathology in wild-type mice, whereas TNF- alpha (-/-) mice had higher numbers of bacteria and leukocytes in lungs, experienced more airway resistance, and died of the infection. Interestingly, an isogenic B. pertussis strain lacking pertussis toxin did not induce these effects in TNF- alpha (-/-) mice and behaved similarly in wild-type and TNF- alpha -deficient hosts. Together, these results indicate that TNF- alpha is essential for the host to overcome the effects of pertussis toxin, allowing both control of B. pertussis numbers and regulation of the inflammation induced by infection.
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PMID:Delayed role of tumor necrosis factor- alpha in overcoming the effects of pertussis toxin. 1795 42


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