Experiments Upon the Cause of Whooping Cough

Rich, Arnold R.; Long, Perrin H.; Brown, J. Howard; Bliss, Eleanor A.; Holt, L. Emmett

doi:10.1126/science.76.1971.330

Cited by 25 publications

(12 citation statements)

References 2 publications

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“…While these models are useful for studying certain aspects of pertussis, none of them adequately reproduces the full spectrum of the disease observed in humans. Previously published studies reported that nonhuman primates develop all of the characteristic markers of human pertussis (5,13,16,21,22,24). However, these studies were published more than 50 years ago, with limited experimental detail, making it difficult to critically evaluate or reproduce these models.…”

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confidence: 98%

Nonhuman Primate Model of Pertussis

et al. 2012

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bPertussis is a highly contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis. Despite nearly universal vaccine coverage, pertussis rates in the United States have been rising steadily over the last 20 years. Our failure to comprehend and counteract this important public health concern is due in large part to gaps in our knowledge of the disease and the mechanisms of vaccine-mediated protection. Important questions about pertussis pathogenesis and mechanisms of vaccine effectiveness remain unanswered due to the lack of an animal model that replicates the full spectrum of human disease. Because current animal models do not meet these needs, we set out to develop a nonhuman primate model of pertussis. We inoculated rhesus macaques and olive baboons with wild-type B. pertussis strains and evaluated animals for clinical disease. We found that only 25% of rhesus macaques developed pertussis. In contrast, 100% of inoculated baboons developed clinical pertussis. A strong anamnestic response was observed when convalescent baboons were infected 6 months following recovery from a primary infection. Our results demonstrate that the baboon provides an excellent model of clinical pertussis that will allow researchers to investigate pertussis pathogenesis and disease progression, evaluate currently licensed vaccines, and develop improved vaccines and therapeutics. Whooping cough is a highly contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis (for a review, see references 10 and 17). The introduction of pertussis vaccines in the 1940s and nationwide coverage in excess of 95% led to a dramatic decrease in the incidence of the disease. However, for unexplained reasons, pertussis rates in the United States have been rising steadily over the last 20 years for infants, children, and adolescents (1). With more than 21,000 reported cases in the United States in 2010, the highest number since the 1950s, pertussis is the most common of the vaccine-preventable diseases (2). This resurgence is mirrored throughout the industrial world, despite similar high rates of vaccination (12,20,31). Several hypotheses have been suggested for the increase in cases, but there is no consensus within the scientific community (9). Our failure to comprehend and counteract this important public health concern is due in large part to gaps in our knowledge of the disease and the mechanisms of vaccine-mediated protection. In order to fill these gaps, a good animal model of pertussis is required.In humans, infection with B. pertussis results in a wide spectrum of clinical manifestations that depends on the age and immune status of the host and ranges from mild respiratory symptoms to a severe cough illness which may be accompanied by the hallmark inspiratory whoop and posttussive emesis (4). Clinical signs include high leukocytosis, hypoglycemia, and reduced pulmonary capacity. Because of the acute nature of pertussis infections and because B. pertussis is a strict human pathogen with...

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confidence: 98%

Nonhuman Primate Model of Pertussis

et al. 2012

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“…Manuscript in preparation]. To a limited scale, results could be refined and confirmed in nonhuman primate studies [97,106,[109][110][111]. Recently, Warfel et al developed a novel pertussis infection model in Olive baboons (Papio anubis) [123].…”

Section: Infection Modelsmentioning

confidence: 99%

“…Also, all experimental animal species will have lifespan restrictions when testing durability of protection. Moreover, no model, not even the human, has disclosed a defined correlate or surrogate of protection for pertussis (Table 1) [12,18,22,[96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113].…”

Section: Expert Commentarymentioning

confidence: 99%

“…Pertussis animal models imply various animal species, each allowing the assessment of one or more experimental parameters, such as strain pathogenicity, host response to infection, or immunogenicity and effectiveness of candidate or registered vaccines, but also having their limitations (Table 1) [95,96]. For instance, nonhuman primates are the most suitable experimental animals for pathogenicity research since these animals can display classical whooping cough or persistent coughing [97,106,[109][110][111]. When compared with rodents their immune responses are likely more similar to humans, and these animals live longer, allowing duration of protection to be studied over time.…”

Section: Expert Commentarymentioning

confidence: 99%

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Resurgence of pertussis calls for re-evaluation of pertussis animal models

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Hozbor²,

Cj³

et al. 2012

Expert Review of Vaccines

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“…As dúvidas existentes, desde há muitos anos, relativamente a etiologia em casos com sintomatologia de coqueluche, in-cluindo uma possível participação viral, provocaram a realização de inúmeras pesquisas. Assim, através da inoculação de B. pertussis, SAUER & HAMBRECHT 57 (1929) e RICH et al 54 (1932), reproduziram o quadro de coqueluche em macacos enquanto que MAC DONALD & MAC DONALD 43 (1933) o fizeram através da infecção experimental em crianças. Por outro lado, McCoRDocK 42 (1932) relatou o encontro de inclusões intranucleares nas células pulmonares de crianças com sintomas de coqueluche, sugerindo uma possível participação viral nesta doença.…”

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Isolamento de bactérias do gênero Bordetella e provas sorológicas, a partir de crianças com sintomas de coqueluche, atendidas no Hospital de Isolamento Emílio Ribas de São Paulo

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1973

Rev. Saúde Pública

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A partir de 255 crianças com sintomas de coqueluche atendidas no Hospital de Isolamento Emílio Ribas de São Paulo, procedeu-se a pesquisa de bactérias do gênero Bordetella. Em 46 delas, determinou-se, também, a elevação dos níveis de anticorpos circulantes aglutinantes e fixadores de complemento contra a B. pertussis, aglutinantes contra a B. parapertussis e fixadores de complemento contra adenovirus. Por outro lado, relacionaram-se os resultados do exame bacteriológico com o período da doença, em semanas, e com alguns sintomas principais apresentados. Foram também relacionados os resultados das provas bacteriológica e sorológica com a confirmação clínica do diagnóstico. Foram discutidos, por outro lado, o valor e as limitações das provas bacteriológica e sorológica no diagnóstico laboratorial da coqueluche.

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Experiments Upon the Cause of Whooping Cough

Cited by 25 publications

References 2 publications

Nonhuman Primate Model of Pertussis

Nonhuman Primate Model of Pertussis

Resurgence of pertussis calls for re-evaluation of pertussis animal models

Isolamento de bactérias do gênero Bordetella e provas sorológicas, a partir de crianças com sintomas de coqueluche, atendidas no Hospital de Isolamento Emílio Ribas de São Paulo

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