Experimental Pertussis

Macdonald, H.; Macdonald, Eleanor J.

doi:10.1093/infdis/53.3.328

Cited by 36 publications

(7 citation statements)

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“…In contrast, humans are likely infected with a smaller inoculum via contact or aerosols, exhibiting comparable clinical symptoms 2–3 weeks after infection (28). This is similar to baboons experimentally infected by contact or aerosol transmission, who showed peak WBC several weeks after infection (29).…”

Section: Discussionmentioning

confidence: 99%

A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

et al. 2015

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In spite of wide-spread vaccination, pertussis rates are rising in industrialized countries and remain high world-wide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. Here, we humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human IgG1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the B. pertussis-induced rise in white blood cell count and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated but not control animals experienced a blunted rise in white blood cell count and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care.

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Section: Discussionmentioning

confidence: 99%

A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

et al. 2015

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“…A paediatric Bp human challenge study was performed in 1933 in which two naive and two vaccinated children were exposed to 140 cfu of intranasal Bp. 21 While the vaccinated children did not develop whooping cough, the naive children developed severe disease including anorexia, fever, severe paroxysmal cough, leucocytosis, lymphocytosis and positive cough plate cultures. They received no treatment and improved by day 35.…”

Section: Discussionmentioning

confidence: 96%

InvestigatingBordetella pertussiscolonisation and immunity: protocol for an inpatient controlled human infection model

et al. 2017

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IntroductionWe summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. Globally Bordetella pertussis is one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage. The acellular vaccine provides relatively short-lived immunity and, in contrast to whole cell vaccines, may be less effective against colonisation and subsequent transmission. To improve vaccine strategies, a greater understanding of human B. pertussis colonisation is required. This article summarises a protocol and does not contain any results.Methods and analysisA controlled human colonisation model will be developed over two phases. In phase A, a low dose of the inoculum will be given intranasally to healthy participants. This dose will be escalated or de-escalated until colonisation is achieved in approximately 70% (95% CI 47% to 93%) of the exposed volunteers without causing disease. The colonisation period, shedding and exploratory immunology will be assessed during a 17-day inpatient stay and follow-up over 1 year. The dose of inoculum that achieves 70% colonisation will then be confirmed in phase B, comparing healthy participants exposed to B. pertussis with a control group receiving a sham inoculum.Ethics and disseminationThis study has been approved by the ethical committee reference: 17/SC/0006, 24 February 2017. Findings will be published in peer-reviewed open access journals as soon as possible.

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“…Indeed, direct inoculation with as few as 140 organisms can cause disease in susceptible children. 4 In a review, attack rates for unvaccinated children in the household setting ranged from 64 to 86% (average 76%) but was much lower (range 0À36% in classroom contract studies). 5 Clearly, transmission required repeated or prolonged exposure and/ or close contact.…”

Section: How Are the Bacteria Transmitted?mentioning

confidence: 99%

Pertussis

Lutwick

Preis

2014

Emerging Infectious Diseases

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A 19-day-old female infant was admitted to a neonatal ICU in Ankara, Turkey. A product of an unremarkable gestation and vaginal delivery at 39 weeks, she began to have symptoms of an upper respiratory infection at the age of 15 days. The illness abruptly worsened 3 days later with cough, cyanosis, periods of apnea, and progressive respiratory failure precipitating her admission. The mother, who had received DPT (diphtheria, pertussis, and tetanus) vaccination as a child, reported a mild cough beginning in the 2 weeks prior to delivery. Upon arrival, the infant was having apneic episodes with cyanosis and her O 2 saturation dropped to 36% during a coughing spasm. An initial white blood cell count was 27,200/µL with 60% lymphocytes and a chest X-ray did not reveal any infiltrates.Despite ampicillin and gentamicin, she deteriorated further and endotracheal intubation was necessary but was discontinued on day 2 of her admission. Nasopharyngeal washings were tested by PCR and were negative for respiratory syncytial virus, influenza A and B, adenovirus, parainfluenza virus, and coronavirus. Based on the infant's symptom complex and lymphocytosis, she had erythromycin therapy added on day 4. Nasopharyngeal aspirates obtained before erythromycin treatment was begun were positive for pertussis by PCR and by culture on BordetÀGengou agar. The infant's serum antibody against pertussis toxin was undetectable. The infant slowly improved with fewer bouts of paroxysmal coughing and she was discharged on hospital day 10. The mother was the only contact who reported cough and was the only contact that was seropositive for pertussis although her culture was negative. 359Emerging Infectious Diseases.

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Experimental Pertussis

Cited by 36 publications

References 0 publications

A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

InvestigatingBordetella pertussiscolonisation and immunity: protocol for an inpatient controlled human infection model

Pertussis

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