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Human Infection Challenge with Serotype 3 Pneumococcus. | LitMetric

AI Article Synopsis

  • Serotype 3 (SPN3) is linked to invasive pneumococcal disease but has low carriage rates, showing less decline compared to other serotypes after the introduction of the PCV13 vaccine, with a notable increase in certain populations.
  • A human challenge study tested SPN3's ability to colonize the nasopharynx using three isolates and varying doses, ensuring patient safety and tracking colonization rates and symptoms over time.
  • Results showed a 30% to 70% colonization rate among 96 healthy participants, with mild symptoms reported but no serious adverse events, suggesting that SPN3 colonization can lead to mild upper respiratory issues.

Article Abstract

serotype 3 (SPN3) is a cause of invasive pneumococcal disease and associated with low carriage rates. Following the introduction of pediatric 13-valent pneumococcal conjugate vaccine (PCV13) programs, SPN3 declines are less than other vaccine serotypes and incidence has increased in some populations coincident with a shift in predominant circulating SPN3 clade, from I to II. A human challenge model provides an effective means for assessing the impact of PCV13 on SPN3 in the upper airway. To establish SPN3's ability to colonize the nasopharynx using different inoculum clades and doses, and the safety of an SPN3 challenge model. In a human challenge study involving three well-characterized and antibiotic-sensitive SPN3 isolates (PFESP306 [clade Ia], PFESP231 [no clade], and PFESP505 [clade II]), inoculum doses (10,000, 20,000, 80,000, and 160,000 cfu/100 μl) were escalated until maximal colonization rates were achieved, with concurrent acceptable safety. Presence and density of experimental SPN3 nasopharyngeal colonization in nasal wash samples, assessed using microbiological culture and molecular methods, on Days 2, 7, and 14 postinoculation. A total of 96 healthy participants (median age 21, interquartile range 19-25) were inoculated ( = 6-10 per dose group, 10 groups). Colonization rates ranged from 30.0-70.0% varying with dose and isolate. 30.0% (29/96) reported mild symptoms (82.8% [24/29] developed a sore throat); one developed otitis media requiring antibiotics. No serious adverse events occurred. An SPN3 human challenge model is feasible and safe with comparable carriage rates to an established Serotype 6B human challenge model. SPN3 carriage may cause mild upper respiratory symptoms.

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Source
http://dx.doi.org/10.1164/rccm.202112-2700OCDOI Listing

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