Dataset Information

New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media.

ABSTRACT: For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2-24 months at scheduled visits and at visits during respiratory infection in 1994-97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media.

SUBMITTER: Auranen K

PROVIDER: S-EPMC4892487 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media.

Auranen Kari K Syrjänen Ritva R Leino Tuija T Kilpi Terhi T

PloS one 20160603 6

For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2-24 months at scheduled visits and at visits during respiratory infection in 1994-97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timi ...[more]

PMID: 27257789

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Project description:Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes. Here, we demonstrate that the viral hemagglutinin (HA) mediates bacterial OM by inducing a pro-inflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings show that it is the inflammatory response that mediates pneumococcal replication; not viral suppression of the immune system or epithelial damage. This study provide the first evidence that HA induced inflammation drives pneumococcal replication in the middle ear cavity, which has important consequences to the treatment of pneumococcal OM. Five-day old C57BL/6 mice were colonised intranasally (i.n.) with 2M-CM-^W103 colony forming units (CFU) of S. pneumoniae EF3030Lux in 3 M-BM-5Ls of PBS. Alternatively, mice were mock-infected with an equivalent volume of phosphate buffered saline (PBS). At 14-days of age, infant mice were infected i.n. with 20 plaque forming units (PFU) (PR8/34, Cambridge/34 and WSN/33) or 102.5 PFU (all other virus strains) of egg-grown IAV in 3 M-BM-5Ls of PBS. Viral doses were selected to ensure a reproducible infection with minimum morbidity and no mortality. Six days post-IAV infection, mice were euthanised and organs were collected for analysis. Six independent biological replicates (where both ears from one mouse were pooled to create one sample) were used for each condition and analyzed using the NimbleGen platform (12M-CM-^W135K Mouse Gene Expression Arrays, Roche Nimblegen, USA). Indirect labeling, hybridization and washing was performed according to the manufacturerM-bM-^@M-^Ys instructions. Array images were acquired with a NimbleGen MS200 scanner, and images were processed with NimbleScan software using the RMA algorithm. Data was processed using Arraystar (DNASTAR, USA) with default settings as described in the manual. Differential expression tests were performed with a moderated T-test implemented in Arraystar, followed by FDR correction of the P values (Q-values) according to the method of Storey and Tibshirani

Dataset Information

New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media.

Publications

New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media.

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