A mathematical model of intrahost pneumococcal pneumonia infection dynamics in murine strains.

The seriousness of pneumococcal pneumonia in mouse models has been shown to depend both on bacterial serotype and murine strain. We here present a simple ordinary differential equation model of the intrahost immune response to bacterial pneumonia that is capable of capturing diverse experimentally determined responses of various murine strains. We discuss the main causes of such differences while accounting for the uncertainty in the estimation of model parameters. We model the bacterial population in both the lungs and blood, the cellular death caused by the infection, and the activation and immigration of phagocytes to the infected tissue. The ensemble model suggests that inter-strain differences in response to streptococcus pneumonia inoculation reside in the strength of nonspecific immune response and the rate of extrapulmonary phagocytosis.

Neighborhood-level disadvantages increase risk for invasive pneumococcal disease.

BACKGROUND: Streptococcus pneumoniae (Spn) infection remains common worldwide despite recent vaccine efforts. Invasive pneumococcal disease (IPD) is the most severe form of Spn infection. Known individual risk factors for IPD include male gender and African American race. However, area-level socioeconomic factors have not been assessed. We examined the association of neighborhood-level disadvantages and risk of IPD in a tertiary medical center located in a socioeconomic diverse urban area in the Southeastern United States. METHODS: Patients hospitalized with culture-confirmed Streptococcus pneumoniae (Spn) infection from 01/01/2010 - 12/31/2019 were identified from electronic health record (EHR). The cohort's demographic and clinical information were obtained from EHR. Patients' residential address was geocoded and matched to 2015 area deprivation index (ADI). The association of ADI and IPD was evaluated using logistic regression after controlling for the demographic information (age, sex, race) and clinical factors (BMI, smoking status, alcoholism, immunosuppressive status, vaccination status, comorbidities). RESULTS: A total of 268 patients were hospitalized with culture-positive Streptococcus pneumoniae infection and 92 (34.3%) of them had IPD. The analysis showed that higher neighborhood deprivation (ADI in 79-100) was associated with increased risk of developing IPD in younger patients with age less than 65 (p = 0.007) after controlling for the individual demographic information and clinical factors. CONCLUSIONS: ADI is a risk factor for IPD in younger adults. Community-level socioeconomic risk factors should be considered when developing prevention strategies such as increasing vaccine uptake in high risk population to reduce the disease burden of IPD.

Subcutaneous BCG vaccination protects against streptococcal pneumonia via regulating innate immune responses in the lung.

Bacillus Calmette-Guérin (BCG) still remains the only licensed vaccine for TB and has been shown to provide nonspecific protection against unrelated pathogens. This has been attributed to the ability of BCG to modulate the innate immune system, known as trained innate immunity (TII). Trained innate immunity is associated with innate immune cells being in a hyperresponsive state leading to enhanced host defense against heterologous infections. Both epidemiological evidence and prospective studies demonstrate cutaneous BCG vaccine-induced TII provides enhanced innate protection against heterologous pathogens. Regardless of the extensive progress made thus far, the effect of cutaneous BCG vaccination against heterologous respiratory bacterial infections and the underlying mechanisms still remain unknown. Here, we show that s.c. BCG vaccine-induced TII provides enhanced heterologous innate protection against pulmonary Streptococcus pneumoniae infection. We further demonstrate that this enhanced innate protection is mediated by enhanced neutrophilia in the lung and is independent of centrally trained circulating monocytes. New insight from this study will help design novel effective vaccination strategies against unrelated respiratory bacterial pathogens.

Roseicella aerolata GB24T from bioaerosol attenuates Streptococcus pneumoniae-introduced inflammation through regulation of gut microbiota and acetic acid.

Streptococcus pneumoniae (Spn) is the most common respiratory pathogen causing community-acquired pneumonia. Probiotics represent a new intervention target for Spn infection. Hence, the discovery and development of new potential probiotic strains are urgently needed. This study was designed to investigate the beneficial effect and mechanism of a new bacterium named Roseicella aerolata GB24T that antagonizes Spn at cellular and animal levels. The results revealed that GB24T strain inhibited the growth of Spn on sheep blood agar plates, forming inhibition circles with a diameter of 20 mm. In cultured bronchial epithelium transformed with Ad 12-SV40 2B (BEAS-2B) cells, Spn infection induced an elevation in the expression levels of interleukin-1ß, interleukin-6, and tumor necrosis factor-α to 4.289 ± 0.709, 5.587 ± 2.670, and 5.212 ± 0.772 folds compared to healthy controls, respectively. Moreover, pre-infection with GB24T for 1.5 h almost eliminated the cellular inflammation caused by Spn infection. Additionally, male Sprague-Dawley rats infected with Spn were randomly allocated into two groups: GB24T pre-infection and Spn infection groups, with healthy rats as control. GB24T significantly alleviated inflammatory lung injury caused by Spn infection, which was associated with obvious changes in the abundance of gut microbiota and a trend toward enhanced secretion of short-chain fatty acids, especially acetic acid. Acetic acid was validated to be effective in alleviating inflammation due to Spn infection in cellular assays. Together, these findings highlight that GB24T strain is an important protective feature in the respiratory tract.

Detachment of a prosthetic valve due to infective endocarditis caused by Streptococcus pneumoniae.

The incidence of infective endocarditis (IE) due to S pneumoniae has decreased, thanks to antibiotics. However, when it does occur, it can be lethal. The present case provides a reminder of the potential lethality of this postoperative infection.

An adult case of invasive pneumococcal disease due to serotype 12F-specific polysaccharide antibody failure following a 23-valent polysaccharide vaccination.

A 68-year-old Japanese man was admitted to our hospital for an acute febrile illness with shivering and impaired consciousness. He was a previous smoker and had a history of chronic obstructive pulmonary disease, for which he inhaled steroid with a long-acting bronchodilator. He had received a 23-valent pneumococcal polysaccharide vaccination 2 years previously. He was intubated and placed on a ventilator in intensive care unit because of acute respiratory failure and hypercapnia. Streptococcus pneumoniae was grown from his blood, sputum, and urine cultures, and he was diagnosed with invasive pneumococcal disease with acute renal failure. He was treated with intravenous beta-lactam and macrolide with continuous hemodiafiltration and was discharged 3 months later. The pneumococcus was identified as serotype 12F, and his serotype-specific IgG and opsonophagocytic index against serotype 12F indicating a lack of protection from IPD among PPV23 serotypes. This case highlights that some individuals may have a serotype-specific polysaccharide antibody failure that makes them susceptible to serotype 12F invasive pneumococcal disease. This case also illustrates the need for serotype-specific IgG and opsonophagocytic index titre cut-offs for each specific pneumococcal serotype in available vaccines to understand the vaccination protection for individual patients better.

23-Valent Pneumococcal Polysaccharide Vaccine Uptake in the United States Air Force HIV Program.

Streptococcus pneumoniae infection is a predominant cause of bacterial infection in HIV-infected individuals. However, reported rates of pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) are variable. We evaluated uptake of PPV23 in patients diagnosed with HIV between 1996 and 2012 (n = 507) in the United States Air Force, a centralized HIV program with free access to care including vaccines and medications. A total of 411 (81.1%) patients received at least 1 PPV23 dose. The PPV23 vaccination within 1 year of diagnosis was greater for those diagnosed between 2004 and 2012 (n = 184, 86%) compared with 1996 to 2003 (n = 104, 56.5%; P < .001). For those with ≥6 years of follow-up, receipt of a second recommended PPV23 dose was greater for those diagnosed between 1996 and 2003 (n = 52, 57.8%) compared with 2004 to 2012 (n = 9, 28.1%; P = .004). Although first PPV23 vaccination was high in recent years, process improvement efforts are underway to overcome barriers and improve uptake of pneumococcal vaccines in our program.