Effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-serotype community acquired pneumococcal diseases among children in China: A test-negative case-control study.

BACKGROUND: In 2016, China licensed 13-valent pneumococcal conjugate vaccine (PCV13) based on a study that demonstrated its immunogenicity is non-inferior to PCV7. However, the real-world effectiveness of PCV13 against vaccine-serotype pneumococcal diseases in China has limited evidence. METHODS: A test-negative case-control study was conducted among children under 5 years old admitted to the Children's Hospital of Soochow University (SCH) with respiratory tract infections from January 2018 to December 2020. Cases were defined as children from whom the isolates were tested positive for Streptococcus pneumoniae (S. pneumoniae) with serotypes included in PCV13. Two control groups were included, one represented children with isolates positive for S. pneumoniae of non-PCV13 serotypes and the other comprised children who tested negative for S. pneumoniae. The S. pneumoniae-negative controls were selected by matching them to the cases based on gender, age and admission date in a 1:1 ratio. Vaccine effectiveness (VE) was calculated using a logistic regression model as (1- adjusted odds ratio) * 100 %. RESULTS: A total of 2371 pneumococcal isolates were included in the analysis, of which 75.0 % (1779/2371) were covered by PCV13 serotypes. Consequently, these 1779 children were classified as cases, and 592 children were designated as non-PCV13 serotype controls. Another 1779 children were correspondingly recruited as S. pneumoniae-negative controls. Overall, 40 cases (2.3 %) and 148 controls (6.2 %) had received vaccination. The overall VE in the PCV13/non-PCV13 serotypes case-control study was 50.0 % (95 % CI: 15.0, 70.7), which was lower than the VE of 74.4 % (95 % CI: 60.7, 83.3) in the matched PCV13/S. pneumoniae-negative case-control study. VE was higher for ≥ 2 or ≥ 3 doses of vaccination compared to ≥ 1 dose. VE against specific PCV13 serotypes (6B, 6A and 19F) was higher than for other serotypes. CONCLUSIONS: PCV13 vaccination demonstrates effectiveness against vaccine-serotype pneumococcal diseases in children, particularly for serotypes 6B, 6A and 19F.

The Role of PTEN/PI3K/AKT Signaling Pathway in Apoptosis of Liver Cells in Cocks with Manganese Toxicity.

PTEN/PI3K/AKT signaling pathway is an important pathway for cell proliferation and apoptosis. Exposure to excess manganese (Mn) can cause damage in organisms. However, whether Mn toxicity can cause apoptosis is still not clear. In order to explore the mechanism of PTEN/PI3K/AKT signaling pathway responsible for Mn-induced apoptotic injury, 160 Hyline cocks were divided into four groups; there were the control group (Con group), the low-dose Mn group (L group), the medium-dose Mn group (M group), and the high-dose Mn group (H group). The cocks in Con group, L group, M group, and H group were fed with MnCl2 diet containing 100, 600, 900, and 1800 mg/kg, respectively. The growth status of cocks in each group was observed on days 30, 60, and 90. Thirty cocks were randomly selected from each group and sacrificed on day 90 for optical microscope observation and fluorescence microscopic observation, as well as for transcription-level expression of apoptosis-related genes and heat shock proteins (HSPs) in the liver. The results showed that the growth status of cocks was gradually depressed with the extension of feeding time and with the increase of Mn dose. On day 90, the results of optical microscope observation and fluorescence microscope observation showed that damage and apoptosis appeared in the cock liver cells under Mn exposure groups. The results of transcription-level detection of apoptosis-related genes and HSPs indicated that Mn exposure upregulated eleven pro-apoptotic genes (including RIP1, RIP3, MLKL, Bax, Caspase-3, FADD, Cyt-C, ERK, JNK, Caspase-8, and P38) and downregulated one anti-apoptotic gene Bcl-2, further meaning that exposure to Mn-induced apoptosis in cock liver cells and PTEN/PI3K/AKT signaling pathway took part in molecular mechanism of apoptosis caused by excess Mn. Moreover, in our experiment, the increase of four HSPs (including HSP27, HSP40, HSP60, and HSP70) was found after Mn treatment for 90 days, which indicated that Mn stress triggered HSPs and HSPs were involved in molecular mechanism of Mn poisoning in cock livers. In addition, we also found there was upregulated dose-dependent manner in fifteen detected genes and there was downregulated dose-dependent manner in Bcl-2, indicating that the apoptosis caused by Mn poisoning in cock liver cells was dose-dependent.