Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents.

The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8+ T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8+ T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8+ T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

Analysis of epidemic characteristics of tuberculosis in schools in Shijiazhuang during 2011-2020 / 中国学校卫生

Objective@#To analyze the trend and characteristics of school tuberculosis epidemic in Shijiazhuang from 2011 to 2020, and to provide reference for school tuberculosis prevention and control.@*Methods@#Descriptive methods were used to analyze the epidemiological characteristics of tuberculosis among students and the epidemic situation of tuberculosis in schools in Shijiazhuang from 2011 to 2020. The χ 2 test and χ 2 trend test were used to analyze the characteristics and trend of school tuberculosis.@*Results@#A total of 4 896 cases of tuberculosis were registered among students in Shijiazhuang from 2011 to 2020. The average annual registered incidence rate of students was 24.69/100 000, and the difference in incidence rate was statistically significant ( χ 2=318.50, P <0.01) the overall registered incidence rate of tuberculosis among students in the past 10 years was on the rise ( χ 2 trend =87.79, P <0.01). Among the student cases, male accounted for 53.89%, female accounted for 46.11%. The age group of students aged >18 and above accounted for the largest proportion(50.35%), followed by the age group aged 16-18( 35.80 %). Most students cases occurred in April and September-November, with September the highest(12.03%). A total of 22 clustered outbreaks (174 cases) and the aggregate epidemic accounted for 3.55% of the total number of students with tuberculosis.@*Conclusion@#The prevention and control of tuberculosis epidemic in schools in Shijiazhuang should not be underestimated, and strengthen the supervision, management, publicity and education of students in key age groups to avoid clusters of outbreaks.

Long-Lasting Virus-Specific T Cell Response with Divergent Features in Self-Resolved and Chronic Hepatitis C Virus Patients 35 Years Postinfection.

Although recognized as a curable disease, the persistence of hepatitis C virus (HCV) in chronically infected patients remains a great burden for public health. T cell immune responses serve a key role in anti-HCV infection; however, the features of T cell immunity in patients after a long-term infection are not well explored. We recruited a special cohort of patients with similar genetic background and natural developing progression of disease who were infected with HCV through blood donation 35 y ago. We found that self-resolved individuals had higher levels of cytokine-secreting T cells than individuals with chronic infections, indicating HCV-specific T cell immunity could be sustained for >35 y. Meanwhile, virus-specific CD8+ T cells in chronic patients were characterized by programmed cell death-1high, TIM-3high expression, which was related to liver injury characterized by aspartate transaminase/alanine aminotransferase levels and morphopathological changes. Unexpectedly, the expression of Lymphocyte-activation gene 3 on CD8+ T cells was lower in chronic patients and negatively correlated with alanine aminotransferase/aspartate transaminase. Our findings provided new insights into HCV-specific T cell responses and may shed light on a way to figure out novel effector targets and explore a way to reverse chronic infections.

Synergistic therapy of magnetism-responsive hydrogel for soft tissue injuries.

Soft tissue injury is very common and associated with pain, tissue swelling and even malformation if not treated on time. Treating methods include cryotherapy, electrical therapy, ultrasound therapy and anti-inflammatory drug, but none of them is completely satisfying. In this work, for a better therapeutic effect, drug therapy and pulsed electromagnetic field (PEMF) therapy were combined. We constructed a drug delivery system using the tetra-PEG/agar hydrogel (PA). By incorporating Fe3O4 NPs into the hydrogel network, a magnetism-responsive property was achieved in the system. The cytotoxicity and in vivo study showed a good biocompatibility of the PA/Fe3O4 hydrogel. A magnetism-controlled release was attained by the incorporation of Fe3O4. Finally, in vivo study showed a better performance of the DS-loaded PA/Fe3O4 compared with the commercially available DS ointment regarding the recovery of the injured soft tissue. Therefore, this magnetism-responsive hydrogel may represent a promising alternative to treat soft tissue injury.

Resolution improvement of low frequency AC magnetic field detection for modulated MR sensors.

Magnetic modulation methods especially Micro-Electro-Mechanical System (MEMS) modulation can improve the sensitivity of magnetoresistive (MR) sensors dramatically, and pT level detection of Direct Current (DC) magnetic field can be realized. While in a Low Frequency Alternate Current (LFAC) magnetic field measurement situation, frequency measurement is limited by a serious spectrum aliasing problem caused by the remanence in sensors and geomagnetic field, leading to target information loss because frequency indicates the magnetic target characteristics. In this paper, a compensation field produced with integrated coils is applied to the MR sensor to remove DC magnetic field distortion, and a LFAC magnetic field frequency estimation algorithm is proposed based on a search of the database, which is derived from the numerical model revealing the relationship of the LFAC frequency and determination factor [defined by the ratio of Discrete Fourier Transform (DFT) coefficients]. In this algorithm, an inverse modulation of sensor signals is performed to detect jumping-off point of LFAC in the time domain; this step is exploited to determine sampling points to be processed. A determination factor is calculated and taken into database to figure out frequency with a binary search algorithm. Experimental results demonstrate that the frequency measurement resolution of the LFAC magnetic field is improved from 12.2 Hz to 0.8 Hz by the presented method, which, within the signal band of a magnetic anomaly (0.04-2 Hz), indicates that the proposed method may expand the applications of magnetoresistive (MR) sensors to human healthcare and magnetic anomaly detection (MAD).

Impact of the Ebola outbreak on routine immunization in western area, Sierra Leone - a field survey from an Ebola epidemic area.

BACKGROUND: Since March 2014, the Ebola Virus Disease (EVD) outbreak in West Africa disrupted health care systems - especially in Guinea, Liberia and Sierra Leone - with a consequential stress on the area's routine immunization programs. To address perceived decreased vaccination coverage, Sierra Leone conducted a catch-up vaccination campaign during 24-27 April 2015. We conducted a vaccination coverage survey and report coverage estimates surrounding the time of the EVD outbreak and the catch-up campaign. METHODS: We selected 3 villages from each of 3 communities and obtained dates of birth and dates of vaccination with measles vaccine (MV) and the 3rd dose of Pentavalent vaccine (Pentavalent3) of all children under 4 years of age in the 9 selected villages. Vaccination data were obtained from parent-held health cards. We calculated the children's MV and Pentavalent3 coverage rates at 3 time points, 1 August 2014, 1 April 2015, and 1 May 2015, representing coverage rates before the EVD outbreak, during the EVD outbreak, and after the Maternal and Child Health Week (MCHW) catch-up campaign. RESULTS: The final sample size was 168 children. MV coverage among age-eligible children was 71.3% (95% confidence interval [CI]: 62.1% - 80.4%) and 45.7% (95% CI: 29.2% - 62.2%) before and during the outbreak of EVD, respectively, and was 56.8% (95% CI: 40.8% - 72.7%) after the campaign. Pentavalent3 coverage among age-eligible children was 79.8% (95% CI: 72.6% - 87.0%) and 40.0% (95% CI: 22.5% - 57.5%) before and during the outbreak of EVD, and was 56.4% (95% CI: 39.1% - 73.4%) after the campaign. CONCLUSIONS: Coverage levels of MV and Pentavalent3 were low before the EVD outbreak and decreased further during the outbreak. Although the MCHW catch-up campaign increased coverage levels, coverage remained below pre-outbreak levels. High-quality supplementary immunization activities should be conducted and routine immunization should be strengthened to address gaps in immunity among children in this EVD-affected area.

A practical community-based response strategy to interrupt Ebola transmission in sierra Leone, 2014-2015.

BACKGROUND: The Ebola virus disease spread rapidly in West Africa in 2014, leading to the loss of thousands of lives. Community engagement was one of the key strategies to interrupt Ebola transmission, and practical community level measures needed to be explored in the field and tailored to the specific context of communities. METHODS: First, community-level education on Ebola virus disease (EVD) prevention was launched for the community's social mobilizers in six districts in Sierra Leone beginning in November 2014. Then, from January to May of 2015, in three pilot communities, local trained community members were organized to engage in implementation of EVD prevention and transmission interruption measures, by involving them in alert case report, contact tracing, and social mobilization. The epidemiological indicators of transmission interruption in three study communities were evaluated. RESULTS: A total of 6 016 community social mobilizers from 185 wards were trained by holding 279 workshops in the six districts, and EVD message reached an estimated 631 680 residents. In three pilot communities, 72 EVD alert cases were reported, with 70.8 % of them detected by trained local community members, and 14 EVD cases were finally identified. Contact tracing detected 64.3 % of EVD cases. The median duration of community infectivity for the cases was 1 day. The secondary attack rate was 4.2 %, and no third generation of infection was triggered. No health worker was infected, and no unsafe burial and noncompliance to EVD control measures were recorded. The community-based measures were modeled to reduce 77 EVD cases, and the EVD-free goal was achieved four months earlier in study communities than whole country of Sierra Leone. CONCLUSIONS: The community-based strategy of social mobilization and community engagement was effective in case detection and reducing the extent of Ebola transmission in a country with weak health system. The successfully practical experience to reduce the risk of Ebola transmission in the community with poor resources would potentially be helpful for the global community to fight against the EVD and the other diseases in the future.

Frequency, Antimicrobial Resistance and Genetic Diversity of Klebsiella pneumoniae in Food Samples.

This study aimed to assess the frequency of Klebsiella pneumoniae in food samples and to detect antibiotic resistance phenotypes, antimicrobial resistance genes and the molecular subtypes of the recovered isolates. A total of 998 food samples were collected, and 99 (9.9%) K. pneumoniae strains were isolated; the frequencies were 8.2% (4/49) in fresh raw seafood, 13.8% (26/188) in fresh raw chicken, 11.4% (34/297) in frozen raw food and 7.5% (35/464) in cooked food samples. Antimicrobial resistance was observed against 16 antimicrobials. The highest resistance rate was observed for ampicillin (92.3%), followed by tetracycline (31.3%), trimethoprim-sulfamethoxazole (18.2%), and chloramphenicol (10.1%). Two K. pneumoniae strains were identified as extended-spectrum ß-lactamase (ESBL)-one strain had three beta-lactamases genes (blaSHV, blaCTX-M-1, and blaCTX-M-10) and one had only the blaSHV gene. Nineteen multidrug-resistant (MDR) strains were detected; the percentage of MDR strains in fresh raw chicken samples was significantly higher than in other sample types (P<0.05). Six of the 18 trimethoprim-sulfamethoxazole-resistant strains carried the folate pathway inhibitor gene (dhfr). Four isolates were screened by PCR for quinolone resistance genes; aac(6')-Ib-cr, qnrB, qnrA and qnrS were detected. In addition, gyrA gene mutations such as T247A (Ser83Ile), C248T (Ser83Phe), and A260C (Asp87Ala) and a parC C240T (Ser80Ile) mutation were identified. Five isolates were screened for aminoglycosides resistance genes; aacA4, aacC2, and aadA1 were detected. Pulsed-field gel electrophoresis-based subtyping identified 91 different patterns. Our results indicate that food, especially fresh raw chicken, is a reservoir of antimicrobial-resistant K. pneumoniae, and the potential health risks posed by such strains should not be underestimated. Our results demonstrated high prevalence, antibiotic resistance rate and genetic diversity of K. pneumoniae in food in China. Improved control and prevention strategies are urgently needed.

The clearance effect of bovine anti-Helicobacter pylori antibody-containing milk in O blood group Helicobacter pylori-infected patients: a randomized double-blind clinical trial.

BACKGROUND: The failure in standard triple therapy has recently increased to high levels in China, primarily because of insufficient patient compliance, antimicrobial resistance, and high costs. Effective prevention and eradication of Helicobacter pylori (H. pylori) by artificial passive immunization with orally administered bovine antibodies in the milk has been demonstrated in many animal studies, but the clinical studies that are available have shown no H. pylori eradication. This study was to evaluate the efficacy and safety of orally administered bovine anti-H. pylori antibodies for the clearance of H. pylori infecting O blood group subpopulations. METHODS: Two local epidemic H. pylori strains that were prevalent locally were screened and then used to immunize dairy cows. After confirmation of the presence of anti-H. pylori polyclonal antibodies in the milk by enzyme-linked immunosorbent assay, the milk was subsequently defatted and processed into sterile milk by pasteurization. This study was designed as a double-blind placebo-controlled randomized clinical trial. Our 61 H. pylori-infected O blood group subjects were assigned to two groups; 31 subjects were treated with bovine milk containing antibodies and 30 subjects with the placebo. The medication-based study was continued for 28 days. Subjects were followed up for 56 days. The effect was assessed by the C-14 urea breath test (UBT). SPSS 17.0 software for Windows was used to analyze the data. RESULTS: Of the 61 subjects enrolled, 58 completed the protocol. One volunteer in the antibodies group and two volunteers in the control group dropped out. Of the 30 antibody-treated subjects, 13 became UBT negative, whereas none of the 30 of the placebo-treated subjects became UBT negative after the medication. Of 13 UBT negative patients, 3 became positive again at the end of the follow-up. Both intention to treat and per-protocol analysis indicated a significant difference in the clearance rate of infected patients between the groups treated with bovine antibody-containing milk and the placebo (P = 0.001, P < 0.05) and no significant difference in adverse effects (P > 0.05 all). CONCLUSIONS: Bovine antibody-based oral immunotherapy appears to be safe and has a significant clearance effect on intragastric H. pylori that infects O blood group adults. TRIAL REGISTRATION: ChiCTR-TRC-14005212.

Risk factors of hepatitis C virus transmission and genotype distribution in former blood donors from Chinese rural area.

BACKGROUND: Illegal commercial plasma and blood donation activities in the late 1980s and early 1990s caused a large number of hepatitis C virus (HCV) infections in rural areas of China. In the present study, we aimed to elucidate the risk factors of HCV RNA positivity and HCV genotype distribution in former blood donors. METHODS: A cross-sectional survey was carried out in a former blood donation village in rural Hebei Province, North China. All residents were invited for a questionnaire interview and testing for HCV antibodies as well as HCV nucleic acids. Questionnaires were administered to collect information about their personal status and commercial blood donation history. Nested PCR was used to amplify HCV nucleic acids in C/E1 region and NS5b region followed by genotyping and phylogenetic analysis. Univariate and multivariate logistic regression were used to analyze the distributions of HCV genotypes in different groups. RESULTS: A total of 512 blood samples were collected. Anti-HCV positive were 148 (28.5%) whereas RNA positive rate was 13.87%. Residents between 50 and 59 years old had the highest RNA positive rate (27/109, 24.77%) (P = 0.0051). Multivariate logistic regression model analysis revealed that plasma donation (OR = 8.666, 95% CI: 1.390-54.025) was the dominant risk factor of HCV infection. Furthermore, HCV subtypes 1b and 2a were found by genotyping and phylogenetic analysis. 36 samples (53.73%) were subtype 1b and 31 samples (46.27%) were subtype 2a. CONCLUSIONS: Unsafe practices during illegal plasma donation led to a high risk of HCV infection. The identification of genotypes 1b and 2a as major HCV genotypes circulating in this region may help to predict the future burden of HCV related diseases and facilitate better medical treatment towards HCV carriers. These results are useful for public healthcare as well as disease control and surveillance.

A case-control study of risk factors for HIV-negative children with cryptococcal meningitis in Shi Jiazhuang, China.

BACKGROUND: Although cryptococcal meningitis (CM) is an emerging disease worldwide, there have been few studies of the characteristics and risk factors of CM in children. METHODS: We used data collected from May 2007 through April 2012 in the Acute Meningitis-Encephalitis Syndrome Surveillance project in Shi Jiazhuang, China to describe the epidemiologic, clinical, and laboratory findings in children with CM. Furthermore, a matched case-control study was used to determine risk factors of CM. RESULTS: Overall 23 HIV-negative children with CM (median age: 10.91 years; range: 5 months-17 years) were enrolled in our study. The average annual incidence of CM was 0.43/100,000 with a fatality rate of 1.7%. Most patients were males (60.87%) and rural children (73.91%). Common clinical symptoms included increased intracranial pressure, such as headaches (78.3%), nausea (60.9%), altered mental status (56.5%), vomiting (52.2%), and seizures (43.5%), and frequent laboratory findings consisted of blood leukocytosis (87.0%), decreased CSF glucose (87.0%), pleocytosis (82.6%), increased intracranial pressure (73.9%) and elevated CSF proteins (65.2%). Epidemiologic, clinical, and laboratory findings were similar between patients with and without underlying diseases. Multivariate logistic regression analysis showed that children who had contact with birds/bird droppings or saprophytes were more likely to be infected than those without such contact (odds ratio(OR) =11.82; 95% confidence interval (CI), 2.21-62.24; P = 0.004). Patients with an interval of ≥20 days from onset to admission were at high risk for CM (OR= 5.31; 95%CI, 1.58-17.89; P = 0.007). CONCLUSIONS: Our findings show that CM is an uncommon disease with a high mortality rate in children. Although additional studies are needed to find effective prevention and treatments for CM, clinicians should consider CM as a potential cause for pediatric meningitis in children, particularly boys from rural areas, who had contact with birds/bird droppings or saprophytes and in children who did not receive prompt medical attention.

[Investigating genotype of HCV distribution among residents in a "blood donation" village in Hebei Province].

OBJECTIVE: To investigate genotype of HCV infection among residents in a rural village, Hebei Province. METHODS: Blood samples of the 520 residents were collected, and C/E1 of HCV genome of the 483 samples were obtained by RT-PCR amplifying, and the gene sequences were analyzed and the polygenetic tree were drawn by the software Mega 4.0. RESULTS: In 483 subjects, HCV-RNA positive objectives are 70, positive prevalence is 14.5%, genotyping for all the samples successfully, including genotypes 1b and 2a, which are 36 (51.4%), 34 (48.6%) respectively. CONCLUSION: HCV RNA positive rate is 14.5%, which is higher than general people. Subtypes 1b and 2a seemed to be the dominant genotypes of HCV in Zhao county area of Hebei Province.