Publications by authors named "Shui-Hua Lu"

24 Publications

  • Page 1 of 1

High rate of completion for weekly rifapentine plus isoniazid treatment in Chinese children with latent tuberculosis infection-A single center study.

PLoS One 2021 11;16(6):e0253159. Epub 2021 Jun 11.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Three months of weekly rifapentine plus isoniazid (3HP) is a short course regimen for latent tuberculosis infection treatment with satisfied safety and efficacy. However, research on its use in children is limited. In this study, we evaluated the completion rate and safety of the 3HP regimen among children in China. Participants aged 1-14 years receiving 3HP for TB prevention at Shanghai Public Health Clinical Center were followed from December 2019 to November 2020 to evaluate the safety and completion rate of the treatment. Thirty-one children were eligible for inclusion, but five were excluded from the analysis (three were treated with a lower than recommended dose, and two were lost to follow-up). Of the 26 children included in the analysis, the treatment completion rate was 100%. Adverse drug reactions (ADRs) were reported in 38.5% (10/26) of the patients. The most common ADRs were gastrointestinal symptoms (19.2%,5/26), and all ADRs were rated as Grade 1. The 3HP regimen has a high completion rate, and it seems well tolerated in our study population. However, further randomized controlled clinical trial with larger sample size are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253159PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195436PMC
June 2021

A Niemann-pick C1 disease child with BCG-itis: a case report and analysis.

BMC Pediatr 2021 05 4;21(1):218. Epub 2021 May 4.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Background: Niemann-Pick C disease is a rare autosomal recessive lysosomal lipid storage disorder. Some primary immunodeficiency diseases patients developed regional disease or disseminated disease after vaccinating BCG. It is unclear whether NPC gene deficiency is associated with Mycobacteria infection.

Case Presentation: We report and discuss a case of a child who presented at the age of 6 months with NPC1 and BCG-itis. The patient was treated with Miglustat and the symptom of lymphadenopathy was improved.

Conclusions: We reasonably speculate that NPC1 is a susceptibility gene of Mtb infection and mainly affects innate immunity. Once diagnosed, the infant should not be vaccinated with BCG and early treated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-021-02671-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094597PMC
May 2021

Safety Evaluation of Recombinant Fusion Protein RP22 as a Skin Test Reagent for Tuberculosis Diagnosis: A Phase I Clinical Trial.

Infect Dis Ther 2021 Jun 7;10(2):925-937. Epub 2021 Apr 7.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Introduction: This phase I clinical trial was conducted to evaluate the safety of RP22 as a skin test reagent for tuberculosis (TB) diagnosis and to explore the appropriate dosage.

Methods: We used a randomized, double-blind, placebo-controlled identification allergen (IA) skin test. A total of 72 healthy adult volunteers with negative chest X-ray results were randomized into six groups and given a QuantiFERON-TB Gold (QFT) test. Of the 12 participants in each group, eight received RP22 and four received placebo. The doses of RP22 in the six experimental groups ranged from 0.1 to 4.0 μg in a single intradermal injection of 0.1 ml. Skin reactions and adverse events were recorded at intervals.

Results: All doses of RP22 except the highest were well tolerated and safe. No serious adverse events associated with the injection were observed in all groups. There were 11 participants who had positive QFT results, eight had a skin reaction with a redness or induration area diameter of greater than 10 mm at 48-72 h, one had no skin reaction. Among the 60 negative-QFT participants, none had a reaction area diameter of greater than 10 mm.

Conclusion: The RP22 skin test was well tolerated and safe, it could play a key role in screening for latent tuberculosis infection (LTBI) by providing a much-wanted alternative to the tuberculin skin test (TST) and interferon-γ release assays (IGRAs).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-021-00435-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116472PMC
June 2021

Stool-based Xpert MTB/RIF Ultra assay as a tool for detecting pulmonary tuberculosis in children with abnormal chest imaging: A prospective cohort study.

J Infect 2021 01 1;82(1):84-89. Epub 2020 Dec 1.

Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; Wenzhou Medical University, Wenzhou, China; TB Center, Shanghai Emerging and Re-emerging Institute, 2901, Caolang Rd, Jinshan, Shanghai 201508, China. Electronic address:

Objectives: To evaluate the diagnostic efficacy of stool-based Xpert MTB/RIF Ultra assay versus other assays for the detection of paediatric pulmonary tuberculosis (PTB).

Methods: A prospective head-to-head comparative study was conducted from Dec 2017 to May 2019 in Shanghai Public Health Clinical Centre. Samples were collected from children (< 15 years) with abnormal chest imaging (X-ray or CT scan) results for the following tests: Ultra on stool sample (Ultra-Stool), Ultra on respiratory tract sample (Ultra-RTS), Xpert MTB/RIF assay (Xpert) on RTS (Xpert-RTS), acid-fast bacilli smear on RTS (AFB-RTS), and Mycobacterium tuberculosis (Mtb) culture on RTS (Culture-RTS). The results were compared with a composite reference standard.

Results: A total of 126 cases with paired results were analysed. Against a composite reference standard, Ultra-RTS demonstrated the highest sensitivity (52%) and specificity (100%). Ultra-Stool showed 84.1% concordance with Ultra-RTS, demonstrating 45.5% sensitivity and 94.7% specificity (kappa = 0.65, 95% CI= 0.51-0.79). The sensitivity of Ultra-Stool was similar to Mtb culture (45.5%, p = 1.000) and higher than AFB-RTS (27.3%, p < 0.05). Assay positivity was associated with age and infiltration range in chest imaging.

Conclusions: When RTS is difficult to obtain, stool sample-based Ultra is a comparable alternative.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2020.10.036DOI Listing
January 2021

Clinical characteristics of foreign-imported COVID-19 cases in Shanghai, China.

Emerg Microbes Infect 2020 Dec;9(1):1230-1232

Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/22221751.2020.1766383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448901PMC
December 2020

Heterologous prime-boost vaccination against tuberculosis with recombinant Sendai virus and DNA vaccines.

J Mol Med (Berl) 2019 12 30;97(12):1685-1694. Epub 2019 Nov 30.

School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, 325000, China.

In an earlier study, a novel Sendai virus-vectored anti-tuberculosis vaccine encoding Ag85A and Ag85B (SeV85AB) was constructed and shown to elicit antigen-specific T cell responses and protection against Mycobacterium tuberculosis (Mtb) infection in a murine model. In this study, we evaluate whether the immune responses induced by this novel vaccine might be elevated by a recombinant DNA vaccine expressing the same antigen in a heterologous prime-boost vaccination strategy. The results showed that both SeV85AB prime-DNA boost (SeV85AB-DNA) and DNA prime-SeV85AB boost (DNA-SeV85AB) vaccination strategies significantly enhanced the antigen-specific T cell responses induced by the separate vaccines. The SeV85AB-DNA immunization regimen induced higher levels of recall T cell responses after Mtb infection and conferred better immune protection compared with DNA-SeV85AB or a single immunization. Collectively, our study lends strong evidence that a DNA vaccine boost might be included in a novel SeV85AB immunization strategy designed to enhance the immune protection against Mtb. KEY MESSAGES: A heterologous prime-boost regimen with a novel recombinant SeV85AB and a DNA vaccine increase the T cell responses above those from a single vaccine. The heterologous prime-boost regimen provided protection against Mtb infection. The DNA vaccine might be included in a novel SeV85AB immunization strategy designed to enhance the immune protection against Mtb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00109-019-01844-3DOI Listing
December 2019

Reply to Tonby et al.

J Infect Dis 2019 06;220(1):176-178

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiz057DOI Listing
June 2019

Mycobacterial Lipoprotein Z Triggers Efficient Innate and Adaptive Immunity for Protection Against Infection.

Front Immunol 2018 16;9:3190. Epub 2019 Jan 16.

Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, China.

Mycobacterial lipoproteins are considered to be involved in both virulence and immunoregulatory processes during () infection. In our previous investigations on the immunoreactivity of more than 30 proteins in active TB patients, we identified mycobacterial lipoprotein Z (LppZ) as one of the most immune dominant antigens. How LppZ triggers immune responses is still unclear. In this study, we analyzed LppZ-mediated innate and adaptive immunity using a murine air pouch model and an infection model, respectively. We found that LppZ could not only recruit inflammatory cells but also induce the production of proinflammatory cytokines inside the pouches. LppZ could also induce strong Th1 responses following immunization and confer protection against challenge with virulent strain H37Rv at a similar level to BCG vaccination but with less pathological damage in the lungs. Furthermore, we revealed the presence of LppZ-specific functional CD4 T cells in the lungs of the challenged mice that were capable of secreting double or triple cytokines, including IFN-γ, IL-2, and TNF-α. Our study thus demonstrates that LppZ is of strong immunogenicity during infection in both humans and mice and has the ability to trigger effective innate and cellular immunity. Considering the limitations of candidate antigens in the pipeline of TB vaccine development, LppZ-mediated immune protection against challenge in the mouse model implies its potential application in vaccine development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2018.03190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343430PMC
October 2019

The predictive values of the tuberculin skin test and interferon-γ release assays for active tuberculosis development.

Lancet Infect Dis 2019 01;19(1):19-20

Shanghai Public Health Clinical Center, Fudan University, 201508 Shanghai, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(18)30712-6DOI Listing
January 2019

Differential T cell responses against DosR-associated antigen Rv2028c in BCG-vaccinated populations with tuberculosis infection.

J Infect 2019 04 5;78(4):275-280. Epub 2018 Dec 5.

School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China; Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Rd., Shanghai 201508, China; School of Laboratory Medicine and Life Science, Jinlin Agriculture University, Changchun 130033, China. Electronic address:

The IFN-γ release assays (IGRAs) based on region of difference 1 (RD1) antigens have improved diagnosis of Mycobacterium tuberculosis (Mtb) infection. However, IGRAs with these antigens could not distinguish latent tuberculosis infection (LTBI) from active tuberculosis (ATB). DosR regulon genes are thought to be important for Mtb dormancy, and their products have higher immunogenicity in LTBI than ATB individuals, suggesting protective immunity mediated by DosR regulon-encoded antigens and potential utility of them for differential diagnostics of Mtb-infected populations or development of therapeutic vaccines against tuberculosis (TB). Among them, Rv2028c is a dormancy-related antigen that has demonstrated potential use in TB control, but its immunological characteristics in the BCG-vaccinated Chinese population are unknown. In this study, a total of 148 individuals, including 98 patients with ATB, 20 cases with LTBI and 30 healthy controls, were tested for Rv2028c-specific T cell responses by using an IFN-γ ELISA assay. The results showed that the T-cell responses in LTBI individuals were almost always higher than those in ATB patients, regardless of the site of infection or the results of bacteriological examination in the patients. This allowed for good differentiation between these two groups of Mtb-infected individuals even in the BCG-vaccinated high TB-incidence setting that pertains in China. In addition, the diagnostic efficacy for ATB was enhanced by combining the results from Rv2028c and RD1 antigen-based IFN-γ ELISA assays. In conclusion, Rv2028c-specific T-cell responses might contribute to natural protection against dormant Mtb infection, and the determination of these responses can aid discrimination between healthy LTBI individuals and ATB patients in the Mtb-infected populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2018.10.016DOI Listing
April 2019

The Role of KLRG1 in Human CD4+ T-Cell Immunity Against Tuberculosis.

J Infect Dis 2018 04;217(9):1491-1503

Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University.

Background: KLRG1 is a marker of terminally differentiated CD8+ T cells in viral infection, but its role in human Mycobacterium tuberculosis infection remains elusive.

Methods: A set of cohorts of patients with tuberculosis was designed, and the expression profiles and functions of KLRG1+CD4+ T cells were determined with and without antibody blocking.

Results: KLRG1 expression on CD4+ T cells was significantly increased in patients with active tuberculosis, compared with healthy controls and patients without tuberculosis. Upon M. tuberculosis-specific stimulation, the ability to secrete interferon γ, interleukin 2, and tumor necrosis factor α was significantly greater in KLRG1-expressing CD4+ T cells than in their KLRG-negative counterparts and was accompanied by a decreased proportion of regulatory T cells and increased Akt signaling. However, KLRG1-expressing CD4+ T cells had a shorter life-span, which was associated with a higher apoptosis rate but a similar proliferative response. Blockade of KLRG1 signaling significantly enhanced interferon γ and interleukin 2 secretion without affecting either cell apoptosis or multiplication. Addition of a specific Akt inhibitor prevented this increased cytokine response, implicating the Akt signaling pathway.

Conclusions: Our study delineated the profile of KLRG1+CD4+ T cells in patients with tuberculosis and suggests that M. tuberculosis infection drives CD4+ T cells to acquire increased effector function in a terminally differentiated state, which is restrained by KLRG1 via KLRG1/Akt signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/infdis/jiy046DOI Listing
April 2018

Determination of Lipoprotein Z-Specific IgA in Tuberculosis and Latent Tuberculosis Infection.

Front Cell Infect Microbiol 2017 30;7:495. Epub 2017 Nov 30.

Department of Microbiology and Immunology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Tuberculosis (TB) remains one of the most severe infectious diseases. It is still of paramount importance to establish more accurate, rapid, and efficient diagnostic methods. Since infection with () is largely mediated through the respiratory tract, IgA responses against mycobacterial proteins are worthy of investigation for their potential clinical utility. In this study, the IgA response targeting lipoprotein Z (LppZ) was determined by using a homemade ELISA with plasma of TB patients ( = 125), LTBI individuals ( = 92), healthy controls (HCs) ( = 165), as well as TB patients undergoing anti-TB treatment ( = 9). In parallel the antigen-specific IFN-γ release from PBMCs triggered by LppZ and -specific ESAT-6 or CFP-10 was detected by using an ELISPOT assay. It was found that the LppZ-specific IgA level was dramatically higher in TB patients than in HCs ( < 0.0001). Compared to that before anti-TB treatment, the LppZ-specific IgA level decreased substantially after 2 months of anti-TB treatment ( = 0.0297) and remained at low levels until the end of the treatment. What is more, pulmonary TB patients exhibited significantly higher LppZ-specific IgA-values than extra-pulmonary TB patients ( = 0.0296). Interestingly, the LppZ-specific IgA-values were negatively correlated to the amounts of IFN-γ released in response to LppZ with statistical significance ( = -0.5806, = 0.0002). LppZ-specific IgA level was also higher in LTBI individuals than in HCs ( < 0.0001). Additionally there were some PPD HC individuals with high LppZ-specific IgA levels but the potential of this assay for identifying leaky LTBI in PPD HCs needs to be further investigated through follow-up studies. The sensitivity of detecting TB solely with ESAT-6 or CFP-10-specific IFN-γ release was increased by including the LppZ-specific IgA results, respectively, from 86.11 to 100% and 88.89 to 100%; the sensitivity of screening for LTBI was increased from 80.36 to 83.93% and 57.14 to 69.64%, respectively. The higher LppZ-specific IgA responses in TB and LTBI populations than in controls indicated high immunoreactivity to LppZ upon infection. Although the assay was not efficient enough for independent application in sero-diagnosis, LppZ-specific IgA might become a complementary biomarker for the improvement of TB and LTBI screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2017.00495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715530PMC
August 2018

Identification of mycobacterial bacterioferritin B for immune screening of tuberculosis and latent tuberculosis infection.

Tuberculosis (Edinb) 2017 12 31;107:119-125. Epub 2017 Aug 31.

Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Immunology, Shanghai, 200025, China; Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, 201200, China. Electronic address:

Objectives: It remains necessary and urgent to search for novel mycobacterial antigens to increase the sensitivity and specificity for tuberculosis (TB) diagnosis and latent TB infection (LTBI) screening. Antigens capable of inducing strong immune responses during Mycobacterium tuberculosis (M.tb) infection would be good candidates.

Methods: Cellular responses specific to M.tb derived bacterioferritin B (BfrB) were assessed by IFN-γ ELISPOT in three human cohorts, including healthy controls (HCs), LTBI population and pulmonary TB (PTB) patients. Its significance in TB diagnosis and LTBI identification was further analyzed.

Results: BfrB-specific IFN-γ responses in PTB and LTBI groups were significantly higher than that in HCs. However, BfrB-specific IFN-γ release was not as strong as that to ESAT-6 or CFP-10 in PTB patients whereas comparable in LTBI cohort with possible complementary properties to ESAT-6 or CFP-10. More interestingly, there were a considerable number of HCs with high BfrB-specific cellular responses. When HCs with high BfrB-specific cellular responses were subgrouped into ESAT-6/CFP-10 (SFUs = 3, 4, 5) and ESAT-6/CFP-10 (SFUs < 3) groups, those who belonged to ESAT-6/CFP-10 group exhibited higher PPD responsiveness than ESAT-6/CFP-10 group.

Conclusions: PTB and LTBI groups exhibit higher BfrB-specific IFN-γ responses than HCs. Although BfrB is not as immunodominant as ESAT-6/CFP-10 during acute M.tb infection, comparable BfrB-specific cellular immune responses are observed in LTBI population with the potential to increase the sensitivity for LTBI screening. Moreover, strong BfrB-specific IFN-γ release in the healthy cohort is probably cautionary in identifying leaky LTBI from HCs. BfrB might thus be considered as an additional biomarker antigen for LTBI identification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tube.2017.08.005DOI Listing
December 2017

Evaluation of a New IFN-γ Release Assay for Rapid Diagnosis of Active Tuberculosis in a High-Incidence Setting.

Front Cell Infect Microbiol 2017 11;7:117. Epub 2017 Apr 11.

Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan UniversityShanghai, China.

Blood-based interferon-gamma (IFN-γ) release assays (IGRAs) have been proven to be useful in the diagnosis of () infection. However, IGRAs have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. The established T-SPOT. assay containing -specific antigens ESAT-6 and CFP10 are widely used for immunodiagonsis of infection, but the high cost is one of the restricting factors against its clinical application in the developing countries. More recently, a cost-saving IGRA assay, TS-SPOT, was approved in China. This new assay contains an additional antigen Rv3615c. Rv3615c contains broadly recognized CD4 and CD8 epitopes, and T-cell responses to Rv3615c are as specific for infection as the responses to ESAT-6 and CFP10 in both -infected humans and -infected cattle. Therefore, we assessed the likely effect of inclusion of Rv3615c as stimulus besides ESAT-6 and CFP10 in an IGRA assay and evaluated the performance of TS-SPOT for diagnosis of infection and active TB compared with T-SPOT.. We tested 155 active TB patients, 90 non-TB lung disease patients, and 55 healthy individuals. The results presented an improved positive rate for diagnosis of active TB and infection, that could be attributable to inclusion of Rv3615c in the mixture of stimulatory antigens. The diagnostic efficiency of TS-SPOT assay for active TB was as follows: sensitivity 80.00%, specificity 83.45%, positive predictive value (PPV) 83.78%, negative predictive value (NPV) 83.45%, positive likelihood ratio (LR+) 4.83, and negative likelihood ratio (LR-) 0.24. The results were similar to those of T-SPOT., with an excellent agreement (κ = 0.91, 95% CI: 0.85-0.95) being observed between these two assays. The sensitivities of the TS-SPOT assay varied for patients with different forms of active TB, with the highest sensitivity for patients with culture-positive pulmonary TB (92.16%) and the lowest for those with tuberculosis meningitis (50.00%). Taken together, the current evidence indicates that this new TS-SPOT assay is a useful adjunct to the current tests for rapid diagnosis of active TB and infection in low-income and high-incidence settings due to its characteristics of cost-effectiveness and high-quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2017.00117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386965PMC
September 2017

Sendai Virus Mucosal Vaccination Establishes Lung-Resident Memory CD8 T Cell Immunity and Boosts BCG-Primed Protection against TB in Mice.

Mol Ther 2017 05 23;25(5):1222-1233. Epub 2017 Mar 23.

Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China; TB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Shanghai 201508, China. Electronic address:

Accumulating evidence has shown the protective role of CD8 T cells in vaccine-induced immunity against Mycobacterium tuberculosis (Mtb) despite controversy over their role in natural immunity. However, the current vaccine BCG is unable to induce sufficient CD8 T cell responses, especially in the lung. Sendai virus, a respiratory RNA virus, is here engineered firstly as a novel recombinant anti-TB vaccine (SeV85AB) that encodes Mtb immuno-dominant antigens, Ag85A and Ag85B. A single mucosal vaccination elicited potent antigen-specific T cell responses and a degree of protection against Mtb challenge similar to the effect of BCG in mice. Depletion of CD8 T cells abrogated the protective immunity afforded by SeV85AB vaccination. Interestingly, only SeV85AB vaccination induced high levels of lung-resident memory CD8 T (T) cells, and this led to a rapid and strong recall of antigen-specific CD8 T cell responses against Mtb challenge infection. Furthermore, when used in a BCG prime-SeV85AB boost strategy, SeV85AB vaccine significantly enhanced protection above that seen after BCG vaccination alone. Our findings suggest that CD8 T cells that arise in lungs responding to this mucosal vaccination might help to protect against TB, and SeV85AB holds notable promise to improve BCG's protective efficacy in a prime-boost immunization regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymthe.2017.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5417795PMC
May 2017

Long-term Follow-up of 5 Survivors after the First Outbreak of Human Infections with Avian Influenza A(H7N9) Virus in Shanghai, China.

Chin Med J (Engl) 2016 09;129(17):2128-30

Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032; Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0366-6999.189061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009600PMC
September 2016

A case with non-typical clinical course of H7N9 avian influenza.

Chin Med J (Engl) 2013 Nov;126(22):4399

Shanghai Public Health Clinical Center Affiliated to Fudan University, Jinshan, Shanghai 201508, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
November 2013

Clinical findings in 111 cases of influenza A (H7N9) virus infection.

N Engl J Med 2013 Jun 22;368(24):2277-85. Epub 2013 May 22.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, First Affiliated College of Medicine, Zhejiang University, Hangzhou, China.

Background: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus.

Methods: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013.

Results: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02).

Conclusions: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1305584DOI Listing
June 2013

Rapid detection and monitoring therapeutic efficacy of Mycobacterium tuberculosis complex using a novel real-time assay.

J Microbiol Biotechnol 2012 Sep;22(9):1301-6

State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, PR China.

We combined real-time RT-PCR and real-time PCR (R/P) assays using a hydrolysis probe to detect Mycobacterium tuberculosis complex (MTBC)-specific 16S rRNA and its rRNA gene (rDNA). The assay was applied to 28 nonrespiratory and 207 respiratory specimens from 218 patients. Total nucleic acids (including RNA and DNA) were extracted from samples, and results were considered positive if the repeat RT-PCR threshold cycle was < or =35 and the ratio of real-time RT-PCR and real-time PCR load was > or =1.51. The results were compared with those from existing methods, including smear, culture, and real-time PCR. Following resolution of the discrepant results between R/P assay and culture, the overall sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of all samples (including nonrespiratory and respiratory specimens) were 98.2%, 97.2%, 91.7%, and 99.4%, respectively, for R/P assay, and 83.9%, 89.9%, 72.3%, and 94.7%, respectively, for real-time PCR. Furthermore, the R/P assay of four patient samples showed a higher ratio before treatment than after several days of treatment. We conclude that the R/P assay is a rapid and accurate method for direct detection of MTBC, which can distinguish viable and nonviable MTBC, and thus may guide patient therapy and public health decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4014/jmb.1202.02032DOI Listing
September 2012

Fungal granuloma of mediastinal lymph nodes in an immunocompetent host.

Chin Med J (Engl) 2011 Aug;124(15):2396-9

Department of Respiratory Diseases, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200433, China.

This is a case report of mediastinal fungal granuloma in an immunocompetent host. The definite diagnosis was made by pathological biopsy via video-assisted thoracoscopy and silver methenamine staining showed aspergillus hyphae and spores in the epithelioid granuloma. In conclusion, opportunistic pathogenic fungi can cause granulomatous inflammation in mediastinal lymph nodes in an immunocompetent host, as it can do in an immunocompromised host. More attention should be paid on tissue biopsy and pathological examination to ensure a correct diagnosis for these kinds of cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2011

Sixty-two severe and critical patients with 2009 influenza A (H1N1) in Shanghai, China.

Chin Med J (Engl) 2011 Jun;124(11):1662-6

Department of Infectious Disease, Shanghai Public Health Clinical Center, Shanghai 201508, China.

Background: Pandemic influenza A (H1N1) emerged rapidly in China in May 2009. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A (H1N1) disproportionately affects younger ages and causes generally mild disease. To characterize disease progress, comorbidities, and treatment outcomes among consecutive severe and critically ill patients in a hospital served as a reference center for the care of patients with H1N1 in Shanghai, China.

Methods: A retrospective study on 62 severe and critically ill patients with 2009 influenza A (H1N1) was conducted in Shanghai Public Health Clinical Center. Demographic data, symptoms, comorbidities, disease progression, treatments, and clinical outcomes were collected for analysis.

Results: Sixty-two severe or critically ill patients were admitted to the hospital with confirmed 2009 influenza A (H1N1) infection. The median age of the study cohort was 40 years old with a range from 18 years to 75 years, and 67.7% were males. All patients presented with fever and respiratory symptoms. At presentation, 34 patients (54.8%) had comorbidities such as smoking (29.0%), hypertension (29.0%) and hepatitis B virus infection (9.7%). The median time from symptom onset to hospital admission was 6 days (interquartile-range 3 - 14 days) and 23 critically ill patients were admitted to Intensive Care Unit after admission. All the patients received neuraminidase inhibitors (oseltaminir), while 60 patients (96.7%) were treated with antibiotics, and 39 (62.9%) with corticosteroids. Twenty-three critical cases received noninvasive mechanical ventilation on the first day of admission, and 3 of them ultimately required invasive ventilation. Four death reports (6.5%) were filed within the first 14 days from the onset of critical illness with the primary causes of severe acute respiratory distress syndrome, hypoxemia, or complications, secondary infection and sepsis, pyopneumothorax and stroke.

Conclusions: Severe illness from 2009 influenza A (H1N1) infection in Shanghai occurred among young individuals. Critical cases were associated with severe hypoxemia, multisystem organ failure, and a requirement for mechanical ventilation. Most patients had a good prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2011

Hospitalized patients with novel influenza A (H1N1) virus infection: Shanghai, June - July 2009.

Chin Med J (Engl) 2010 Feb;123(4):401-5

Department of Emergency, Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai 201508, China.

Background: From late May 2009, sporadic imported cases of novel influenza A (H1N1) were continuously confirmed in Shanghai, but there were few reports on its clinical presentation in China. The aim of the study was to investigate the demographic and clinical features of the laboratory-confirmed cases and the treatment with oseltamivir.

Method: We performed a retrospective study in the Shanghai Public Health Clinical Center (SHAPHC), reviewing the medical records of the laboratory-confirmed patients derived from June 10 to July 20, 2009.

Results: A total of 156 cases were enrolled, of whom 152 had a history of recent travel. The mean age was 22.6 years and 89 cases (57.1%) were males. The most common symptoms were fever, cough, and sore throat, with children more likely to run a temperature above 38.5 degrees C than adults. The mean leucocyte count was 5.4 x 10(9)/L, the mean neutrophil count 3.2 x 10(9)/L and the mean lymphocyte count 1.4 x 10(9)/L. Other findings included a normal range or elevated level of C-reactive protein (CRP) and glutamic-pyruvic transaminase and a normal or decreased level of prealbumin; the levels of prealbumin and CRP were significantly lower in the children than in the adults. Fifty-two patients had abnormal chest CT results, with small unilateral or bilateral pulmonary infiltrates, axillary and mediastinal lymphadenopathy and local pleural thickening, while no cases showed symptoms of hypoxia. All the patients received oseltamivir and recovered without complications, but the duration of fever and virus shedding were significantly longer in the children than in the adults.

Conclusions: Travel-related circulation may be an important reason for the H1N1 epidemic in the non-epidemic areas, and the virus caused mild respiratory symptoms. The infection in children was more severe in terms of prealbumin levels, temperature, the duration of fever and virus shedding. Oseltamivir was effective for H1N1, but more effective in the adults than in the children.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2010

Pulmonary miliary tuberculosis and intestinal tuberculosis co-infected with AIDS.

J Dig Dis 2009 Aug;10(3):225-7

Gastroenterology Section, Shanghai Public Health Clinical Center Affiliated to Fudan University, Shanghai, China.

Infections with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis account for 25 million patients worldwide. Tuberculosis is the most common opportunistic infectious disease in HIV-infected subjects, and HIV infection is a high-risk factor for tuberculosis. The convergence of HIV and tuberculosis is a disaster practically unequalled in medical history. This is a rare case report on the topic of pulmonary miliary tuberculosis and intestinal tuberculosis with AIDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1751-2980.2009.00389.xDOI Listing
August 2009

[Bacteriological examination on needle biopsy specimens of cavity and tuberculoma after a short course chemotherapy in initially sputum positive pulmonary tuberculosis patients].

Zhonghua Jie He He Hu Xi Za Zhi 2006 Dec;29(12):832-4

Shanghai Public Health Center, Shanghai Public Health Center Affiliated to Fudan University, Shanghai 201508, China.

Objective: To evaluate the therapeutic effect of a short course chemotherapy on initially sputum positive cavitary pulmonary tuberculosis or tuberculoma by bacteriological examination of specimens through percutaneous lung biopsy after the chemotherapy.

Methods: Eighty-three cases of initially sputum positive pulmonary tuberculosis with cavities or tuberculoma were included from Jan. 2002 and May. 2004. The patients finished a course of chemotherapy (2HREZ/4HR), and the sputum was converted to smear-negative and culture-negative, but cavities or tuberculoma remained on the chest X-ray. Lung specimens were obtained from the wall or content of the cavity or from the tuberculoma by CT-guided percutaneous lung biopsy for bacteriological examination within one month after the course.

Results: All the needle biopsy specimens were smeared and cultured for Mycobacterium tuberculosis. Eight cases (8/83, 9.6%) showed positive results: 3 were smear-positive and culture-positive, and 5 smear-negative but culture-positive. Drug susceptibility test showed that 7 of them were drug-sensitive and the remaining 1 was resistant to rifampin and isoniazid. After follow-up of 24 months, 6 of them converted to sputum smear-positive.

Conclusion: Our study showed that 90.4% (75/83) of the tuberculosis cases achieved real bacteriological negative result on biopsies after a short course chemotherapy, and the bacteriological positive cases on biopsy experienced 75.0% (6/8) sputum bacteriological recurrence. The result suggests that the evaluation criteria with sputum on therapeutic effect of pulmonary tuberculosis needs to be reassessed.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2006
-->