Sensitivity, Specificity, and Safety of a Novel ESAT6-CFP10 Skin Test for Tuberculosis Infection in China: 2 Randomized, Self-Controlled, Parallel-Group Phase 2b Trials.

BACKGROUND: Diagnostics to identify tuberculosis infection are limited. We aimed to assess the diagnostic accuracy and safety of ESAT6-CFP10 (EC) skin test for tuberculosis infection in Chinese adults. METHODS: We conducted 2 randomized, parallel-group clinical trials in healthy participants and tuberculosis patients. All participants were tested with the T-SPOT.TB test, then received an EC skin test and tuberculin skin test (TST). The diameter of skin indurations and/or redness at injection sites were measured at different time periods. A bacillus Calmette Guerin (BCG) model was established to assess the diagnosis of tuberculosis infection using an EC skin test. RESULTS: In total, 777 healthy participants and 96 tuberculosis patients were allocated to receive EC skin test at 1.0 µg/0.1 mL or 0.5 µg/0.1 mL. The area under the curve was 0.95 (95% confidence interval [CI], .91-.97) for the EC skin test at 1.0 µg/0.1 mL at 24-72 hours. Compared with the T-SPOT.TB test, the EC skin test demonstrated similar sensitivity (87.5, 95% CI, 77.8-97.2 vs 86.5, 95% CI, 79.5-93.4) and specificity (98.9, 95% CI, 96.0-99.9 vs 96.1, 95% CI, 93.5-97.8). Among BCG vaccinated participants, the EC skin test had high consistency with the T-SPOT.TB test (96.3, 95% CI, 92.0-100.0). No serious adverse events related to the EC skin test were observed. CONCLUSIONS: The EC skin test demonstrated both high specificity and sensitivity at a dose of 1.0 µg/0.1 mL, comparable to the T-SPOT.TB test. The diagnostic accuracy of the EC skin test was not impacted by BCG vaccination. CLINICAL TRIALS REGISTRATION: NCT02389322 and NCT02336542.

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

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.

Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection.

A unique avian-origin A/H7N9 influenza virus has so far caused 134 cases with 44 deaths. Probing the host factors contributing to disease severity, we found that lower levels of plasma inflammatory cytokines on hospital admission correlated with faster recovery in 18 patients with A/H7N9 influenza virus, whereas high concentrations of (in particular) IL-6, IL-8, and macrophage inflammatory protein-1ß were predictive of a less favorable or fatal outcome. Analysis of bronchoalveolar lavage samples showed up to 1,000-fold greater cytokine/chemokine levels relative to plasma. Furthermore, patients with the rs12252-C/C IFN-induced transmembrane protein-3 (IFITM3) genotype had more rapid disease progression and were less likely to survive. Compared with patients with the rs12252-T/T or rs12252-T/C genotype of IFITM3, patients with the C/C genotype had a shorter time from disease onset to the time point when they sought medical aid (hospital admission or antiviral therapy) and a shorter interval to development of the acute respiratory distress syndrome stage (reflected by shorter intervals between clinical onset and methylprednisolone treatments and higher rates of mechanical ventilator use), as well as experiencing elevated/prolonged lung virus titers and cytokine production and higher mortality. The present analysis provides reported data on the H7N9 influenza-induced "cytokine storm" at the site of infection in humans and identifies the rs12252-C genotype that compromises IFITM3 function as a primary genetic correlate of severe H7N9 pneumonia. Together with rs12252 sequencing, early monitoring of plasma cytokines is thus of prognostic value for the treatment and management of severe influenza pneumonia.

Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance.

BACKGROUND: On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. METHODS: We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. FINDINGS: All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. INTERPRETATION: Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. FUNDING: National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.

Impact of Tuberculosis on Disease Severity and Viral Shedding Duration in COVID-19 Patients.

Accumulating evidence show a potential association between tuberculosis and COVID-19 disease severity. To further clarify the impact of tuberculosis on COVID-19 disease severity and viral shedding duration, a retrospective study was conducted on 223 COVID-19 patients, including 34 with tuberculosis and 189 without tuberculosis. Clinical information and viral load shedding time were collected. A higher percentage of severe/critical COVID-19 diagnosis and deaths was observed in patients with tuberculosis than in those without tuberculosis (8.8% vs. 3.2%, p = 0.142; 2.9% vs. 1.1%, p = 0.393), and COVID-19 patients with tuberculosis had longer viral shedding than those without tuberculosis (median: 15.0 days vs. 11.0 days; p = 0.0001). Having tuberculosis (HR = 2.21, 95% CI 1.37-3.00; p = 0.000), being of elderly age (HR = 1.02, 95% CI 1.01-1.03; p = 0.001) and being diagnosed with severe or critical COVID-19 (HR = 5.63, 95% CI 2.10-15.05; p = 0.001) were independent factors associated with prolonged virus time of SARS-CoV-2. COVID-19 patients with tuberculosis receiving anti-tuberculosis therapy time (ATT) for <2 months had a significantly longer virus shedding duration than those receiving ATT for ≥ 4 months (17.5 vs. 11.5 days, p = 0.012). Our results demonstrated that COVID-19 patients with tuberculosis tend to have more severe disease and a worse prognosis, and tuberculosis prolonged viral shedding, highlighting special attention and/or care required for COVID-19 patients with tuberculosis receiving ATT for <2 months.

Clinical findings for early human cases of influenza A(H7N9) virus infection, Shanghai, China.

A novel strain of influenza A(H7N9) virus has emerged in China and is causing mild to severe clinical symptoms in infected humans. Some case-patients have died. To further knowledge of this virus, we report the characteristics and clinical histories of 4 early case-patients.

Clinical comparison of one recovered case and one fatal case of human infection with H7N9 avian influenza in Shanghai Public Health Clinical Center in China.

H7N9 avian influenza is the latest subtype of influenza virus to emerge in the world. By April 17, 2013 in Shanghai, a total of 31 confirmed cases were reported, and 11 of these patients died. The epidemiological characteristics and the clinical progress of this new human flu infection are still not clear. Thirteen confirmed patients have now been treated in Shanghai Public Health Clinical Center. Among the first batch of patients, hospitalised at the beginning of April 2013, two who were admitted with the same estimated date of onset of disease had very different outcomes. After active treatment at the Centre, one recovered by April 18, 2013, but one patient entered critical condition and died on April 11, 2013. The clinical and laboratory characteristics in hospital are here analysed and compared to learn more about H7N9 avian influenza. Confirmation that the observed differences are valuable for prognosis and treatment decisions for H7N9 patients awaits authentication by analysis of more patients.

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

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).

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

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.

[Clinical features and prognosis of the mild cases of pandemic influenza H1N1 virus infection].

OBJECTIVE: Analyze the clinical characteristics of the mild cases of pandemic influenza H1N1 virus infection, as well as the relationship of clinical characteristics and patient genders. METHODS: A total of 245 influenza A (H1N1) patients confirmed by viral nucleic acid detection were included in the study. The patients' personal information, signs and symptoms, lab and iconography data, disease course, negative seroconversion duration of new influenza A (H1N1) viral nucleic acid after antiviral treatment and hospitalization stay were analyzed. Measurement data were analyzed using one-way analysis of variance (ANOVA) by software SPSS 11.5. P < 0.05 was defined as statistically significant. RESULTS: (1) Among the 245 patients, 130 were males and 115 were females, yielding a sex ratio of 1.13:1. Almost 52.0% (127/245) of the patients came from Australia, and 64.5% (158/245) were between 18 and 40 years old. (2) Clinical manifestations included fever (98.4%, 241/245), cough (80.8%, 198/245) and throat congestion (95.9%, 235/245), and lab findings were characterized by elevated C-reaction protein (CRP, 71.0%, 174/245) and neutrophil (52.2%, 128/245). (3) Female patients had significantly lower serum Prealbumin (pre-A) levels than male patients [(245.04 ± 75.3) vs (273.34 ± 92.18) mg/L, F = 5.55, P = 0.019]. (4) The patients' serum CRF levels significantly decreased after the treatment [(4.06 ± 3.47) vs (14.54 ± 14.68) mg/L, F = 6.18, P = 0.016], while the levels of CD3, CD4 and CD8 were significantly increased after treatment [(1451.23 ± 443.97) vs (819.97 ± 375.75) cell/µl, F = 32.61, P = 0.000; (771.33 ± 251.92) vs (435.36 ± 215.35) cell/µl, F = 44.43, P = 0.000; (593.16 ± 237.19) vs (342.47 ± 180.12) cell/µl, F = 28.518, P = 0.000, respectively]. (5) Approximately 30.6% (75/245) of the patients had abnormal signs on chest CT iconography, and 22.0% (54/245) had obvious signs indicating pneumonia. The average disease course was (3.9 ± 1.2) days, the average hospitalization stay was (5.0 ± 1.4) days, and the negative seroconversion duration of the mRNA after antiviral treatment was (3.8 ± 1.4) days. CONCLUSION: The influenza A (H1N1) virus was characterized by fever, cough and throat congestion, with elevated CRP and neutrophil being the most significant lab findings. The influenza A (H1N1) strain was able to affect multiple organs, including being able to affect hepatic synthesis of pre-A as well as immune functioning. The influenza A (H1N1) influenza virus strain was mild clinically, with short disease course and good prognosis.

[Involvement of endoplasmic reticulum stress in development of fatty liver fibrosis induced by methionine-choline-deficient diet in rats].

OBJECTIVE: To study role of endoplasmic reticulum stress in the development of fatty liver fibrosis induced by methionine-choline-deficient diet in rats. METHODS: Non-alcoholic steatohepatitis was induced by 10 weeks- methionine-choline-deficient diet (MCDD), Markers of endoplasmic reticulum stress were determined by immunoblotting and real-time PCR. RESULTS: The number of apoptotic hepatocytes, The expression levels of endoplasmic reticulum stress markers were increased significantly in MCDD group compared to control group (probability value less than 0.05 or probability value less than 0.01), while ratio of hepatocyte proliferation/apoptosis was decreased in MCDD group (probability value less than 0.01). The number of hepatocytes apoptosis, and the expression levels of endoplasmic reticulum stress markers were decreased significantly 2 weeks after the feeding with normal diet in MCDD group (probability value less than 0.05 or probability value less than 0.01). CONCLUSION: MCDD induces endoplasmic reticulum stress and fibrosis in rats.

Performance of Xpert/MTB/RIF assay for childhood pulmonary tuberculosis among HIV negative children with real world evidence in China.

BACKGROUND: Rapid and accurate notification of childhood pulmonary tuberculosis (PTB) is a worldwide challenge. Although the Xpert MTB/RIF assay (Xpert) has been endorsed as the initial test for suspected PTB in many countries, limited studies have reported the performance of Xpert in childhood PTB. The aim of this study is to evaluate the real-world performance of Xpert for the detection of childhood PTB among HIV negative children in China. METHODS: We consecutively extracted the data of all patients ≤14 years with pulmonary disease through the electronic medical record (EMR) systems of Shanghai Public Health Clinical Center from January 2014 to December 2017. The clinical profile, the decision-making tests including AFB smear, solid/liquid culture, pathological examination and Xpert result were matched and assessed. The real diagnostic accuracy and the all-factors case notification rate for childhood PTB with the implementation of Xpert were evaluated. RESULTS: 519 HIV negative cases ≤14 years with pulmonary disease were extracted from the data base. Of these, 145 had matched results, there were 374 non-matched cases including 346 with incomplete or unavailable data and 28 with NTM, BCG or an unidentified strain. For matched data, the overall sensitivity and specificity of the Xpert assay were 66.7% (32/48, 95%CI 0.52-0.80) and 87.6% (85/97, 95%CI 0.87-0.98) respectively against the gold standard; 34.6% (44/127, 95%CI 26.6-43.7) and 100% against the composite clinical reference standard (CCRS). The all-factors case notification rate by Xpert was 29%. CONCLUSION: Xpert/MTB RIF assay has acceptable sensitivity and excellent specificity for rapid diagnosis of children with pulmonary TB as well as for the detection of RIF resistance in China. However, implementation of Xpert for the initial diagnosis of childhood PTB is inadequate to meet the urgent requirement for rapid and accurate detection of childhood PTB.

[Mechanism of hepatocyte regeneration inhibition in rats with liver fibrosis induced by lipogenic methionine-choline- deficient diet].

OBJECTIVE: To obtain the evidence of fibrotic resolution in fatty liver by changing the diet and to clarify the mechanism of hepatocyte proliferation inhibition in rat with fatty liver fibrosis. METHODS: (1) Nonalcoholic steatohepatitis with advanced fibrosis was induced in rats by giving them a methionine-choline-deficient diet (MCDD) for 10 weeks (group M). A methionine-choline-control diet (MCCD) instead of MCDD was given for the last 2 weeks to the experimental group (group R). (2) Fibrosis and inflammation were determined by tissue staining. The activation of hepatic stellate cells and Kupffer cells were determined by immunostaining, immunoblot or quantitative RT-PCR respectively. (3) Hepatocytic apoptosis and proliferation were determined by TUNEL and BrdU staining respectively. Expressions of IL-6, STAT3, JNK-1, c-Jun, p21, C/EBPalpha, HNF6 and HGF-alpha were evaluated by quantitative RT-PCR and immunoblot to clarify the mechanism of hepatocytic proliferation inhibition. RESULTS: (1) Changing the diet from MCDD to MCCD triggered the reduction of fat in hepatocytes and a decrease in inflammatory response. (2) The regression of fibrosis was accompanied by the disappearance of activated stellate cells and macrophages. (3) Compared with control group (group C), hepatocytic apoptotic number increased significantly in group M (68 +/- 16 vs 40 +/- 8, P < 0.05) and the ratio of hepatocytic proliferation/apoptosis decreased markedly in group M (0.10 +/- 0.03 vs 0.19 +/- 0.03, P < 0.01); compared to group M, hepatocytic apoptotic number decreased significantly in group R (48 +/- 6, P < 0.05) and hepatocytic proliferation number and the ratio of hepatocytic proliferation/apoptosis increased markedly in group R (17.2 +/- 4.4 vs 7.5 +/- 3.0, 0.41 +/- 0.09 vs 0.10 +/- 0.03 respectively, P < 0.01). (4) Compared with group C, the mRNA level of IL-6, JNK-1, c-Jun, C/EBPalpha, p21 and HNF6 mRNA decreased significantly (0.34 +/- 0.18 vs 1.33 +/- 0.44, 0.41 +/- 0.11 vs 0.83 +/- 0.26, 0.19 +/- 0.03 vs 1.53 +/- 1.2, 1.94 +/- 0.64 vs 4.51 +/- 1.15, 0.34 +/- 0.20 vs 1.30 +/- 0.75, 0.47 +/- 0.21 vs 0.92 +/- 0.16 respectively, P < 0.05 or P < 0.01), and protein level of IL-6, STAT3, JNK-1, c-Jun, C/EBPalpha, P21 and HNF6 also decreased significantly in liver fibrotic stage (P < 0.05 or P < 0.01) while only IL-6, JNK-1 and p21 recovered immediately after a changed diet from MCDD to MCCD (P < 0.05 or P < 0.01). CONCLUSION: Food intake is a very important factor for controlling the fatty status and pathology of liver. Hepatocytic proliferation inhibition is associated with the arrested G(0)-S phasic transition in fatty liver fibrosis and the up-regulated expression of IL-6, JNK-1 and p21. These factors play a very important role in the recovery of fatty liver fibrosis.

Genetic and Clinical Profiles of Disseminated Bacillus Calmette-Guérin Disease and Chronic Granulomatous Disease in China.

Background: Disseminated Bacillus Calmette-Guérin disease (D-BCG) in children with chronic granulomatous disease (CGD) can be fatal, while its clinical characteristics remain unclear because both diseases are extremely rare. The patients with CGD receive BCG vaccination, because BCG vaccination is usually performed within 24 h after delivery in China. Methods: We prospectively followed-up Chinese patients with CGD who developed D-BCG to characterize their clinical and genetic characteristics. The diagnoses were based on the patients' clinical, genetic, and microbiological characteristics. Results: Between September 2009 and September 2016, we identified 23 patients with CGD who developed D-BCG. Their overall 10-year survival rate was 34%. We created a simple dissemination score to evaluate the number of infected organ systems and the survival probabilities after 8 years were 62 and 17% among patients with simple dissemination scores of ≤3 and >3, respectively (p = 0.0424). Survival was not significantly associated with the CGD stimulation index or interferon-γ treatment. Eight patients underwent umbilical cord blood transplantation and 5 of them were successfully treated. The genetic analyses found mutations in CYBB (19 patients), CYBA (1 patient), NCF1 (1 patient), and NCF2 (1 patient). We identified 6 novel highly likely pathogenic mutations, including 4 mutations in CYBB and 2 mutations in NCF1. Conclusions: D-BCG is a deadly complication of CGD. The extent of BCG spreading is strongly associated with clinical outcomes, and hematopoietic stem cell transplantation may be a therapeutic option for this condition.

Immune Repertoire Diversity Correlated with Mortality in Avian Influenza A (H7N9) Virus Infected Patients.

Specific changes in immune repertoires at genetic level responding to the lethal H7N9 virus are still poorly understood. We performed deep sequencing on the T and B cells from patients recently infected with H7N9 to explore the correlation between clinical outcomes and immune repertoire alterations. T and B cell repertoires display highly dynamic yet distinct clonotype alterations. During infection, T cell beta chain repertoire continues to contract while the diversity of immunoglobulin heavy chain repertoire recovers. Patient recovery is correlated to the diversity of T cell and B cell repertoires in different ways - higher B cell diversity and lower T cell diversity are found in survivors. The sequences clonally related to known antibodies with binding affinity to H7 hemagglutinin could be identified from survivors. These findings suggest that utilizing deep sequencing may improve prognostication during influenza infection and could help in development of antibody discovery methodologies for the treatment of virus infection.

Multiple gene mutations identified in patients infected with influenza A (H7N9) virus.

Influenza A (H7N9) virus induced high mortality since 2013. It is important to elucidate the potential genetic variations that contribute to virus infection susceptibilities. In order to identify genetic mutations that might increase host susceptibility to infection, we performed exon sequencing and validated the SNPS by Sanger sequencing on 18 H7N9 patients. Blood samples were collected from 18 confirmed H7N9 patients. The genomic DNA was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Genome analysis Tool. SNPs were verified by independent Sanger sequencing. The DAVID database and the DAPPLE database were used to do bioinformatics analysis. Through exon sequencing and Sanger sequencing, we identified 21 genes that were highly associated with H7N9 influenza infection. Protein-protein interaction analysis showed that direct interactions among genetic products were significantly higher than expected (p = 0.004), and DAVID analysis confirmed the defense-related functions of these genes. Gene mutation profiles of survived and non-survived patients were similar, suggesting some of genes identified in this study may be associated with H7N9 influenza susceptibility. Host specific genetic determinants of disease severity identified by this approach may provide new targets for the treatment of H7N9 influenza.

Clinical and laboratory observation of Bacillus Calmette-Guérin infections.

OBJECTIVE: To study the clinical features of BCG infection in children. METHODS: 51 cases confirmed with BCG infection from all over China were enrolled and followed up for at least 6 months. All cases were treated with anti-tuberculosis drugs. A random, open, group control study was designed in non-disseminated cases to evaluate curative effects of anti-tuberculosis drugs for early stage BCG infection. Disseminated cases were also closely monitored, and patients were given combined anti-tuberculosis drug therapy. RESULTS: In 34 (66.7%) non-disseminated cases, 19 children with local infections were treated with Isoniazid (Group A) and 15 were treated with Isoniazid and Rifampin (Group B). In the first 3 months, Group B responded better to anti- tuberculosis drug therapy than Group A (P<0.05). At the end of 6 months drug therapy, improvement rate was 100% of Group B vs. 89.5% of Group A (P<0.05). 33.3% children were admitted with disseminated BCG disease and were initially treated with Isoniazid and Rifampin. Most of these children responded poorly to drug therapies: Both isolated strains and BCG vaccination strain showed resistance to isoniazid, but susceptible to other First-line anti-tuberculosis drugs (Rifampin, Ethambutol and Streptomycin). CONCLUSION: INH does not perform well for treating BCG Chinese infections. Multiple drug regimens are necessary for treatment and preventing Drug-Resistance. Even for non-disseminated cases, preventive therapy using mono-isoniazid regimen is not suitable. BCG infections also occur in children without clear immunodeficiency, so parental education and awareness of health-care workers is essential for promptly recognition and handling BCG infections.

Influencial factors of the performance of interferon-γ release assays in the diagnosis of childhood tuberculosis.

Diagnosis of active tuberculosis (TB) in children remains difficult. This study aimed at evaluating the ability of interferon-gamma release assays (IGRAs) in the detection of active TB in human immunodeficiency virus-negative children vaccinated with Bacille Calmette-Guérin and investigating the effect of prednisolone treatment on the IGRAs performance. Among the 162 children with suspected TB disease recruited in China, 60 were tested with QuantiFERON-TB Gold In Tube (QFT-GIT) and 102 were tested with T-SPOT.TB. QFT-GIT presented a sensitivity of 83.9 % (95 % CI 66.9-93.4 %) and a specificity of 88.5 % (95 % CI 70.2-96.8 %), while T-SPOT.TB had a sensitivity of 75.9 % (95 % CI 63.4-85.2 %) and a specificity of 94.7 % (95 % CI 81.8-99.5 %). The positive predictive value was high in both assays, 92.9 % for QFT-GIT and 95.7 % for T-SPOT.TB. In total of these two kinds of IGRAs, false negative rate was significantly higher in children receiving systemic prednisolone (1 mg/kg/day) therapy for >1 week (two tested with T-SPOT.TB and five tested with QFT-GIT) than in those with ≤1 week of prednisolone therapy and without prednisolone therapy (57.1 vs. 18.3 %, p = 0.035). There was no significant difference of the positive rate of both tests in children <5 years old compared with those ≥5 years old. Both types of IGRAs showed good diagnostic values in detecting childhood TB before microbiological evidence was available. Glucocorticoids had a significant negative influence on IGRAs if treated for >1 week. Age made no difference on the performance of these tests in children.

Prognosis of 18 H7N9 avian influenza patients in Shanghai.

PURPOSE: To provide prognosis of an 18 patient cohort who were confirmed to have H7N9 lung infection in Shanghai. METHODS: Patients' history, clinical manifestation, laboratory test, treatment strategy and mortality were followed and recorded for data analysis. RESULTS: A total of 18 patients had been admitted into Shanghai Public Health Clinical Center from April 8th to July 29, 2013. 22.2% of the patients were found to have live poultry contact history and 80% were aged male patients with multiple co-morbidities including diabetes, hypertension and/or chronic obstructive pulmonary disease (COPD). This group of patients was admitted to the clinical center around 10 days after disease onset. According to laboratory examinations, increased C reactive protein (CRP), Procalcitonin (PCT), Plasma thromboplastin antecedent (PTA) and virus positive time (days) were indicative of patients' mortality. After multivariate analysis, only CRP level showed significant prediction of mortality (P = 0.013) while results of prothrombin time (PT) analysis almost reached statistical significance (P = 0.056). CONCLUSIONS: H7N9 infection induced pneumonia of different severity ranging from mild to severe pneumonia or acute lung injury/acute respiratory distress syndrome to multiple organ failure. Certain laboratory parameters such as plasma CRP, PCT, PTA and virus positive days predicted mortality of H7N9 infection and plasma CRP is an independent predictor of mortality in these patients.