Clinical features of patients with severe dengue in Guangdong Province from 2013 to 2019 / 中华传染病杂志

Objective:To analyze the clinical features of patients with severe dengue (SD) in Guangdong Province, and to improve the understanding of the diagnosis and treatment of SD in China.Methods:The clinical data, laboratory examination and etiological test results of 257 SD cases from 29 dengue fever designated hospitals in Guangdong Province from January 1, 2013 to December 31, 2019 were respectively collected. The relevant indicators of the criteria for severe organ involvement were quantified. Logistic regression analysis was performed to analyze the risk factors for the development of multiple organ failure in SD patients.Results:Among the 257 SD patients, age was (64.1±20.1) years old, with 65.4%(168/257) of them ≥60 years old, 142 were male and 115 were female. One hundred and fifty-two (59.1%) patients had underlying conditions, including 115(44.7%) patients with hypertension. The clinical manifestations were mainly fever (98.4%(253/257)), fatigue (70.0%(180/257)), cough or expectoration (44.4%(114/257)), lethargy or irritability (39.3%(101/257)), vomiting (30.4%(78/257)), abdominal pain or tenderness (20.6%(53/257)), hepatomegaly (2.3%(6/257)), bleeding tendency (59.5%(153/257)), and pleural effusion or ascites (43.6%(112/257)). Platelet count levels were decreased in 90.9%(231/254) of the cases, and 97.1%(234/241) of patients had normal or decreased hematocrit. The most common of severe manifestations were severe organ involvement (61.1%(157/257)), followed by severe bleeding (37.0%(95/257)) and severe plasma leakage (30.0%(77/257)). Severe organ involvements were more common in the kidney (27.6%(71/257)) and heart (26.8%(69/257)). Multivariate logistic regression analysis showed that age (odds ratio ( OR)=1.051, 95% confidence interval ( CI) 1.004 to 1.100, P=0.035), hypertension ( OR=5.224, 95% CI 1.272 to 21.462, P=0.022), elevated aspartate aminotransferase (AST) level ( OR=1.002, 95% CI 1.001 to 1.003, P=0.001), blood urea nitrogen (BUN) ( OR=1.050, 95% CI 1.005 to 1.098, P=0.030), and international normalized ratio (INR) ( OR=4.604, 95% CI 1.601 to 13.238, P=0.005) were risk factors for the development of multiple organ failure in SD patients. The detection results of serum samples form 113 SD patients in acute phase showed that dengue virus (DENV)-1 accounted for 89.4%(101/113), DENV-2 accounted for 9.7%(11/113), and DENV-3 accounted for 0.9% (1/113). Conclusions:Elderly and those with co-existing conditions such as hypertension in SD patients in Guangdong Province are more common. Severe organ involvement such as kidney and heart is the main cause of SD. DENV-1 infection is predominant. Significant elevated levels of AST, BUN and INR may be related to a poor prognosis.

The relationship between level of cytokines and onset of severe dengue and their role as early warning signs / 中华微生物学和免疫学杂志

Objective:To compare the levels of cytokines in patients with dengue fever (DF) and severe dengue (SD) at different time points during the course of disease, to seek the cytokines that can be used as early warning signs of SD, and to explore the relationship between the immune response and the pathogenesis of SD.Methods:Plasma samples at different time points were collected from 60 hospitalized patients including 48 mild cases and 12 severe cases in Guangzhou Eighth People′s Hospital during June to December, 2014. Levels of 19 cytokines including TNF-α, IL-6, IL-8, IL-10, IL-15, IL-17A, IFN-α2, IP-10, MCP-1, RANTES, GRO-α, PDGF-AA, PDGF-AB/BB, MIF, VEGF, sVCAM-1, sICAM-1, sFas and sFasL were determined by a multiplex Luminex system.The viral loads were determined by using fluorescence quantitative RT-PCR and the correlation between viral loads and cytokine level were analyzed.Results:The levels of TNF-α, IL-6, IL-8, IL-10, IL-15, IFN-α2, IP-10, MCP-1 and sVCAM-1 increased in dengue patients, while RANTES, GRO-α and PDGF decreased.The levels of IL-17A, MIF, VEGF, sICAM-1, sFas and sFasL did not change. The levels of TNF-α, IL-6, IFN-α2, IP-10 and sVCAM-1 in SD patients were significantly higher than those in DF patients at the early stage (Day 2-5 after disease onset), and the differences were statistically significant. On day 6-10, the levels of TNF-α, IL-6, IL-8, IL-10, IL-15, PDGF, RANTES, IFN-α2, IP-10 and sVCAM-1 were significantly different between DF and SD patients. The results of correlation analysis showed that the level of IL-15 was moderately correlated with viral load, while other cytokines was only weakly correlated or not.Conclusions:TNF-α, IL-6, IFN-α2, IP-10 and sVCAM-1 can be used as early warning signs of SD. The level of cytokines is related to the severity of dengue fever.

Serotype distribution and phylogenetic analysis of virus complete genome from indigenous dengue patients in Guangzhou in 2019 / 中华微生物学和免疫学杂志

Objective:To investigate the serotype distribution and phylogenetic analysis of virus complete genome from indigenous dengue patients in Guangzhou in 2019 and provide evidence for the development of prevention and treatment strategies.Methods:Dengue virus serotypes of indigenous dengue cases in 2019 were detected using serotype specific fluorescent PCR kits. Complete genome in the culture was performed on Illumina platform. Phylogenetic analysis was conducted on complete genomes extracted from ViPR and the isolates from this study with MEGA7.0 software.Results:In 2019, three prevalent serotypes of dengue virus were found in Guangzhou, among which serotype 1 accounted for 80.35%, serotype 2 accounted for 12.97% and serotype 3 accounted for 6.68%. There were no significant differences in gender, age and severity among three serotypes. Phylogenetic analysis of virus complete genome showed that serotype 1 belonged to genotypeⅠand had two origins, which was close to the Cambodian strain; serotype 2 belonged to genotype cosmopolitan, which was close to the epidemic strain in Southeast Asia; serotype 3 belonged to genotypeⅢ, which was in the same branch as the Indian strain.Conclusions:The dengue epidemic was caused by dengue virus serotypes 1, 2 and 3 in Guangzhou in 2019. Each serotype belonged to a genotype.

Analysis of immunological features of 135 patients with corona virus disease 2019 in Guangzhou City / 中华传染病杂志

Objective:To investigate the immunological features of 135 patients with corona virus disease 2019 (COVID-19), and to provide reference for the pathogenesis of the disease.Methods:The clinical and laboratory data of 135 confirmed COVID-19 patients in Guangzhou Eighth People′s Hospital from January 23 to February 29, 2020 were collected. The features of lymphocytes (CD4 + and CD8 + T lymphocytes, B lymphocytes, natural killer cells and natural killer T cells), and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ) of patients at a median of 19 (14, 27) days of admission were analyzed. Kruskal-Wallis test, Mann-Whitney U test, chi-square test and Spearman rank correlation were used for statistical analysis. Results:Patients were divided into three groups according to the relevant diagnostic criteria, including mild group (14 cases), ordinary group (92 cases) and severe group (29 cases). Decreased CD4 + T lymphocytes were found in 44.4% (60/135) patients, while decreased CD8 + T lymphocytes were found in 42.2%(57/135) patients. Compared to mild group and ordinary group, level of CD4 + T lymphocytes in severe group was significant lower ( Z=4.379 and 3.799, respectively, both P<0.01), and level of CD8 + T lymphocytes was also significant lower ( Z=2.684 and 3.306, respectively, P=0.022 and 0.003, respectively). Decreased B lymphocytes were found in 25.3% (24/95) patients and significant different among the three groups, with the lowest levels ((88(56, 189)/μL; Z=6.199, P=0.045) and most frequency of decreased levels ((52.2%(12/23); χ2=11.723, P=0.003) in the severe group. Compared to the mild group and the ordinary group, IL-6 level in severe group was significant higher ( Z=-4.022 and -4.108, respectively, both P<0.01) and IL-10 level was also significant higher ( Z=-3.261 and -4.006, respectively, both P<0.01). Similar levels of IL-2, IL-4, TNF-α and IFN-γ were found among three groups (all P>0.05). The IL-6 level was positively correlated with the persistence of viral shedding ( r=0.301, P=0.007). Conclusion:The immune-mediated inflammation may be the important cause of disease deterioration of COVID-19, which might be the key target of the treatment of severe cases.

Analysis of nine death cases with severe dengue fever / 中华传染病杂志

Objective To analyze the clinical features of death cases of dengue fever and the causes of their deaths.Methods The clinical data and death reports of nine death cases of dengue fever in Guangdong Province from June 23,2014 to September 10,2019 were retrospectively analyzed.All of nine cases were positive for serum dengue virus RNA as confirmed by reverse transcription polymerase chain reaction,and some of the virus strains were serotyped.Results The median age of the nine patients was 57.5(range: 18-80)years.Among them,six patients were females; eight patients were local cases and one was imported case; all of nine cases occurred in September and October.The median time from onset to visit hospital and diagnosis was three and four days,respectively.Three of the nine patients had underlying diseases.All of nine cases had fever,including three with double-peak fever.Eight of the cases had three or more severe dengue fever warning indexes before admission.Three cases had severe bleeding upon admission,one case had shock,and six cases had organ failure.Three cases underwent invasive examination,including arterial puncture catheterization,endoscopic titanium clip hemostasis,and percutaneous transluminal coronary angiography.Two cases developed malignant arrhythmia and one had massive hemorrhage of subcutaneous soft tissue after operation.The death cases included four cases of cardiogenic shock and fatal arrhythmia,three cases of encephalitis and encephalopathy,one case of refractory shock,and one case of acute liver failure.Among the six cases that underwent serological typing,four were identified as dengue virus type 1(DEN-1)and two were DEN-2.Conclusions Severe organ failure is the major cause of dengue fever-related death,especially fulminant myocarditis,and DEN-1 is most common.Early diagnosis and treatment,and avoidance of invasive procedures can effectively reduce the mortality rate of the severe dengue fever patients.

Analysis of nine death cases with severe dengue fever / 中华传染病杂志

Objective@#To analyze the clinical features of death cases of dengue fever and the causes of their deaths.@*Methods@#The clinical data and death reports of nine death cases of dengue fever in Guangdong Province from June 23, 2014 to September 10, 2019 were retrospectively analyzed. All of nine cases were positive for serum dengue virus RNA as confirmed by reverse transcription polymerase chain reaction, and some of the virus strains were serotyped.@*Results@#The median age of the nine patients was 57.5 (range: 18-80) years. Among them, six patients were females; eight patients were local cases and one was imported case; all of nine cases occurred in September and October. The median time from onset to visit hospital and diagnosis was three and four days, respectively. Three of the nine patients had underlying diseases. All of nine cases had fever, including three with double-peak fever. Eight of the cases had three or more severe dengue fever warning indexes before admission. Three cases had severe bleeding upon admission, one case had shock, and six cases had organ failure. Three cases underwent invasive examination, including arterial puncture catheterization, endoscopic titanium clip hemostasis, and percutaneous transluminal coronary angiography. Two cases developed malignant arrhythmia and one had massive hemorrhage of subcutaneous soft tissue after operation. The death cases included four cases of cardiogenic shock and fatal arrhythmia, three cases of encephalitis and encephalopathy, one case of refractory shock, and one case of acute liver failure. Among the six cases that underwent serological typing, four were identified as dengue virus type 1 (DEN-1) and two were DEN-2.@*Conclusions@#Severe organ failure is the major cause of dengue fever-related death, especially fulminant myocarditis, and DEN-1 is most common. Early diagnosis and treatment, and avoidance of invasive procedures can effectively reduce the mortality rate of the severe dengue fever patients.

Expression of genes associated with pattern recognition receptors in peripheral blood mononuclear cells from patients with dengue fever / 中华微生物学和免疫学杂志

Objective@#To investigate the roles of pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), retinoic acid-inducible geneⅠ-like receptors (RLRs) and nucleotide binding oligomerization domain-like receptors (NLRs) in the pathogenesis of dengue fever (DF) and the induction of immune responses to dengue virus.@*Methods@#Blood samples were collected from patients with DF at three different time points to isolate peripheral blood mononuclear cells (PBMCs) by density gradient centrifugation. Then PBMCs were used to extract ribonucleic acid (RNA). Expression of genes was detected by polymerase chain reaction (PCR) array.@*Results@#Expression of genes relating to PRRs signaling pathways in DF patients increased significantly in the early stage of the disease as compared with those in healthy controls, but decreased gradually during the recovery period. Expression of genes encoding TLR7 and TLR8 was enhanced at the early stage of DF. No significant changes in the expression of TLR3 and TLR9 genes were observed during the course of the disease. The genes encoding RIG-Ⅰ, MDA5 and LGP2 of RLRs family as well as NOD2 and OAS2 of NLRs family were all up-regulated.@*Conclusion@#Signaling pathways mediated by PRRs including TLR7/8, RIG-Ⅰ, MDA5 and so on play an important role in the pathogenesis of DF and the induction of immune responses to dengue virus.

Dynamic changes of dengue viral loads and IgM antibody and their relationships with disease severity / 中华微生物学和免疫学杂志

Objective To investigate the dynamic changes of dengue viral loads and IgM antibody in patients with dengue fever ( DF) and to analyze their relationships with disease severity. Methods A to-tal of 1 508 serum samples were collected from 1 140 hospitalized patients including 1 050 mild cases and 90 severe cases within 10 days after the onset of DF in Guangzhou in 2014. The viral loads were determined by using fluorescence quantitative RT-PCR. ELISA was performed to measure the dengue virus ( DENV)-spe-cific IgM antibody. Results In general, the DENV viral loads in patients declined gradually from 108 copies/ml on day 1 to 103 copies/ml on day 10 after the onset of DF. The viral loads in severe cases were significantly higher than those in mild cases on days 5 to 7 (P<0. 05). The positive rates of DENV RNA in serum samples also decreased with the disease progression from 100% on day 1 to 40% on day 10. Com-pared with the mild cases, the patients with severe DF showed higher positive rates of DENV RNA on day 6 and day 8 (P<0. 05). The DENV-specific IgM antibody could be detected on day 2 and the secretion of IgM antibody increased gradually with the disease progression. The levels of IgM antibody in mild cases were sig-nificantly higher than those in severe cases (P<0. 001). The positive rates of IgM antibody in patients in-creased form 8% on day 2 to 95% on day 6. Higher positive rates of IgM antibody were detected in mild ca-ses on days 5 and 6 as compared with those in patients with severe DF (P<0. 05). Conclusion High viral load and low level of IgM antibody during the fastigium of DF were closely associated with the disease severity.

Characteristics of Traditional Chinese Medical Syndrome Types of Dengue Fever Patients Admitted in Guangzhou and Xishuangbanna in the Year of 2013:An Analysis of 117 Cases / 广州中医药大学学报

Objective To investigate the characteristics of traditional Chinese medical syndrome types of fulminant and epidemic dengue fever patients admitted in Guangzhou and Xishuang banna in the year of 2013,and to ex plore the differences of etiology and pathogenesis, illness, and treatment for the patients in the two regions. Methods We collected the clinical data of 78 cases receiving integrative Chinese and western medicine from 255 patients admitted in Guangzhou Municipal Eighth People’s Hospital, and the clinical data of 39 cases receiving integrative Chinese and western medicine from 120 patients admitted in the People’s Hospital of Xishuangbanna Dai Nationality Autonomous Prefecture in the year of 2013. The traditional Chinese medical syndrome types and the syndrome scores of the total of 117 cases were investigated. The method of phenology was used for the analysis of epidemic time and epidemic region of dengue fever, and the theory of defense-qi-nutrient-blood syndrome differentiation of seasonal febrile diseases was used for the analysis of etiology and pathogenesis of dengue fever. Results ( 1) Dengue fever was epidemic in the first ten days of July and in the middle ten days of November of the year 2013 in Guangzhou region, and was epidemic in the middle ten days of August and the first ten days of October in Xishuangbanna region. The epidemicity of dengue fever in Guangzhou covered the end of summer and the whole autumn, and then disappeared before the coming of winter. In Xishuangbanna , the epidemicity of dengue fever was obvious in autumn, and disappeared in late autumn. ( 2) In the two hospitals, dengue fever patients were dominated by the syndromes of excessive heat in both Qifen and Xuefen, blood stasis blended with toxicity, excessive heat in Qifen, and lingering pathogens in order. (3) Before treatment, the scores of fever were higher in patients of Xishuangbanna hospital than those in patients of Guangzhou Eighth People’s Hospital ( P0.05) . After treatment for 6 days, fever disappeared in patients of both hospitals. (4) Before treatment, the scores of syndromes were higher in patients of Xishuangbanna hospital than those in patients of Guangzhou Eighth People’s Hospital ( P<0.05) . After treatment for 3 days, syndorme scores were improved in both hospitals ( P<0.01) , but the syndrome scores were higher in Xishuangbanna hospital than those in patients of Guangzhou Eighth People’s Hospital. After treatment for 6 days, syndrome scores were much improved in patients of both hospitals compared with those after treatment for 3 days (P<0.01) . Conclusion In dengue fever patients admitted in Guangzhou and Xishuangbanna region, the syndrome of excessive heat in both Qifen and Xuefen is the leading type, and then comes blood stasis blended with toxicity. The illness state of patients in Guangzhou region is milder than that of the patients in Xishuangbanna region, the time for symptom relief is about one week, and similar therapeutic effect can be achieved in the two regions .

Retrospectively analyze 27 cases of death in AIDS patients with Penicilliosis marneffei / 实用医学杂志

Objective To investigate the clinical characters of death in AIDS patients with Penicilliosis marneffei (PSM), improving the diagnosis and treatment of PSM. Methods Retrospectively analyze the data of 27 AIDS patients died of PSM from January 2009 to December 2011 and review the relevant literatures in the past several years. Results The etiology diagnosis time ranged from 4 to 7 (4.9 ± 1.4) days from admission. There were 22 (81.5%) cases complicated with septic shock and 25 (92.6%) cases complicated with metabolic acidosis. There were 12 (44.4%) cases co-infected with pneumocyst pneumonia , 7 (25.9%) cases with TB. The main reasons accounting for the death were as follow:15(55.6%) cases died of septic shock, 5(18.5%) cases died of respiratory failure. Conclusion The death cases of AIDS patients with PSM showed the characters of relatively late etiology diagnosis and pathogenic therapy , mostly complicated with other opportunistic infections and often died of septic shock. Therefore, timely etiology diagnosis and earlier pathogenic therapy are the keys to treat the disease. Effectively controlling of the complications and co-infections may decrease the mortality.

Myocardial injury in 40 patients with dengue fever / 中华临床感染病杂志

Objective To investigate the myocardial injury in patients with dengue fever. Methods Three hundred and ninety-eight patients with dengue fever were included in the study. Blood myocardial enzyme spectrum and electrocardiography were examined in all patients. Results Abnormal myocardial enzyme spectrum was detected in 40 patients ( 10. 1% ), including the elevation of blood CK-MB, CK, LDH, α-HBDH and AST levels and increased cTnT levels were also detected in 5 patients. In these 40 patients, 34 showed abnormal electrocardiogram. Sinus bradycardia was the most common complication, other complications including ST or T wave changes. Some patients had more than two kinds of electrocardiogram abnormalities. Conclusion Dengue vires infection may induce myocardial injury, which suggests that examinations for myocardial enzyme spectrum and electrocardiography are necessary.

Analysis of clinical laboratory diagnosis in 484 Dengue fever patients / 中华检验医学杂志

Objective To analyze the characteristics of laboratory test resuits of dengue fever(DF)patients in Guangzhou area.Methods Routine tests were performed in the patients admission to hospital. Serology examination was performed in the patients in acute phase or recovery phase.The clinieal symptoms and teatures were analyzed and positive numbers and positivity ratios were calculated.Results The clinical symptoms of the dengue fever were typieal,with the features of fever,headache,myalgia and rash.The leukopenia rate was 76.0%,and the thromboeytopenia rate was 62.6%.The levels of ALT increased in 56.7%patients,and the levels of AST increased in 84.0%patients.Hypopotassemia was found in 46.1%patients.Dengue virus antibody IgM(DF-IgM)was detected positive from the first day to the 16th day of the onset,and the positive rate was 85.9% on the 8th day.Virus loads were positive by fluorescence real-time PCR in seven acute serum samples(within 3 days of the onset)of 51 cases whose DE-IgM were negative all the time, and the results was 105 -106 copies/ml(＜103 copies/ml means negative).Conclusions Clinical manifestations of this DF epidemic were typical including fever,headache,myalgia and skin rash.Most of the patients had decreased leukocyte and thrombocyte obviously.Liver damage was common but kidney damage was seldom.Halt of the patients got hypopotassemia.DF-IgM appeared in very early and persisted for a long time.The detection of DF-IgM within 7 days of the onset was helpful for diagnosis as early as possible.Viral load detected by real-time PCR could be another indicator of early pathogen diagnosis which provides complementation for antibody detection.

Clinical analysis of 54 serious severe acute respiratory syndrome patients with multiple organ injury / 中国呼吸与危重监护杂志

Objective To study the clinical characteristics of the severe acute respiratory syndrome(SARS) patients who progressed into multiple organ injury Methods Retrospective analysis was performed on the clinical data of 54 severe SARS patients with multiple organ injury in our hospital Results In 54 SARS patients,systemic inflammatory response syndrome(SIRS) developed in all cases and multiple organ injury developed in 49 cases and the mortality of patients with multiple organ injury was 22 2% Among the involved organs,lungs were the most frequently involved organ,followed by liver,heart,brain,kidney and blood system The injury in other organs was rare Conclusions Serious SARS is predisposed to progress into multiple organ injury The mortality was correlated to the number of organs involved Recognization and treatment of multiple organ injury at early stage are critical with improve cure rate of serious SARS with multiple organ injury

Clinical characteristics of 277 cases with dengue fever in Guangzhou during an epidemic of 2006 / 中华全科医师杂志

Objective To explore the clinical and laboratory characteristics of patients with dengue fever(DF)in Guangzhou from July to September in 2006 and to improve the awareness of dengue virus infection for physicians.Methods Clinical data of 277 patients with DF admitted to our hospital in Guangzhou were retrospectively analyzed.Dengue virus was isolated from patients' blood specimens by C6/36 cell culture and typed by reverse transcriptase-polymerase chain reaction(RT-PCR)assay and gene sequencing.Results Age of the 277 patients,148 males and 129 females,averaged 36 years with a standard deviation of 17 years,ranging from 9 months to 78 years.Their most common symptoms included fever(100.0%),skin rash(85.2%),headache(69.3%),myalgia(51.3%),bone soreness (39.0%)and nausea or vomiting(39.4%),and leucopenia and/hromboeytopenia occurred in 75.5% and 62.5% of them,respectively.Elevated alanine aminotransferase(ALT)was found in 59.6%,elevated aspartate aminotransferase(AST)in 81.6%,and hypopotassemia in 53.8% of them.Serum positivity of antibody against dengue virus IgM was 90.6%,which could be detected 3 to 10 days after onset of the illness,with a mean of 6.2 days with a standard deviation of 1.9 days.Cell-cultured virus from 20 patients were identified as typed by RT-PCR and RNA sequence analyses.All patients were clinically classified as typical DF and all of them completely recovered.Conclusions DF during this epidemic in Guangzhou was caused by dengue virus-1,with typical manifestations in all the patients but more damage in the liver.Some patients demonstrated hypopotassemia,but no dengue hemorrhagic fever or dengue shock syndrome was found.All the patients experienced a good prognosis with timely diagnosis and treatment.