Coxsackievirus Research Articles

Correlation between the levels of plasma brain natriuretic peptide and coxsackie virus A6 in hand, foot and mouth disease

Objective To investigate the clinical value of plasma brain natriuretic peptide (BNP) levels in predicting the severity of hand, foot and mouth disease (HFMD) in children with coxsackie virus A6 (CV-A6) infection. Methods A total of 305 children with CV-A6 type HFMD admitted to Xi′an Children′s Hospital from January 2017 to December 2018 were divided into general group (200 cases) and severe group (105 cases) according to the severity of the disease.The receiver operating characteristic curve was used to calculate the value of plasma BNP levels to predict the severe CV-A6 HFMD.Multivariate logistic regression analysis was used to analyze the correlation between the related factors and the severity of CV-A6 HFMD. Results Compared with the normal group, children in the severe group had statistically significant differences in WBC level, BNP level, neurological symptoms, circulatory disorders, and blood glucose levels(all P 15×109/L, blood glucose> 8.3 mmol/L, and BNP>294.85 ng/L were related to the severity of CV-A6 HFMD(OR=2.275, P=0.013; OR=6.057, P=0.028; OR=1.008, P<0.001). Conclusion BNP>294.85 ng/L is closely related to the severity of CV-A6 HFMD and has predictive value.It is an early warning factor for the severity of CV-A6 HFMD. Key words: Hand, foot and mouth disease; Coxsackie virus A6; Brain natriuretic peptide; Risk factors

Disseminated Cryptococcosis revealed by transverse myelitis in Immunocompetent patient: a case report and review of the literature

BackgroundTransverse myelitis (TM) is due to inflammatory spinal cord injury with bilateral neurologic involvement, which is sensory, motor, or autonomic in nature. It may be associated with autoimmune disease, vaccination, intoxication and infections. The most common infection cause of TM is Coxsackie virus and Mycoplasma pneumoniae. The cryptococcosis is rare. We present the case of disseminated cryptococcosis revealed by transverse myelitis in an immunocompetent 55-year-old male patient. The literature review is also stated.Case presentationThe 55-year-old man suffered from gradual numbness, weakness in both lower limbs and finally paralyzed in the bed. The thoracic spine Computed tomography (CT) was normal, but multiple nodules in the lung were accidentally discovered. Thoracic Magnetic Resonance Imaging (MRI) showed diffused thoracic spinal cord thickening and extensively intramedullary T2 hyper intensity areas. Gadolinium contrast enhanced T1WI showed an intramedullary circle-enhanced nodule at 9th thoracic level. Diagnosis was made by histological examination of the bilateral lung biopsy. The patient was treated successfully with systemic amphotericin B liposome and fluconazole and intrathecal dexamethasone and amphotericin B liposome.ConclusionsThis is a patient with disseminated cryptococcosis involving the lung, spinal cord and adrenal glands, which is rare in the absence of immunodeficiency.

Hand-foot-and-mouth disease virus receptor KREMEN1 binds the canyon of Coxsackie Virus A10

Coxsackievirus A10 (CV-A10) is responsible for an escalating number of severe infections in children, but no prophylactics or therapeutics are currently available. KREMEN1 (KRM1) is the entry receptor for the largest receptor-group of hand-foot-and-mouth disease causing viruses, which includes CV-A10. We report here structures of CV-A10 mature virus alone and in complex with KRM1 as well as of the CV-A10 A-particle. The receptor spans the viral canyon with a large footprint on the virus surface. The footprint has some overlap with that seen for the neonatal Fc receptor complexed with enterovirus E6 but is larger and distinct from that of another enterovirus receptor SCARB2. Reduced occupancy of a particle-stabilising pocket factor in the complexed virus and the presence of both unbound and expanded virus particles suggests receptor binding initiates a cascade of conformational changes that produces expanded particles primed for viral uncoating.

Viral serology in “infarct-like” acute myocarditis: Useful or useless?

The most common cause of myocarditis is viral infection, especially from cardiotropic viruses (Parvovirus B19, Human Herpesvirus 6 and Coxsackie) resulting in a destruction of the myocardium. Moreover, a serological analysis is not systematic and their value remains unclear. The objectives of this study were to assess the viral serology of the patients with acute myocarditis and the relation with clinical and CMR parameters at the acute phase and at distance. All cases of infarct-like acute myocarditis confirmed by CMR from April 2012 to January 2018 were included in a prospective study at Dijon University Hospital. A blood sampling including viral serology is obtained at the moment of the diagnostic. One-year follow-up included a complete clinical and rhythmic evaluation, and a CMR control. Among the patients with “infarct like” acute myocarditis, serological analyses were performed in 62 patients and cardiotropic viruses are found in 29 patients. No statistical difference was observed regarding demographic and clinical parameters. However, concerning CMR parameters, the extent of myocarditis is more important in the “cardiotropic viruses” group at the acute phase (10.4 vs. 7.3 – P = 0.05) and at three months (6.3 vs. 2.7 – P = 0.007) compared to the “no cardiotropic viruses” group. At one year, there was no significant difference between the two groups regarding CMR parameters. Cardiotropic viruses (HHV6, Parvovirus B19 and Coxsackie virus) were found in almost 50% of cases in “infarct like” acute myocarditis. According the presence or absence of cardiotropic viruses, CMR parameters were different. Furthermore, use of quantitative PCR (detection of viral genomes) or detection of viral DNA and RNA via in situ hybridization would be a challenge for the future identification of viruses in myocarditis.

Burchellin and its stereoisomers: total synthesis, structural elucidation and antiviral activity.

Burchellin and its analogues are a class of neolignan natural products containing a rare core with three contiguous stereogenic centers. In previous reports, racemic burchellin was synthesized without accessing each of the enantiomers. In this paper, a concise and efficient total synthetic route to divergently access the enantiomers of burchellin and those of its 1'-epi-diastereoisomer over six steps for each is disclosed, where each of the enantiomers was obtained by preparative chiral phase HPLC purification. The key steps include the construction of a 2,3-dihydrobenzofuran moiety by two Claisen rearrangements and a one-step rearrangement/cyclization and subsequent tandem ester hydrolysis/oxy-Cope rearrangement/methylation to furnish the basic skeleton of burchellin. The structures and absolute configurations of the four stereoisomers were determined using spectroscopic data analyses and comparison of experimental and calculated electronic circular dichroism data. These stereoisomers were found to have potent antiviral effects against coxsackie virus B3, and is the first time that bioactivity has been reported for these compounds.

The State of The Jak/Stat Pathway Affects the Sensitivity of TumorCells to Oncolytic Enteroviruses

A test of the sensitivity of seven colon cancer cell lines to a panel of 12 nonpathogenic human enteroviruses revealed significant differences in the ability of tumor cells to become infected and replicate different viral strains. Among the factors that can affect the sensitivity of cells to viruses are differences in the state of the mechanisms of antiviral protection, associated with a reaction to type I interferons. Using the two colon cancer cell lines CaCo2 and LIM1215 as a model, significant differences were revealed in the ability of cells to defend themselves against virus infection after 16 hours of treatment with 1000 units/mL of interferon-alpha. To study the effect of the state of the interferon response system, represented by the Jak/STAT signaling pathway, on the sensitivity of cells to different strains of enteroviruses, HEK293T cell lines were used. These are capable of supporting replication of each of the tested enteroviruses, as well as maintaining the ability to protect against viral infection after the treatment with interferon. Using the CRISPR/Cas9 system, HEK293T sublines with knockouts of the IFNAR1 and STAT2 genes were obtained. The sensitivity of control and knockout cells to infection with five strains of enteroviruses and the vesicular stomatitis virus was analyzed. It was noted that knockout of the IFNAR1 and STAT2 genes resulted in an increased sensitivity to all tested viruses. In knockout cells, the levels of reproduction of the vaccine derived of poliovirus type 1, Echoviruses 7 and 30, and Coxsackie viruses B5 and A7 were also significantly increased in comparison with the control HEK293T cells. Thus, deficiencies in the Jak/STAT signaling pathway in tumor cells lead to an overall increase in the sensitivity to oncolytic viruses.

Etiology analysis of hand, foot and mouth disease cases and genetic characteristics of coxsackievirus A6 in six prefectures/cities of Yunnan Province in 2018

Objective To detect the enterovirus VP4 and VP1 genes in 510 stool samples collected from hand, foot and mouth disease (HFMD) cases and analyze the phylogenetic characteristics of the entire VP1 genes of coxsackievirus A6 (CV-A6) strains in six prefectures/cities of Yunnan Province in 2018. Methods Viral RNA was abstracted from the stool samples. VP4 gene sequences were amplified by RT-PCR and sequenced using the MD91/OL68-1 primer pair to identify viral genotypes. Whole VP1 gene sequences were amplified and sequenced using appropriate primer pairs. The whole VP1 gene sequences of CV-A6 reference strains were downloaded from GenBank. MEGA5.2 software was used to analyze the similarity in nucleotide and amino acid sequences between different strains and phylogenetic tree was constructed for analysis of genetic characteristics and molecular epidemiology. Results VP4 and VP1 gene sequences were obtained from 57 out of 510 stool samples with a positive rate of 11.17% (57/510). There were 43 CV-A6 (8.43%, 43/510), six CV-A10 (1.17%, 6/510), two enterovirus A71 (EV-A71, 0.39%, 2/510) and two CV-A9 (0.39%, 2/510) strains. The other four strains were CV-A4 (0.19%, 1/510), CV-A5 (0.19%, 1/510), CV-B1 (0.19%, 1/510) and E11 (0.19%, 1/510). The phylogenetic analysis showed that all 43 CV-A6 strains belonged to sub-genotype D3. Conclusions In the 510 HFMD samples, CV-A6 strains were mostly detected with a detection rate of 8.43% and accounted for 75.44% (43/57) of all isolates, followed by CV-A10 (1.17%, 6/510) and EV-A71 (0.39%, 2/510). There was a large HFMD outbreak mainly caused by CV-A6 in Yunnan Province in 2018. The outbreak was caused by CV-A6 of sub-genotype D3, as was the case with pervious outbreaks in China. Key words: Hand, foot and mouth disease; Etiology; Coxsackievirus A6; VP4 gene; VP1 gene; Genetic characteristics analysis

Assessment of in vitro bioactivities of Pis v 1 (2S albumin) and Pis v 2.0101 (11S globulin) proteins derived from pistachio (Pistacia vera L.)

We studied the biological activity of Pis v 1 (2S albumin) and Pis v 2.0101 (11S globulin) against Coxsackie viruses (CV) B2, B3, B4 and B5 as well as their cytotoxicity against six cell lines. Results showed that the two allergens of pistachio significantly reduce the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against four Gram-positive and four Gram-negative bacteria as well as two fungi. Moreover, they exerted significant in vitro cytotoxic activities against Human ovarian carcinoma (A2780), human colon carcinoma (HTC), human glioblastoma (U-87-MG), human breast adenocarcinoma (MCF-7), and human prostate cell lines (PC3 and DU-145). Our findings revealed that the highest antimicrobial effect of the allergens was found against M. loteus (MIC = 10 µg/mL). The lowest IC50 value was found for Pis v 2.0101 allergen (11S globulin) against CV-B4 (30.20 ± 1.01 µg/mL). Furthermore, in vitro cytotoxicity assay showed IC50 values ranging from 21.09 ± 0.55 to 34.52 ± 0.90 and 26.34 ± 0.88 to 38.63 ± 0.80 µg/mL for Pis v 2.0101 (11S globulin) and Pis v 1 (2S albumin), respectively. As these allergens presented considerable effects against biofilm-related infections, CV-B2-5, and several cell lines, they might be employed as alternative/complementary treatments after further preclinical and clinical studies.

Clinical and Molecular Investigations of Hand, Foot and Mouth Disease Outbreak in Navi Mumbai, India

An outbreak of Hand, Foot and Mouth Disease (HFMD) was reported in Navi Mumbai in July-October 2018. Of 15 HFMD cases, two had recurrences within a month while three had lesions extending to trunk. Coxsackie virus A6 and A16 were detected from 13 cases (CV-A6 from 10 cases and CV-A16 from 3 cases) indicating co-circulation of these viruses. The present study highlights an urgent need of HFMD surveillance.

Onychomadesis and potential association with HFMD outbreak in a kindergarten in Hubei province, China, 2017

BackgroundIn 2017, an outbreak of onychomadesis occurred in kindergarten H, Hubei province, China. We investigated the field to learn about the magnitude and reason of the outbreak.MethodsThe case definition was that a child with onychomadesis or transverse ridging (Beau’s line) in fingernails and toenails without previous traumatic or systemic disease in kindergarten H from Sep. 1st to Nov. 30th, 2017. A retrospective cohort study was carried out to analyze the epidemiological relationship between onychomadesis and the hand-foot-mouth disease (HFMD) in Primary Class #2, kindergarten H. We also performed a serological survey for neutralizing antibodies against coxsackie virus A6 (CVA6), coxsackie virus A10 (CVA10) among 15 cases and six healthy children in the kindergarten. Meanwhile, some children were carried out with routine blood, fungal microscopic and microelement tests. Indoor environment examinations had been done for all classes.ResultsA total of 20 cases were identified in Kindergarten H. Seventy-five percent (15/20) cases occurred in Primary Class #2. Fifty-five percent of the cases (11/20) had suffered from HFMD within two months. The median time between onychomadesis and HFMD was 45 days (ranging from 31 to 58 days). A retrospective cohort study in Primary Class #2 showed the attack rate was 90.0% among 10 children who suffered from HFMD in the past two months compared to 30.0% among 20 children who didn’t (Rate Ratio [RR] =3.0, 95% Confidence Interval [CI] =1.5–6.0). The positive rates of neutralizing antibodies were 66.7% for CVA6 and 26.7% for CVA10 in tested cases. The result of routine blood, fungal microscopic, microelements tests were normal in cases. The indicators of environment were within the normal range.ConclusionThe results of this study suggested that the outbreak of onychomadesis in Hubei province was probably associated with HFMD epidemic within two months.

The clinical manifestations and treatment of hand, foot and mouth disease caused by Coxsackievirus A6

Hand-foot-and-mouth disease (HFMD) is a common infectious disease caused by human enterovirus (EVs). It is more common in children under 5 years of age.The clinical symptoms are mainly rash and herpes in the hands, feet, mouth and other parts.Some serious cases may suffer from serious complications in nervous system, respiratory system or circulatory system.Since 1998, HFMD has been mainly caused by enterovirus 71 and coxsackievirus A16 (CV-A16). In the past 10 years, coxsackievirus A6(CV-A6) has gradually replaced EV-71 and CV-A16, and become a main pathogen of HFMD.Many literatures have shown that CV-A6 often causes atypical HFMD, which is mainly characterized by a wider and more serious rash and desquamation, and even onychomadesis.At present, there are some reports on the prevalence and detection methods of HFMD caused by CV-A6.The paper reviewed on CV-A6 related etiology, epidemiology, clinical manifestations and treatment of HFMD. Key words: Hand, foot and mouth disease; Coxsackie A6; Pathogen; Epidemiology; Clinical manifestations; Treatment

Etiological and clinical characteristics of severe hand, foot and mouth disease in Xi′an in 2018

Objective To understand the etiological and clinical characteristics of children with severe hand, foot and mouth disease (HFMD) in Xi′an in 2018, and to provide the evidence for clinical diagnosis and treatment. Methods The children with severe HFMD admitted at Xi′an Children′s Hospital from January to December 2018 were selected as the research objects.Clinical data were collected, and the anal swab were detected by adopting real time(RT)-polymerase chain reaction(PCR). Results Ninety-five cases of HFMD were treated in Xi′an Children′s Hospital in 2018, of which 92 cases were severe and 3 cases were critical.Eighty-seven cases were positive for enterovirus nucleic acid, 30 cases were enterovirus 71(EV71)(31.6%), 39 cases were coxsackievirus A6(CA6) (41.0%), 3 cases were CA16(3.2%), 2 cases were CA10(2.1%) and 13 cases were other enteroviruses (13.7%). Among 95 patients, the ratio of male to female was 1.1∶1.0; the peak period of incidence of HFMD was from May to July, and the main age of onset of severe HFMD was under 3 years old.The main clinical manifestations were mental retardation, vomiting, irritability, lethargy and convulsion.Severe cases of CA6 are prone to convulsion.The main form of rash in CA6 cases was bullous rash, and demethylation may occur in recovery period.The rash in EV71 cases was small, thick, hard and few.After active treatment, only one child with EV71 infection died because of severe cerebral dysfunction, frequent convulsions and neurogenic pulmonary edema.The other child was discharged with hemiplegia and language dysfunction.The other severe children were cured and discharged from hospital. Conclusions In 2018, CA6 was the main pathogen of severe HFMD in Xi′an, with bullae was the main manifestation of skin rash, and nail removal could occur during convalescence.Critical and death cases were still caused by EV71. Key words: Severe hand, foot and mouth disease; Clinical characteristics; Etiology; Coxsackievirus A6

Transmission and serotype features of hand foot mouth disease in household contacts in Dong Thap, Vietnam

BackgroundHand, foot and mouth disease (HFMD) has emerged as a major public health issue in Vietnam since 2003. We aimed to investigate the household transmission of HFMD and its causative viruses from 150 households in a high incidence province in Vietnam.MethodsA longitudinal study was conducted in patients presenting to the provincial hospital with a HFMD-like syndrome, along with their household members between April and August 2014 in Dong Thap Province. Each participant was followed up for 2 weeks. We enrolled 150 patients aged under 15 who were clinically diagnosed with HFMD in Dong Thap Hospital, 600 household members, and 581/600 household members completed the study. All participants were interviewed using a standard questionnaire. Throat swabs and blood samples were taken for molecular detection of viruses and assessment of neutralizing antibodies, respectively. Index cases were defined using a clinical case definition, household contact cases were defined using a similar definition applied to the 2 weeks before admission and 2 weeks after discharge of the index case. Characteristics of index cases, household contacts, the attack rate, serotype features and related factors of HFMD were reported.ResultAmong 150 index cases, 113 were laboratory confirmed: 90/150 were RT-PCR-positive, 101/142 had a ≥ 4-fold increase of neutralizing antibody against Enterovirus A71 (EV-A71), Coxsackievirus (CV) A6 or CV-A16 across the two samples collected. 80/150 (53%) were males, and 45/150 (30%) were under the age of 1. The predominant serotype was CV-A6, identified in 57/87 (65.5%) of the specimens. No deaths were reported. Among 581 household contacts, 148 were laboratory confirmed: 12/581 were RT-PCR-positive, 142/545 had a ≥ 4-fold increase of neutralizing antibodies against EV-A71, CV-A6 or CV-A16; 4 cases experienced HFMD in the past 4 weeks. Attack rate among household contacts was 148/581 (25.5%). In 7/12 (58%) instances, the index and secondary cases were infected with the same serotype. Having a relationship to index case was significantly associated with EV infection.ConclusionThe attack rate among household contacts was relatively high (25.5%) in this study and it seems justified to also consider the household setting as an additional target for intervention programs.

Viral Etiology of Acute Respiratory Infections in Pediatric Patients in Lebanon.

BackgroundAcute respiratory infections (ARI) are the leading cause of death worldwide, especially among children. The majority of these infections in children are of viral etiology. In this study, we evaluated the incidence of viral ARI among children in Lebanon.Patients and MethodsChildren presenting with symptoms of ARI were prospectively recruited between September 2009 to February 2012. Nasopharyngeal aspirates were obtained from patients and screened for 11 respiratory viruses using a multiplex Luminex-based PCR assay.ResultsTwo hundred twenty-one patients were recruited with a median age of 1 year (IQR: 0 – 5). Out of 221 patients, 116 (52.5%) were positive for at least one virus, the majority (103/116; 88.8%) of which were in children under 6-year of age. Overall, 188 viruses were detected. Rhinovirus (RhV) was the most common virus detected in 81 (69.8%) patients followed by coxsackie virus and echovirus (CVEV) which were detected as one target in the panel in 45 (38.8%), and parainfluenza viruses (PIV types: 1, 2, 3, 4) in 24 (20.7%) patients. Coinfection with more than one virus was detected in 49 (42.9%) patients. RhV and CVEV were the most common viruses associated with co-infections and higher risk of rhinorrhea.ConclusionsViral pathogens account for at least half of the ARIs in Lebanon, with a high frequency of co-infections being detected.

Role of autophagy in the pathogenesis of myocarditis

Myocarditis refers to diffuse or focal inflammatory cell infiltration of the myocardial interstitium and necrosis or degeneration of adjacent myocardial fiber caused by infection or other causes, which is one of the common diseases that cause the death of infants and adolescents.Viral infection is the main pathogenic factor, but the pathogenesis of myocarditis has not yet been fully elucidated.Autophagy is a highly conservative process of self-digestion, which can provide amino acids, ATP and other substances for cells in the state of inflammation or starvation to help cells survive the energy crisis under excessive stimulation.However, excessive autophagy can promote the replication of viruses, which leads to autophagic death.In recent years, some researchers found that autophagy is closely related to the process of viral myocarditis associated with Coxsackie virus B3.The role of autophagy in the pathogenesis of myocarditis is reviewed in this article. Key words: Viral myocarditis; Autophagy; Coxsackie virus B3

Advancement of Mechanisms of Coxsackie Virus B3-Induced Myocarditis Pathogenesis and the Potential Therapeutic Targets.

Viral myocarditis is a cardiac disease caused by Group B Coxsackie virus of Enterovirus genus in the Picorna viridae family. It causes heart failure in children, young and adults. Ten Percent (10%) of acute heart failure and 12% of sudden deaths in young and adults who are less than 40 years is due to this viral myocarditis. If treatment action is not taken earlier, the viral disease can develop into chronic myocarditis and Dilated Cardiomyopathy which lead to congestive heart failure. And these eventually result in a reduced cardiac function which finally brings the victim to death. The only treatment option of the disease is heart transplantation once the acute stage of disease develops to chronic and Dilated Cardiomyopathy. Currently, there is a limitation in daily clinical treatments and even some available treatment options are ineffective. Therefore, focusing on search for treatment options through investigation is imperative. Recent studies have reported that biological molecules show a promising role. But their mechanism of pathogenesis is still unclear. A detailed study on identifying the role of biological molecules involved in Coxsackie B3 virus induced myocarditis and their mechanisms of pathogenesis; compiling and disseminating the findings of the investigation to the scientific communities contribute one step forward to the solution. Therefore, this review is aimed at compiling information from findings of current studies on the potential therapeutic role of micro RNA, cytokines and chemokines on the mechanism of pathogenesis of Coxsackie virus B3- induced myocarditis to give brief information for scholars to conduct a detailed study in the area.

Virucidal Effect of Guggulsterone Isolated from Commiphora gileadensis.

Commiphora gileadensis, locally known as becham, is a plant used in traditional Arabian medicine for treating headache, constipation, stomach, joint pain, and inflammatory disorders. Several studies have reported its antibacterial properties; however, no study has demonstrated its antiviral activity. This study aimed to evaluate the antiviral activity of C. gileadensis as well as to isolate its active compound and investigate its mode of action. This activity was evaluated using 4 viruses, herpes simplex virus type 2 (HSV-2), respiratory syncytial virus type B (RSV-B), coxsackie virus B type 3, and adenovirus type 5 by performing the plaque reduction assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for enveloped and nonenveloped viruses, respectively. The methanol extract of C. gileadensis leaves only showed antiviral activity against enveloped viruses with a selectivity index of 11.19 and 10.25 for HSV-2 and RSV-B, respectively. The study of the mechanism underlying antiviral activity demonstrated a virucidal effect by direct contact with these target viruses. The active compound, isolated using bio-guided assays involving TLC, was identified as guggulsterone by HPLC-diode array detection coupled with electrospray ionization mass spectrometry. Guggulsterone is an antagonist of the bile acid receptor and a modulator of cholesterol metabolism; however, its antimicrobial properties have been reported for the first time in this study.

Characteristics of the pathogen for hand-foot-and-mouth disease in Longhua District, Shenzhen in 2018

Objective The analysis of the characteristics of the pathogen for hand-foot-and-mouth disease (HFMD) in Longhua District, Shenzhen in 2018 provides scientific basis for developing and modifying the prevention and control strategies for the disease in the jurisdiction. Methods Use fluorescent quantitation RT-PCR method to conduct nucleic acid test for enteroviurs(EV), enteroviurs A71(EV-A71), coxsackievirus A16(CV-A16), Coxsackievirus A6 (CV-A6), Coxsackievirus A10 (CV-A10) of anal swab samples in 223 HFMD clinically diagnosed cases submitted by sentinel hospitals, while determine VP1 region sequence of Enteroviruses to analyze the subtype identification and the system evolution. Results There were 166 lab-confirmed cases with the positive rate of 74.44%, the first three pathogens in turn were CV-A6 (43.37%), CV-A16 (31.33%), CV-A10 (13.86%) ; The epidemic EV-A71 in Longhua District in 2018 was of the evolutionary branch of C4a. CVA16 ( n =18) was of the evolutionary branch of B1a (38.89%, 7/18) and B1b (61.11%, 11/18), and the homology of nucleotide and amino acid were 89.0%-99.9% and 98.3%-99.7% respectively. CV-A6 ( n =54) was of the evolutionary branch of D3, and the homology of nucleotide and amino acid were 95.1%-99.9% and 98.1%-99.0% respectively. While CV-A10 ( n =12) was of the evolutionary branch of C evolution, the homology of nucleotide and amino acid were 93.5%-99.8% and 97.6%-99.7% respectively. Conclusion The HFMD monitoring in the district shall be further strengthened, and continuous attention to pathogen spectrum composition and evolution of important pathogens in Longhua District, Shenzhen. 摘要： 目的 分析2018年深圳市龙华区手足口病病原学特点, 为辖区手足口病预防和控制策略的制定和调整提供 科学依据。 方法 采用荧光定量RT-PCR方法对哨点医院送检的223份手足口病临床诊断病例的肛拭子样本进行肠 道病毒 (Enteroviurs, EV) 、肠道病毒A 组71 型 (Enteroviurs A71, EV-A71) 、柯萨奇病毒A 组16 型 (Coxsackievirus A16, CV-A16) 、柯萨奇病毒A组6型 (Coxsackievirus A6, CV-A6) 、柯萨奇病毒A组10型 (Coxsackievirus A10, CV-A10) 核酸 检测, 并对EV核酸阳性样本进行VP1区序列测定、同源性分析、亚型鉴定和系统进化分析。 结果 实验室确诊病例有 166例, 阳性率为74.44%, 构成比前3位的病毒亚型依次为CV-A6 (43.37%), CV-A16 (31.33%), CV-A10 (13.86%) ; 2018 年深圳市龙华区流行的主要肠道病毒中, EV-A71属于C4a进化分支; CV-A16 ( n =18) 核苷酸同源性为89.0%~99.9%, 氨 基酸同源性为98.3%~99.7%, 属于B1a (38.89%, 7/18) 和B1b (61.11%, 11/18) 进化分支; CV-A6 ( n =45) 核苷酸同源性为 95.1%~99.9%, 氨基酸同源性为98.1%~99.0%, 均属于D3进化分支; CV-A10 ( n =12) 核苷酸同源性为93.5%~99.8%, 氨基 酸同源性为97.6%~99.7%, 均属于C进化分支。 结论 深圳市龙华区应进一步加强辖区手足口病监测, 持续关注病原 谱构成和重要病原体进化情况。

2237 Double Trouble: Coxsackie A and B Induced Hepatitis in an Adult

INTRODUCTION: Coxsackie virus which was first isolated in 1948 is a relatively common virus predominantly effecting children. There are 23 serotypes of Coxsackie A and 6 serotypes of the Coxsackie B viral strains. Clinical manifestations are generally mild in nature. We present a rare case of a 41yo female with Coxsackie A and B virus induced hepatitis. CASE DESCRIPTION/METHODS: 41yo F PMH DM, presented 36 weeks pregnant c/o 4 days of severe SOB and b/l LE edema. Home medications included metformin, insulin and pre-natals. No recent travel or use of herbal supplements. VS were T-98.3F, BP 130/92, HR 130, RR-22. PE showed LE edema and crackles on auscultation. Pt had severe features of preeclampsia and echo showed Global Cardiomyopathy (EF 21-25%). Labs showed Ph-7.21, CO2-33, HCO3-13, Cr-0.8, LDH-252, Alb-2.7, Bili-0.9/0.3, AST-40, ALT-23, ALP-184, WBC-11.8, Plt-172, INR-1.1, high urine protein. She was intubated for airway protection and taken for C-section. Over the next 3 days pt became febrile, hypotensive, tachycardic and worsening of her labs was noted, Cr-1.5, LDH-1528, Alb-2.1, Bili-0.9/0.5, AST-767, ALT-597, ALP-127, WBC-25.9, Plt-219, INR-1.3 before they started to improve. Pt was managed with aggressive diuresis, broad spectrum abx, and IV pressors for presumed septic/cardiogenic shock. Work up was positive for Coxsackie A and B virus. Pts bilirubin never increased beyond its current values. The rest of liver disease work up was unremarkable. Pt was discharged after stabilization and optimization of her medical condition. DISCUSSION: Coxsackie belongs to the Enterovirus genus, a member of the Picornaviridaefamily. It spreads via the fecal oral route, direct contact with bodily secretions or inhalation. Diagnosis is established with a positive viral culture or an increase in IgM titers. Coxsackie virus infection presents with nonspecific febrile illness, but may include pericarditis, myocarditis, hepatitis and encephalitis. Coxsackie A causes Hand foot and mouth disease, while Coxsackie B is the culprit of hepatitis. Hepatitis as a result of Coxsackie A strain is a very rare clinical phenomenon especially in the adult population. As seen in this case, the pts hepatitis and severe cardiomyopathy were likely secondary to Coxsackie virus. Treatment of Coxsackie virus infection is mainly supportive. Although commonly viral hepatitis is a results of Hepatitis A, B, C, D, E virus, HSV, EBV, and HIV, the possibility of Coxsackie virus induced hepatitis should always be considered.

TAKING VIRUSES TO HEART: AN INTERESTING CASE OF COXSACKIE MYOCARDITIS

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Diagnosing the cause of heart failure in young, healthy adults can be challenging and often associated with high morbidity. Here, we present a case of heart failure associated with viral myocarditis in a patient with a bicuspid aortic valve. CASE PRESENTATION: A 28-year-old man with no medical history presented with epigastric pain, nausea, vomiting, chest pain, and chills. On initial evaluation, he was afebrile, with a blood pressure of 102/72 mmHg, and a heart rate of 127 bpm. A 2/6 mid-systolic murmur and 2/6 early diastolic murmur were heard without jugular venous distension. Otherwise, his exam was unrevealing. Labs were significant for elevated liver function tests (AST 372 U/L and ALT 422 U/L), elevated creatinine of 1.64 mg/dL (no baseline available), and an elevated white blood cell count of 14.7 K/uL. Abdominal computed topography was unremarkable. A transthoracic echocardiogram showed a dilated left ventricle with moderate to severe global hypokinesis with an ejection fraction of 30%. A large 2.8 cm x 1.0 cm mass on the aortic valve was seen causing aortic stenosis and moderate to severe aortic regurgitation, concerning for endocarditis. The patient was empirically initiated on gentamicin and vancomycin but clinically deteriorated into presumptively septic shock requiring supplemental oxygen, vasopressors, and continuous renal replacement therapy for renal failure. He was taken to the operating room for emergent resection and replacement of the aortic valve. However, intraoperatively the surgeon found and removed a heavily calcified bicuspid aortic valve. His blood cultures and microbiology of his valve revealed no infectious organisms; antibiotics were discontinued. Slowly he improved clinically. Without clear reason for his decompensation, a viral panel was obtained and returned positive for coxsackie B virus. DISCUSSION: In the United States, myocarditis is uncommon, impacting only one percent of the population. The Coxsackie viruses are the most common cause of infectious myocarditis, and predominantly affect men with the average age of onset being 42 years old. The cardiac manifestations of the virus typically occur two weeks after viral infection and are caused by direct cytopathic effects, pathologic immune responses, or autoimmunity triggered by the infection. Therapy with ribavirin has shown to reduce mortality in rodent models if initiated soon after inoculation which limits its applicability in human treatment. In this patient, his viral illness precipitated his acute clinical condition in the setting of a congenital bicuspid aortic valve with calcification, and he was treated with supportive therapy. CONCLUSIONS: This case highlights the importance of evaluating for viral myocarditis in young patients with acute heart failure and nonspecific symptoms and the need to remain vigilant for undiagnosed structural heart defects in otherwise healthy patients. Reference #1: Tam, Patricia E. "Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.” Viral immunology 19.2 (2006): 133-146. Reference #2: O.V. Blagova, O.V. Blagova, A.V. Nedostup, E.A. Kogan, V.P. Sedov, Y.U.V. Frolova, S.L. Dzemeshkevich, A.G. Kupryanova, V.A. Zaidenov, A.E. Donnikov; High prevalence of viral and immune myocarditis in patients with "idiopathic” and genetic dilated cardiomyopathy: biopsy proved diagnosis, European Heart Journal, Volume 34, Issue suppl_1, 1 August 2013, P4238, https://doi.org/10.1093/eurheartj/eht309.P4238 DISCLOSURES: No relevant relationships by Kara Calhoun, source=Web Response No relevant relationships by Jennifer Duke, source=Web Response No relevant relationships by Brandy McKelvy, source=Web Response No relevant relationships by Abin Puravath, source=Web Response