A 14-year-old boy with severe erythema multiforme due to amoxicillin.

The most common cause of erythema multiforme (EM) in children is infectious diseases which account for approximately 90% of cases. Drug eruptions are another common cause. Here we are reporting about a male patient aged 14 years with lymphadenitis who developed severe diffuse erythema during the course of treatment with medications including several antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Based on the pathological findings of the skin biopsy, the skin rash was due to EM. Upon investigating the underlying cause of EM, viral antibody was positive for Coxsackie A6, lymphocyte transformation testing (LTT) was positive for one of the NSAIDs, and the patch test (PT) was positive for amoxicillin. Based on the pattern of distribution of the skin rash, the cause of EM was considered to be drug-induced eruption due to amoxicillin. In this case, we did not derive a diagnosis of drug eruption without investigating the possibility of drug induction, because most cases of EM in children are induced by infection and the antibody against Coxsackie A6 was elevated. To diagnose the possibility of amoxicillin-induced EM, it was important to distinguish between the distribution patterns of infectious versus drug-induced EM and to evaluate the possibility of drug induction by both LTT and PT. If the diagnosis of amoxicillin-induced EM, had not been made, the potential recurrence of EM with amoxicillin could have occurred.

Clinico Virological Characterization of Hand, Foot and Mouth Disease in a Tertiary Care Hospital, South India.

Introduction: Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease, caused by enteroviruses (EVs) which can present with typical or atypical lesions. Although the disease is self-limiting, it can also lead to serious complications. In the era of polio eradication, it is important to understand the population dynamics of enteroviruses causing HFMD as one of the circulating strains may become dominant. Methods: It was a collaborative study carried out in the Department of Dermatology and Microbiology of a tertiary care teaching hospital. The throat swabs were collected from 132 suspected HFMD cases. Real-time polymerase chain reaction (PCR) was performed to detect the presence of pan enteroviruses, followed by genotype-specific PCR targeting Human Enterovirus 71 (HEV-71) and Coxsackie virus A16 (CVA-16) and CVA-6 for pan Enterovirus-positive samples. Follow-up samples were collected from 14 children in the 2nd week and subjected to molecular testing to detect enteroviruses. Results: Among 132 children suspected to have HFMD, 44 were girls and 88 were boys, and the majority of them 76.5% (101/132) were under 2 years of age. A history of exposure to a similar clinical presentation was present in 15 children. Of 132 suspected cases, 60 samples (45.5%) were positive for pan Enterovirus. The predominantly circulating genotype was found to be CVA-6 (31.6% [19/60]). There were about 10 cases (16.6%) which had co-infection with both HEV71 and CVA-6. Rash with fever was the most common presentation (57%). In most of the cases with HEV 71, 92.3% (12/13) presented within 3 days of illness to the health-care facility. Of 60 positive cases, 25% (15/60) of children had the atypical distribution of rashes in the face, trunk, genitalia, thigh, neck, and axilla and 16.7% of children (10/60) had the atypical type of lesion either only papular lesions or erythema multiforme. Out of 14 follow-up samples, 13 were negative for EVs; one was positive for pan EV in the 2nd week, however, the patient lost to follow-up after that. Conclusion: HFMD outbreaks in our region were caused by various genotypes of enteroviruses. No severe complications were seen in the affected children. Nearly 30% had atypical presentation either in the form of lesion or site. Robust molecular epidemiological surveillance of HFMD is required to know the strain variations and other emerging genotypes in our setup.

Synthesis and antiviral activity of 1,2,3-triazolyl nucleoside analogues with N-acetyl-d-glucosamine residue.

A series of 1,2,3-triazolyl nucleoside analogues bearing N-acetyl-D-glucosamine residue was synthesized by the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction of N1-ω-alkynyl derivatives of uracil, 6-methyluracil, thymine and 3,4,6-tri-O-acetyl-2-deoxy-2-acetamido-ß-D-glucopyranosyl azide. Antiviral assays revealed the lead compound 3f which showed both the same activity against the influenza virus A H1N1 (IC50=70.7 µM) as the antiviral drug Rimantadine in control (IC50=77 µM) and good activity against Coxsackievirus B3 (IC50=13.9 µM) which was one and a half times higher than the activity of the antiviral drug Pleconaril in control (IC50=21.6 µM). According to molecular docking simulations, the antiviral activity of the lead compound 3f against Coxsackie B3 virus can be explained by its binding to a key fragment of the capsid surface of this virus.

LncRNA XIST knockdown reduces myocardial damage in myocarditis by targeting the miR-140-3p/RIPK1 axis.

Viral myocarditis (MC) is caused by Coxsackie virus B3 (CVB3)-induced cardiomyocyte apoptosis and inflammation, and changes in miRNA and lncRNA are linked to cardiac remodeling. The long non-coding RNA XIST (XIST) has been identified as a regulator in various pathological processes in heart diseases, but its role in CVB3-induced MC is not well understood. This research aimed to evaluate the impact that XIST has on CVB3-induced MC as well as the mechanism behind this effect. XIST expression in CVB3-exposed H9c2 cells (H9c2 cells) was evaluated by qRT-PCR. In CVB3-exposed H9c2 cells, reactive oxygen species production, inflammatory mediators, and apoptosis were experimentally observed. An investigation into and confirmation of the existence of an interaction involving XIST, miR-140-3p, and RIPK1 were carried out. The findings showed that CVB3 induced upregulation of XIST in H9c2 cells. However, XIST knockdown reduced oxidative stress, inflammation, and apoptosis of CVB3-exposed H9c2 cells. XIST was specifically bound to miR-140-3p, and there was mutual negative regulation between the two. Moreover, XIST downregulated RIPK1, which was mediated by miR-140-3p. The study suggests that downregulating XIST can alleviate inflammatory injury in CVB3-exposed H9c2 cells through the miR-140-3p/RIPK1 axis. These findings provide novel insights into the underlying mechanisms of MC.

Clinical profile and molecular typing of viral etiological agents associated with Hand, Foot and Mouth Disease (HFMD): A study from Udhampur, Northern India.

PURPOSE: Hand, Foot and Mouth disease (HFMD) is a contagious pediatric viral disease caused due to enteroviruses (EV) of the family Picornaviridae. Cases of HFMD were reported from a tertiary care health centre, Udhampur, (Jammu and Kashmir), Northern India. The present study highlights the clinical and molecular virological aspects of HFMD cases. MATERIAL AND METHODS: Cases reported during August 2016-September 2017, and clinically diagnosed as HFMD of all age groups were included. Clinical, Biochemical and molecular virology aspects were compared. Clinical samples (n â€‹= â€‹50) such as vesicle swab, buccal and throat swabs were collected for enterovirus detection. EV-RNA was detected by 5'NCR based RT-PCR and genotyping by VP1 gene amplification and cycle sequencing. RESULTS: Of the cases of HFMD enrolled (n â€‹= â€‹50), highest (84%) were of children aged <5 years, presented either or both anathemas and exanthemas with prodromal symptoms (fever, irritability). Clinical presentations involved mainly oral ulcers on lips and tongue (48%). Oral erosions were either single or multiple in numbers. Exanthemas were seen on hand and palm, widely spread up to buttocks, legs, arms and trunk. Of these, six patients were found anemic. Complete blood count (CBC) indicated lymphocytosis and C-reactive protein (n â€‹= â€‹10) in children aged <5 years. EV-RNA was detected in 78% (39/50) of the clinical samples. VP1 gene based typing indicated the presence of CV-A16, CVA6 and EV-A71 types. CONCLUSIONS: The study highlights association of EVs in HFMD cases in the reported region. CV-A16, CV-A6 and EV-A71 types were reported for the first time from Udhampur (J&K), Northern India. No differences were observed in the clinical profile of EV strains detected. Circulation of the strains warrant and alarm outbreaks. More focused studies on HFMD and monitoring of viral strains is mandatory.

Distribution and type characteristics of HPV infection of women in Shiyan , Hubei Region / 公共卫生与预防医学

Objective To analyze the distribution and type characteristics of human papillomavirus (HPV) infection in women in Shiyan, Hubei region, so as to provide a basis for the prevention and treatment of HPV infection. Methods From January 2019 to December 2020, a sample of 3,180 women in XX region who had sexual intercourse experience were randomly selected, and their HPV genotypes were tested using flow-through hybridization, then the distribution characteristics and types of HPV infection in women of different ages were observed. Results Among of 3 180 patients, HPV infection was predominant in women aged 31-50 years , with 25.85% (822/3 180) aged 31-40 years and 22.08% (702/3,180) aged 41-50 years. HPV infection was the least prevalent in the ≤25 and >60 years age groups, with 428 cases and 289 cases respectively. HPV infection occurred in 1 310 out of 3 180 women , with a positive infection rate of 41.19% (1 310/3 180). HPV infection was most prevalent in the ≤25 years and ≥60 years age groups, accounting for 56.78% and 67.13% respectively. Single infection was the main infection type in all age groups, accounting for 76.03%. Twenty-one HPV genetic subtypes were detected in the subjects, out of a total of 1 918 strains of the virus. The main high-risk subtypes for single infection were HPV16, HPV52 and HPV58, accounting for 13.92%, 13.87% and 12.57% respectively, followed by HPV53 and HPV33, accounting for 7.61% and 5.58% respectively. The predominant low-risk subtypes for single infection were HPV11, HPV8 and HPV6, with accounting for 7.51%, 5.47% and 5.01% respectively. Conclusion HPV infection in women in Shiyan, Hubei region is predominantly in the ≤25 and ≥60 years age groups, and early clinical screening and preventive measures such as vaccination for high-risk HPV typing are of vital importance.

Antiviral activity of Inonotusin A an active compound isolated from Boletus bellinii and Boletus subtomentosus.

Mushrooms produce various classes of secondary metabolites that could be used as antivirals in the future. The aim of this study was to determine the antiviral activity of methanolic extracts obtained from two edible mushrooms, Boletus bellinii (B. bellinii) and Boletus subtomentosus (B. subtomentosus), collected from the north forests of Tunisia, against Herpes Simplex Virus type 2 and Coxsackie Virus B type 3. In vitro micro-inhibition assays and cytotoxicity screening were performed on Vero cells. The tested Boletus methanolic extracts were found to be non-cytotoxic at high doses (50% cytotoxic concentration - CC50 > 1 mg/mL) and exhibited relevant viral inhibition with 50% inhibitory concentration, i.e., IC50 of 3.60 ± 0.66 µg/mL and 35.70 ± 7.42 µg/mL for B. bellinii, and 5.67 ± 1.02 µg/mL and 56.88 ± 9.56 µg/mL for B. subtomentosus, against HSV-2 and CVB-3, respectively. Interestingly, Boletus methanolic extracts showed high selectivity index (SI) values against both viruses, with the highest values against HSV-2 (SI > 800). Both viral strains were inhibited when treated with extracts during the early stages of virus replication. Inonotusin A was isolated and identified as the compound responsible for these activities. The latter is a novel antiviral agent that may have clinical utility or serve as a lead compound for further development. This study is the first attempt to investigate the antiviral activity of inonotusin A, isolated from the genus Boletus. The information from the present work should be a valuable reference for future studies on the antiviral activity of inonotusin A.

Viral Versus Vaccine-Associated Acute Transverse Myelitis With Neuromyelitis Optica Immunoglobulin G Antibody and Myelin Basic Protein: A Case Report.

Transverse myelitis is a rare spinal cord disorder caused by local inflammation. Usually, this occurs as a complication from infection or autoimmune disease; however, there have been reported idiopathic causes such as vaccinations. A 73-year-old female with a medical history significant for Hashimoto's thyroiditis presented with new-onset paresthesias in her lower extremities. Her symptom onset was about five weeks after receiving influenza and tetanus, diphtheria, and pertussis (TDaP) vaccines. Magnetic resonance imaging (MRI) of the spine revealed an increased T2 signal of the lower cervical and thoracic spine. Lumbar puncture was also performed, and cerebrospinal fluid (CSF) serology showed elevated myelin basic protein (MBP) at 108.3 ng/mL (reference range: 0-5.5 ng/mL). Serology panel revealed Coxsackie virus type B4 antibody at 1:80 (reference range: <1:10) and Echovirus type 6 antibody at 1:640 (reference range: <1:10). Neuromyelitis optica (NMO) immunoglobulin G (IgG) antibody was 24.6 U/mL (reference range: <2.9 U/mL). She was diagnosed with acute transverse myelitis (ATM) and treated with alternating steroids and plasma exchange (PLEX) therapy for five days each. This case highlights the possible associations of vaccines with transverse myelitis. Although ATM is a rare disorder with serious complications, it has a favorable prognosis in the setting of rapid detection and treatment. Vaccine-related ATM remains controversial, but patients with these adverse reactions need to be cautioned regarding potential recurrence risk.

Enteroviral Infections in Infants.

Enteroviruses (EVs) are major pathogens in young infants. These viruses were traditionally classified into the following four subgenera: polio, coxsackie A and B, and echoviruses. Now that poliomyelitis seems to be controlled in most parts of the world, coxsackie and echoviruses are gaining more attention because (i) the structural and pathophysiological similarities and (ii) the consequent possibilities in translational medicine. Enteroviruses are transmitted mainly by oral and fecal-oral routes; the clinical manifestations include a viral prodrome including fever, feeding intolerance, and lethargy, which may be followed by exanthema; aseptic meningitis and encephalitis; pleurodynia; myopericarditis; and multi-system organ failure. Laboratory diagnosis is largely based on reverse transcriptase-polymerase chain reaction, cell culture, and serology. Prevention and treatment can be achieved using vaccination, and administration of immunoglobulins and antiviral drugs. In this article, we have reviewed the properties of these viruses, their clinical manifestations, and currently available methods of detection, treatment, and prognosis.

Multimodal Imaging of Unilateral Acute Maculopathy Associated with Hand, Foot, and Mouth Disease: A Case Series.

We described clinical and multimodal imaging findings in 4 patients with unilateral acute idiopathic maculopathy (UAIM) associated with hand, foot, and mouth disease. Four eyes of 4 patients (3 women and 1 man) with a mean age of 35 years (range: 24-40 years) were included. A bacillary detachment was observed in 3 out of the 4 eyes and was strongly suspected in the remaining eye. This particular detachment was resolved within 5-10 days in our series. A choriocapillaris involvement was supported by the multimodal imaging findings. On indocyanine green angiography, a hypofluorescence was observed throughout the sequence, and OCT angiography showed a defect of the choriocapillaris perfusion. In this case series, a complete multimodal retinal assessment allowed identifying the choriocapillaris as the primary tissue involved in UAIM associated with coxsackie virus infection. In 3 out of our 4 cases, a bacillary detachment with a transient evolution was identified.

Constrictive pericarditis caused by viral myocarditis in children: a brief report.

BACKGROUND: Constrictive pericarditis is more common in adults and has a low incidence in children. Here is a case of coxsackie virus induced myocarditis in children, resulting in constrictive pericarditis. CONCLUSION: Chronic inflammation of viral myocarditis can cause inflammatory changes of pericarditis and cause constrictive pericarditis.

miR-19b-3p/PKNOX1 Regulates Viral Myocarditis by Regulating Macrophage Polarization.

Objective: The purpose of this study was to study the role and mechanism of miR-19b-3p in regulating myocardial inflammation and injury of viral myocarditis in viral myocarditis induced by Coxsackievirus B3 (CVB3). A CVB3 infection mouse model was established, the survival rate of mice was recorded after different treatments, cardiac function was detected, the degree of myocardial inflammatory infiltration and injury was detected by immunohistochemical and biochemical analyses, miR-19b-3p and PKNOX1 expression in cardiac tissue and cardiac infiltrating macrophages was detected using RT-PCR, and isolated mouse bone marrow-derived macrophages and the differentiation of macrophages after different transfections were detected. Finally, the binding of miR-19b-3p and PKNOX1 was verified by the dual luciferase reporter gene. The results showed that the expression of miR-19b-3p was significantly downregulated in the cardiac tissue and infiltrating macrophages of CVB3-infected mice, while the expression of PKNOX1 was upregulated. Upregulation of miR-19b-3p has protective effects against CVB3-induced myocardial injury in mice, such as weight gain, prolonged survival, increased left ventricular ejection fraction and left ventricular short axis shortening, reduced inflammation, creatine kinase isoenzyme (CK)-MB, and lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) levels decreased, while interferon-γ and interleukin-6 (IL-6) increased, and the M2/M1 cell ratio was upregulated. In conclusion, miR-19b-3p can regulate macrophage polarization by targeting PKNOX1, and has a protective effect against CVB3-induced inflammation and myocardial injury.

A Rare Case of Dilated Cardiomyopathy, Focal Segmental Glomerulosclerosis, and Bell's Palsy in a 29-Year-Old Male After Coxsackievirus Infection.

Dilated cardiomyopathy (DCM) is a severe myocardial disease with diversified etiologies. Coxsackievirus serotype B (CV-B) is a known cause of infectious myocarditis that leads to DCM. The pathogenesis of CV-B myocarditis is complex and involves a combination of tissue destruction from viral proliferation and host immune response. Diagnosis is based on clinical findings and the presence of post-infection elevated titers of IgM antibodies to CV-B. Echocardiography is an important imaging modality that plays a key role in diagnosing DCM. Rare complications of coxsackievirus infection may include facial paralysis and chronic kidney disease with nephrotic syndrome. Here we present a rare case of a 29-year-old-male with recent Bell's palsy who presented with new-onset heart failure with left ventricular ejection fraction of 5% and focal segmental glomerulosclerosis nephrotic syndrome in the setting of elevated antibodies to CV-B.

Implication of inflammation on Coxsackie virus and Adenovirus receptor expression on cardiomyocytes and the role of platelets in patients with dilated cardiomyopathy.

BACKGROUND: Coxsackie Virus and Adenovirus Receptor (CXADR or CAR) is involved in the pathogenesis of inflammatory dilated cardiomyopathy (DCM). We aimed to examine the relationship of CAR expression on platelets and cardiomyocytes with virus persistence, local and systemic inflammation and platelet activity in patients with DCM. METHODS: Endomyocardial biopsy (EMB) samples of 38 patients (mean age 39.5±11.3 years, 20 male) with DCM were analyzed for CAR expression, local inflammation grade by immunohistochemistry and virus persistence by real-time PCR. Platelet morphology was analyzed in all patients and 30 healthy subjects (HS) using scanning electron microscopy, platelet activity by light transmission aggregation, and CAR persistence by immunofluorescence. Platelets of 20 patients were analyzed for cytomegalovirus and herpes simplex virus 1-2 by immunofluorescence. Serum levels of tumor necrosis factor alpha (TNF α) and Interleukin-6 were assessed using ELISA in all studied subjects. RESULTS: CAR expression in EMB samples was related to the heart failure functional class and the level of IL-6. Platelets from DCM patients showed enhanced spontaneous and ADP induced aggregation. Platelets' CAR expression was >4 fold higher in DCM than HS and was observed predominantly at sites of intercellular communications in microaggregates and leukocyte-platelet aggregates. CAR-positive patients showed significantly higher TNF-α and IL-6 serum levels in CAR-negative patients. Platelets of 6 (30%) DCM patients revealed the mature cytomegalovirus and herpes simplex viruses particles. CONCLUSION: Tight junction protein CAR may serve as a docking pin creating a new type of contact structure that could be responsible for signaling between neighboring cells in pathological conditions.

Fulminant Coxsackievirus Myocarditis in an Immunocompetent Adult: A Case Report and Literature Analysis.

Myocarditis is an inflammatory condition that impacts cardiac myocytes and is caused mostly by viruses. It can manifest as chest pain, dyspnea, palpitations, fatigue, syncope, shortness of breath, and in severe cases frank cardiogenic shock. It accounts for around 10 percent of all sudden cardiac deaths in young adults, who are described as being in their early thirties. Inflammatory cardiomyopathy resulting from acute myocarditis may also appear as new-onset heart failure (HF), delaying the diagnosis and treatment of these patients. It is crucial to recognize the sensitivity of symptom onset, especially in young individuals; mildly elevated troponin levels that are inconsistent with the severity of left ventricular ejection fraction (LVEF) impairment and associated left ventricular dilatation strongly suggest inflammatory cardiomyopathy rather than acute myocarditis. The current treatment for myocarditis is primarily supportive, with an emphasis on the management of heart failure and arrhythmias in accordance with clinical practice guidelines. In this case report, we describe a male in his early forties who presented with abrupt onset exertional shortness of breath and chest discomfort. His cardiac catheterization did not show evidence of coronary artery disease; however, an echocardiogram revealed new-onset heart failure with reduced ejection fraction, the diagnosis of coxsackievirus myocarditis was made based on his clinical presentation, and a positive coxsackievirus immunoassay.

An unusual location of hand, foot and mouth disease.

Hand, foot, and mouth disease (HFMD) is a childhood febrile disease. Oral lesions and papulovesicular lesions on the hands and feet are the clinical signs of the disease. In our case, a 17-year-old boy presented to the emergency department, where he was diagnosed with HFMD. After 6 days, he felt intense pain in his right testicle, and therefore an ultrasound (US) examination was performed. US detected a hypoechoic mass-like area in the right testis. Viral etiology was suspected, and no therapy was prescribed. After a little more than 3 months, US examination showed a reduced lesion size. Viral epididymo-orchitis should be suspected in young men with a recent history of HFMD and testicular pain.

Late Contralateral Recurrence of Unilateral Acute Idiopathic Maculopathy: Adaptive Optics Findings.

PURPOSE: To report a case of late contralateral recurrence of unilateral acute idiopathic maculopathy (UAIM) and its sequelae by using adaptive optics. METHODS: A 46-year-old woman positive for coxsackie virus presented with a typical UAIM, followed 3 years later by a recurrence in the fellow eye. At an early stage, spectral domain-OCT showed a localized loss of the inner segment/outer segment and cone outer segment tips lines, while flood-illumination adaptive optics displayed pigment clumpings and transient small hard exudates, associated with a persistent blurring of the cone mosaic. RESULTS: These findings support the hypothesis of an outer retinal blood-barrier breakdown, inducing a disruption limited to the outer segment of the photoreceptors, followed by a progressive though incomplete normalization of the cone mosaic characterized by a persistent misalignment of outer segment tips. CONCLUSION: This would explain the acute clinical presentation of UAIM, followed by a spontaneous, partial, recovery, with a relative scotoma remaining over time.

Prenylated C6-C3 derivatives from the stems and branches of Illicium ternstroemioides A. C. Smith with antiviral activity.

Thirteen compounds were isolated from the lipid-soluble extracts of Illicium ternstroemioides A. C. Smith, including eleven previously undescribed prenylated C6-C3 compounds, a previously undescribed prenylated C6-C3 derivative-abscisic acid ester hybrid, and a known compound (4S)-illicinone I. Their structures and configurations were mainly elucidated by spectroscopic analyses, CD experiments and X-ray crystallography. (2S,4R,11S)-4-O-methyl-12-chloroillifunone C, (2S,4R,11R)-2,3-dihydro-4-O-methyl illioliganfunone D, and illiternfunol A were found to exhibit weak activity against Coxsackievirus B3, with IC50 values ranging from 27.8 to 33.3 µM. Illiternone B exhibited more potent activities against Coxsackievirus B3 and influenza virus A than did its geometric isomer illiternone A, with IC50 values of 7.7 µM and 2.5 µM, respectively. None of these compounds displayed cytotoxic activities.

Advances in viral oncolytics for treatment of multiple myeloma - a focused review.

INTRODUCTION: Oncolytic viruses are genetically engineered viruses that target myeloma-affected cells by detecting specific cell surface receptors (CD46, CD138), causing cell death by activating the signaling pathway to induce apoptosis or by immune-mediated cellular destruction. AREAS COVERED: This article summarizes oncolytic virotherapy advancements such as the therapeutic use of viruses by targeting cell surface proteins of myeloma cells as well as the carriers to deliver viruses to the target tissues safely. The major classes of viruses that have been studied for this include measles, myxoma, adenovirus, reovirus, vaccinia, vesicular-stomatitis virus, coxsackie, and others. The measles virus acts as oncolytic viral therapy by binding to the CD46 receptors on the myeloma cells to utilize its surface H protein. These H-protein and CD46 interactions lead to cellular syncytia formation resulting in cellular apoptosis. Vesicular-stomatitis virus acts by downregulation of anti-apoptotic factors (Mcl-2, BCL-2). Based upon the published literature searches till December 2020, we have summarized the data supporting the advances in viral oncolytic for the treatment of MM. EXPERT OPINION: Oncolytic virotherapy is an experimental approach in multiple myeloma (MM); many issues need to be addressed for safe viral delivery to the target tissue.