Coxsackievirus B Infection Is Highly Related with Missed Abortion in Korea

PURPOSE: This study investigated the possible relationship between viral infection and first trimester pregnancy loss. MATERIALS AND METHODS: A prospective study was performed on 51 gravidas with missed abortion, fetal anomaly, pre-term delivery, and full-tem delivery at Hanyang University Hospital. Enteroviruses were detected by semi-nested reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in abortive tissues and placentas. Enterovirus serotypes were confirmed by genome sequencing. Herpesviruses were detected by PCR. RESULTS: Coxsackievirus B3 (CVB3) was detected in 8 of 14 missed abortion cases, 1 of 27 full-term cases, and none of the 9 pre-term cases. Coxsackievirus B1 (CVB1) was detected in an encephalocele case. Herpes simplex virus type 1 was found in 4 full-term cases, 3 pre-term cases, and none of the missed abortion cases. CONCLUSION: The prevalence of CVB3 was significantly higher in missed abortion cases compared to full-term or pre-term delivery cases. CVB infection may therefore be an important etiological agent of missed abortion.

Acute Viral Myopericarditis Presenting as a Transient Effusive-Constrictive Pericarditis Caused by Coinfection with Coxsackieviruses A4 and B3

Acute myopericarditis is usually caused by viral infections, and the most common cause of viral myopericarditis is coxsackieviruses. Diagnosis of myopericarditis is made based on clinical manifestations of myocardial (such as myocardial dysfunction and elevated serum cardiac enzyme levels) and pericardial (such as inflammatory pericardial effusion) involvement. Although endomyocardial biopsy is the gold standard for the confirmation of viral infection, serologic tests can be helpful. Conservative management is the mainstay of treatment in acute myopericarditis. We report here a case of a 24-year-old man with acute myopericarditis who presented with transient effusive-constrictive pericarditis. Echocardiography showed transient pericardial effusion with constrictive physiology and global regional wall motion abnormalities of the left ventricle. The patient also had an elevated serum troponin I level. A computed tomogram of the chest showed pericardial and pleural effusion, which resolved after 2 weeks of supportive treatment. Serologic testing revealed coxsackievirus A4 and B3 coinfection. The patient received conservative medical treatment, including nonsteroidal anti-inflammatory drugs, and he recovered completely with no complications.

Expression of CAR in myocardial of viral myocarditis and dilated cardiomyopathy / 法医学杂志

OBJECTIVE@#In order to improve accuracy and reliability of forensic diagnosis of sudden cardiac death, pathogenesis and relationship between the viral myocarditis (VMC) and dilated cardiomyopathy (DCM) were investigated.@*METHODS@#Improved immunohistochemical technique was used to detect the expression of the CAR in myocardium samples, including 22 deceased with VMC, 20 deceased with DCM and 16 control deceased.@*RESULTS@#The brown staining on the cell membrane of myocardium showed positive result. There was a prominent CAR expression in VMC group and DCM group, which were statistically significant difference compared with control group (P < 0.05).@*CONCLUSION@#The CAR expression showed significantly higher in VMC and DCM groups. The viral infection can result in myocardial necrosis and impaired cardiac functions. These abnormalities can trigger a cascade of events that contributed to the progress of VMC to DCM.

Circulating adhesion molecules in patients with Keshan disease and their relationship with Coxsackie B virus infection / 华中科技大学学报（医学）（英德文版）

This study determined the levels of serum soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecular-1 (sVCAM-1) in patients with different types of Keshan disease (KD), examined the relationship between Coxsackie B virus-specific IgM antibody (CBV-IgM) and sICAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum sICAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease (CKD), 27 with latent Keshan disease (LKD) and 28 healthy controls. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction (LVEF) in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of sICAM-1 and sVCAM-1 than LKD patients and healthy controls (P<0.01 for all). And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls (P<0.05). A negative correlation was found between LVEF and sICAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum sICAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of sICAM-1 and sVCAM-1 suggests the progression of inflammation in KD. sICAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum sICAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

Coxsackievirus B3 infection induced viral myocarditis by regulating the expression pattern of chemokines in cardiac myocytes

Viral myocarditis is a common cardiovascular disease, which has greatly threatened human health. However, up to now, the pathogenesis of viral myocarditis has been unclear, which leads to the lack of its effective treatments. To investigate the role of chemokines in pathogenesis of viral myocarditis, mRNA expression for a panel of 19 chemokines detected by RT-PCR in myocardial tissue of BALB/c mice that were inoculated intraperitoneally with coxsackievirus B3. Moreover primary cultured cardiac myocytes were infected with coxsackievirus B3 following extraction of RNA, from myocytes the expression of 19 chemokines was detected by by RT-PCR. Our results showed that there was much difference in the expression pattern of chemokines in myocardial tissue between infected mice with viral myocarditis and uninfected control mice. The expression of chemokines was varied significantly in clusters in myocardium post coxsackievirus B3 infection. There were also complexity and imbalance in the change of the expression of chemokines. In the meantime, Coxsackievirus B3 infection also influenced the expression pattern of chemokines in cardiac myocytes in vitro. However the expression of monocyte chemoattractant protein-1 alone was upregulated in cardiac myocytes post coxsackievirus B3 infection in the 19 detected chemokines. The chemokine expression pattern changed in complexity and imbalance manner both in myocardium and in primary cultured cardiac myocytes after coxsackievirus B3 infection. Coxsackievirus B3 infection may start viral myocarditis by regulating the expression pattern of chemokines in cardiac myocytes. MCP-1 may be one of key chemokines in the initial stage of viral myocarditis

The expression of coxsackie B virus adenovirus receptor (CAR) in viral myocarditis and dilated cardiomyopathy patients / 法医学杂志

OBJECTIVE@#To explore etiology and pathogenesis of viral myocarditis (VMC) and dilated cardiomyopathy (DCM).@*METHODS@#The expression of Coxsackie B virus and adenovirus receptors (CAR) were detected with modified immunohistochemical (IHC) technique in myocardium of left ventricle, right ventricle, interventricular septum, and septal papillary muscle from 28 patients with viral myocarditis, 31 patients with dilated cardiomyopathy and 17 control patients (including normal, hypertension heart disease, myocardial infarction and coronary atherosclerotic heart disease).@*RESULTS@#The brown staining on the cell membrane of myocardium represents positive result. 100% (28 of 28) of VMC patients (IHC surface integral: 4.3975 +/- 0.0365) and 84% (26 of 31) of DCM patients (4.2064 +/- 0.052 6) had prevalent CAR expression compared to 0% (0 of 19) control patients (0.073 1 +/- 0.0362). There were statistically significant differences between VMC/DCM and control patients (P < 0.05).@*CONCLUSION@#The prevalence of CAR expression was significantly higher in VMC and DCM patients (100% and 84% vs. 0% in control). In contrast, there was no difference found between VMC and DCM patients. These results suggest that both VMC and DCM involve viral etiology and could share a similar pathogenesis.

Viral investigation of acute hemorrhagic conjunctivitis outbreak (2003) in Nepal using molecular methods.

A nationwide outbreak of acute hemorrhagic conjunctivitis (AHC) occurred in Nepal during August to September 2003, which affected nearly half of the population. Sixty conjunctival swabs from AHC patients were collected at Tilganga Eye Center in Kathmandu. For the first time in Nepal, we demonstrated the etiologic viral agents of AHC, namely, Coxsackievirus A24 variant (CA24v) by reverse transcription real time polymerase chain reaction (PCR). Of the 60 samples, 19 were positive for CA24v. No difference in the two genders was observed. Conversely, Adenovirus (AdV) was detected in 32 samples, which suggested that the epidemic was caused by mixed infection. AdV was detected also on 10 rupee notes. Findings indicated that inadequate personal hygiene was the main cause of the spread of these highly contagious viruses in the community environment in Nepal during the summer of 2003.

Eccema coxsackium / Eczema coxsackium

Presentamos un caso de erupción variceliforme de Kaposi en una niña con dermatitis atópica que previamente había tenido una erupción típica de enfermedad mano-pie-boca (eccema coxsackium). Las lesiones se desarrollaron en la zona del pañal, sobreimpuestas en una dermatitis preexistente que afectaba esa zona.

Acute hemorrhagic conjunctivitis outbreak in Thailand, 1992.

The 260 cases of acute hemorrhagic conjunctivitis seen at Siriraj Hospital during October to December, 1992 were studied. Evidence of coxsackie virus A24 variant (CA24v) infections was demonstrated in 76.8% of 95 cases. The isolation rates from conjunctival swabs and throat swabs were 68.2% and 32.8%, respectively. A four-fold rising titer of neutralizing antibody was shown in 59.5% of 42 cases. The disease was characterized by a short incubation period, sudden onset, a mild and self-limited course within 5 days without ocular sequelae. Lacrimation, swelling lida, itching, foreign body sensation and periorbital pain were common features with bilateral involvement in the majority of cases. Approximately 48% of eyes had a mucopurulent discharge. Preauricular lymphadenopathy, keratitis and subconjunctival hemorrhage were observed in 16.2%, 12.6%, and 10.1% of affected eyes, respectively. Respiratory disturbances accompanied the eye signs in some cases. Only one case developed neurological complications: facial palsy was observed for three months without recovery.

Incidence of coxsackie (B) virus infection in diabetics.

45 diabetic patients were screened for raised titres against Coxsackie group of viruses. 11 diabetic patients showed raised titres of neutralising antibodies against one of the coxsackie group of viruses, as against 3 in 25 controls.

Varied manifestations of viral myocarditis.

Nine children in the age group of new born to 10 years were seen during the period October 1989 to January 1993 with varying manifestations of Myocarditis. This ranged from cardiogenic shock due to fulminant cardiac failure, recurrent wheezy episodes (mistakenly treated as bronchial asthma) bronchiolitis and rhythm disturbances. Clinical picture was collaborated by radiological evidence of cardiomegaly, ECG changes of low voltage QRS complexes with ST depression, T wave inversion or signs of left ventricular dilatation. SGOT, SGPT, CPK, LDH were elevated significantly in 7 cases. Echocardiographic changes ranged from left ventricular dilatation to global hypokinesia and mild mitral incompetence. Viral studies suggested infection with Coxsackie B1 in 4 cases, B4 in 2, B5 in 2 and Dengue 3 in 1 case. All the children recovered well with routine anti failure measures and treatment of arrhythmias and 2 children needed steroid therapy. At the end of follow up of 6 months to 1 year there has been complete reversal of ECHO changes to normal. Viral Myocarditis can manifest in varied ways in children and if treated adequately may lead to complete recovery.

Coxsackie virus infections in rheumatic fever.

The close relationship between Group A beta Hemolytic Streptococci (GABS) and rheumatic fever is a well established one. However, the concept of the streptococcus as the sole etiologic agent of the rheumatic heart disease (RHD) has been challenged over the past years. Since coxsackievirus group B (CVB) has long been proposed as a cause of acquired valvular disease simulating rheumatic fever, we attempted in this study to document infections with this group of viruses in patients with rheumatic fever. We obtained blood samples from 106 patients with old (quiescent) rheumatic fever/rheumatic heart disease [group I], 94 patients with acute rheumatic fever (ARF) [group II], and 74 normal matched controls. We tested for the presence of neutralizing antibodies to the 6 serotypes of CVB by a micro neutralization test. We have found that infection with CVB, especially types B2 and B4, was common in the studied population. Forty-two percent of normal individuals had evidence of infection with any of the 6 serotypes of CVB. Patients of group I had significantly more frequent infections with CVB 2. Patients in group II had significantly more frequent infections with CVB 2 and CVB 6. There was no clear correlation between such infections and the clinical course of rheumatic fever. There was no difference in the incidence of CVB infections between patients with definite ARF, and patients with suspected ARF. We set a low order association between rheumatic fever and infection with CVB types B2 and B6. We emphasize the importance of pursuing the investigation of the role of CVB in relation to RHD.

T-lymphocyte mediated injury of beta cells in dual-aetiology diabetes mellitus in Swiss albino mouse.

Earlier we had described a dual aetiology diabetes mellitus (DADM) in mice injected with a sub-diabetogenic dose of streptozotocin (SD-SZN) and afterwards infected with coxsackie B3 virus (CBV). Further experiments were conducted to understand the mechanism of diabetogenesis. In in vitro stimulation and proliferation tests, the splenic lymphocytes (SLC) of mice given either SD-SZN or CBV infection showed lower responses to two T cell mitogens than those of control mice, indicating an immunosuppressive effect. Unexpectedly, SLC of mice given both SD-SZN and CBV showed enhanced response, indicating immunoactivation; they were not stimulated to proliferation in response to CBV antigen, indicating that the immunoactivation was not directed against CBV, but against streptozotocin or cellular elements. When mice were depleted of T cells by injecting with anti-thymocyte serum, the diabetogenic effect of SD-SZN and CBV infection was abrogated, without diminishing the replication of virus in the pancreas. Thus beta cell injury in DADM appears to be T cell-mediated.

Virus Coxsackie B em crianças com miocardite aguda / Coxsackie B virus in children with acute myocarditis

Estudar aspectos etiopatológicos e de evoluçäo em portadores de miocardite. Dentre 44 crianças com miocardite aguda estudadas clínica e virologicamente, foram selecionados 16 casos positivos para Coxasackie B. O protocolo clínico incluiu dosagens enzímicas, radiografia de tórax, eletro e ecocardiograma. A investigaçäo virológica para Coxsacke B1, B3, B4, B5 e B6 se baseou em cultura, teste de neutralizaçäo e pesquisa de IgM por imunofluorescência indireta. Obtivemos vírus B4 em 9 (57%), B5 em 4 (25%), B1 em 2 (12%) e B3 em 1 (6%). Nenhum paciente foi submetido à terapêutica imunossupressora. A evoluçäo de pelo menos 1 ano foi; 7 (43%) permaneceram com miocardiopatia dilatada, 1 (6%) faleceu e 4 (25%) tiveram alta hospitalar, mas näo seguiram o acompanhamento. Uma das pacientes que teve evoluçäo crônica (extra-sístoles ventriculares, BAV do 2§ grau) está agora assintomática. Näo observamos diferença significativa entre os vários tipos de Coxsackie B em relaçäo à evoluçäo clínica

Coxsackie viral myocarditis: a clinical and echocardiographic study.

Thirty two patients with acute onset of cardiac symptoms following an episode suggestive of viral infection, were studied. 11 patients had Coxsackie viral myocarditis. All had 4 fold rise of neutralising Coxsackie viral antibody titres on paired sera tested. Coxsackie B virus types 2 and 4 were commonly detected. Among the eleven patients, 8 presented with congestive heart failure, 2 with ventricular arrhythmias and one with chest pain and S3 gallop. All had ECG changes. Echocardiographic examination showed global left ventricular dysfunction in 7, regional wall motion abnormalities in 2 and normal left ventricular function in one. Serial echocardiographic examination showed progressive myocardial dysfunction in 3 and improvement in myocardial function in two patients. Two patients died during the follow up period. Echocardiography helped in assessing the course of patients with viral myocarditis.