COXSACKIE VIRUSES—A Review of Pathologic,Epidemiologic, Diagnostic and Etiologic Observations

Coxsackie disease comprises three clinical entities—herpangina, so-called non-paralytic poliomyelitis, and epidemic pleurodynia. Several strains of antigenically-related viruses, Groups A and B, designated as Coxsackie virus have been isolated from stool specimens and from material from the throat of many patients with the diseases mentioned. Inasmuch as the virus has also been recovered from normal persons, there is as yet uncertainty as to causal relationship between the presence of the virus and the disease. Reports of the isolation of Coxsackie virus and poliomyelitis virus from the same patient make difficult the interpretation of the findings.The diagnosis of Coxsackie disease entails animal inoculation and serologic procedures. Emphasis is placed on the necessity of obtaining stool specimens, throat washings, and “paired” blood specimens from patients suspected of the disease.     

Coxsackie virus in Southern California; isolation of a strain from stools of a patient

Thirty-three stool specimens from 29 patients were examined for Coxsackie virus by the inoculation of suckling mice. Such a virus, designated "California I," was obtained from two stool specimens collected on successive days from a patient with so-called nonparalytic poliomyelitis. Neutralizing antibodies for the California I strain of Coxsackie virus could not be demonstrated in serum obtained from the patient early in the illness, but were present in convalescent serum.Serum from the patient's daughter, who previously had had a similar illness, neutralized the strain of virus isolated from the father. In pathologic examination of the skeletal muscles of mice infected with the California I virus, lesions typical of those produced by Coxsackie virus, group A, were noted. California I strain of the virus was not neutralized by immune serum prepared from several other strains of Coxsackie virus.     

COXSACKIE VIRUS IN SOUTHERN CALIFORNIA—Isolation of a Strain from Stools of a Patient

Thirty-three stool specimens from 29 patients were examined for Coxsackie virus by the inoculation of suckling mice. Such a virus, designated “California I,” was obtained from two stool specimens collected on successive days from a patient with so-called nonparalytic poliomyelitis.Neutralizing antibodies for the California I strain of Coxsackie virus could not be demonstrated in serum obtained from the patient early in the illness, but were present in convalescent serum.Serum from the patient''s daughter, who previously had had a similar illness, neutralized the strain of virus isolated from the father.In pathologic examination of the skeletal muscles of mice infected with the California I virus, lesions typical of those produced by Coxsackie virus, group A, were noted.California I strain of the virus was not neutralized by immune serum prepared from several other strains of Coxsackie virus.     

A mixed epidemic of poliomyelitis and Bornholm's disease (pleurodynia)

Summary During a mixed epidemic of poliomyelitis and Bornholm's disease in the summer of 1951, evidence was obtained of the involvement of at least 6 different immunological types of Coxsackie virus, among which the Albany A₂ type dominated. Poliomyelitis virus was isolated from the stools of 6 out of 20 patients suffering from paralytic poliomyelitis; Coxsackie virus from 1, and both poliomyelitis and Coxsackie virus from 2 out of these 20 patients. During the whole year, Coxsackie virus was recovered from the stools of patients suffering from paralytic poliomyelitis, aseptic meningitis, pleurodynia and summer grippe in approximately equal percentages (11 to 14%), but during the epidemic months from July to October, 25% of the patients with poliomyelitis, and 16% of the patients with pleurodynia gave positive results for Coxsackie virus. The sparing or the enhancing effect of Coxsackie virus infection on the development of paralysis in patients with dual infections is discussed. Aided by a grant from the National Health Research Council T.N.O.     

Congenital absence of the gallbladder; case report

The virus of human poliomyelitis has been demonstrated in excretions before onset of the disease, during the disease, and in convalescence. It may be confused with different viruses likely to be found in the same sources in clinical conditions resembling poliomyelitis.Immunologic differences between strains of poliomyelitis virus have been detected so that three types are now evident. The distribution of these types and their importance as causes of epidemics are not known. This multiplicity of immunologic types is an important factor in considering immunization of humans. Commercial manufacture of vaccines faces many technical problems. Recently the Coxsackie virus has been demonstrated in humans with a disease closely resembling poliomyelitis.     

Congenital Absence of the Gallbladder: Case Report

The virus of human poliomyelitis has been demonstrated in excretions before onset of the disease, during the disease, and in convalescence. It may be confused with different viruses likely to be found in the same sources in clinical conditions resembling poliomyelitis.Immunologic differences between strains of poliomyelitis virus have been detected so that three types are now evident. The distribution of these types and their importance as causes of epidemics are not known. This multiplicity of immunologic types is an important factor in considering immunization of humans. Commercial manufacture of vaccines faces many technical problems.Recently the Coxsackie virus has been demonstrated in humans with a disease closely resembling poliomyelitis.     

RELATION OF A STREPTOCOCCUS TO EPIDEMIC POLIOMYELITIS-Studies in Etiology,Diagnosis and Specific Treatment

The production in 1915 of herpes zoster or "posterior" poliomyelitis in animals with a streptococcus led to further research on the etiologic importance of streptococci in "anterior" poliomyelitis.A specific streptococcus was demonstrated consistently in persons with poliomyelitis and in well persons having contact with them or merely inhabiting an area in which poliomyelitis was epidemic. That the organism was not present in areas remote from contact with the disease was likewise demonstrated.The streptococcus has been isolated from filtrates of poliomyelitis virus and from the tissues and exudates which harbor the virus. It appears in the spinal fluid in the preparalytic stage of poliomyelitis and disappears from the spinal fluid during the severe stage of the disease. Antibody and antigen prepared from the streptococcus were used to determine the presence of antigen and antibody indicative of streptococcal infection in many patients with poliomyelitis and in well persons. The intensity of reaction indicating specific streptococcal antigen was directly proportional to the degree of paralysis in patients; the reaction was greater in persons whose age, sex and previous isolation from the disease would normally indicate greater susceptibility. The test for antibody gave opposite results. Specific agglutinins for the streptococcus and neutralizing antibody for the virus were present consistently in the serum of persons and monkeys during recovery from poliomyelitis. Virus produced in vitro from the associated streptococcus caused all the clinical and pathologic features of poliomyelitis in monkeys inoculated with it, and the animals that recovered from the disease thus induced were proved to be immune thereafter to the natural virus. Antistreptococcic serum prepared in horses was used to treat poliomyelitis. In a group of monkeys inoculated with the virus of the disease, 6 per cent of those receiving the serum before inoculation died of the disease; of the control group, 82 per cent. In a series of poliomyelitis patients treated with the serum the mortality rate was 8 per cent; in a control series, 21 per cent. In a series treated in all stages of the disease by the author, 10 per cent died; of those who did not receive the serum, 25 per cent. An antibody has been prepared from the streptococcus which appears to prevent paralysis and otherwise mitigate poliomyelitis and to provide immunization from the disease.The conclusion is reached that the virus of poliomyelitis is a form of the specific streptococcus, which is the agent in primary infections and in the development of the immunizing antibody.     

2007年内蒙古一起手足口病暴发的流行病学和病原学分析

2007年内蒙古自治区鄂尔多斯市准格尔旗暴发了一起手足口病疫情,患者大多出现发热症状,在手、足、口腔和臀部等一个或多个部位出现斑丘疹或疱疹。患者以5岁以下散居幼儿为主,暴发过程中有一个明显的发病高峰。从28名住院儿童采集了23份粪便标本和6份咽拭子标本进行病毒分离,共分离到了15株肠道病毒,其中9株鉴定为人肠道病毒71型(HEV71,分离率为31.03%),1株鉴定为柯萨奇病毒A组16型(CVA16)。结合分析这起暴发中患者的临床表现、流行病学调查结果以及实验室检测结果,表明HEV71可能是引起这起HFMD暴发的主要病原体。9株HEV71分离株在全长VP1区核苷酸水平和氨基酸水平上差异都较小,核苷酸和氨基酸同源性分别高于99.4%和99.0%,说明这起疫情是由同一个病毒传播链引起的。同源性进化分析结果表明,从这起疫情中分离到的HEV71属于C4基因亚型,而C4基因亚型自1998年首次在广东省深圳市报道以来,一直在我国持续流行,是中国大陆HEV71流行的优势基因亚型,提示C4基因亚型HEV71在中国大陆可能有较广泛的分布和传播。     

RELATION OF A STREPTOCOCCUS TO EPIDEMIC POLIOMYELITIS—Studies in Etiology,Diagnosis and Specific Treatment

The production in 1915 of herpes zoster or “posterior” poliomyelitis in animals with a streptococcus led to further research on the etiologic importance of streptococci in “anterior” poliomyelitis.A specific streptococcus was demonstrated consistently in persons with poliomyelitis and in well persons having contact with them or merely inhabiting an area in which poliomyelitis was epidemic. That the organism was not present in areas remote from contact with the disease was likewise demonstrated.The streptococcus has been isolated from filtrates of poliomyelitis virus and from the tissues and exudates which harbor the virus. It appears in the spinal fluid in the preparalytic stage of poliomyelitis and disappears from the spinal fluid during the severe stage of the disease.Antibody and antigen prepared from the streptococcus were used to determine the presence of antigen and antibody indicative of streptococcal infection in many patients with poliomyelitis and in well persons. The intensity of reaction indicating specific streptococcal antigen was directly proportional to the degree of paralysis in patients; the reaction was greater in persons whose age, sex and previous isolation from the disease would normally indicate greater susceptibility. The test for antibody gave opposite results.Specific agglutinins for the streptococcus and neutralizing antibody for the virus were present consistently in the serum of persons and monkeys during recovery from poliomyelitis.Virus produced in vitro from the associated streptococcus caused all the clinical and pathologic features of poliomyelitis in monkeys inoculated with it, and the animals that recovered from the disease thus induced were proved to be immune thereafter to the natural virus.Antistreptococcic serum prepared in horses was used to treat poliomyelitis. In a group of monkeys inoculated with the virus of the disease, 6 per cent of those receiving the serum before inoculation died of the disease; of the control group, 82 per cent. In a series of poliomyelitis patients treated with the serum the mortality rate was 8 per cent; in a control series, 21 per cent. In a series treated in all stages of the disease by the author, 10 per cent died; of those who did not receive the serum, 25 per cent.An antibody has been prepared from the streptococcus which appears to prevent paralysis and otherwise mitigate poliomyelitis and to provide immunization from the disease.The conclusion is reached that the virus of poliomyelitis is a form of the specific streptococcus, which is the agent in primary infections and in the development of the immunizing antibody.     

NONPOLIOVIRUSES AND PARALYTIC DISEASE

A number of nonpolioviruses have been implicated as the probable etiologic agents of paralytic illness clinically resembling poliomyelitis, including certain immunotypes of Coxsackie group A, Coxsackie group B, and ECHO viruses, and the viruses of mumps, herpes simplex and arthropod-borne encephalitides. A number of well documented cases provide evidence that some of these viruses may on occasion be the causative agents of severe, even fatal, myelitis, bulbomyelitis or encephalomyelitis, but they have been associated much more frequently with cases of “poliomyelitis” in which there has been slight to moderate paresis. In the aggregate, various “nonpolioviruses” have been encountered in approximately 10 per cent of the patients with clinical poliomyelitis studied, but it is uncertain how many of these cases may represent coincidental infections not causally related to the current illness.     

Enterovirus Infections: Etiologic,Epidemiologic and Clinical Aspects

The term enteroviruses was introduced in 1957 to bring together in one large family the polioviruses, Coxsackie A and B and echoviruses, all agents for which the human alimentary tract is the natural habitat. At present more than 60 distinct members are recognized: three polioviruses, 24 Coxsackie A, six Coxsackie B and 30 echoviruses. The list of new members, particularly in the echo-group, grows regularly. The viruses are frequently widely disseminated in the summer and fall of the year, circulating chiefly among young children, causing both apparent and inapparent infection. The enteroviruses are responsible for a wide spectrum of clinical manifestations, including non-specific febrile illness, sometimes with rash, aseptic meningitis, paralytic disease, respiratory infections, pericarditis and myocarditis. There is considerable overlap in biologic behavior, and the same syndrome can be induced by many different agents.In a few instances the clinical pattern is distinct enough to suggest the group of agents involved. Thus, herpangina is associated with the Coxsackie A viruses and epidemic myalgia (devil''s grip) with the Coxsackie B group. Paralytic disease is caused primarily by the polioviruses, but recently it has been found that other members, particularly the Coxsackie B viruses and Coxsackie A7 can also cause “paralytic poliomyelitis.”The ultimate potential of enteroviruses in terms of central nervous system disease and other manifestations is unpredictable. Great variety in terms of clinical and epidemiologic behavior of known and “new” viruses has been the pattern in the past, and is likely to continue.     

Enteroviral Syndromes in Toronto, 1964

Virological or serological investigations of 72 children in Toronto and environs, who were hospitalized between January and October 1964 with a variety of syndromes, revealed evidence of enteroviral infection in 29 subjects. Coxsackie B2 was the dominant enterovirus, being isolated from feces and/or cerebrospinal fluid (CSF) of three children with aseptic meningitis, three with pleurodynia, one with myalgia and one with pericarditis; four additional patients showed rising antibody titres to this virus. Coxsackie B1 virus, which has not been isolated in Toronto since 1950, was recovered from feces of three patients with pleurodynia, CSF of one patient with myalgia, and peritoneal fluid of a child with primary peritonitis; one patient with pericarditis showed a rising antibody titre to Coxsackie B1 virus. Coxsackie B3, B4 and Echo 23 viruses were associated with one case each of pleurodynia. Coxsackie B5 virus infected five patients with aseptic meningitis, and one each with pericarditis and myocarditis.     

云南省新平县家鼠鼠疫疫原地小肠结肠炎耶尔森菌的调查分析

目的了解新平县家鼠鼠疫疫源地小肠结肠炎耶尔森菌的分布及病原学特征。方法采集家鼠盲肠、舌头和猪粪便、咽喉粘液以及腹泻患者粪便标本进行小肠结肠炎耶尔森菌的检测与分析。结果检测家鼠盲肠、鼠舌头、猪粪便、猪咽喉粘液物、腹泻患者粪便的标本数分别为722、722、467、237和107份,共分离到61株小肠结肠炎耶尔森菌,总检出率为2. 71%,5种标本的检出率分别为2. 63%、1. 39%、3. 85%、2.53%和7. 48%,差异有统计学意义（x^2= 16. 422,P = 0. 003）;分离株包括致病株10株、非致病株51株,有1A、2、3三种生物型和0：3、0：5、0：8等多种血清型,以及六种毒力基因型。猪、鼠、腹泻患者标本检出致病菌株数分别为9、1、0株。结论新平县家鼠鼠疫自然疫源地猪、鼠、腹泻患者是小肠结肠炎耶尔森菌的重要宿主,分离菌株具有遗传多样性,猪、鼠是小肠结肠炎耶尔森菌病的主要传染源。     

Rash Associated with Coxsackie A9 Infection

Coxsackie A9 virus was identified by the authors during the fall of 1965 in Montreal in six children with fever and exanthem. Three of the six children were siblings. The exanthem was centrally distributed as described by Lerner et al. and consisted of discrete maculopapules 3 to 4 mm. in diameter. The viral agent was recovered and identified in tissue culture in five cases, while in the sixth Coxsackie type-A lesions were produced in suckling mice. Serological confirmation was obtained in two patients from whom sera were available. In contrast, no exanthem was observed in three older patients with a diagnosis of aseptic meningitis associated with Coxsackie A9 virus. In only one of 16 patients with Coxsackie B virus infection was an exanthem observed during the same period.The true incidence of Coxsackie A9-associated exanthems is difficult to determine because of the benign nature of the disease.     

Proved viraemia in asian influenza (Hong Kong variant) during incubation period

During an outbreak of influenza specimens were obtained from 21 patients with influenza-like illnesses and from 29 healthy subjects in close contact with the patients. Throat washings from 12 of the patients were positive for influenza virus but virus was not detected from the blood specimens. One healthy contact became ill 12 hours after the specimens were obtained, and the virus was isolated from his blood and throat washings. The remaining contacts showed no clinical illness; but the virus was isolated from the throat washings of four of them, with no viral isolation from the blood specimens.     

Incidence of poliomyelitis; the effect of tonsillectomy and other operations on the nose and throat

A statistical survey was made of all the cases of poliomyelitis occurring in all of Los Angeles County during the three years of 1949, 1950 and 1951 in an attempt to determine the effect of operations on the nose and throat on the incidence of poliomyelitis. Tonsillectomy and adenoidectomy were the only operations noted with any degree of frequency. Yet, in the total of 3,601 cases of poliomyelitis that occurred in this three-year period there were only 20 (0.55 per cent) in which the patient had had recent tonsillectomy and adenoidectomy. The incidence of this disease in patients who had had tonsillectomy and adenoidectomy was compared with the "expected" incidence as determined from the incidence in other patients, in the same age group. There was no significant difference between actual and expected incidence even during the summer months when most cases of poliomyelitis occurred. The same was true with regard to recently tonsillectomized patients in the epidemic months of July through October. In a separate survey of 675 patients with poliomyelitis, it was noted that only 30 per cent ever had had tonsillectomy or adenoidectomy. Inasmuch as it is estimated that one of every three persons in the general young population nowadays has had tonsillectomy and adenoidectomy, this figure is no more or less than could be expected.     

Clinical,Virological and Immunological Features from Patients Infected with Re-Emergent Avian-Origin Human H7N9 Influenza Disease of Varying Severity in Guangdong Province

BackgroundThe second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region.MethodsFive patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery.ResultsFour patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/β, IL-1β and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%).ConclusionExpectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.     

肠道传播非甲非乙肝炎在恒河猴中的传代研究

用ET-NANBH感染的两只猴(R5和R6)含病毒颗粒的粪便悬液和肝组织悬液分别接种7只和4只恒河猴,分别有5只猴和4只猴在攻毒后20—49天内ALT开始升高,持续时间为7—10天,肝组织学的特征性改变为肝细胞的嗜酸性变和嗜酸小体的形成。在猴ALT升高前2—3天和升高后一周内均检查到大量的27—34nm的病毒样颗粒,这些颗粒只与ET-NANBH病人血清、黑猩猩和猴感染后急性期和恢复期血清发生特异性聚集。在猴感染后血清中未检出抗-HAV、抗-HAV-IgM、HBsAg和抗-HBe-IgM。结果提示:恒河猴是研究ET-NANBH较适宜的动物模型;病人和猴粪便中的27—34nm的病毒样颗粒是ET-NANBH的病原因子。     

荧光定量RT-PCR检测甲型H1N1病毒核酸的临床意义

目的观察荧光定量RT-PCR技术在检测甲型H1N1病毒核酸的临床意义。方法对135例经确诊为甲型H1N1的感染患者的咽式子采用荧光定量PCR技术检测H1N1病毒核酸,同时对40例健康体检者的咽式子做为对照组一同进行甲型H1N1病毒核酸检测。结果 135例确诊为甲型H1N1的患者经荧光定量PCR检测阳性129例,符合率为96.99%。40例健康体检者结果全阴性。结论荧光定量PCR检测甲型H1N1病毒核酸具有快速、特异性高等特点,在采用此方法诊断甲型H1N1时,阳性即可确诊,阴性者要结合临床。     

Selenite inhibition of Coxsackie virus B5 replication: implications on the etiology of Keshan disease.

Keshan disease is a cardiomyopathy of unknown origin reported in some areas of China. Because of epidemiologic features, this disease was ascribed to an infectious agent, likely a Coxsackie virus, but it has also been thought to depend on selenium deficiency, mainly because selenite is effective in its prophylaxis. We examined the hypothesis that pharmacological activity of selenite on Coxsackie virus growth was associated with prevention of Keshan disease. We studied the antiviral effects of three selenium compounds on Coxsackie virus B5 replication: five microM selenite reduced viral replication, whilst 10 microM selenate and selenomethionine did not exhibit any antiviral activity. The inhibitory activity of selenite on viral replication was due to its toxicity following its interaction with thiols, as that activity could be blocked by dithiothreitol, a sulfhydryl-protecting agent known to reverse several toxic effect of selenite. Zinc, another inhibitor of selenite toxicity, also counteracted the antiviral effect of selenite. The selenium compounds showed only limited activity against herpes simplex 1 virus and IHD strain of vaccinia virus. A direct inhibitory effect of selenite on Coxsackie virus replication might explain the efficacy demonstrated by this compound in the prophylaxis of Keshan disease.