• Sign Up

Group B Coxsackie Virus


Group B Coxsackie Virus

Article Author:
Naveen Tariq
Article Editor:
Chris Kyriakopoulos
Updated:
7/16/2020 9:06:54 AM
For CME on this topic:
Group B Coxsackie Virus CME
PubMed Link:
Group B Coxsackie Virus

Introduction

Coxsackievirus Group B is a member of the family Picornaviridae, genus Enterovirus. The enterovirus (EV) is a positive-sensed, single-stranded RNA virus named for their enteric, or gastrointestinal route of transmission.[1] Before being reclassified as EV A-D, the enteroviruses were categorized according to their pathogenesis in humans and laboratory animals into four groups, polioviruses, coxsackie A viruses (CA), coxsackie B viruses (CB), and echoviruses.[2] The species of enterovirus that cause disease in human beings include enterovirus A-D and rhinovirus A-C.

Coxsackieviruses are non enveloped viruses with linear single-stranded RNA. Group A coxsackieviruses were noted to cause flaccid paralysis, which was caused by generalized myositis. In contrast, group B coxsackieviruses were observed to cause a spastic paralysis because of the degeneration of neuronal tissue and focal muscle injury. At least twenty-three serotypes (1-22, 24) of group A and six serotypes (1-6) of group B are recognized: CV-B1, CV-B2, CV-B3, CV-B4, CV-B5, and CV-B6.[3] Group B coxsackieviruses cause infection of the heart, pleura, pancreas, and liver, causing pleurodynia, myocarditis, pericarditis, and hepatitis.[4] It also causes systemic neonatal disease.[5] This article will focus on coxsackievirus subgroup B.

Etiology

Coxsackie group B virus is responsible for several syndromes:

  • Viral prodrome including fever, fatigue, malaise, myalgia, gastrointestinal upset such as nausea, vomiting, diarrhea and abdominal pain  
  • Exanthema  
  • Aseptic meningitis  
  • Encephalitis  
  • Pleurodynia 
  • Myopericarditis  
  • Pancreatitis leading to beta-cell destruction and type one diabetes mellitus.[1][6][7]

Epidemiology

Coxsackie group B affects males and females equally and can occur worldwide. Infection usually occurs during warm summer months.[8][9] In general, population trends are studied according to presenting disease syndromes rather than specific serotypes. For 2 to 3 years, coxsackievirus B1 was the predominant serotype. Infections due to coxsackievirus B4 was associated with higher mortality than other serotypes. The age of the patient seems to play a role in the development of the different types of manifestations of the infection.[10] Children and adults tend to have a milder disease course with less likelihood of severe complications than neonates.[11][6] 

Enteroviruses are the predominant cause of viral meningitis in adults, but most of the cases occur in infants and children less than five years old.[12][13][14] Encephalitis occurs in all ages with a modest inclination for children and young adults. Pleurodynia is most common amongst adults.[10] Out of the 21 viruses that can cause cardiovascular disease, the coxsackie B virus is the major cause of viral myocarditis, especially in neonates and younger children.[15][16]

Pathophysiology

The pathogenesis of coxsackieviruses depends upon specific virus-receptor interactions. These interactions determine the location and the origin of the primary infection and also influence the viral spread to other organs during the post viremic stage. The coxsackievirus-adenovirus receptor (CAR) and the decay-accelerating factor (DAF) are the notable receptor proteins that play an important role in the pathogenesis of Coxsackie B virus infections.

DAF is expressed in epithelial and endothelial cells. CAR is present in intercalated discs, which are structures that link the myocardial cells and relay signals between cells. Interactions with these receptors facilitate Coxsackie B virus entry into the myocardial cells, eventually leading to myocarditis.[17]

CNS infections may occur by hematogenous spread or by axonal transport. Viral replication or activation of the autoimmune system can lead to injury of CNS tissues. While the exact mechanisms that cause cell injury and death remain unknown, viral inhibition of cellular macromolecular production, the toxicity of viral proteins, and virus-induced apoptosis are thought to play a role.[18]

History and Physical

Symptoms of infection with viruses in the Coxsackie B grouping include headache, fever, sore throat, gastrointestinal distress, extreme fatigue, chest pain, and myalgia. The severity of infection varies depending on the host's age, and immune status as well as the presenting disease syndrome and organ system attacked. The incubation period also varies within syndromes, and maximum transmission occurs within the first two weeks of infection.[19] 

  • Exanthema presents as maculopapular eruptions surrounded by an erythematous halo. They appear on the face and neck and then spread to the trunk and extremities within twenty-four hours. The lesions spare the palms and soles. They can be associated with petechiae and cervical adenopathy.[20][21]
  • Aseptic meningitis presents as fever and irritability in infants and as fever, headache, stiff neck, nausea, and vomiting in children or adults.[22][23]
  • Encephalitis presents with confusion and or seizures. Severity can range from mild to fatal disease.
  • Coxsackieviruses are known to be associated with epidemic pleurodynia or Bornholm disease. Pleurodynia is characterized by chest pain that worsens with breathing, and can often be confused with myocardial infarction. The pain can last from two days to two weeks. Many patients have associated fever, abdominal pain, and tender muscles of the trunk and extremities.[20]
  • Myopericarditis causes inflammation of the subepicardial myocardium and pericardium. Patients present with shortness of breath, chest pain, and an irregular heartbeat. The illness can last for a few hours up to a few months. Severity varies from asymptomatic to fulminant heart failure due to dilated cardiomyopathy and sometimes cardiac arrest.[24]
  • Pancreatitis presents with abdominal pain, nausea, vomiting, and elevated pancreatic enzymes amylase and lipase. Severe pancreatitis due to Coxsackie group B can lead to pancreatic beta-cell destruction and the development of type one diabetes mellitus.[7]

Evaluation

Usually, a clinical diagnosis is all that is required due to the self-limiting course of the infection. However, more severe cases such as myocarditis, aseptic meningitis, encephalitis, and neonatal infection can sometimes require identification of the specific organism. Furthermore, laboratory diagnosis can be epidemiologically useful, especially during epidemics. 

Enterovirus infection is diagnosed mainly through RT-PCR, viral cultures, or serological tests. RT-PCR is the most commonly used modality.[25] It can detect Enterovirus RNA in respiratory secretions, urine, serum, and CSF. While RT-PCR is a quick and sensitive test, it is unable to identify the serotype.[26][27] Viral cultures allow typing of an isolate, but they are time-consuming and sixty-five to seventy-five percent sensitive.[28] Serological tests are reserved for the diagnosis of an enterovirus infection when a particular serovar is suspected.[29] 

Other appropriate investigations include:

  • CBC
  • Comprehensive metabolic profile  
  • Erythrocyte sedimentation rate
  • Chest X-ray
  • Abdominal CT
  • Head CT
  • Lumbar puncture for CSF cell count, culture and sensitivity, Gram stain, protein, and glucose, viral PCR 
  • Lactic acid
  • Procalcitonin

Treatment / Management

The virus is self-limited with no specific recommended treatment. Symptomatic and supportive care for the associated syndromes is appropriate. Patients with neurological complications may need antiepileptics for seizures and sedation for delirium.[30] Initial supportive measures for myocarditis include supplemental oxygen and fluid resuscitation. Furthermore, patients may also require heart failure therapy and treatment of arrhythmias. 

Differential Diagnosis

Overlap of symptoms occurs amongst various viral infections. There are several important viruses to keep in mind that mimic Coxsackie Group B that may have targeted treatment plans or other severe complications. These include:

  • Human immunodeficiency virus
  • Hepatitis B and C predispose to hepatocellular carcinoma
  • JCV causes progressive multifocal leukoencephalopathy
  • Measles causes subacute sclerosis panencephalitis
  • Herpes simplex virus encephalitis
  • Rabies encephalitis
  • Poliomyelitis
  • Epstein Barr virus causes splenomegaly and possible splenic rupture
  • Cytomegalovirus

Prognosis

Infections are usually self-limited. Most syndromes result in complete recovery, with a few exceptions. While aseptic meningitis due to Enterovirus has an excellent prognosis, some patients may experience malaise and fatigue for a couple of weeks. Infants and children who suffer from aseptic meningitis may have mild intellectual complications. Myocardial syndromes can sometimes lead to poor outcomes.[30]

Complications

Complications arise from infections that target the central nervous system leading to aseptic meningitis and encephalitis as well as cardiac involvement leading to viral myopericarditis, and fulminant heart failure.[1][6]

Deterrence and Patient Education

Since no treatment or vaccine protects against Coxsackie B virus infection, healthcare professionals must emphasize on promoting infection control strategies like maintaining effective hand and environmental hygiene.[31] Pregnant women can develop perinatal complications like a severe neonatal disease if exposed to persons with an enterovirus infection and hence, should avoid contact with anyone with suspected infection.[6]

Enhancing Healthcare Team Outcomes

To improve the outcome of enterovirus infections, the interprofessional team should be aware of the severe complications that can occur and anticipate the need for supportive care in such situations. It is also paramount to practice effective handwashing and to maintain good sanitization to reduce disease transmission amongst patients.


References

[1] Kühl U,Pauschinger M,Noutsias M,Seeberg B,Bock T,Lassner D,Poller W,Kandolf R,Schultheiss HP, High prevalence of viral genomes and multiple viral infections in the myocardium of adults with     [PubMed PMID: 15699250]
[2] THE ENTEROVIRUSES; Committee on the Enteroviruses, National Foundation for Infantile Paralysis. American journal of public health and the nation's health. 1957 Dec;     [PubMed PMID: 13487867]
[3] Adams MJ,Lefkowitz EJ,King AM,Harrach B,Harrison RL,Knowles NJ,Kropinski AM,Krupovic M,Kuhn JH,Mushegian AR,Nibert M,Sabanadzovic S,Sanfaçon H,Siddell SG,Simmonds P,Varsani A,Zerbini FM,Gorbalenya AE,Davison AJ, Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016). Archives of virology. 2016 Oct;     [PubMed PMID: 27424026]
[4] Lim BK,Ju ES,Lao DH,Yun SH,Lee YJ,Kim DK,Jeon ES, Development of a enterovirus diagnostic assay system for diagnosis of viral myocarditis in humans. Microbiology and immunology. 2013 Apr     [PubMed PMID: 23586632]
[5] Muehlenbachs A,Bhatnagar J,Zaki SR, Tissue tropism, pathology and pathogenesis of enterovirus infection. The Journal of pathology. 2015 Jan     [PubMed PMID: 25211036]
[6] Kaplan MH,Klein SW,McPhee J,Harper RG, Group B coxsackievirus infections in infants younger than three months of age: a serious childhood illness. Reviews of infectious diseases. 1983 Nov-Dec;     [PubMed PMID: 6318288]
[7] Sioofy-Khojine AB,Lehtonen J,Nurminen N,Laitinen OH,Oikarinen S,Huhtala H,Pakkanen O,Ruokoranta T,Hankaniemi MM,Toppari J,Vähä-Mäkilä M,Ilonen J,Veijola R,Knip M,Hyöty H, Coxsackievirus B1 infections are associated with the initiation of insulin-driven autoimmunity that progresses to type 1 diabetes. Diabetologia. 2018 May;     [PubMed PMID: 29404673]
[8] Gear JH,Measroch V, Coxsackievirus infections of the newborn. Progress in medical virology. Fortschritte der medizinischen Virusforschung. Progres en virologie medicale. 1973;     [PubMed PMID: 4572439]
[9] Avoiding the danger of enteroviruses to newborn infants. Lancet (London, England). 1986 Jan 25;     [PubMed PMID: 2868212]
[10] JOHNSSON T, Studies on the etiology of Bornholm disease (epidemic pleurodynia). II. Epidemiological observations. Archiv fur die gesamte Virusforschung. 1954 Apr 12;     [PubMed PMID: 13171858]
[11] KIBRICK S, CURRENT STATUS OF COXSACKIE AND ECHO VIRUSES IN HUMAN DISEASE. Progress in medical virology. Fortschritte der medizinischen Virusforschung. Progres en virologie medicale. 1964;     [PubMed PMID: 14310575]
[12] Rotbart HA, Viral meningitis. Seminars in neurology. 2000;     [PubMed PMID: 11051293]
[13] Wilfert CM,Lehrman SN,Katz SL, Enteroviruses and meningitis. Pediatric infectious disease. 1983 Jul-Aug;     [PubMed PMID: 6310537]
[14] Rotbart HA,Brennan PJ,Fife KH,Romero JR,Griffin JA,McKinlay MA,Hayden FG, Enterovirus meningitis in adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1998 Oct;     [PubMed PMID: 9798053]
[15] Esfandiarei M,McManus BM, Molecular biology and pathogenesis of viral myocarditis. Annual review of pathology. 2008;     [PubMed PMID: 18039131]
[16] Blauwet LA,Cooper LT, Myocarditis. Progress in cardiovascular diseases. 2010 Jan-Feb;     [PubMed PMID: 20109598]
[17] Selinka HC,Wolde A,Sauter M,Kandolf R,Klingel K, Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism. Medical microbiology and immunology. 2004 May;     [PubMed PMID: 12920584]
[18] Berger JR,Chumley W,Pittman T,Given C,Nuovo G, Persistent Coxsackie B encephalitis: Report of a case and review of the literature. Journal of neurovirology. 2006 Dec;     [PubMed PMID: 17162666]
[19] Richardson M,Elliman D,Maguire H,Simpson J,Nicoll A, Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and preschools. The Pediatric infectious disease journal. 2001 Apr;     [PubMed PMID: 11332662]
[20] ALTMAN R, CLINICAL ASPECTS OF ENTEROVIRUS INFECTION. Postgraduate medicine. 1964 May;     [PubMed PMID: 14163253]
[21] Artenstein MS,Cadigan FC Jr,Buescher EL, Clinical and epidemiological features of Coxsackie group B virus infections. Annals of internal medicine. 1965 Oct;     [PubMed PMID: 5891278]
[22] Rorabaugh ML,Berlin LE,Heldrich F,Roberts K,Rosenberg LA,Doran T,Modlin JF, Aseptic meningitis in infants younger than 2 years of age: acute illness and neurologic complications. Pediatrics. 1993 Aug;     [PubMed PMID: 8337018]
[23] Wilfert CM,Lauer BA,Cohen M,Costenbader ML,Myers E, An epidemic of echovirus 18 meningitis. The Journal of infectious diseases. 1975 Jan;     [PubMed PMID: 1167369]
[24] Cooper LT Jr, Myocarditis. The New England journal of medicine. 2009 Apr 9;     [PubMed PMID: 19357408]
[25] Sawyer MH,Holland D,Aintablian N,Connor JD,Keyser EF,Waecker NJ Jr, Diagnosis of enteroviral central nervous system infection by polymerase chain reaction during a large community outbreak. The Pediatric infectious disease journal. 1994 Mar;     [PubMed PMID: 8177623]
[26] Rotbart HA,McCracken GH Jr,Whitley RJ,Modlin JF,Cascino M,Shah S,Blum D, Clinical significance of enteroviruses in serious summer febrile illnesses of children. The Pediatric infectious disease journal. 1999 Oct;     [PubMed PMID: 10530582]
[27] Rotbart HA,Ahmed A,Hickey S,Dagan R,McCracken GH Jr,Whitley RJ,Modlin JF,Cascino M,O'Connell JF,Menegus MA,Blum D, Diagnosis of enterovirus infection by polymerase chain reaction of multiple specimen types. The Pediatric infectious disease journal. 1997 Apr;     [PubMed PMID: 9109145]
[28] Rotbart HA,Sawyer MH,Fast S,Lewinski C,Murphy N,Keyser EF,Spadoro J,Kao SY,Loeffelholz M, Diagnosis of enteroviral meningitis by using PCR with a colorimetric microwell detection assay. Journal of clinical microbiology. 1994 Oct;     [PubMed PMID: 7814507]
[29] Bell EJ,McCartney RA,Basquill D,Chaudhuri AK, Mu-antibody capture ELISA for the rapid diagnosis of enterovirus infections in patients with aseptic meningitis. Journal of medical virology. 1986 Jul;     [PubMed PMID: 3016164]
[30] Jubelt B,Lipton HL, Enterovirus/picornavirus infections. Handbook of clinical neurology. 2014;     [PubMed PMID: 25015496]
[31] Hyöty H,Leon F,Knip M, Developing a vaccine for type 1 diabetes by targeting coxsackievirus B. Expert review of vaccines. 2018 Dec;     [PubMed PMID: 30449209]