Coxsackievirus Infection: Transmision, Incubation, Spread, Symptoms, Treatment, Prevention

Coxsackievirus is included in enterovirus group along with polio and echovirus. The Coxsackievirus is single stranded RNA (ss-RNA) virus and its transmission, incubation period and spread is similar to poliovirus. It is important to know about coxsackievirus infection, the mode of transmission, incubation period, symptoms, diagnosis and treatment.

Coxsackievirus mostly spreads in endothelial cells of upper gastrointestinal system and respiratory system during the initial phase after incubation period. Later viruses encroach into reticuloendothelial cells and nervous system.

The common means through which transmission of coxsackievirus infection include

• Fecal oral route- The coxsackievirus resulting in upper respiratory or gastrointestinal infection as well as hand-foot-mouth and Bornholm disease are discharged in feces. The contamination of surrounding furniture and objects by spread of fecal particles by infected individual causes rapid spread of disease.
• Droplets- Coxsackieviruses are contagious and viruses are also discharged in air as droplets. Transmission occurs when an individual suffering with upper respiratory tract infection sneezes or coughs and spreads the virus to a healthy individual.
• Smearing of Secretion- The nasal or respiratory mucus secretion is smeared over toys, utensils or objects by an individual suffering with coxsackievirus infection. The sharing of contaminated toys, utensils and objects by a healthy person results in transmission of infection by patient suffering with viral infection as well as Hand-Foot-Mouth Disease or Bornholm disease (Pleuritis or pleurodynis).
• Contaminated Diapers- Diapers covered with infected feces can be source of coxsackievirus and often spread infection to healthy garbage cleaners or garbage bag pickers who may not be using disposable hand gloves.

The incubation period of coxsackievirus infection is between 2 to 5 days. The initial infection could be asymptomatic or restricted to the upper gastrointestinal or respiratory system.

It is important to understand the way in which the virus spreads after it enters into the body.

• Initial Mucosal tissue spread- The Coxsackieviruses after entering into healthy individual through oral cavity spread rapidly through gastrointestinal and respiratory system. The mucosal infection spreads through the pharynx, bronchi, stomach and small intestine.
• Autoimmune deficiency- If the infection is ignored or individual has inadequate resistance because of immune deficiency then viruses spread in to lymph nodes, blood and large organs like heart, liver, alveoli of lungs, pancreas, meninges and muscles. The spread of infection in distant organs causes symptoms and signs of Hand-Foot-Mouth Disease and Bornholm disease (Pleuritis or pleurodynis).
• Source of Infection- The coxsackievirus are found in respiratory tracts for up to three weeks and then in feces up to eight weeks after initial infection.

The outburst of the coxsackievirus disease may not be wide spread in various geographical locations same time, but it does spread rapidly in population exposed to infected individual. In United States 10 million individuals includes children and adults are infected with mild to severe viral infection every year. The coxsackieviral infection is a cause of 16 to 24% of the viral infection. The mortality is rare among the children and adult but 25% of the fatal cases caused by viral infection are often caused by infection involving coxsackievirus.

Some of the risk factors for coxsackievirus infection include

• Age- The coxsackievirus infection is observed in all ages but most common among children.
• Sex- The coxsackievirus infection as well as Hand-Foot-Mouth Disease and Bornholm disease (Pleuritis or pleurodynis) is more often observed in male than female. Male to female- 2: 1.
• Newborns- The coxsackievirus infection is rare among pregnant women. Pregnant women may get infected following repeated exposure to infected child or adult. The infection in pregnant women may transmit to newborn. The serious infection of pregnant mother may cause coxsackievirus infection of fetus in the womb and newborn. The mild exposure during the time of delivery is often resolved in few days and may not transmit infection to newborn. Severe coxsackieviral infection of mother may transmit viruses in newborn resulting in mild to fatal neonatal newborn viral infection.

The symptoms of coxsackievirus infection depend on the stages and the areas affected.

Coxsackievirus causes mild to severe infection. Mild infection results in no symptoms. Coxsackieviruses most often transmits to healthy individual through fecal content of infected individual.

• The initial coxsackievirus infection spreads to mucosal membrane of upper gastrointestinal (GI) and respiratory system.
• Severe coxsackievirus infection spreads through lymph node, reticuloendothelial tissue and nervous system resulting in symptoms like muscle pain, meningitis, hand-foot-mouth disease, Bornholm disease (Pleuritis or pleurodynis) and flaccid paralysis.
• The coxsackievirus infection later spread in organs like pancreas, liver and heart.

Coxsackievirus is subdivided in group A and B. Coxsackievirus group A has 23 and group B has 6 subtypes. The symptoms and signs caused by Coxsackievirus group A infection is often known as Hand-Foot-Mouth Disease. The symptoms of Coxsackievirus infection based on these types are as follows

• Fever
• Running nose and sneezing
• Sore throat and cough
• Skin rash
• Blisters on mouth, feet and buttocks.

• Fever
• Running nose,
• Sneezing and
• Cough.

• Fever
• Vomiting and
• Diarrhea

• Fever
• Mild running nose and
• Throat pain
• Conjunctivitis– Inflamed and congested red eye observed with watery discharged.
• Subconjunctival bleeding- Conjunctival hemorrhage or spread of blood under conjunctiva observed.

• Painful blisters- Children and young adult often suffer with painful blisters, which are spread around mouth, throat, hands and feet.
• Upper respiratory tract infection- Herpangina is often associated with upper respiratory tract infection caused by coxsackievirus. Symptoms observed are fever, throat pain and cough

• Fever
• Muscle pain- The muscle pain either localized or wide spread seen in adults. Young children are often unable to described muscle pain.
• Muscle pain is caused by generalized myalgia or muscle inflammation.
• Flaccid Paralysis-
• Muscle weakness- The condition is rare but may be observed in children and adults following long standing upper respiratory or gastrointestinal infection. The condition is reversible.
• Rarely may end up in irreversible weakness in muscles often results in clinical manifestation as observed in polio.

• Fever with chills
• Headache
• Light sensitivity
• Photophobia
• Vomiting
• Loss of appetite
• Child- irritable and frequent crying

Most often coxsackievirus infection causes mild to moderate symptoms of upper gastrointestinal and respiratory infection. Rarely in patients with less resistance or immune deficiency condition, the infection spreads to single or multiple distant organs resulting in systemic disease as well as Bornholm disease (Pleuritis or pleurodynis).

The symptoms of coxsackievirus infection in this type include the following:

• Non-specific fever
• Pharyngitis- cough and throat pain
• Bronchitis– cough and secretions (expectorant)

• Abdominal pain
• Nausea and vomiting
• Diarrhea

• Chest pain
• Fever with chills often not responding to NSAIDs
• Palpitation- older children and adult feel rapid heart beats
• Irregular heart beat and murmur felt during auscultation of heart.
• Night sweat
• Blood in urine
• Retention of fluid causes swollen feet and legs as well as shortness of breath
• Enlarged spleen

• Chest pain
• Dyspnea– short of breath
• Fever
• Fatigue
• Shortness of breath
• Palpitation
• Light headedness and dizziness
• Diaphoresis- cold clammy skin and sweating
• Low blood pressure

• Unilateral lower chest or upper abdomen pain
• Fever
• Short of breath with pleuritic rib pain
• Bornholm disease mainly affects children and young adults.
• It usually lasts for few days to 3 weeks

• Nausea,
• Vomiting
• Loss of appetite
• Pain right side abdomen
• Dark urine
• Jaundice: Yellow Conjunctiva

• Fever
• Abdominal pain
• Nausea and vomiting
• Increase heart rate
• Insulin dependent diabetes caused by severe damage of insulin producing cells.

• Seen following pancreatitis as a result of insulin deficiency
• Fasting and post prandial blood sugar level is significantly high.
• Blood sugar often difficult to control and need insulin

• High fever
• Headache
• Stiff neck
• Seizures
• Confusion and sleepiness
• Nausea and vomiting

Diagnosis of coxsackievirus infection is based on following investigations. Some of the test results in each condition commonly include:

• Immunofluorescent assay
• Enzyme linked immunosorbent assay (ELISA)
• Coxsackie or picornavirus detection
• Sensor detection of viral infection
• Antigen or antibody Assays- During initial phase of the disease surface antigen are detected in blood. Surface antigen are not seen during later phase of the disease. The most reliable test to diagnosed hepatitis B is to detect Ig M antibodies during chronic stage of disease. Higher rate of viral replication often causes increase concentration of antigen HBeAg, which is also detected in blood examination.

• Abnormal EKG
• Cardiac enzymes are elevated

• X-ray- shows signs of pleuritis
• CT or MRI- suggest signs of pleuritis

• Liver enzymes elevated
• Alkaline phosphatase level elevated

• Level of blood amylase and lipase enzymes elevated
• Abnormal glucose tolerance test
• Abnormal pancreas observed over ultrasound scan
• CT scan or MRI suggests abnormal pancreas
• Biopsy of pancreas suggests inflammation and scarring

Treatment of coxsackievirus infection is based on the symptoms. Treatment for each symptom of coxsackievirus infection include

• Fever caused due to coxsackievirus infection is treated with anti-inflammatories (NSAIDs). Most common NSAIDs used are motrin, naproxen and celebrex.
• Treatment of Muscle Ache and Joint Pain Caused Due to Coxsackievirus Infection
• NSAIDs- Motrin, Naproxen and celebrex
• Muscle relaxants- Flexeril,

• Anti-vomiting or anti-emetic medications are prescribed for nausea and vomiting.
• Medications prescribed are Compazine, Phenergan and Thorazine.

• Anti-diarrheal is given. Kao-pectin, Pepto-Bismol as an oral liquid, Imodine pills

• Antiviral drugs- Adefovir, Epivir, tenofovir and telbivudine.

• Flaccid paralysis is treated with physiotherapy during initial phase
• Polio like condition or spastic paralysis is aggressively treated with various options of physical therapy.
• Stretching exercise

• Low protein diet and lactulose are advised if individual is suffering with signs of encephalopathy.

• Dehydration caused by vomiting and diarrhea
• Serious illness and patient is unable to take oral feeding
• Route for intravenous antibiotics

• Treatment is necessary for patient suffering with end stage liver disease.

Here are certain measures that need to be adopted for effective prevention of coxsackievirus infection.

1. Individual Suffering With Coxsackievirus Infection-

   1. Prevent or Avoid Spread- Infected individual should take appropriate precautions to prevent spread of disease. Coxsackievirus infection are transmitted from infected individual through nasal secretion, cough droplets, saliva, sweat, semen, feces, vaginal fluids, breast milk and contact with urine.
   2. Frequent Washing of Hand- The coxsackieviruses are transmitted by touch of infected feces. Individual suffering with disease should wash hands with antiseptic solution after defecation.
   3. Use Gloves- Health care worker or relatives taking care of patient should use gloves and wash hand frequently to prevent spread of coxsackievirus infection.
   4. Avoid Smearing of Secretions- Patient should prevent smearing nasal secretion, sputum, urine and feces over the utensils, surrounding objects and furniture.
   5. Cover Mouth- Individual suffering with coxsackievirus infection should cover mouth and nose while coughing or sneezing.

2. Healthy Individuals Exposed to Infected Patient-

   1. Frequent hand wash is a must to prevent getting coxsackievirus infection
   2. Frequently clean furniture and appliances by antiseptics solution.
   3. Pick up contaminated clothes and paper towels while using hand gloves.
   4. Avoid using smeared utensils or furniture if suspected of spread of infection.
   5. Consider prophylactic antiviral therapy with medical advice.
   6. Avoid needle sharing

3. Pregnancy-

   Pregnant women should be considered for cesarean section delivery and breast feeding should be avoided to prevent spread of coxsackievirus infection.

4. Prophylactic Immunoglobulin-

   Immunoglobulin has been used as a therapeutic agent for neonates with enterovirus disease. However, clinical efficacy has not been proven and specialist advice should be sought.

Also Read:

• How Does Poliovirus or Enterovirus Spread, Know its Risk factors & Treatment
• Rhinovirus Infection or Common Cold Virus: How Does it Spread, Symptoms, Treatment
• How Does Viral Infection Spread, Know the classification and symptoms of Viral Infection
• Clinical Manifestation of Adenovirus & Diseases Caused by Adenovirus Infection & its Treatment
• Clinical Manifestation of Orthomyxovirus or Influenza & Its Symptoms, Treatment, Transmission
• Hepandnavirus or Hepatitis B Virus
• Hepatovirus: Infectious Hepatitis or Hepatitis A: Transmission, Incubation, Symptoms, Diagnosis, Prognosis, Prevention
• Parvovirus Infection in Humans: Incubation, Transmission, Symptoms, Treatment
• Reovirus: Clinical Manifestation, Diseases Caused by Reovirus, its Symptoms, Treatment
• Retrovirus or HIV Infection: Transmission, Treatment, Clinical Manifestation, Prevention, Opportunistic Infections
• What is Norovirus: How Does it Spread, How Long does Norovirus Symptoms Last, Treatment, Prevention
• Antiviral Medications for Treating Viral Infections
• How Do Antiviral Drugs Work?

References

1. Coxsackie Myocarditis and Hepatitis with Reactivated Epstein-Bar Virus (EBV): A Case Report.
   Atti V1, Anderson NM1, Day MB1., Am J Case Rep. 2017 Feb 15;18:166-169.

2. Detection and localization of viral infection in the pancreas of patients with type 1 diabetes using short fluorescently-labelled oligonucleotide probes.
   Busse N1, Paroni F1, Richardson SJ2, Laiho JE3, Oikarinen M3, Frisk G4, Hyöty H3,5, de Koning E6,7, Morgan NG2, Maedler K1., Oncotarget. 2017 Jan 29.

3. Coxsackie B virus serology and Type 1 diabetes mellitus: a systematic review of published case-control studies. Green J1, Casabonne D, Newton R., Diabet Med. 2004 Jun;21(6):507-14.

4. Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses.
   Ornoy A1, Tenenbaum A., Reprod Toxicol. 2006 May;21(4):446-57.

5. Vertical transmission of human echovirus 11 at the time of Bornholm disease in late pregnancy.
   Tang JW1, Bendig JW, Ossuetta I., Pediatr Infect Dis J. 2005 Jan;24(1):88-9.

6. Probable intrafamilial transmission of coxsackievirus b3 with vertical transmission, severe early-onset neonatal hepatitis, and prolonged viral RNA shedding.
   Cheng LL1, Ng PC, Chan PK, Wong HL, Cheng FW, Tang JW., Pediatrics. 2006 Sep;118(3):e929-33.

7. Co-circulation of coxsackieviruses A6 and A10 in hand, foot and mouth disease outbreak in Finland.
   Blomqvist S1, Klemola P, Kaijalainen S, Paananen A, Simonen ML, Vuorinen T, Roivainen M., J Clin Virol. 2010 May;48(1):49-54