Let us make an in-depth study of the enteric viral infections. The below given article will help you to learn about:- 1. Poliomyelitis 2. Coxsackie and Echo Viruses and 3. Hepatitis Viruses.
Viruses of poliomyelitis and those of coxsachie and Enteric Cytopathogenic Human Orphan (ECHO) groups are included in Enteroviruses, as they multiply primarily in the human gastro-intestinal tract, produce clinical diseases involving central nervous system (brain and spinal cord). Respiratory Enteric Orphan virus (REO Virus) is constantly associated with diarrhoea than with respiratory symptoms.
Another virus, infectious hepatitis (IH) or epidemic hepatitis, present in the intestine which is transmitted by faecal-oral route is not considered under entero group virus, as they multiply in the liver, not in the intestine or central nervous system.
Poliomyelitis:
Though poliomyelitis is known as one of the most ancient contagious diseases, its infectious nature was ascertained only in 1905 by Wickman; later, in 1908-09, it was proved to be of viral aetiology. Poliovirus ranges from 8-27 nanometer (nm) – nanometer (1 nm = 10 meter) or equal to millimicron (mn) and forms intra-nuclear inclusions. It is cultivated in vitro in tissue culture of monkey kidney or He La cells.
There are three types of viruses which do not possess common immunogenic properties:
Type I viruses include Brunhilde strains which are pathogenic to man and monkey.
Type II viruses include the Lansing strains which are responsible for diseases in man, monkey and rodents (rats, mice, hamsters etc.).
Type III viruses (the Leon strain) are pathogenic only to man and monkeys and differ immunologically from two types.
Resistance:
The poliomyelitis virus survives in sterile water at room temperature for more than 100 days; in milk for 90 days; in faeces in cold for more than 6 months and in sewage for several months. It withstands exposure to 0.5-1 per cent phenol solution and remains viable for several weeks at pH 3.8 – 8.5. It is very sensitive to calcium chloride, formalin, potassium permanganate and hydrogen peroxide. It is rapidly killed on boiling.
Pathogenesis and disease in man:
The virus is extremely neurotropic. It causes the degenerative inflammatory process in the anterior horns of spinal cord and in the grey substance of the brain. However, the virus circulates in the blood. It may be discharged in the faeces of patients and convalescents for 2-7 weeks and is discharged through the nasopharyngeal mucous membrane secretion and sometimes up to 4 months and during the incubation period. Healthy carriers also excrete the virus with the feces.
This virus may be found in the nasopharyngeal mucus and tonsils approximately 3 days before the temperature rises and for 3 days after the onset of the disease. According to the clinical symptoms, three forms of poliomyelitis are distinguished; abortive, non-paralytic and paralytic.
Immunity:
There are three immunologically distinct types of polioviruses: I, II and III. Immunity to one does not confer immunity to another. A very stable immunity is produced following the disease. No case of reinfection has been described. Immunity is associated with the presence of virus neutralizing antibodies in the blood.
Polio vaccine:
In 1949, Enders, Weller and Robbins (Nobel Prize winners) were able to cultivate poliomyelitis virus in tissue cultures, made from human, monkey kidneys, human intestinal tissues, human embryonic tissues and human cancer (Ha La cells).This virus multiplies and kills the tissue cells.
The Salk vaccine was prepared by Jones Salk by cultivating poliovirus Type 1, 11, 111 in live monkey kidney tissue cells and after an incubation, the dead tissue cells and other debris are removed and the remaining fluid containing poliovirus is collected and formaldehyde (1:4,000) is added to kill the virus and allowed to act for one week and excess of formaldehyde is removed. Safety tests were then carried out to determine whether the virus is really killed and the fluid is not contaminated with bacteria. If satisfactory, the preservative is added and the vaccine is ampouled and used.
Use and effectiveness of Salk vaccine:
Three doses are recommended; first two doses at an interval of about four to six weeks apart and the third at an interval of 1 -3 years or more. This vaccine does not prevent poliomyelitis, but the incidence is reduced to a very low level, when it is used consistently, because of the antibodies in the blood and the tissues of vaccinated persons which interpose a barrier between the gastrointestinal source of virus and the central nervous system. Thus, the most important effect of the vaccine is to prevent severe paralytic polio, e.g., crippling and deadly “spinal paralysis. This vaccine is 90 percent effective in preventing the paralytic polio.
Vaccination in Pregnancy:
Immunization of the mother with the vaccine probably gives some passive protection to the infants for a few months.
The Sabin or Oral Polio vaccine:
On cultivation, the poliovirus would probably lose its virulence for man and become available as living, attenuated virus vaccine. Sabin and World Health organisation conducted a large scale experiment with this living attenuated virus vaccine and the vaccine was found to be excellent and approved in 1962 for general use. The vaccine is given routinely by oral route to.mil- lions of people by incorporating it in candy, food, beverage.
Following the oral administration of the Sabin vaccine, the virus multiplies in the alimentary canal and the virus is discharged in the faeces. No symptoms are observed. In addition to the excellent antibody response, the intestinal infection apparently results in an immunization of the intestinal tract as well, thus preventing subsequent reinfection.
Triple Living Polio Vaccine:
A second type of oral vaccine (Orimune) containing all types of live, attenuated poliovirus was licensed in 1963 by the United States Public Health Service. This vaccine yields a high degree of immunity if given in only two doses two months apart.
Polio and Surgery:
The injury or wound due to tonsillectomy, adenoidectomy or tooth extraction and other surgical procedures during the season of epidemic of poliomyelitis is open door for the entry of the virus through the damaged tissues. Therefore, such procedures should be avoided during the season of poliomyelitis.
However, the paralysis of the legs and arms may frequently occur at the site of injection of vaccine or penicillin during the epidemics of poliomyelitis. Thus, the risk of paralysis and also infection may be increased due these injections.
Epidemiology:
Faeces provide a rich and persistent source of the poliovirus. Sewage in urban areas contain this virus. Water supply may be contaminated by sewage and in rural areas this may be a means by which the infection is spread. Fly may carry the virus on their feet or by regurgitating after feeding on the exposed faeces or sewage.
Application to Nursing:
A professional nurse shall be vigilant in proper disposal of all respiratory secretions during the first two or three weeks from the onset of the infection. The nurse’s hands, objects and dishes used by the patient should be well-disinfected to prevent the spread of the disease. Since boiling and adequate exposure to chloride of the lime will inactivate the poliomyelitis virus, these procedures should be applied by the nurse while dealing with poliomyelitis.
Coxsackie and Echo Viruses:
Diseases caused by Coxsackie and Echoviruses were discovered by Dall dorb and Sickles in 1948 in Coxsackie (New York State) from children suffering from paralysis and other infections resembling poliomyelitis. ECHO virus (enteric cytopathogenic human orphans) virus were discovered by Melnick and others. Coxsackie virus is extremely small and resembles poliomyelitis virus. They are grown on tissue cultures (human and monkey kidney cells) and pathogenic to new born mice. The majority of ECHO viruses are non-pathogenic to new born mice.
Resistance:
Coxsackie and ECHO virus possess relatively high resistance. They survive for a long time at -70°C. In the refrigerator, they survive for more than a year. They survive at pH 2,3 – 9.4 for 24 hours and at pH 4.0 – 8.0 for 7 days. At temperature of 50 – 55°C kills these viruses in 30 minutes and they are extremely sensitive to hydrochloric acid and formaldehyde.
Pathogenesis and disease in man:
There are several forms of the diseases:
(a) Aseptic serous meningitis;
(b) Pleurodynia;
(c) Aseptic meningitis;
(d) Three day fever; Both these viruses are responsible for a number of other disease; non-diphtheric croup; influenza like disease.
Application to Nursing:
The methods adopted for the prevention of urine or faeces-borne diseases should be applied by the nurse for the control of the disease.
Hepatitis Viruses:
There are five major types of primary hepatotrophic acute hepatitis viruses. Besides, other viruses are also responsible for acute viral hepatitis.
Hepatitis A Virus (HAV):
In 1973, Feinstone et al first discovered HAV in feces of infected patients by immune electron microscopy. World Health Organisation (WHO) considered that this infection is prevalent worldwide, particularly in countries where over-crowding, poor hygiene and sanitation are common. Recent outbreaks in 1988 in China involving 1.2 million persons were presumed due to over-crowding, poor hygienic condition.
HAV was classified as picornavirus. However, there is now more evidence to support that HAV is different from well-studied four genera of this virus family.
Two HAV cell systems have been very recently described in which replication of HAV seemed to be paralleled by virus specific cytopathology.
The pathogenic mechanism of liver cell damage in acute HAV infection is not yet well understood.
There are two recent studies which strongly proved that the cytotoxic T cells capable of lysing HAV-infected target cells developed in the course of HAV infection.
Usually, HAV causes a minor or unnoticed illness in children and young adults and high mortality in patients over 60 years of age.
Laboratory Findings:
In HAV infection, elevated serum transaminases are often accompanied by nonspecific rise of Ig M, Ig G, anti smooth muscle antibodies and acute phase proteins. The raised Ig M is mainly polyclonal and only a small proportion is directed against HAV antigen. The extent of serum transaminases elevation does not appear to be of diagnostic significance.
Immunization:
High titer serum immunoglobulin preparations have value in the prophylaxis against HAV infection. HAV infection is an important source of morbidity and economic losses, although it does not lead to chronic hepatitis and cirrhosis. Killed HAV vaccine has been found to be safe and efficient in animals and it is under clinical trials.
Hepatitis B Virus:
World Health Organisation (WHO) estimated that in 1988 there are about 300 million chronic HBcAg carriers in the world and suggested that 40 per cent of them will eventually die of chronic liver disease and or hepatoma. HBV genome has been well-characterised and consists of 4 overlapping open reading frames designated S, C, P and X.
HBV Polypeptides:
Both HBC Ag and HBs Ag are encoded by C gene. The presence of HBs Ag in the blood is, therefore, an indication of on-going viral replication. The X protein presence may also be suggestive of HBV replication.
Liver Damage:
In the natural host, man, HBV is not cytopathogenic because there is existence of HBV carriers state for many years without evidence of parenchymal liver damage and it may not be the same in the animal experimentation. Recently, it has been shown that HBV itself can inhibit interferon production in an in vitro system thus explaining the decreased interferon production in a group of patients.
Serological Features of Viral Hepatitis:
There is serological evidence showing that the acute HBV infection progresses to chronic HBV infection. Reverse passive Hemagglutination (RPHA), Counter immuno electrophoresis (CIEP) and ELISA Tests can detect HBc Ag.
Aniviral Therapy:
At present, interferon-alpha is the only promising mode of therapy. Further studies are still conducted to evaluate the role of new drug combination therapy and continuous low dose interferon-alpha therapy in the interferon-alpha resistant patients. Agents that have been studied in the treatment of chronic HBV infection.
Active Immunization:
In 1981, the first generation plasma derived HBV vaccines were licensed. There was limitation regarding their acceptance and use, because of their high production cost and the fear of the possible transmission of blood borne disease.
Much more rapid progress had been done by the vaccination of the high risk group (health personnel’s and babies born to HBSAg seropositive mothers) with the second generation yeast derived recombinant HBV vaccine launched in 1986. Routine HBV vaccination was recommended by WHO for countries that possess the economic capacity to purchase the vaccine.
Now, the third generation synthetic peptide vaccines have been developed; their safety, immunogenecity and protectively against HBV infection are under evaluation and these vaccines may become cheap and efficient.
Hepatitis B vaccine consists of purified hepatitis B surface antigen (HBsAg).The vaccine induces neutralizing HBsAg antibodies which confer protection against Hepatitis B virus.
Plasma derived HBV vaccine is no longer available in USA, but the two yeast derived recombinant vaccines are qualitatively similar to plasma derived vaccine.
Engerix – B, the only genetically engineered Hepatitis B vaccine, is at present available in India. Engerix – B is supplied in a 20 µg dose and Recombivax in a 10 µg dose.
Hepatitis C Virus:
There was a proportion of cases clinically viral hepatitis without defined etiology, after the isolation of HBV in 1960s and HAV in 1970s.The majority of these cases occurred after blood transfusion of intravenous drug users and led to chronic hepatitis. The term non-A non-B hepatitis (NANB) was carried to describe these cases. The clinical diagnosis of NANB hepatitis was imprecise. There are two blood borne NANB hepatitis agents; NANB hepatitis virus was between 30-60 nm. diameter.
Identification of Hepatitis C Virus:
Because of the recent advances in molecular cloning technique, non-A non-B virus has been recently identified and termed as HCV. Half of the patients with presumed chronic NANB hepatitis become positive when recent polymerase chain reaction (PCR) was used to detect HCV RNA in tissue and serum.
Recent Serology:
It has been very recently shown that the anti- HCV antibodies appeared only several weeks after the infection, but persisted for more than 10 years in most patients. A recombinant immuno-blot assay (RIBA) was established by utilizing the western blotting technique and was found to be more sensitive and specific. Serum HCV RNA was successfully detected by employing the polymerase chain reaction and molecular hybridisation. All these newly developed techniques need to be confirmed for their specificities.
Hepatitis D Virus (Delta Agent, Dane Particle)
A new viral antigen was observed by Rizzitto et al in the nuclei of hepatocytes in patients suffering from HAV infection. Later studies showed that this antigen was related to a new virus, now named as HDV. HDV is an incomplete single stranded circular RNA virus that depends on the helper function of HBV to replicable. It is uncoated in HBS Ag and RNA genome. Thus, it appears that HDV requires HBs Ag for its hepatotropism and propagation, but it does not depend on HBV for replication.
Epidemiology:
HDV infection is endemic in Italy, Middle East, Africa and South America. The major route of transmission in non-endemic areas is the intravenous drug use. Placental transmission may not be always important route.
Liver Disease (Hepatitis):
Replicating HDV appears to be mostly associated with liver damages suggesting that HDV may be directly hepatotoxic. The possible similarity in the pathogenic mechanisms of HBV and HDV may be due to the similar pattern of T-cells infiltration in chronic HBV and HDV infection.
Clinical Features and Laboratory Diagnosis:
In chronic HBsAg carriers, infection with HDV may occur simultaneously with HBV infection (co- infection) or as a super infection; but these two infections have two different clinical courses and outcomes. As acute HBV infection, co-infection is usually self- limiting, although morbidity may be higher. A massive infecting dose may be associated with a more severe outcome.
Super infection of HBsAg carriers with HDV may cause severe acute hepatitis and lead to chronic hepatitis and cirrhosis in over 70 per cent cases. Chronicity in HDV super infection is usually accompanied by a decrease in HBV replication markers. A sub acute, rapidly progressive form of HDV super infection has been reported.
The diagnosis of different forms of HDV infection relies in detection of HD Ag in liver biopsies and serum HD Ag, HDVRNA and Ig M, Ig G and anti-HD antibodies. In acute HDV infection, HDVRNA and HD Ag appear transiently in serum of about 25% cases.
Ig M and anti-HDV occurred in 93% lasting for about 2-10 weeks. In those patients who develop chronic HDV infection, serum HDVRNA and Ig M anti-HDV usually persist and HD Ag can be found consistently in the liver. In chronic HBSAG carriers with HDV super-infection, the suppression of HDV replication may lead to a transient absence of HDV markers in the serum and liver.
Antiviral Therapy and Immunization:
Interferon-alpha has an inhibitory effect on HDV replication but beneficial effect is transient in most cases. Fulminant HDV infection may respond to treatment with trisodium phosphonoformate. Control of HDV infection is by vaccination against HDV.
Hepatitis E Virus:
In 1983, virus-like particles (VLPs) measuring 27- 32 nm. were demonstrated by immune electron microscopy in the stools of three of nine cases of HEV infections in Taskhent of the-then, USSR.A volunteer developed an acute hepatitis with anti-bodies detectable to the VLP by immune electron microscopy IEM after ingesting a dilute suspension of stools pooled from patients. In the liver of experimentally infected macaques an antigen related to HEV (HEV Ag) was detected. In the early phase of experimental infection, there is a granular distribution in up to 90% of hepatocytes.
Clinical Features and Laboratory Findings:
In the well-characterised Indian epidemics, many clinical cases were detected. The incubation period was between 3-9 weeks. The attack rate was higher in young adults (2.9%) than children (1.4%) or in those aged over40 (2.0%). A prodrome illness with anorexia, nausea, vomiting and abdominal pain is followed by jaundice.
The disease is usually benign and self-limiting with no chronic sequelae. Fulminant hepatic failure has been reported in 2.8% of men and 22% of pregnant women in whom it is usually fatal. It may cause severe form of the disease during third trimester of pregnancy.
An antibody blocking assay was developed with the development of fluorescent linked anti-HEV Ag, as a prototype test for identification and titration of specific anti-HEV Ag antibody in the serum samples. The immune electron microscopy (IEM) findings have confirmed this test which is available only in specialised countries.
Epidemiology:
The first and most massive outbreak of an enteric non-A, non-B epidemic was reported in 1955 when drinking water was contaminated by the overflow of an open sewer in Delhi (India). A total of 29,000 residents developed an acute hepatitis which ran a benign course in the majority and was self-limited.
However, 10% women, affected in their third trimester of pregnancy, died of fulminant hepatic failure. There reports confirmed the existence of fecal-orally transmitted type of non-A non-B hepatitis with completely different characteristics to blood borne NANB hepatitis of 10 Indian hepatitis epidemics subsequently investigated. None has been found to be due to epidemic of enteric NANB hepatitis HEV.
Treatment and Control:
The treatment is purely supportive as in the case of HAV. The supply of clean water and adequate sanitation can control the disease. Viral antigen obtained by recombinant technology may be used for the diagnostic test and for the development of vaccine.
Following the initial report of HEV epidemics in India, similar epidemics were also reported in Asia, Africa, America. A reservoir of HEV infection is therefore required to perpetuate the infection in the absence of the carrier state. Recently, Russian research workers were able to transmit HEV to pigs with the hepatitis illness. Besides, they have also found anti-HEV antibody in rats from areas where the disease is endemic.
Serum Hepatitis:
Immunoglobulin’s can be administrated for passive immunity against hepatitis B virus.
Development of Vaccine:
A vaccine has been prepared by purifying HBsAg associated with the 22 nm. particles from healthy HBsAg – positive carriers. Fortunately, protection is conferred by antibody to the “a” antigen, an antigen that is common to all subtypes.
Control and Prevention:
1. Clothes of jaundice patients should be washed separately in boiling water;
2. Jaundice patients should be kept in isolation wards;
3. All syringes, needles and equipment’s should be autoclaved to prevent the entry of hepatitis B virus in the body;
4. Australia antigen test should be conducted by the most sensitive method to detect HBsAg in:
(a) Jaundice patients;
(b) Blood donors;
(c) Persons to be operated;
5. Cleanliness and hygiene should be maintained at all public eating places;
6. Drinking water should be chlorinated;
7. Laboratory investigators should wear gloves, while testing sera of ‘patients;
8. Used materials and glass wares should be discarded in formalin (1:4,000);
9. Laboratory and hospital wards should be fumigated.