Water borne disease range in severity from mild to life threatening illness, and their significance is often under-estimated. These disorders may also cause chronic health problems. Water-borne diseases constitute a wide spectrum, and are manifested by acute watery diarrhoea contributing to 50% of diarrhoea-related deaths, 30-35% are due to persistent diarrhoea and 15-20% due to dysentery.
In cities, especially in slums, high diarrhoeal morbidity occurs despite access to piped and supposedly clean water for several reasons – inadequate water quantity, unhygienic household storage of water and food, and leaking pipelines.
The diarrhoeal morbidity is highest in rural areas and in urban slums where under-fives may suffer 6-8 episodes of diarrhoea. Diarrhoea may result from infections with a number of different pathogens.
The disease cholera is caused by a gram-negative curved organism known as Vibrio cholerae. Currently, 192 serogroups of V. cholerae have been identified. However, of these 192 serogroups, only two namely O1 and O139 are known to produce cholera toxin (CT) and are capable of causing the disease.
Additionally, only these two serogroups are associated with epidemics. The O1 serogroup has two biotypes namely Classical and EI Tor, each biotype is further sub-classified into Ogawa and Inaba serotypes. The remaining 190 serogroups usually do not produce CT, are not associated with epidemics and cause sporadic cases of gastroenteritis.
The most significant observation in EI Tor is its high degree of human asymptomatic infection. Studies by Sinha et al., and Dizon have observed cholera carrier rates ranging between 1.3% and 21.7% depending on the association with cholera patient and the number of stool samples examined. About 75% of these carriers were transient carriers.
The excretion of cholera organism in their stools is intermittent. These carriers are mainly responsible for the maintenance of endemicity of the disease in an area and its spread to other areas. Of course, prevailing poor sanitary conditions and lack of safe water supply and hygienic sense help a great deal in the perpetuation of the organism and the disease.
The EI Tor cholera strain is sturdier than classical biotype and is, therefore, capable of surviving in the environment for a longer period, which further facilitates its transmission. For decades it was thought that the only reservoir of V. cholerae O1 was the human intestine.
However, in the late 1970s, it was observed in Australia and USA that V. cholerae O1 could also live freely in environment besides the human gut. These extra-human reservoirs were found responsible for causing a few outbreaks of cholera in otherwise non-endemic areas.
Gangarosa and Mosley (1974), while studying the epidemiology of cholera have incriminated water as the prime source of infection of this disease. The water sources include river water, pond water, water from wells, springs and tube-wells. Untreated river and pond water have caused transmission of cholera in African, Latin American and Asian countries.
In rural India, ponds, wells, sometimes slow-flowing or stagnant rivers, tube-wells having broken platforms (which allow seepage of contaminated water down the pipeline) etc., are very often, responsible for the spread of cholera infection.
In urban setting also, the ancient piped water supply system can get contaminated by surroundings, thereby making the water supply unsafe. According to Felsenfeld (1995), EI Tor V. cholerae is capable of more rapid multiplication and longer survival in many food items as compared to the classical biotype. This is influenced by pH, moisture, temperature, organic matter and presence or absence of competing flora.
EI Tor V. cholerae O1 in contaminated foods can survive from 2 to 14 days. When food after cooking is stored un-hygienically, it is liable to get contaminated by either infected fingers of cholera carriers or by previously contaminated utensils. Seafood has also been incriminated as transmission agent for cholera in many parts of Asia, Africa, Europe and America where these are considered delicacies. In many of these areas people eat them raw which increases the risk further.
Cholera often occur as epidemics or outbreaks, when case fatality tends to be high. A pattern of global cholera epidemics, called pandemics is being reported and at least seven have been recorded in the last 150 years. Blake (1994), in his study, gives a historical perspective on pandemics of cholera. The seventh pandemic caused by Vibrio cholerae O1 biotype EI Tor, started in 1961 in Indonesia, spread to Peru in 1991 and then spread to other countries.
Ramamurthy et al. (1993) described a new strain of cholera, O139 in India in 1992, it then spread to Pakistan and China. In India and Bangladesh, the classical Vibrio cholerae O1 has again become predominant but O139 remains a threat. The economic impact of cholera epidemics is profound.
Cholera is an ancient scourge of mankind but still many areas of the world are very much in the grip of this disease. Safe water supply, environmental sanitation, chlorination and boiling of water are proven methods of prevention of cholera. Oral rehydration drastically cuts down mortality and has revolutionized the treatment of cholera, supplemented, where necessary, with antibiotics.
Control of cholera can be achieved by ensuring safe water supply, good sanitation, food safety, effective treatment of patients and by vaccinating people (with killed whole cell or B sub-unit oral vaccine) in defined situations (such as displaced population either coming from or located in endemic areas). However, it cannot be overemphasized that, to date, cholera vaccine cannot be substitute for effective case management for all patients and maintenance of appropriate hygienic measures.
Typhoid fever is an old problem that still persists. Typhoid fever is estimated to have caused 21.6 million illnesses and 2,16,500 deaths globally in the year 2000. Salmonella are pathogenic for humans and animals when acquired by the oral route. They are transmitted from animals and animal products to humans. Salmonella typhi (S. typhi) is primarily infective for humans. The organisms almost always enter via oral route usually with drink and food. Sidley has recently given a good account of typhoid outbreaks occurred due to inadequate water system.
The mean infective dose to produce clinical or sub-clinical infections in humans is 105-108 salmonella. Enteric fever is the syndrome that is produced mainly by S. typhi and S. paratyphii A. The ingested salmonella reach the small intestine, from which they enter the lymphatic and then the blood stream.
The organism multiply in intestinal lymphoid tissue and are excreted in stools. Eight to 48 hours after ingestion of salmonella, symptoms like nausea, headache, vomiting and profuse diarrhoea appear. Inflammatory lesions of the small and large intestines (enterocolitis) are present.
Bacteraemia is rare except in immuno-deficient patients. Paratyphoid fever caused by S. paratyphi A constituted almost one fourth of the total cases of enteric fever in contrast to the typhoid fever, which was more prevalent in children under 5 years, majority of the paratyphoid fever cases occurred in those older than 5 years.
After manifest of sub-clinical infection, some individuals continue to harbour salmonellae in their tissues for variable lengths of time. Three per cent of previously infected persons or survivors of typhoid, become permanent carriers, harbouring the organisms in gall bladder, biliary tract or, rarely, the intestine or urinary tract. In a recent study, Bhan et al. have described the various aspects of typhoid and paratyphoid fever.
Treatment with chloramphenicol and ampicillin had reduced the mortality considerably in the past. However, after resistant to chloramphenicol as described by Anderson and Smith, drugs like ciprofloxacin, noifloxacin, cefazoline, amikacin and ceftriaxone have been the main stay of treatment.
However, there are reports by Bhan et al. (2005) regarding occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Salmonella typhi is a notorious organism for high frequency of drug resistance; nearly 50% of strains isolated in clinical cases being resistant to commonly-used antibiotics.
Levine and Lepage (2005), have suggested that the decision to introduce vaccination (with Vi or Ty21 A) for the control of typhoid must be made in relation to the economic or socio-economic burden of the disease, the health benefits occurring from vaccination and the relative ranking of other vaccine-preventable diseases in terms of their costs and benefits. Sanitary measures must be taken to prevent contamination of water and food.
Diarrhoea may be defined as the passage of loose and watery stools, usually at least three times in 24 hours period. When the stool contains blood and mucus, it is known as acute bloody diarrhoea or dysentery. This is usually accompanied by tenesmus, abdominal cramps, anorexia and fever. Acute bloody diarrhoea may be caused by Shigella species, Entamoeba histolytica, Enteroinvasive Escherichia coli, Vibrio parahaemolyticus. Of these, Shigella species are responsible for majority of the episodes of acute bacterial bloody diarrhoea in children.
Disease caused by Shigella species is known as Shigellosis. Niyogi (2005) has given a detailed account of bacillary shigellosis encompassing all aspects of the disease. Shigellosis is a major threat in Asia, as it accounts for nearly one fourth of childhood diarrhoeal deaths. The case fatality rates are high due to emergence of multi-drug resistant strains. Occurrence of epidemics due to multi-drug resistant Shigella in recent years is accompanied by high case fatality rates.
Pal et al. (1989) described in one of their initial study showed shigellosis as the sole cause of 6,00,000 deaths every year globally. Shigellosis is caused by different species, e.g., Shigella dysenteriae, Shigella sonnei, Shigella boydii and Shigella flexneri serotypes (most common is serotype 2a). Shigella dysenteriae type 1 is the only species responsible for epidemics. Since its discovery in the last decade of the 19th century, the S. dysenteriae type 1 also known as shiga bacillus, has been recognised as an unusually virulent pathogen causing widespread epidemics with high case fatality rate; but after 1920s, the infection virtually disappeared from both the developed and developing countries of the world.
However, since 1969, S. dysenteriae type 1 epidemics have been reported from Central America and Mexico (1969-72), Bangladesh (1972-77), Southern India (1972-78), Somalia (1976), Sri Lanka and Maldives (1976-82), Central Africa (1979-86), Tanzania (1982-83), Eastern India (1984), Myanmar (1984-85), Thailand (1985-86), Nepal (1984-85), and Andaman and Nicobar Islands (1986). These epidemics were not equally calamitous or rapid in spread; those in Central America, Central Africa and Bangladesh were of greater magnitude and had more serious consequences.
Only 10 to 100 Shigellae bacilli can cause disease in human adult volunteers. This low infectious dose and person-to-person transmission explains why epidemics are difficult to stop. Man is the only host and the reservoir. S. dysenteriae type 1 causes more severe disease. Case fatality is higher in infants, elderly and malnourished patients. Overall attack rate is higher in overcrowded areas with poor water supply, sanitation and hygiene.
Attack rate in children aged 1-4 years is highest during epidemics. Lee et al. (2005) have shown that shigellosis is an important problem in Thailand. Incidence of shigellosis peaks during hot, humid and rainy season; this is also true in case of epidemics. About 10-20 organisms are excreted per gram of the stool of infected patients, but they quickly die off as stool becomes acidic.
Multiple drug resistance is one of the important characteristics of the S. dysenteriae type 1 strains. In 1940s, they acquired resistance to sulpha drugs, in 1950s to tetracycline and chloramphenicol, in 1970s to ampicillin, in 1980s to trimethoprim-sulphamethoxazole (Septran) and nalidixic acid. It is generally agreed that antimicrobials shorten the duration of illness, reduce the risk of serious complications and fatality and shorten the duration with visible blood in the stool with or without mucus. The choice of antimicrobials will depend on the drug-susceptibility pattern of the prevalent strains in the locality.
Recently, norfloxacin and ciprofloxacin have been found to be highly effective against shigellosis. Emergence of quinolone-resistant Shigella dysenteriae type 1 have been reported in Canada. Drug available for symptomatic relief of abdominal cramps and tenesmus, e.g., loperamide, and opinum containing preparations should not be used in the treatment of shigellosis as they can potentially increase the severity of dysentery by delaying clearance of the causative organisms. In young children, these drugs have been shown to cause respiratory depression, altered consciousness and ileus with abdominal distension.
Laboratory diagnosis of shigellosis has often been delayed or even misdiagnosed as amoebiasis. This is largely due to lack of adequate laboratory facilities and shortage of trained microbiologists in the affected countries. Bhattacharya et al., (1988) had shown in a study conducted in Andaman and Nicobar Islands, where patients with shigellosis were treated with anti-amoebic drugs for the first few months.
Diarrhoea caused by protozoa are an important cause of morbidity especially in developing countries. Entamoeba histolytica (E. histolytica) and Giardia lamblia (G. lamblia) both are well established enteric pathogens though, both cause symptomatic infection only in a per cent of those harbouring the parasite. E. histolytica is the common cause of non-bacterial dysentery i.e., amoebic dysentery.
Diarrhoeagenic protozoa other than G. lamblia i.e., Cryptosporidium spp., Isospora belli, Microsporidium spp. and Cyclospora cayetanensis came to attention in the last decade only because the diseases they cause are greatly amplified in patients with Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS).
Centuries after the discovery of G. lamblia by Antony van Leeuwenhoek, a pathogenic status was assigned to this parasite. Acute giardiasis commonly occurs in children, in travellers to endemic areas, amongst homosexuals and patients with AIDS. Outbreaks are associated with surface contamination of drinking water. Caccio et al. (2005) have described this protozoan to be cosmopolitan and is endemic throughout the world and prevalence ranges from 1 %-30% with highest prevalence in the tropics and subtropics.
All age groups are affected, though infection is more common (5-12%) in younger children (0-4 yrs). Transmission is direct, person to person or indirect by contaminated water and occasionally through food. Humans are the main reservoir of the parasite.
Giardia is a flagellate which alternates between trophozoite and cyst stages. Only two morphologically distinct species one G. lamblia (intestinalis/duodenalis) infects humans and the other G. muris infects primarily rodents. G. lamblia has been typed using various techniques (i.e., isoenzyme analysis, endonuclease restriction analysis of DNA and response to in vitro encystation and culture technique). Variations within G. lamblia have implications in the pathogenic potential of the parasite strain.
The cysts of G. lamblia can survive up to 3 months in cool, damp conditions and can withstand concentrations of chlorine. Ingestion of 10 to 100 cysts ensure infection in humans. Incubation period ranges between 3-42 days with an average of 8 days.
The clinical outcome depends on such factors as inoculum size, duration of infection, individual host and perhaps parasite factors. The clinical manifestations range from asymptomatic infection to acute self-limiting diarrhoea to chronic recurrent diarrhoea, malabsorption and steatorrhea.
Children under 5 years of age usually suffer abdominal cramps/discomfort, intermittent loose stool and constipation, whereas infants have diarrhoea, vomiting, loss of appetite and failure to thrive. The acute stage in adult usually begins with a feeling of intestinal uneasiness followed by nausea, anorexia, low grade fever and chills leading to explosive, watery, foul smelling diarrhoea; marked abdominal gurgling and distension. Acute infection commonly resolves spontaneously.
Some may become asymptomatic carriers and others may develop chronic recurrent diarrhoea with malabsorption and steatorrhea. Small intestinal biopsies reveal marked villous atrophy in such individuals. Chronic giardiasis is common in individuals with hypogammaglobulinaemia particularly, those with secretory Immunoglobulin A (S-IgA) deficiency. The role of intestinal lymphocytes in immunopathology of giardiasis have been shown by Tellez et al. (2005).
Physical occlusion of mucosa by trophozoites of G. lamblia, causing a mechanical barrier to absorption of nutrients; bile salt deconjugation; villous atrophy and brush border injury; enzyme disaccharidases deficiency, release of prostaglandin E2; bacterial overgrowth have been incriminated in the pathogenesis of giardiasis. Host factors like diet, bowel motility, nutritional status may also pay a role in pathogenesis of giardiasis. S-IgA and IgM play a role in eradication of the parasite.
Parasites do not release any enterotoxin or cytotoxin. The attachment triggers humoral and cell mediated immune responses and causes rapid turnover of enterocytes resulting in immature cells lining the crypt villi and decreased villous-crypt ratio. Malabsorption may be due to both these factors. Symptomatic giardiasis is more common in individuals with hypogammaglobulinaemia, hypochlorhydria and achlorhydria.
Direct microscopy of three consecutive stool specimens to detect cyst or trophozoites either by direct or formal-ether concentration of faeces is the method of choice for diagnosis. Examination of duodenal fluid and mucus collected by Entero-test capsule for trophozoite, examination of mucosal impression smear after Giemsa staining are also used. Detection of specific antigen in stool by capture enzyme-linked immunosorbent assay (ELISA) and specific antibodies of IgA and IgM classes by ELISA or indirect immunofluorescent assay (IIF) have also been used.
ii. Cryptosporidium Species:
Cryptosporidium was described by Tyzzer in laboratory mice and was named Cryptosporidium muris (C. muris) and, subsequently, another species known as C. parvum. Genus Cryptosporidium comprises of 6 species, each a group of heterogenous strains. Most human infections are caused by C. parvum. Since the first report of two patients presenting with severe watery diarrhoea due to this protozoa, a number of cases of diarrhoea in immunocompromised hosts have been documented.
Chronic infections were also associated with HIV/AIDS. Asymptomatic and symptomatic infections are now reported in both immunocompetent and immunocompromised hosts. Cryptosporidium is distributed worldwide. Prevalence on coprological surveys on diarrhoeic samples ranged between 0.1- 31.5% and from 0.1-27.1% in developing and developed countries, respectively.
In India, the prevalence ranged from 3-13%. Higher prevalence may be related to poor sanitation, contaminated water supplies, overcrowding and frequent association or contact with domestic animals. Mannheimer and Soave (1994) showed prevalence among homosexuals with symptomatic AIDS was 28%. Serological surveys suggest far greater levels of exposure to infection. However, correlation of serological result with clinical disease cannot be determined.
Cryptosporidium is an enteric coccidian parasite. The developmental stages include oocyst, sporozoites, trophozoites meronts, gamonts (gametocytes) and zygote. Upon ingestion of the oocysts, excystation occur in the gut with release of sporozoites which subsequently attach to the mucosal cells and develop into trophozoites (inside the parasitophorous vacuoles) and undergo merogony. Some of the merozoites develop into gametocytes, zygote is formed which result in the production of oocysts. Oocysts are excreted in faeces and can survive in water and soil for 3 months at ambient temperatures.
Incubation period may be one day to 2 weeks. The most common clinical manifestation is profuse watery diarrhoea often with mucus but rarely blood and leucocytes as well. Other symptoms include crampy abdominal pain, low grade fever, nausea, vomiting and some nonspecific constitutional symptoms.
The duration and severity of clinical disease depends on the immune status of the host. Most immunocompetent persons experience mild transient enteritis which resolves spontaneously within 1-2 weeks, whereas many immunocompromised patients experience severe unremitting diarrhoea which resolves slowly or persists to become life threatening, as in AIDS.
Malnutrition, pregnancy and concomitant viral infections predispose to prolonged symptomatic infections. Adherence to epithelial cells and release of cytotoxins which damage the brush border leading to malabsorption and/or damage to mucosal cells by immunological mechanisms have been implicated in pathogenesis. Occurrence of severe prolonged infections in immunosuppressed and/or immunodeficient hosts points to the importance of CMI in host resistance.
Chronic infections have been seen in symptomatic AIDS patients and patients undergoing immunosuppressive chemotherapy for various medical conditions. Malnutrition and depleted iron status in young children have also been found to be associated with increased susceptibility to infection. Specific antibodies of IgG, IgM, IgA and IgE classes have been detected by ELISA using purified oocysts as antigen. Specific S-IgA may be involved in protective immunity by neutralizing the intraluminal stages of the parasite.
O’Donoghue (1995) have reported detection of acid-fast oocysts in faeces using modified acid- fast stain. It is a sensitive and cost-effective method for diagnosis. Immunofluorescent staining of oocysts in faeces using labeled monoclonal antibodies and detection of specific antigen in faeces by ELISA have also been used.
Hematoxylin and Eosin (H and E) or Giemsa stain of biopsied material to demonstrate intracellular developmental stages of the parasite have rarely been used. Culture is possible in many cell lines. However, it is being done mostly for academic and research purposes, Serological methods are useful for epidemiological surveys/studies.
iii. Microspordium spp., Isospora spp, and Cyclospora spp.:
These protozoa are the ‘new’ gastrointestinal spore (oocyst) forming pathogens with many common features and are being recognised with increasing frequency since the onset of AIDS epidemic. Goodgame (1996) in his study has shown that these protozoa in fact coccidian have also been implicated as pathogens in otherwise healthy individuals.
The new enteric protozoa include Isospora belli, Cyclospora cayetanensis, Enterocytozoon bieneusi (Microsporidia) and Septata intestinali. Certain species infect humans indicating human to human spread. The developmental stages are similar. The spore (oocyst) is the infective form. Sporozoites released on ingestion of the oocyst, the infective form, invade the enterocyte. The protozoa multiply asexually (merogony) and sexually (sporogony) for Cryptosporidium.
The infection spreads too many enterocytes and oocysts, are shed from the dying enterocytes into the gut lumen to be excreted in faeces. So, all three protozoa replicate and mature within the enterocytes, though the size and intracellular location of the parasite varies and this helps in making specific morphologic diagnosis by examination of stool, duodenal aspirate or small bowel biopsy. Isospora is the biggest in size and Microsporidia are the smallest in size.
Distribution is worldwide, more common in developing than developed countries. Most infections are acquired through fecal-oral route either through contaminated water or food. Person to person contact infections can also occur. Outbreaks in institutions with Isospora belli have been reported both from developed and developing countries.
The frequency with which this protozoa causes infection in AIDS patients depends upon the endemicity of the parasite in the environment. Microsporidial infections have mostly been reported in AIDS patients from all over the world. Cyclospora infections have been identified both in immunocompetent as well as immunocompromised persons with diarrhoea.
Clinical manifestations depend upon the immune status of the host. Asymptomatic infections do occur with these protozoa. Both Isospora and Cyclospora cause acute diarrhoea in normal as well as immunodeficient persons whereas, microsporidia mostly cause diarrhoea in the later. Transient and self-limiting diarrhoea is more common in patients with less severe immunosuppression whereas fulminant diarrhoea occur in severely immunosuppressed AIDS patients.
Infection may be associated with normal small bowel morphology to severe pathologic changes such as villous shortening, crypt hyperplasia and increased number of leukocytes in the lamina propria and epithelium. Release of soluble factors by leukocytes cause secretion of chloride and water and inhibition of absorption. Invasion usually do not occur. Heavy intestinal infections are associated with structural and functional changes of enterocyte.
Specific diagnosis depends upon the laboratory demonstration and identification of these protozoa. Modified acid-fast (Ziehl-Neelsen) stain, fluorescent auramine stain and/or fluorescent antibody stain are methods for detection of oocysts of Isospora and Cyclospora. Modified trichrome stain is used for detection of Microsporidia. Wet preparations and stained smears prepared from duodenal aspirates are also used to detect the presence of oocyst.
Light microscopy of H and E stained sections and electron microscopy are used to study the morphology and location of the protozoa in the enterocyte for specific diagnosis. Serological methods for studying the antibody response are not available for these protozoa.
The protozoan parasite Giardia and the oocyst/spore forming protozoa namely Cryptosporidia, Microsporidia, Isospora and Cyclospora are important causes of endemic diarrhoeas in tropics and underdeveloped countries, travellers diarrhoea, institutional and community outbreaks of diarrhoea and acute sporadic childhood gastroenteritis. All are important causes of AIDS associated diarrhoea.
Since transmission of most of these protozoa is on account of poor sanitation, contaminated water and food intake, poor personal hygiene and overcrowding, preventive measures should aim at improving sanitation, effective treatment of water (filtration and treatment with higher than recommended levels of chlorine), education of community and prompt specific treatment of patients. All these modalities combine can interrupt transmission and thus control protozoal diarrhoeas.
Helminthic infections (worm infestations) impair physical growth, nutrition and development of children and young women in particular. These effects of helminthiasis have been difficult to quantitate precisely because poor growth and development have multiple causes which usually coexist.
Intervention trials of periodic supplementation with broad spectrum anti-helminthics have not been very helpful as the benefits have greatly varied across studies. Iron deficiency is frequently caused by hookworm infection in children and pregnant women but the contribution of this factor to the total anemia morbidity is highly variable in different parts of the country.
The rural Indian lives in symbiosis with environment that is heavily contaminated because of unhygienic practices. The lack of sufficient availability of water also contributes to this.
Among soil-borne diseases, intestinal parasitic infections caused by worms account for the greatest proportion. The prevalence varies from 10 to 70 per cent in different parts of India. Poor sanitation and consequent contamination of the environment with human excreta is the major factor in transmission. The contaminated soil may be carried long distances in foot or foot wear into households. Esrey et al. (1991) have found much decreased worm infestation upon improved water supply and sanitation.
Viral hepatitis is a major cause of morbidity and mortality throughout the world. The problem is particularly serious in the developing countries. In India, the fecal contamination of water is frequent and childhood infections due to water borne viruses are rampant. There are six hepatitis viruses described till date named alphabetically A through G with F remaining unconfirmed. Of these A and E are transmitted by fecal-oral route.
Hepatitis A and E virus infections are major diseases transmitted by contaminated water and food. It manifest as jaundice. Epidemic outbreaks of jaundice caused by hepatitis A and E viruses are second only in frequency to epidemics of gastroenteritis. Hepatitis E virus infection in pregnant women is associated with high mortality. The mainstay of prevention is once again improving the quality of drinking water. No effective vaccine against HEV has as yet been developed, but effective formalinised vaccines have been developed against HAV.
Hepatitis A Virus is a picorna virus which shares the genomic organization and other properties of the group. It is small round virus of 20 nm diameter. It has a RNA genome of approximately 7.5 kb in length. Waeitz et al., showed that virus replicates through a negative strand RNA intermediate and produces a single poly-protein which gets processed to produce all the viral proteins. One of the most remarkable features of HAV is liver tropism. Study by Schulman et al. (1976) showed that liver cells remain the primary site for virus replication.
Subsequently Karayiannis et al. (1986) showed in their study large amounts of virus that are shed into bile and excreted in feces, after undergoing replication in the intestinal epithelium. In case of fecal-oral transmission, the virus reaches liver within days, however, the mechanism of this transport remains undermined. Intestinal adsorption of hepatitis A virus occurs over the apical surface and is associated with expression of receptor for the virus in a polar manner. In several instances, the viraemia is sustained and may persist in 10% of the acute cases up to six months.
The viraemia and virus shedding are temporally matched. The incubation period after the infection is 2-4 weeks. During infection secondary intra-hepatic spread is sustained by viraemia. The HAV infection is non-cytotoxic. Vallbracht et al. (1989) and Fleischer et al. (1988) showed that damage due to HAV is mostly immune mediated and CD8-CTL plays a key role in cell damage. The viral clearance involves multiple specific mechanisms including the induction of cytokines such as alpha interferon. The severity of disease possibly depends upon induction of γ-interferons by CTLs.
The HAV infection accounts for about 55% sporadic acute hepatitis in children and is involved in a similar proportion of acute liver failure. The disease has a clinical course which is typically associated with prodrome, icteric phase and recovery. Acute complications are generally infrequent. Epidemiology of infectious hepatitis have been described by Vishwanathan (1957). HAV epidemic in children have been noted in India.
In certain instances mixed epidemic (both HAV and HEV) have also been recorded. Children are mostly infected by HAV whereas hepatitis in adults is mostly due to HEV infection. This goes well with the fact that more than 90% of adult Indian population has anti-HAV antibody.
The virus is 26-36 nm in diameter rounded with icosahedral symmetry. The surface has cup shaped depressions and spikes. On the basis of the morphological structure the virus has been classified as a calcivirus by Miller et al. The genome is 7.2 kb long, positive stranded RNA and codes for three proteins. ORF-2 and ORF-3 are the two structural proteins described by Bradley and Purdy (1994). A possible viral replication through a negative strand intermediate has also been described by Nanda et al. (1994).
In India, epidemic jaundice is only second most frequent to epidemics of gastroenteritis. It is primarily a disease of urban. Smaller cities with poorly designed improperly maintained sewer system and intermittent water supply are the most frequently affected. However, the epidemics have also been described from large cities as well as from villages. One of the best epidemiologically investigated HEV epidemic occurred in 1955 in Delhi has been studied by Vishwanathan (1957).
Almost all epidemics in India are due to hepatitis E virus (HEV). The epidemic hepatitis E affects mostly young adults between 20-40 years of age. However, children and old people are not immune to this disease. Pregnant women are most susceptible to HEV during an epidemic is about 1% of the affected population.
The mortality rate is about 2-3% at maximum. Dutta et al. and Khuroo et al. (1981) have described sporadic disease due to HEV that is responsible for about 40% of total acute hepatitis. The cholestatic features are more frequent than other varieties.
Both acute and sub-acute hepatic failures are frequently seen. In children, mixed infection due to HEV and HAV or other hepatitis viruses frequently lead to acute liver failure and increase in mortality have been shown by Arora et al. (1996). No chronicity has been observed.
However, Nanda et al. (1994) have shown that HEV can persist for upto 6 months in a minority of cases. Several old world and new world primates are susceptible to the virus. Recently the virus has been demonstrated to infect pigs and rats by Balayan et al. (1990). The role of these animals in maintaining a reservoir of infection needs further investigation.
The problem of serodiagnosis of HEV infection studied by Mushahwar et al. (1993) and Clay son et al. (1995) showed that IgM response is transient in nature and it disappears rapidly within first few weeks of symptomatic icterus. The viremia is usually universal but lasts only for 2 weeks from onset of jaundice. However, using the currently available tests it has been observed that antibody (IgG-anti HEV) is present in 11-20% of adults. An increasing antibody prevalence has been observed in children over 10 years of age.
Goldsmith et al. (1993) by western blot assays using recombinant structural protein (ORF-2) showed antibody positivity in above 90% of normal adults. Reverse transcription nested polymerase chain reaction (RT-nested PCR) studied by Reyes et al. has proved to be the best test available for diagnosis of acute hepatitis. This test can detect virus in serum as well as in feces. The fluorescent inhibition assay and immune electron microscopy are mainly of research use.