Hepatitis PDF

## EPIDEMIOLOGY OF COMMUNICABLE DISEASES ### Viral Hepatitis Viral hepatitis may be defined as infection of the liver caused by any of half dozen viruses. Twenty years ago, hepatitis A virus (HAV) and hepatitis B virus (HBV) were the only known aetiological agents of viral hepatitis. Today, in ad...

## EPIDEMIOLOGY OF COMMUNICABLE DISEASES ### Viral Hepatitis Viral hepatitis may be defined as infection of the liver caused by any of half dozen viruses. Twenty years ago, hepatitis A virus (HAV) and hepatitis B virus (HBV) were the only known aetiological agents of viral hepatitis. Today, in addition to HAV and HBV hepatitis viruses C, D, E and G have also been identified and are recognized as aetiological agents of viral hepatitis. It is known that many other viruses may be implicated in hepatitis such as cytomegalovirus (CMV), Epstein-Barr virus, yellow fever virus and rubella virus. Viruses of herpes simplex, varicella and adenoviruses can also cause severe hepatitis in immunocompromised individuals, but are rare. ### Hepatitis A Hepatitis A (formerly known as "infectious" hepatitis or epidemic jaundice) is an acute infectious disease caused by hepatitis A virus (HAV). The disease is heralded by non-specific symptoms such as fever, chills, headache, fatigue, generalized weakness and aches and pains, followed by anorexia, nausea, vomiting, dark urine and jaundice. The disease spectrum is characterized by the occurrence of numerous subclinical or asymptomatic cases. The disease is benign with complete recovery in several weeks. The case fatality rate of icteric cases is less than 0.1 per cent, usually from acute liver failure and mainly affects older adults. Although the disease has, in general, a low mortality (0.1%), patients may be incapacitated for many weeks. ##### Problem statement Being an enterovirus infection like poliomyelitis, hepatitis A is endemic in most developing countries, with frequent outbursts of minor or major outbreaks. The exact incidence of the disease is difficult to estimate because of the high proportion of asymptomatic cases. However, based on an ongoing reassessment of the global burden of hepatitis A, WHO estimates suggest that about 1.4 million cases occur every year world-wide. ##### Geographical areas can be characterized as having high, intermediate or low levels of hepatitis A infection. ###### Areas with high levels of infection In developing countries with very poor sanitary conditions and hygienic practices, most children have been infected with the hepatitis A virus before the age of 10 years. Those infected in childhood do not experience any noticeable symptoms. Epidemics are uncommon because older children and adults are generally immune. Symptomatic disease rates in these areas are low and outbreaks are rare. ###### Areas with intermediate levels of infection In developing countries, countries with transitional economies, and regions where sanitary conditions are variable, children often escape infection in early childhood. Ironically, these improved economic and sanitary conditions may lead to a higher susceptibility in older age groups and higher disease rates, as infections occur in adolescents and adults, and large outbreaks can occur. Thus, paradoxically, with the transition from high to intermediate endemicity, the incidence of clinically significant hepatitis A increases. ###### Areas with low levels of infection In developed countries with good sanitary and hygienic conditions, infection rates are low. Disease may occur among adolescents and adults in high-risk groups, such as injecting-drug users, homosexual men, people travelling to areas of high endemicity, and in isolated populations such as closed religious communities. The exact incidence of HAV in India is not known. The Indian literature is replete with numerous reports of sporadic and epidemic occurrence of this disease in various cities, residential colonies and campuses. Epidemics of hepatitis A often evolve slowly, involve wide geographic areas and last many months, but, common source epidemics (e.g., faecal contamination of drinking water) may evolve explosively. * **Epidemiological determinants** ##### Agent factors * AGENT: The causative agent, the hepatitis A virus, is an enterovirus (type 72) of the Picornaviridae family. It multiplies only in hepatocytes. Faecal shedding of the virus is at its highest during the later part of the incubation period and early acute phase of illness. Only one serotype is known. * RESISTANCE : The virus is fairly resistant to low pH, heat and chemicals. It has been shown to survive more than 10 weeks in well water. It withstands heating to 60 deg C for one hour, and is not affected by chlorine in doses usually employed for chlorination. Formalin is stated to be an effective disinfectant. The virus is inactivated by ultraviolet rays and by boiling for 5 minutes or autoclaving. In short the virus survives for long periods under variable conditions and resists many procedures that eliminate or inactivate most bacterial agents. * RESERVOIR OF INFECTION : The human cases are the only reservoir of infection. The cases range from asymptomatic infections to severe ones. Asymptomatic (anicteric) infections are especially common in children. These cases play an important role in maintaining the chain of transmission in the community. There is no evidence of a chronic carrier state. * PERIOD OF INFECTIVITY: The risk of transmitting HAV is greatest from 2 weeks before to 1 week after the onset of jaundice. Infectivity falls rapidly with the onset of jaundice. * INFECTIVE MATERIAL: Mainly man’s faeces. Blood, serum and other fluids are infective during the brief stage of viraemia. * VIRUS EXCRETION : HAV is excreted in the faeces for about 2 weeks before the onset of jaundice and for up to 2 weeks thereafter. There is little evidence for HAV transmission by exposure to urine or naso-pharyngeal secretions of infected patients. * Haemodialysis plays no role in the spread of hepatitis A infections to either patients or the staff. ##### Host factors * AGE: Infection with HAV is more frequent among children than in adults. However, people from all ages may be infected if susceptible. In young children, infections tend to be mild or subclinical; the clinical severity increases with age. The ratio of anicteric to icteric cases in adults is about 1:3; in children, it may be as high as 12:1. However, faecal excretion of HAV antigen and RNA persists longer in the young than in adults. In India, by the age of 10 years, 90 per cent of healthy persons have serological evidence of HAV infection. * SEX: Both sexes are equally susceptible. * IMMUNITY: Immunity after attack probably lasts for life; second attacks have been reported in about 5 per cent of patients. Most people in endemic areas acquire immunity through subclinical infection. The IgM antibody appears early in the illness and persists for over 90 days. IgG appears more slowly, and persists for many years. ##### Environmental factors Cases may occur throughout the year. In India the disease tends to be associated with periods of heavy rainfall. Poor sanitation and overcrowding favour the spread of infection, giving rise to water-borne and food-borne epidemics. Paradoxically, when standards of hygiene and sanitation are improved, morbidity from infection with enteric viruses may increase. This is what happened with hepatitis A. ##### Modes of transmission * FAECAL-ORAL ROUTE: This is the major route of transmission. It may occur by direct (person-to-person) contact or indirectly by way of contaminated water, food or milk. Water-borne transmission, is not a major factor in developed countries, where food-borne outbreaks are becoming more frequent. For example, consumption of salads and vegetables, and of raw or inadequately cooked shellfish and oyesters cultivated in sewage polluted water is associated with epidemic outbreaks of hepatitis A. Direct transmission comprises an array of routes such as contaminated hands or objects such as eating utensils. Direct infection occurs readily under conditions of poor sanitation and overcrowding. * PARENTERAL ROUTE: Hepatitis A is rarely, if ever, transmitted by the parenteral route (i.e., by blood and blood products or by skin penetration through contaminated needles). This may occur during the stage of viraemia. This mode of transmission is of minor importance as viraemic stage of infection occurs during prodromal phase and there is no carrier state. * SEXUAL TRANSMISSION: As a sexually transmitted infection hepatitis A may occur mainly among homosexual men because of oral-anal contact. * Food handlers are not at increased risk for hepatitis A because of their occupation, but are noteworthy because of their critical role in common-source food-borne HAV transmission. Health care personnel do not have an increased prevalence of HAV infection and nosocomial HAV transmission is rare. Children play an important role in HAV transmission as they generally have asymptomatic or unrecognized illness. ##### Incubation period 10 to 50 days (usually 14-28 days). The length of the incubation period is proportional to the dose of the virus ingested. ##### Clinical spectrum The onset of jaundice is often preceded by gastrointestinal symptoms such as nausea, vomiting, anorexia, and mild fever. Jaundice may appear within a few days of the prodromal period, but anicteric hepatitis is more common. Hepatitis A resolves completely in 98 per cent of cases but relapse of symptoms are noted in 3-20 per cent cases. The outcome of infection with HAV is as shown in Table 1. | Outcome | Children | Adults | |:-----------------------------------|:--------|:-------| | Inapparent (sub-clinical) infection | 80-95% | 10-25% | | Icteric disease | 5-20% | 75-90% | | Complete recovery | >98% | >98% | | Chronic disease | None | None | | Mortality rate | 0.1% | 0.3-2.1% | | *Source: (6)* | | | * **Diagnosis** * **Prevention and containment** ##### Control of reservoir Control of reservoir is difficult because of the following factors: (a) faecal shedding of the virus is at its height during the incubation period and early phase of illness (b) the occurrence of large number of subclinical cases (c) absence of specific treatment, and (d) low socio-economic profile of the population usually involved. Strict isolation of cases is not a useful control measure because of (a) and (b). However, attention should be paid to the usual control measures such as complete bed rest and disinfection of faeces and fomites. The use of 0.5 per cent sodium hypochlorite has been strongly recommended as an effective disinfectant. ##### Control of transmission The best means of reducing the spread of infection is by promoting simple measures of personal and community hygiene, e.g., hand washing before eating and after toilet; the sanitary disposal of excreta which will prevent contamination of water, food and milk; and purification of community water supplies by flocculation, filtration and adequate chlorination. A question is often asked how much chlorine is needed to inactivate the virus. Studies indicated that 1 mg/L of free residual chlorine can cause destruction of the virus in 30 minutes at pH values of 8.5 or less. The water treatment and distribution system should be improved. During epidemics, boiled water should be advocated for drinking purposes. Several countries of the world have achieved control of water-borne HAV infection. Other control measures include proper disposal of sewage within communities. If all these measures are properly implemented, a substantial reduction of HAV infection can be expected. ##### Control of susceptible population Targeted protection of high-risk groups should be considered in low and very low endemicity, settings. Groups at increased risk of hepatitis A include travellers to areas of intermediate or high endemicity, those requiring life-long treatment with blood products, men having sex with men, workers in contact with non-human primates, and injection drug users. In addition, patients with chronic liver disease are at increased risk for fulminant hepatitis A and should be vaccinated. Use of hepatitis A vaccine rather than passive prophylaxis with immune globuline should be considered for pre-exposure prophylaxis (e.g. for travellers) and post-exposure prophylaxis (e.g. for close contacts of acute cases of hepatitis A. ###### Vaccines Two types of hepatitis A vaccines are currently used worldwide: * **Formaldehyde inactivated vaccines** - produced in several countries and which are most commonly used worldwide. * **Live attenuated vaccinces** are manufactured in China and are available in several countries. Inactivated hepatitis A vaccine are licensed for use in persons ≥ 12 months of age. The complete vaccination schedule consists of 2 dose administration into the deltoid muscle. The interval between the first (primary) dose and second (booster) dose is commonly 6-12 months; however, the interval between the doses is flexible and can be extended to 18-36 months. It can be administered simulteneously with other vaccines. Following 2 doses of vaccine the protective efficacy is about 94 per cent. The live attenuated vaccine is administered as a single subcutaneous dose. ##### Human immunoglobulin The protective efficacy of immune globulin (Ig) against HAV infection is well documented. The duration of protection is, however, limited to approximately 1-2 months and 3-5 months following administration of IgG at dose of 0.02 and 0.06 ml/kg body weight, respectively. Prophylaxis is achieved within hours of injection and is 80 to 90 per cent effective when administered before or no laster than 14 days after exposure. The use of Ig worldwide is now declining because of insufficient concentration of anti-HAV IgG in non-specific Ig preparations, the high cost of specific HAV IgG preparations, the limited duration of protection following passive IgG prophylaxis against HAV infection, and because hepatitis A vaccines have been shown to induce rapid protection against HAV after first dose. ### Hepatitis B Hepatitis B (formerly known as "serum" hepatitis) is an acute systemic infection with major pathology in the liver, caused by hepatitis B virus (HBV) and transmitted usually by the parenteral route. It is clinically characterized by a tendency to a long incubation period (4 weeks to 6 months) and a protracted illness with a variety of outcomes. Usually, it is an acute self-limiting infection, which may be either subclinical or symptomatic. In approximately 5 to 15 per cent of cases, HBV infection fails to resolve and the affected individuals then become persistent carriers of the virus. Persistent HBV infection may cause progressive liver disease including chronic active hepatitis and hepatocellular carcinoma. There is also evidence of a close association between hepatitis B and primary liver cancer. Hepatitis B virus can form a dangerous alliance with delta virus and produce a new form of virulent hepatitis which is considered to be a widespread threat for much of the world. ##### Problem statement WORLD Hepatitis B is endemic throughout the world, especially in tropical and developing countries and also in some regions of Europe . Its prevalence varies from country to country and depends upon a complex mix of behavioural, environmental and host factors. In general, it is lowest in countries or areas with high standards of living. More than 2 billion people worldwide have evidence of past or current HBV infection and 350 million are chronic carriers of the virus, which is harboured in the liver, and causes an estimated 780,000 deaths from cirrhosis of liver and hepatocellular carcinoma. The virus causes 60­­­­80 per cent of all primary liver cancer. Between 5 per cent and 10 per cent of adults, and upto 90 per cent of infants infected with HBV become carriers. Among these, 25 per cent, in the long term, develop serious liver disease. Hepatitis B is endemic in China and other parts of Asia. In these regions most people become infected in childhood and 8-10 per cent of the adult population are chronically infected. In the Middle East and Indian sub-continent, an estimated 2-5 per cent of the general population is chronically infected. In Western Europe and North America less than 1 per cent population is infected. Based on the different HBsAg carrier rates, countries can be divided into three categories: high endemicity (≥ 8 per cent), intermediate (≥2-8 per cent), and low endemicity (<2 per cent). Countries of the Region can be divided into three epidemiological patterns. The Type 1 occurs in Nepal and Sri Lanka and is characterized by a low HBsAg carrier rate of 0.9 to 1.0 per cent. The second pattern (Type 2) can be found in Bhutan, India, Indonesia and Maldives where carrier rate is high in the general population (5 to 7 per cent). In India alone there are an estimated 43 to 45 million HBsAg carriers and, among them 10 to 12 million also have HBeAg. Type 3 is observed in Bangladesh, DPR Korea, Myanmar and Thailand, where the carrier rate is very high and ranges from 9 per cent to 12 per cent. Transmission of HBV infection by blood transfusion and in other medical interventions in both modern and traditional health practices is also common in the Region. In India, the carrier rate of HBsAg in hospital staff has been found to be higher than in voluntary blood donors and in the general population. In India there are only 806 licensed blood banks and the incidence of post transfusion hepatitis in multiple-transfused patients is as high as 18 to 30 per cent . * **Epidemiological determinants** ##### Agent factors * AGENT: Hepatitis B virus was discovered by Blumberg in 1963. Efforts to grow this virus have been so far unsuccessful. HBV is a complex, 42-nm, double-shelled DNA virus, originally known as the "Dane particle". It replicates in the liver cells. HBV occurs in three morphological forms in the serum of a patient: (a) small spherical particles with an average diameter of 22-nm. These particles are antigenic and stimulate production of surface antibodies; (b) tubules of varying length and diameter, and (c) the Dane particle which corresponds morphologically to hepatitis B virus. A person who is serologically positive for the surface antigen is circulating all morphological forms, of which 22-nm particles constitute the bulk. Of the three morphological forms, only the Dane particle is considered infectious, the other circulating morphological forms are not infectious. * RESERVOIR OF INFECTION: Man is the only reservoir of infection which can be spread either from carriers or from cases. The continued survival of infection is due to the large number of individuals who are carriers of the virus. The persistent carrier state has been defined as the presence of HBsAg (with or without concurrent HBeAg) for more than 6 months. Cases may range from inapparent to symptomatic cases. * INFECTIVE MATERIAL: Contaminated blood is the main source of infection, although the virus has been found in body secretions such as saliva, vaginal secretions and semen of infected persons. * RESISTANCE: The virus is quite stable and capable of surviving for at least 7 days on environmental surfaces. It can be readily destroyed by sodium hypoclorite, as is by heat sterilization in an autoclave for 30 to 60 minutes. * PERIOD OF COMMUNICABILITY: The virus is present in the blood during the incubation period (for a month before jaundice) and acute phase of the disease. Period of communicability is usually several months (occasionally years in chronic carriers) or until disappearance of HBsAg and appearance of surface antibody. ##### Host factors * AGE : The outcomes of HBV infection are age-dependent. Acute hepatits B occurs in approximately 1 per cent of perinatal, 10 per cent of early childhood (1-5 years of age), and 30 per cent of late (> 5 years age) HBV infections. Mortality from fulminant hepatitis B is approximately 70 per cent. The development of chronic HBV infection is inversely related to age and occurs in approximately 80-90 per cent of persons infected perinatally, in 30 per cent infected in early childhood (less than 6 years of age) and in 5 per cent infected after 6 years of age. * HIGH-RISK GROUPS : Certain groups carry higher risks. The annual incidence of HBV infection in surgeons is estimated to be 50 times greater than that in the general population, and is more than twice that of other physicians. Other high risk groups comprise recipients of blood transfusions, health care and laboratory personnel, homosexuals, prostitutes, percutaneous drug abusers, infants of HBV carrier mothers, recipients of solid organ transplants and patients who are immunocompromised. Serological screening and vaccination of high-risk groups is highly recommended. * HEPATITIS B AND HIV INFECTION: It is estimated that 10 per cent of the 40 million people infected with HIV worldwide are coinfected with HBV. Although HBV infection appears to have a minimal effect on the progression of HIV, the presence of HIV markedly increases the risk of developing HBV-associated liver cirrhosis and hepatocellular carcinoma. The mortality rate increases among HIV-positive people due to HBV coinfection both before and after commencement of highly active anti-retroviral therapy. * HUMORAL AND CELLULAR RESPONSES: Hepatitis B virus has three distinct antigens a surface antigen, also known as "Australia antigen" (HBsAg), a core antigen (HBcAg), and an "e" antigen (HBeAg). They stimulate the production of corresponding antibodies e.g., surface antibody (anti-HBs), core antibody (anti-HBc) and "e" antibody (anti-HBe). These antibodies and their antigens constitute very useful markers of HBV infection. Patients with HBV infection are expected to have one or more HBV markers. The course of a typical acute hepatitis is outlined in Fig. 1. ##### Modes of transmission * Parenteral route Hepatitis B is essentially a blood-borne infection. It is transmitted by infected blood and blood products through transfusions, dialysis, contaminated syringes and needles, pricks of skin, handling of infected blood, accidental inoculation of minute quantities of blood such as may occur during surgical and dental procedures, immunization, traditional tattooing, ear piercing, nose piercing, ritual circumcision, accupuncture, etc. Accidental percutaneous inoculations by shared razors and tooth brushes have been implicated as occasional causes of hepatitis B. * Perinatal transmission Spread of infection from HBV carrier mothers to their babies appears to be an important factor for the high prevalence of HBV infection in some regions, particularly China and SE Asia. The risk of infection varies from country to country and unless vaccinated at birth, the majority of children born to mothers who are HBeAg-positive become chronically infected. The mechanism of perinatal infection is uncertain. Although HBV can infect the foetus in utero, this rarely happens and most infections appear to occur at birth, as a result of a leak of maternal blood into the baby’s circulation, or ingestion or accidental inoculation of blood. Infection of the baby is usually anicteric and is recognized by the appearance of surface antigen between 60-120 days after birth. * Sexual transmission There is ample evidence for the spread of infection by intimate contact or by sexual route. The sexually promiscuous, particularly male homosexuals, are at very high risk of infection with hepatitis B. * Other routes Transmission from child-to-child, often called horizontal transmission, is responsible for a majority of HBV infections and carriers in parts of the world other than Asia. The researchers believe that the spread occurs through physical contact between children with skin conditions such as impetigo and scabies, or with cuts or grazes. Often transmission occurs when children play together or share the same bed. In short, transmission occurs in a wide variety of epidemiological settings. It can spread either from carriers or from people with no apparent infection, or during the incubation period, illness or early convalescence. ##### Incubation period 30 to 180 days. Lower doses of the virus result often in longer incubation period. The average incubation period is about 75 days. ##### Clinical picture The symptoms and manifestations of hepatitis B are similar to those of the other types of viral hepatitis. But the picture is complicated by the carrier state and by chronic liver disease, which may follow the infection. Chronic liver disease may be severe, and may progress to primary liver cancer which, in some parts of the world, is one of the commonest human cancers, particularly in men. The clinical course of hepatitis B in adults is as shown in Fig. 2. <br> * **Prevention and containment** ##### Hepatitis B vaccine The recombinant hepatitis B vaccine was introduced in 1986 and has gradually replaced the plasma-derived hepatitis B vaccine. The active substance in recombinant hepatitis B vaccine is HBsAg. Hepatitis B vaccine is available as monovalent formulation, or in fixed combination with other vaccines, including DPT, Hib, hepatitis A and inactivated polio. The immune response and safety of these combinations of vaccines are comparable to those observed when the vaccines are administered separately. When immunizing against HBV at birth, only monovalent hepatitis B vaccine should be used. Internationally marketed hepatitis B vaccines are considered immunologically comparable and can be used interchangeably. The dose for adults is 10-20 micrograms initially (depending on the formulation) and again at ­ 1 and 6 months. Children under 10 years of age should be given half of the adult dose at the same time intervals. For greatest reliability of absorption, the deltoid muscle is preferred for injection as gluteal injection often results in deposition of vaccine in fat rather than muscle, with fewer serologic conversion. For infants and children under 2 years, anterolateral aspect of thigh is used as vaccination site. Intradermal administration is not recommended because the immune response is less reliable particularly in children. The hepatitis B vaccine does not interfere with immune response to any other vaccine and vice-versa. The birth dose of hepatitis B can be given safely together  with BCG vaccine. However, the vaccines should be given at different sites. There are multiple options for incorporating the hepatitis B vaccine into national immunization programmes. The choice of schedule depends on the local epidemiological situation and programme considerations. The recommended schedule for vaccination can be divided into those that include a birth-dose and those that do not. Schedules with a birth-dose call for the first dose at birth, followed by a second dose and third dose at the time of the first and third dose of DPT vaccination respectively. Alternatively, a four-dose schedule may be used where the dose at birth is followed by three additional doses at 6, 10 and 14 weeks with DPT vaccination. These doses may be given either as monovalent vaccine or as a combination (e.g. with DPT and/or Hib) following the schedules commonly used for these vaccines. The minimum recommended interval between the doses is four weeks. Longer dose intervals may increase the final anti-HBs titres but not the sero-conversion rates. These schedules will prevent most perinatally acquired infection. In countries where a high proportion of HBV infection is acquired perinatally, specifically in countries where the prevalence in the general population of chronic HBV infection is more than 8 per cent, the first dose of hepatitis B vaccine should be given within 24 hours after birth to prevent perinatal transmission. The complete vaccine series induces protective antibody levels in more than 95 per cent of infants, children and young adults. After the age of 40 years, protection following the primary vaccination series drops below 90 per cent; by 60 years, protective antibody levels are achieved in only 65­-75 per cent of the vaccinees. The duration of protection is at least 15 years and based on current scientific evidence, life long. Some infants born prematurely with low birth weight (< 2000 g) may not respond well to vaccination at birth. However, by one month of chronological age, all premature infants, regardless of initial birth weight or gestational age, are likely to respond adequately. In such cases the vaccine dose given at birth should not be counted towards the primary series and 3 additional doses should be given according to the national immunization schedule. Immunosuppressive illness such as advanced HIV infection, chronic liver disease, chronic renal failure, and diabetes are associated with reduced immunogenicity of the vaccine. Data on immunogenecity suggest that in any age group, interruption of the vaccination schedule does not require restarting of the vaccine series. If the primary series is interrupted after the first dose, the second dose should be administered as soon as possible and the second and the third doses separated by a minimum interval of 4 weeks; if only the third dose is delayed, it should be administered as soon as possible. ##### Immunization in adults Routine pre-exposure vaccination should be considered for groups of adults who are at increased risk of HBV infection. Adults 20 years of age and older should receive 1 ml of adult formulation. The usual schedule for adults is two doses separated by no less than 4 weeks, and a third dose 4 to 6 months after the second dose. If an accelerated schedule is needed, the minimum interval between first and second dose is 4 weeks and the minimum interval between the second and third dose is 8 weeks. However, the first and the third doses should be separated by no less than 16 weeks. Doses given at less than these minimum intervals should not be counted as part of the vaccination series. It is not necessary to restart the series or add doses because of an extended interval between doses. The high-risk persons for whom the vaccination is recommended are persons with high-risk sexual behaviour, partners and household contacts of HBsAg-positive persons, injecting drug users, persons who frequently require blood or blood products, recipients of solid organ transplantation, those at occupational risk of HBV infection, including health care workers, as well as for international travellers to HBV endemic countries. Hepatitis B vaccine is contraindicated for individuals with a history of allergic reactions to any of the vaccine’s components. Neither pregnancy nor lactation is a contraindication for use of this vaccine. The vaccine should be stored at 2-8°C. Freezing must be avoided as it dissociates antizen from the alum adjuvant. ##### Serological testing in vaccine recipients Prevaccination serological testing: Prevaccination serological testing is not indicated before routine vaccination of infants and children. It is recommended for all persons born in Africa, Asia, the Pacific Islands, and other regions with HBsAg prevalence of 2 per cent or higher; household, sex and needle sharing contacts of HBsAg-positive persons; homosexuals; injecting drug users; certain persons receiving cytotoxic or immunosuppressive therapy. Postvaccination serological testing: Not routinely recommended following vaccination of infants, children, adolescents, or most adults. It is recommended for - chronic haemodialysis patients; other immunocompromised persons; persons with HIV infection; sex partners of HBsAg+ persons; infants of HBsAg+ women; and certain health workers. Vaccine nonresponse: Several factors have been associated with nonresponse to hepatitis B vaccine. These include vaccine factors (e.g., dose, schedule, injection site) and host factors. Older age (40 years and older), male gender, obesity, smoking and chronic illness have been independently associated with non-response to hepatitis B vaccine. Further vaccination of persons who fail to respond to a primary vaccinaton series, administered in the deltoid muscle, produces adequate response in 15 to 25 per cent of vaccinees after one additional dose and in 30 per cent to 50 per cent after three additional doses. The second vaccine series should be given on the usual 0, 1 and 6 month schedule. Revaccinated personnel should be tested 1-2 months later after completion of the second vaccine series. Fewer than 5 per cent persons receiving six doses of hepatitis B vaccine fail to develop detectable anti-HBs antibody. One reason for persistant nonresponse is that the person is chronically infected with HBV. They should be tested for HBsAg. Persons who fail to respond to two three-dose series and who are HBsAg negative should be considered susceptible to HBV infection and should be counselled regarding precautions to prevent HBV infection . ##### Hepatitis B immunoglobulin (HBIG) For immediate protection, HBIG is used for those acutely exposed to HBsAg-positive blood, for example (a) surgeons, nurses or laboratory workers (b) newborn infants of carrier mothers (c) sexual contacts of acute hepatitis B patients, and (d) patients who need protection against HBV infection after liver transplantation. The HBIG should be given as soon as possible after an accidental inoculation (ideally within 6 hours and preferably not later than 48 hours). At the same time the victim’s blood is drawn for HBsAg testing. If the test is negative, vaccination should be started immediately and a full course given. If the test is positive for surface antibody, no further action is needed. The recommended dose is 0.05 to 0.07 ml/kg of body weight; two doses should be given 30 days apart. HBIG provides short-term passive protection which lasts approximately 3 months. Since the median incubation period is said to be lower than 100 days, two doses of HBIG given one month apart should suffice. The general use of HBIG for long-term prophylaxis has not been recommended because of its limited availability, its high cost and risk (although remote) of complications through repeated use over a long period of time . ##### Passive-active immunization The simultaneous administration of HBIG and hepatitis B vaccine is more efficacious than HBIG alone. HBIG does not interfere with the antibody response to the hepatitis B vaccine. This combined procedure is ideal both for prophylaxis of persons accidentally exposed to blood known to contain hepatitis B virus, and for prevention of the carrier state in the newborn babies of carrier mothers. HBIG (0.05-0.07 ml/kg) should be given as soon as possible and within 24 hours, if possible. Hepatitis B virus vaccine 1.0 ml (20 mcg/1.0 ml) should be given intramuscularly within 7 days of exposure, and second and third doses should be given one and six months, respectively, after the first dose. ##### Other measures All blood donors should be screened for HBV infection, and those positive for Australia antigen should be rejected. Voluntary blood donation should be encouraged because purchased blood has shown a higher risk of post-transfusion hepatitis. Health personnel should be alerted to the importance of adequate sterilization of all instruments and to the practice of simple hygienic measures. Carriers should be told not to share razors or tooth brushes and use barrier methods of contraception; they should not donate blood. ### Hepatitis C Hepatitis C is a contagious liver disease that results from infection with the hepatitis C virus. It can range in severity from a mild illness lasting a few weeks to a serious, lifelong illness. It is among the most common virus that infect the liver and it has been shown to be a major cause of parenterally transmitted hepatitis. Every year, 3-4 million people are infected with the hepatitis C virus. About 130-150 million people are chronically infected and are at risk of developing liver cirrhosis and/or liver cancer. More than 500,000 people die from hepatitis C - related liver diseases every years. ##### Transmission The hepatitis C virus is most commonly transmitted through exposure to infectious blood. This can occur through: (a) receipt of contaminated blood transfusions, blood products and organ transplants (b) injections given with contaminated syringes and needle-stick injuries in health-care settings; (c) injection drug use; and (d) being born to a hepatitis C-infected mother. Hepatitis C, may be transmitted through sex with an infected person or sharing of personal items contaminated with infectious blood, but these are less common. Hepatitis C is not spread through breast milk, food or water, or by casual contact such as hugging, kissing and sharing food or drinks with an infected person. ##### Incubation period The incubation period for hepatitis C is 2 weeks to 6 months. ##### Symptoms Following initial infection, approximately 80% of people do not exhibit any symptoms. Those people who are acutely symptomatic may exhibit fever, fatigue, decreased appetite, nausea, vomiting, abdominal pain, dark urine, grey-coloured faeces, joint pain and jaundice. About 75-85% of newly infected persons develop chronic disease and 60-70% of chronically infected people develop chronic liver disease; 5-20% develop cirrhosis and 1-5% die from cirrhosis or liver cancer. In 25% of liver cancer patients, the underlying cause is hepatitis C. ##### Diagnosis Diagnosis of acute infection is often missed because a majority of infected people have no symptoms. Common methods of antibody detection cannot differentiate between acute and chronic infection. The presence of antibodies against the hepatitis C virus indicates that a person is or has been infected. The hepatitis C virus recombinant immunoblot assay (RIBA) and hepatitis C virus RNA testing are used to confirm the diagnosis. Diagnosis of chronic infection is made when antibodies to the hepatitis C virus are present in the blood for more than six months. Similar to acute infections, diagnosis is confirmed with an additional test. Specialized tests are often used to evaluate patients for liver disease, including cirrhosis and liver cancer. Early diagnosis can prevent health problems that may result from infection and prevent transmission to family members and other close contacts. Some countries recommend screening for people who may be at risk for infection. These include: (a) people who recevied blood, blood products or organs before screening for hepatitis C virus was implemented, or where screening was not yet widespread. (b) current or former injecting drug users (even those who injected drugs once many years ago); (c) people on long-term haemodialysis (d) health-care workers (e) people living with HIV; (f) people with abnormal liver tests or liver disease, and (g) infants born to infected mothers. ##### Treatment Hepatitis C does not always require treatment. There are 6 genotypes of hepatitis C and they may respond differently to treatment. Careful screening is necessary before starting the treatment to determine the most appropriate approach for the patient. Combination antiviral therapy with interferon and ribavirin has been the mainstay of hepatitis C treatment.