Problem, Prevalence and Prevention of Viral Hepatitis in Pakistan Prof. Dr. K.A.

Karamat1
BACKGROUND Many illnesses and conditions can cause inflammation of the liver, for example, drugs, alcohol, chemicals, autoimmune diseases, the E.B. virus of mononucleosis and the cytomegalovirus. When we speak of viral hepatitis, it means hepatitis caused by a few specific viruses that primarily attack the liver. These are named as types A, B, C, D, E, and G. As our knowledge of hepatitis viruses grows, it is likely that this alphabetical list will become longer. The most common hepatitis viruses are types A, B, and C. Due to the improvement in diagnostic facilities, the cases are being precisely diagnosed for viruses A to E. The congestion of the population had led to the tremendous pressure on the existing drainage system. The rusting of pipes, leaking joints and valves, passage through open drains had provided chance for contamination. Consequently, supply of pure water may not be ensured. During the seasons of draught, alternative sources of water are looked for and at times contaminated water from streams is supplied. This all has led to explosive epidemics of faeco-orally transmitted hepatitis E virus (HE) while almost all the adult population had already acquired hepatitis A virus (HAV) in the past. Thanks to long lasting immunity against HAV which protects them for rest of their lives. Sporadic cases of HEV associated acute viral hepatitis constitute more than three fourth of the cases admitted in services hospitals. The gradual increase in their numbers has made the situation serious at epidemiological, clinical and administrative level.

There is a growing awareness about the problems caused by hepatitis B and C virus (HBV and HCV). These are parenterally transmitted viruses and may persist in the

Senior Consultant (Health) Planning Commission

body to lead the chronic sequelae. The chronic liver disease may haunt the patient for many years and might end in a miserable terminal stage either in the form of decompensated cirrhosis or primary liver cancer. Moreover, such patients become reservoir for the transmission of these viruses to others, if the chances for their transmission exist through contaminated needles, syringes, sharp instruments or exposure to unscreened blood or blood products. Recently, as the diagnostic facilities became freely available, it was known that almost 4% of the population carries the HBV and 5% person are infected with the HCV in Pakistan. Viral hepatitis A (HAV) accounts for about 150,000 of the 500,000-600,000 new cases of viral hepatitis that occur each year in the United States. The hepatitis caused by HAV is an acute illness (acute viral hepatitis) that never becomes chronic. At one time, hepatitis A was referred to as "infectious hepatitis" because it could be spread from person to person like other viral infections. Infection with hepatitis A virus can be spread through the ingestion of food or water, especially where unsanitary conditions allow water or food to become contaminated by human waste containing hepatitis A (the fecaloral mode of transmission). Hepatitis A typically is spread among household members and close contacts through the passage of oral secretions or stool (poor hand washing). It also is common to have infection spread to customers in restaurants and among children and workers in day care centers if hand washing and sanitary precautions are not observed. Viral Hepatitis B (HBV) was at one time referred to as "serum hepatitis," because it was thought that the only way hepatitis B virus (HBV) could spread was through blood or serum. It is now known that hepatitis B can spread by sexual contact, the transfer of blood or serum through shared needles in drug abusers, accidental needle sticks, blood transfusions, hemodialysis, and by infected mothers to their newborns. The infection also can be spread by tattooing, body piercing, and sharing razors. About 6-10% of patients with hepatitis B develop chronic HBV infection (infection lasting at least six months and often years to decades) and can infect others as long as they remain infected. Patients with chronic hepatitis B infection also are at risk of developing cirrhosis, liver failure and liver cancer. Considerable number of HBV infected population may become

asymptomatic carriers (depending upon age and immune status). Though recovery is possible but it may proceed to chronic hepatitis. Control measures for prevention of HBV infection include improved surgical practices, vaccination of at risk groups, use of high titre hepatitis B immunoglobulin when indicated, proper selection and screening of blood donors and health education regarding the mode of transmission of HBV. The contaminated sharp instruments have to be avoided at every cost. It is estimated that there are 1.2 million people in the United States and 200-300 million people world-wide who suffer with chronic hepatitis B infection. There are 200,000-300,000 new cases of viral hepatitis B (HBV) infection each year in the United States. Over 20 million people are infected annually with this virus worldwide and there are around 350 million chronic carriers worldwide. More than one million deaths occur per year which are directly related to Hepatitis B infection. Modern diagnostic serological techniques are available which can give accurate information regarding the exposure to the virus, active disease, chronicity of the disease and degree of immune status of the patient. The HBV DNA provides a clear picture of the infection. Moreover, serial testing might be important for prognostic and therapeutic purpose.

Viral Hepatitis C was previously referred to as "non-A, non-B hepatitis. It is spread by shared needles among drug abusers, blood transfusion, hemodialysis, and needle sticks. Approximately 90% of transfusion-associated hepatitis is caused by hepatitis C. Transmission of the virus by sexual contact has been reported, but is considered rare. An estimated 50-70% of patients with acute hepatitis C infection develop chronic HCV infection. Patients with chronic hepatitis C infection can continue to infect others and are at risk for developing cirrhosis, liver failure, and liver cancer. It is estimated that there are about 3.5 million people with chronic hepatitis C infection in the United States. There are about 150,000 new cases of hepatitis C each year. Seventy percent patients on dialysis are also carriers of HCV. Fifty to Seventy percent of carriers progress to chronic liver disease. The progression of the disease is slow and it might take upto 20 years for a full blown disease to appear. For appropriate diagnostic purpose, biochemical test (like LFTs and serum albumin) liver biopsy, haemotological parameters, (platelets count and coagulation tests like prothombin time) and virological tests based

upon serology and molecular biology are all very important. The management of a case is based upon careful serial long term monitoring. Diagnosis is possible by demonstrating the presence of viral specific antibody in the serum by ELISA and viral RNA in the serum by PCR. The latter is an expensive test and may accurately be done by very few centres. No specific vaccine or protective immunoglobulin is available and treatment with interferon/Ribavirin is not only expensive but relapses do occur frequently. Monitoring requires serial PCR testing. There are also viral hepatitis types D, E, and G. The hepatitis D virus (HDV), also known as the delta virus is a small virus that requires concomitant infection with hepatitis B to survive. HDV cannot survive on its own because it requires a protein that the hepatitis B virus makes (the envelope protein, also called surface antigen) to enable it to infect liver cells. The ways in which hepatitis D is spread are by shared needles among drug abusers, contaminated blood, and by sexual contact, essentially the same ways as for hepatitis B. Patients who already have chronic hepatitis B infection can acquire delta virus infection at the same time as they acquire the hepatitis B infection or, alternatively, on top of a chronic hepatitis B infection. Patients with chronic hepatitis due to hepatitis B and hepatitis D viruses develop cirrhosis (severe liver scarring) rapidly. Moreover, the combination of delta and B virus infection is very difficult to treat. Acute fulminant hepatitis Rarely, individuals with acute infections with hepatitis A and hepatitis B develop severe inflammation, and the liver fails (acute fulminant hepatitis). These patients are extremely ill with the symptoms of acute hepatitis and the additional problems of confusion or coma (due to the liver's failure to detoxify chemicals) and bruising or bleeding (due to a lack of blood clotting factors). In fact, up to 80% of people with acute fulminant hepatitis can die within days to weeks; therefore, it is fortunate that acute fulminant hepatitis is rare. For example, less than 0.5% of adults with acute infection with hepatitis B will develop acute fulminant hepatitis.

Chronic viral hepatitis Patients infected with hepatitis B and hepatitis C can develop chronic hepatitis. (hepatitis that lasts longer than 6 months). In chronic hepatitis, the viruses live and multiply in the liver for years or decades. For unknown reasons, these patients' immune systems are unable to eradicate the viruses. Chronic hepatitis can lead to the development of extensive liver scarring (cirrhosis), liver failure, and liver cancer. Liver failure from chronic hepatitis C infection is the most common reason for liver transplantation in the United States. Patients with chronic viral hepatitis can transmit the infection to others. Diagnosis Diagnosis of viral hepatitis is based on symptoms, physical findings as well as blood tests for liver enzymes, viral antibodies, and viral genetic materials. Symptoms and physical findings Diagnosis of acute viral hepatitis often is easy, but diagnosis of chronic hepatitis can be difficult. When a patient reports symptoms of fatigue, nausea, abdominal pain, darkening of urine, and then develops jaundice, the diagnosis of acute viral hepatitis is likely and can be confirmed by blood tests. On the other hand, patients with chronic hepatitis due to hepatitis B and hepatitis C often have no symptoms or only mild nonspecific symptoms such as chronic fatigue. Typically, these patients do not have jaundice until the liver damage is far advanced. Therefore, these patients can remain undiagnosed for years to decades. Blood tests There are three types of blood tests for evaluating patients with hepatitis: liver enzymes, antibodies to the hepatitis viruses, and viral proteins or genetic material (viral DNA or RNA). Liver enzymes. Among the most sensitive and widely used blood tests for evaluating patients with hepatitis are the liver enzymes, called aminotransferases. They

include aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT). These enzymes normally are contained within liver cells. If the liver is injured (as in viral hepatitis), the liver cells spill the enzymes into the blood, raising the enzyme levels in the blood and signaling that the liver is damaged. The normal range of values for AST is from 5 to 40 units per liter while ALT is from 7 to 56 units per liter of serum. Patients with acute viral hepatitis (for example, due to hepatitis A or hepatitis B) can develop very high AST and ALT levels (sometimes in the thousands of units) . These high AST and ALT levels will become normal in several weeks or months as the patients recover completely from their acute hepatitis. In contrast, patients with chronic hepatitis B and hepatitis C infection typically have only mildly elevated AST and ALT levels, but these abnormalities can last for years or decades. Since most patients with chronic hepatitis are asymptomatic (no jaundice or nausea), their mildly abnormal liver enzymes are often unexpectedly encountered on routine blood screening tests. Elevated blood levels of AST and ALT only means that the liver is inflamed, and elevations can be caused by many agents other than hepatitis viruses, such as medications, alcohol, bacteria, fungus, etc. In order to prove that a hepatitis virus is responsible for the elevations, blood must be tested for antibodies to each of the hepatitis viruses as well as for their genetic material. Viral antibodies. Antibodies against the hepatitis A, B, and C viruses usually can be detected in the blood within weeks of infection, and the antibodies remain detectable in the blood for decades thereafter. Blood tests for the antibodies can be helpful in diagnosing both acute and chronic viral hepatitis. In acute viral hepatitis, antibodies not only help to eradicate the virus, but they also protect the patient from future infections by the same virus, (immunity). In chronic hepatitis, however, antibodies and the rest of the immune system are unable to eradicate the virus. The viruses continue to multiply and are released from the liver cells into the blood where their presence can be determined by measuring the viral proteins and genetic

material. Therefore in chronic hepatitis, both antibodies to the viruses and viral proteins and genetic material can be detected in the blood. Examples of tests for viral antibodies are: anti-HAV (hepatitis A antibody) antibody to hepatitis B core, an antibody directed against the inner core (nucleus) of the virus (core antigen) antibody to hepatitis B surface, an antibody directed against the outer surface envelope of the virus (surface antigen) antibody to hepatitis B e, an antibody directed against the genetic material of the virus (e antigen) hepatitis C antibodyantibody against the C virus Viral proteins and genetic material. Examples of tests for viral proteins and genetic material are: hepatitis B surface antigen hepatitis B DNA hepatitis B e antigen hepatitis C RNA Prevention Prevention of hepatitis involves measures to avoid exposure to the viruses, using immunoglobulin in the event of exposure, and vaccines. Administration of immunoglobulin is called passive protection because antibodies from patients who have had viral hepatitis are given to the patient. Vaccination is called active protection because killed viruses or non-infective components of viruses are given to stimulate the body to produce its own antibodies. Prevention of viral hepatitis, like any other illness, is preferable to reliance upon treatment. Taking precautions to prevent exposure to another individual's blood (exposure to dirty needles), semen (unprotected sex), and other bodily waste (stool) will help prevent the spread of these viruses.

Use of Immunoglobulin Immune serum globulin (ISG) is human serum that contains antibodies to hepatitis. A. ISG can be administered to prevent infection in individuals who have been exposed to hepatitis A. ISG works immediately upon administration, and the duration of protection is several months. ISG usually is given to travelers to regions of the world where there are high rates of hepatitis A infection and to close or household contacts of patients with hepatitis A. ISG is safe with few side effects. Hepatitis B immune globulin or HBIG, is human serum that contains antibodies to hepatitis B. HBIG is made from plasma that is known to contain a high concentration of antibodies to the hepatitis B surface antigen. If given within 10 days of exposure to the virus, HBIG almost always is successful in preventing infection. Even if given a bit later, however, HBIG may lessen the severity of HBV infection. The protection against hepatitis B lasts for about three weeks after the HBIG is given. HBIG also is given at birth to infants born to mothers known to have hepatitis B infection. In addition, HBIG is given to individuals exposed to HBV because of sexual contact or to healthcare workers accidentally stuck by a needle known to be contaminated with blood from an infected person. Vaccination Hepatitis A. Two hepatitis A vaccines are available in the US, Havrix and Vaqta. Both contain inactive (killed) hepatitis A virus. For adults, two doses of the vaccine are recommended. After the first dose, protective antibodies develop in 70% of vaccine recipients in 2 weeks and more than 95% of recipients in 4 weeks. After two doses of the hepatitis A vaccine, immunity against hepatitis A infection is believed to last for many years. Individuals at increased risk for acquiring hepatitis A and individuals with chronic liver disease (e.g., cirrhosis or chronic hepatitis C) should be vaccinated. Although individuals with chronic liver disease are not at increased risk for acquiring hepatitis A,

they can develop serious (sometimes fatal) liver failure if infected with hepatitis A and, thus, they should be vaccinated. Individuals at increased risk of acquiring hepatitis A are: Travelers to countries where hepatitis A is common Men who have sex with men Illegal drug users (either injection or non-injection drug use) Researchers working with hepatitis A. Patients with clotting factor disorders who are receiving clotting factor concentrates that can transmit hepatitis A Some local health authorities or private companies may require hepatitis A vaccination for food handlers. Because protective antibodies take weeks to develop, travelers to countries where hepatitis A is common should be vaccinated at least 4 weeks before departure. The Centers for Disease Control (CDC) recommends immunoglobulin be given in addition to vaccination if departure is prior to 4 weeks. Immunoglobulin provides quicker protection than the vaccines, but the protection is short-lived. Hepatitis B For active vaccination, a harmless hepatitis B antigen is given to stimulate the body's immune system to produce protective antibodies against the surface antigen of hepatitis B. Vaccines that are currently available in the United States are made (synthesized) using recombinant DNA technology (joining DNA segments). These recombinant hepatitis B vaccines (Engerix-B and Recombivax-HB) are constructed to contain only that part of the surface antigen that is very potent in stimulating the immune system to produce antibodies. The vaccine contains no viral component other than the surface antigen and is not infectious. Hepatitis B vaccines should be given in three doses with the second dose 1-2 months after the first dose, and the third dose 4-6 months after the first dose. For the best results, the vaccinations should be given in the deltoid (shoulder) muscles and not in the buttocks.

Hepatitis B vaccines are 95% effective. Five percent of vaccinated individuals will fail to develop the necessary antibodies for immunity after the three doses. Patients with weakened immunity (such as HIV infection), elderly patients, and patients undergoing kidney hemodialysis are more likely to fail to respond to the vaccines. Hepatitis B vaccine is recommended for: All infants Adolescents under 18 years of age who did not receive hepatitis B vaccine as infants People occupationally exposed to blood or body fluids Residents and staff of institutions for the developmentally disabled Patients receiving kidney hemodialysis Hemophiliacs and other patients receiving clotting factor concentrates Household contacts and sexual partners of patients infected with hepatitis B chronically Travelers who will spend more than 6 months in regions with high rates of hepatitis B infection Injection drug users and their sexual partners Men who have sex with men, men or women with multiple sex partners.

All pregnant women should have a blood test for the antibody to hepatitis B surface antigen. Women who test positive for hepatitis B risk transmitting the virus to their infants during labor, and, therefore, infants born to mothers with hepatitis B infection should receive HBIG in addition to hepatitis B vaccine at birth. The reason for giving both immunoglobulin and vaccine is that even though hepatitis B vaccine can offer long lasting, active immunity, immunity takes weeks or months to develop. Until active immunity develops, the short-lived, passive antibodies from the HBIG protect the infant. Unvaccinated individuals exposed to materials infected with hepatitis B (such as healthcare workers stuck by a contaminated needle) will need HBIG in addition to

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hepatitis B vaccine for the same reason as infants born to mothers with hepatitis B infection. Hepatitis C There is currently No Vaccine for Hepatitis C. Population based Hepatitis B&C Survey in Pakistan The results of the prevalence of hepatitis B and C in the general population of Pakistan shows that over all 2.5% population is hepatitis B virus positive and 4.9% for hepatitis C antibody making a cumulative figure of 7% or 12 million population.

Province wise disease shows high (4.3%) figures of hepatitis B in Balochistan, while hepatitis C is high in Punjab (6.7) and Sindh (5.0%) NWFP has 1% each of hepatitis B and C. There are certain districts in Punjab and Sindh that have very high figures for these viruses ranging from 6% - 13% and they need to be specially tackled on priority basis, similar is the case for Balochistan where hepatitis B vaccination to new born and the high risk families has to be undertaken on priority basis. Prognosis The prognosis of viral hepatitis for most patients is good. Symptoms of viral hepatitis such as fatigue, poor appetite, nausea, and jaundice usually subside in several weeks to months, without any specific treatment. In fact, virtually all patients with acute infection with hepatitis A and most adults (greater than 95%) with acute hepatitis B recover completely. Complete recovery from viral hepatitis means. 1. the hepatitis virus has been completely eliminated from the liver by the body's immune system, 2. the inflammation in the liver subsides, 3. the patient develops immunity to future infection with the same virus, and 4. the patient cannot transmit the infection to others.

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Unfortunately, not all patients with viral hepatitis recover completely. Five percent of patients with acute hepatitis B infection and 80% of patients with acute hepatitis C infection develop chronic hepatitis. Acute viral hepatitis needs no specific treatment. Patients who develop chronic infection have chronic viral hepatitis and often need treatment to prevent further liver damage. Prime Ministers Programme for Prevention and Control of Hepatitis

The hepatitis has emerged as another public health emergency in the country mainly owing to lack of screening of blood and blood products, reuse of syringes, unsafe practices by dentists, barbers, unsafe sex behavior and lack of safe drinking water. In cognizance to the emergent problem of hepatitis, the National Programme for Prevention and Control of Hepatitis was launched on 29th August, 2005, with the aim to substantially decrease the prevalence, morbidity and mortality due to hepatitis in the country. For the fiscal year 2006-07 Rs.450 million has been allocated for the program. Vaccine has been procured to vaccinate 3,99,600 health workers and prison inmates during 2005-06. Furthermore, screening and vaccination of healthcare personnel is underway in all provinces and areas, while vaccination of prison inmates has also been completed in all prisons of Sindh, NWFP, Balochistan and Punjab. During fiscal year 2006-07 the vaccination of 120,000 high risk segments of the population was planned with the cost of Rs.30 million. Till todate 435342 people have received all these doses of hepatitis B vaccine against a target of 425000. In addition, recently Hepatitis vaccination has been included in routine immunization. As per information collected from EPI programme 5, 814, 384 infants 0-11 months of age were identified as target population for the purpose. As yet 5,018411 infants have been administered HBV-1; 4,661,277 have been given HBV-II while 4,536,634 have been administered HBV III. The percentages are 86%, 80% and 78% respectively.

The facilities of diagnosis and treatment of viral hepatitis at 61 Sentinal sites in teaching and DHQ hospitals have been made operational where services of viral hepatitis diagnosis and its management are being provided. During 2006-07 another 43

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hospitals have been identified for provision of requisite facilities with a cost of Rs.150 million. The laboratory refrigerators and dot matrix printers have been installed in sentinel sites at the cost of Rs.5.3 million. The disposable syringes, gloves, needle cutters etc. have been supplied to the Provincial Departments of Health. Hospital waste management is another innovative approach of the program. The program is installing incinerators in 48 selected hospitals in the country with a cost of Rs.72 million. The need assessment has been completed for strengthening of Water Quality Control Laboratory at NIH. The installation of Water purification system at 50 selected hospitals has been completed with the cost of Rs.15 million. The programme has provided treatment to 2644 patients of Hepatitis B and 22779 patients of Hepatitis C till todate.

The major components of the program are:

a. Hepatitis B vaccination to high risk groups (health care providers, prison, inmates, patients with chronic renal failure, hemophiliacs, thallasemics, patients with hepatitis C, others like relatives of high risk groups, personal of Paramilitary Forces and Sanitary workers. b. Safety of blood and blood products c. Safe injections, invasive medical devices and solid hospital waste management d. prevention and control of viral hepatitis A&E e. Behavior change communications communications through media and interpersonal

f. Capacity building for prevention and control of viral hepatitis g. Surveillance, diagnostic laboratory services and epidemic response h. Operational research including monitoring and evaluation i. Counseling and treatment interventions at teaching and DHQ hospitals The program has completed half of its age. It is imperative to asses the programme performance with regard to its scope and the increasing demand of the public affected with viral hepatitis. Hence special committee has been constituted by the

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Monitoring & Evaluation Department of Planning Commission to identify its success, weakness and deviations so that corrective measures could be taken timely to make use of this comprehensive program by revising the scope of existing PCI-I. Discussion Prime Minister, National Programme for Prevention and Control of Viral Hepatitis set up in August 2005, the Rs2.5 billion project was envisioned as a five-year exercise to prevent the spread of the viral forms of the illness, and provide subsidised treatment to patients registered under the programme. Figures available indicate that about five to six per cent of the population is infected with Hepatitis-C (an estimate based on 220 healthcare facility-based studies conducted in different provinces). Even conservatively extrapolated over the countrys population, this would indicate that there are currently about 7.5 million Hepatitis-C patients in the country. The same baseline data suggests between three and four per cent of the countrys population is infected with Hepatitis-B. A comprehensive survey is yet to be conducted, Pakistan Medical Research Council, the ministry of health is in the process of finalising a viral Hepatitis-B and -C prevalence survey which will depict the representative disease burden in the provinces. Meanwhile, with the programmes funding approved until 2010, the figures available show that even the numbers of patients registered under the programme are a mere drop in the ocean given the likely scale of the problem nearly 34,000 Hepatitis-C patients have been registered across the country, of which over 10,000 patients are yet to receive treatment. Bottlenecks in the process of getting oneself registered under the programme and glitches in the supply of Interferon injections appear to have left a very large number of patients without hope although it must be noted that every Hepatitis-B or -C patient does not require Interferon injections.

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Registration issues In order to have themselves registered under the prime ministers hepatitis control programme, patients must undergo a polymerase chain reaction (PCR) test. Most healthcare facilities charge around Rs4, 000 for this test and there are few places such as the Liaquat University of Medical and Health Sciences in Sindh and the Hayatabad Medical Complex in the NWFP, where it is offered free of cost. This becomes an impediment in the path of citizens hoping to benefit under the programme. In this regard, according to the agreed-upon terms of reference regarding the roles and responsibilities of the federal, provincial and district levels, it was predominantly the responsibility of provincial and district health departments to make efforts in this regard they were meant to take the supplies under the prime ministers programme as supplemental to their own resources, which were to be explored and diverted in this regard. However, the programme has tried to ease their responsibilities by arranging this provision free of cost through the Centre of Excellence in Molecular Biology, Lahore. The First Anti-Cancer Vaccine

Vaccination against hepatitis B virus (HBV) prevents the transmission of HBV infection and thereby reduces the incidence of liver cancer by reducing the number of chronic carriers. Consequently, the Centres for Disease Control and Prevention (CDC) and the World Health Organization (WHO) regard hepatitis B vaccine as the first anticancer vaccine since it prevents the serious consequences of hepatitis B infection. The WHO states that hepatitis B vaccine is the first and currently the only vaccine against a major human cancer.

The most common form of primary liver cancer is hepatocellular carcinoma, which is one of the ten most common cancers in the world. Primary liver cancer is one of the three top causes of cancer deaths in much of sub-Saharan Africa, Asia and the Pacific Basin. Epidemiological data from case-control and cohort studies and from laboratory investigations indicate that there is a consistent and specific causal association between

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infection with HBV and hepatocellular carcinoma. Up to 80% of the worlds primary liver cancer cases are attributed to HBV. HBV is second only to tobacco among the known human carcinogens.

Persistent HBV infection is an essential factor in the development of hepatocellular carcinoma because of the progression to chronic liver disease in about 25% of carriers. HBV has a propensity to persist after perinatal infection by a carrier mother or after infection in early life, but also after 10-15% of acute infections in adults. The WHO estimates that worldwide, there are over 350 million chronic HBV carriers. The risk of hepatocellular carcinoma has been estimated to be 100 times as high in chronic HBV carriers as in uninfected populations.

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Brief Review of National Hepatitis Program Program Service Delivery Performance: S# Intervention Target for FY 200506 No. of persons 185,000 vaccinated Key Performance Indicators Target for FY 2006-07 120,000 Cumulative Target by 30th June 2007 305,000 Actual Physical Achievement 399,600 Targets for FY 2007-08 120,000

1.

2.

3.

Hepatitis B Vaccination of high risk personnel Establishment of diagnosis and treatment facilities in Teaching and DHQ Hospitals Provision of Medicines for Hepatitis B Patients

No. Hospitals equipped

of

60

43

103

104

46

4.

Provision of Medicines for Hepatitis C Patients

5.

6.

7.

Supplies for Waste Management to teaching and DHQ Hospitals Installation of Water Purification Plants in Teaching and DHQ Hospitals Behavior Change Communication

No. of Hepatitis B patients extended treatment facilities No. of Hepatitis C patients extended treatment facilities No. of Hospitals provided HWM supplies No. of Water Filtration Plants Installation

1,000

1,000

2,000

2,644

1,000

2,150

2,000

4,150

22,779

1,500

48

48

96

48

72

50

50

50

100

No. of spots in electronic and print media Advocacy and awareness events

304

304

604

1,069

352

267

271

271

117

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Procured and supplied Hepatitis B vaccine for 621,329 high risk individuals. Strengthened and upgraded 104 hospitals laboratory status with provision of laboratory equipments and required consumables & reagents, to be able for provision of laboratory services for disease surveillance and diagnostic services to the viral hepatitis patients. Drugs and Biological for 22,779 of Hepatitis C Patients and 2644 of Hepatitis B Patients supplied to the designated Program sentinel sites (104) through provincial health directorates. 50 Water Filtration Plants installed in the Teaching and DHQ Hospitals across the country for Prevention of Hepatitis A & E, along with provision for hepatitis A&E epidemic response measures.

Installation of autoclaves & Incinerator Plants in 48 DHQ Hospitals across the country for proper Hospital Waste Management and its safe transportation in Ist phase and remaining 72 in subsequent phases. Need assessment of 46 new program sentinel sites completed, where by target of 150 will be achieved. Five Guidelines along with trainers & trainee manuals have been developed and training of all stake holders has been planed and is ready for execution , Guidelines are as below:a) National guidelines for Viral Hepatitis Case Management & Counseling. b) National guidelines for injection safety, devices control and hospital/biological waste disposal management c) National community-based guidelines for safe drinking water and sanitation. d) Sterilization guidelines for invasive devices/instruments used in medical, surgical and dental interventions.

Program Implementation and Management: Gaps and Constraints: The program inputs are being executed through the existing health infrastructure, both at the federal and provincial/regional levels, and for the sake of sustainability; the federation units have to complement and own the interventional activates and finances made available from the Provincial ADPs. The Prime emphasis should be on the development of surveillance system i.e. laboratory & field based up to the district level in

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three phases; and limited quantity of drugs and biologicals for treatment be made available for the eligible deserving poor patients; which will serve as a safety net for the poorest of the poors; and additionally will be an incentive at the health facility level to actualize the allied health preventive and promotive interventions; The Federal inputs should be perceived as an augmentation to the resources made available by the Provincial & District Governments; and hospitals concerned, Pakistan Bait ul Maal; and Zakat & Ushar departments. Hepatitis B & C patients should be selected through hospital based Viral Hepatitis Management Committee, for initiation of treatment; and the available resources should be pooled so as to maximize the coverage and avoid duplication. 1. Molecular Diagnosis: The National Program for Prevention & Control of Hepatitis has no provision for PCR Qualitative and Quantitative testing in its PC-I; this blood test is essential; as a component of acute Surveillance System and its relevance in the patient selection for treatment and in maintenance of therapy. Currently by temporally arrangements the Center for Excellence for Microbiology (CEMB), Lahore (under Ministry of Science & Technology) is performing free of cost testing of patients and samples of blood are being handled through OCS from 104 designated sentinel sites across the country. The workload is enormous; it needs to be mutually addressed by the Federal Ministry of Health & Provincial Health departments. 2. Cold Chain Facilities: The program has supplied 100 refrigerator of 800 liters capacity to 100 sentinel sites for the purpose to maintain the cold chain of kits & consumables at District Headquarter Hospital (DHQ) level, but the capacity of one refrigerator is not enough to accommodate the supplies. The Program is also using the EPI stores and Provincial Government is also supplementing this component. 3. Lack of Counterpart financing from provincial governments in order to extend the

scope of services particularly surveillance and treatment provisions, as there is enormous demand of Hepatitis C treatment.

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4.

Inadequate regulatory control over rampant quackery in medical practice and

uncontrolled advertisement on electronic media. Recommendations for improvement of implementation: General Recommendations: 1. The provinces should be encouraged to develop their own PC-Is to address the existing deficiencies. 2. A sustainable regulatory control over rampant quackery is essential and it should be enforced by the Provincial Governments; and the Ministry of Information imposes control on advertisements of quacks/Hakims on electronic and print medias. 3. Development & establishment of Acute Viral Hepatitis Surveillance System at all tiers of the health system; and to be funded by GOP and encouragement of collaboration with International partners, like WHO, Centre of Disease Control Atlanta USA.

Specific Recommendations: a. Existing level of Quality of Care and how can it be further improved?

The quality of care can be further improved through continues monitoring from Federal Implementation Unit (FIU) and Provincial Implementation Unit (PIU) of the National Program for Prevention & Control of Hepatitis as well as through the monitoring visit of Planning & Development Division; and continuously by the District Government and health department. b. Decentralization of Management to Provinces:

The present PC-I is a federal and it is not an umbrella type. Provinces have developed their own PC-Is in their respective Annual Development Plan (ADP) (especially Punjab & NWFP have developed PC-Is but their scope is very limited); the scope should be enhanced; and to continue the interventions un interrupted, it is of paramount importance that the activities for combating viral hepatitis should be owned and sustained by the provincial health departments.. c. Integration to routine health services:

Integration of key intervention with National Programs like EPI & NACP.

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Provision of Hepatitis B vaccination to High risk adults population through existing Expended Program on Immunization (EPI); It has complete infra structure and manpower from federal level up to the first level health care facility (where community has first contact for any ailment). Joint Health education & media campaign with National AIDS control program especially for prevention of blood born Hepatitis B, C & D.

The Way Forward Future strategies and action on how Pakistan should address the control and prevention issues of hepatitis:

1.

Hospital Infection Control and Injection Safety:

a.

Hospital infection control committee should be formulated in each hospital having an infection control officer. Autodestruct syringe should replace the conventional syringe.

b.

Multi dose vials of the injections should be discouraged and a syringe should be made mandatory with each injection.

c.

Syringes should be procured on large scale for public sector health facilities and control their reuse.

2.

Hepatitis B vaccination

a)

Up scaling of Hepatitis B vaccination through EPI and building hepatitis B immune generation for the future:

This should be prioritized and 30% children who are still being missed through EPI should be vaccinated by strengthening/collaborative efforts of the program with LHWs/NGOs and private practitioners. b). Vaccination of high risk groups:

Special emphasis needs to be given to vaccination of health care providers, HCV infected cases, patients on dialysis and other eligible groups, under close supervision of program manager, Provincial and district health managers.

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3.

Surveillance:

In future a strong surveillance system supported by solid hepatitis monitoring and evaluation should be established to investigate and control epidemics, follow diagnostic standards and case referral. This should also link with diagnostic laboratories and monitor the quality and their performance.

4.

Blood Safety:

National Blood Transfusion Authority and a National Program fully and exclusively responsible to organize a national blood transfusion network needs to be established. The hepatitis program should liaison with this body regarding issues related to blood safety and identify the gaps where found.

5.

Behavior Change Communications:

Health education programs and promotion of hepatitis pre service training should be launched in institutions about hepatitis awareness and control. Continued Medical Education (CME) should be conducted for postgraduates and family practitioners.

6.

Evaluatory Operational Research:

Monitoring and evaluatory research is important to evaluate the effectiveness of program interventions and outcomes. It should be conducted by institutions like Pakistan Medical Research Council in collaboration with public sector hospitals and health services academy to see the program impact. 6. Treatment of eligible cases:

Treatment of patients should not be generalized. Treatment should become partly the responsibility of the provinces where it could be provided through funds mobilized through Zakat, Baitul Mal and other philanthropic organizations.

22

Although serious efforts were made by the program to treat a large number of patients but clinical follow-up to evaluate treatment response and failure was difficult to undertake without a technically viable and evaluable methodology. This matter needs to be reviewed by Technical Committee to streamline treatment and ensure adherence to treatment guidelines.

A subsidized reduction in the cost of interferon is also likely to make treatment easy for many cases. In order to address water borne type of viral hepatitis i.e. A&E, the NIH, PCRWR, Water and Sewage board and Ministry of Environment for the purpose to regularly ensure the provision of safe drinking water and sanitation and maintain quality standards of drinking water, so as a proxy indicator water filtration plants are to be encouraged.

POSITION PAPER ON VIRAL HEPATITIS PREVENTION AND CONTROL IN PAKISTAN

1. Purpose of the Paper:

This paper presents the situation analysis with regards to the Viral Hepatitis Prevention and control across Pakistan and highlights the associated strengths and weaknesses as well as the available opportunities guiding future course of action for the policy makers and managers of various programs implementing interventions related to the subject

2.

Background: 1. Viral hepatitis is a serious global public health problem. At present, six distinct types of hepatitis virus have been identified as hepatitis A, B, C, D, E and G viruses. Viral infections are mostly acute but in case of HBV, HCV, and HDV can also result in chronic infections and therefore requires selective treatment provisions. The prevalence of hepatitis has reached alarming levels in Pakistan; on the basis of 220 studies conducted by individual researchers in different cities in Pakistan, the prevalence of Hepatitis is estimated to be 3-4% of Hepatitis B and 5-6% Hepatitis C; which translates a burden of around 12 million affected individuals.

23

2. In response to this situation, the Ministry of Health initiated a National Program for Prevention and Control of Hepatitis worth of Rs.2.594 billion for 5 years; which is first of its kind being initiated on 29th August 2005; with a small provision of treatment for Hepatitis B & C patients only for deserving poor patients. This 5 year program aims to reduce prevalence by 50% by 2010, with the following interventions, along with updated status:

Rs.in million 1. Extending Hepatitis B vaccination to High Risk Personnel including healthcare workers, prison inmates, Intravenous Drug Users, frequent blood recipients and others Physical Target as per Financial Allocation Physical Fund Utilization PC-I in Five Years as per PC-I for Five Achievement years 665,000 166,250,000 621,329 76,250,000 Persons Persons

2. Safe Injection, invasive devices & Hospital Waste Management Components Physical Target as Financial Allocation Physical Achievement per PC-I in Five as per PC-I for Five Years years Disposable Syringes 15,000,000 30,000,000 3,251,505 Syringes Syringes Autoclave & Time 11,100,000 50 Nos. Steam Temperature 150 Nos. indicator Incinerators & Allied 120 Nos. 242,548,000 48 Nos. Consumables Vehicle for collection waste 125 Vehicles 103,382,000 96 Nos.

3. Hepatitis A & E (Installation of Water purification systems/plants) Physical Target as Financial Allocation as per Physical Achievement per PC-I in Five PC-I for Five years Years 150 Nos. 80,500,000 50 Nos.

24

4. Behavior Change Communication Components Physical Target as per Financial Allocation Physical PC-I in Five Years as per PC-I for Five Achievement years Program 1150 101,400,000 1069 Communication Spots/Messages Spots/Messages Advocacy & Social 885 Mobilization Events 23,775,000 271 Events

5. Capacity building of the partners for effective prevention and control of viral hepatitis in the country Components Physical Target as Financial Allocation as Physical Achievement per PC-I in Five per PC-I for Five years Years 60 Sessions 14,246,000 10 Sessions 05 Guidelines

Training of Health professionals Technical Guidelines

05 16,500,000 Guidelines

6. Surveillance-Diagnostic & lab. Services for Hepatitis and epidemic response (Established 150 sentinel sites working as screening /diagnosis, counseling along with provision of hepatitis B&C treatment facilities at teaching and DHQ Hospitals in 3 phases manner) Components Physical Target as per Financial Allocation as Physical PC-I in Five Years per PC-I for Five years Achievement Elisa & 150 57,500,000 150 Associated Hospitals Hospitals Equipments Hepatitis B, C 64,800 736,264,000 21,237 & E testing Kits Kits Kits

25

7. Counseling and treatment interventions (Treatment interventions at Teaching & District Headquarter Hospitals) Type of Physical Target as per Financial Allocation as Physical Treatment PC-I in Five Years per PC-I for Five years Achievement Intervention Hepatitis B 4900 220,500,000 3,644 Patients Patients Patients Hepatitis C 8,450 507,000,000 24,279 Patients Patients Patients

3. The impact of the Program has not been as significant as desired. The Prime Minister has taken cognizance of this burgeoning epidemic and has directed the Ministry of Health to identify needs and gaps in the present efforts and launch a National Program to be called the Prime Ministers Program for Eradication of Hepatitis immediately and has emphasized to precisely conceive and to respond to the serious threat posed by viral hepatitis ,both types, i.e. water born (A&E) and blood born (B,C & D); and the interventions are strengthened to be in line with the best available practices, the covenant elements devised / upgraded aiming at prevention & control and finally eradication of viral Hepatitis. These are to be implemented in all four provinces including AJK, FATA and FANA on equitable basis. 4. The Ministry of Health has started an urgent consultative process to comply with the PM Directives. This takes a multilayered approach with i. ii. iii. iv. An exhaustive audit of the current program and detailed review, progress and practical relevance of each component of the program. Engagement of both in-house experts and other national international agencies development partners. Consultations with liver disease specialists and epidemiologists in the country. Obtaining input from professionals abroad with specific expertise.

5. Initial analysis suggests that the revised strategies would entail significant directional changes in the existing program on the following lines: i) Putting into place a robust viral Hepatitis Surveillance system, including Diagnostics and limited treatment facilities, especially for B&C Viral Hepatitis, as a safety net for the eligible deserving poor in the Federal, Provincial, Teaching and DHQ Hospitals & Tehsil level Hospitals (150 Districts, including 6 sub districts of Karachi; thus linking all 425 major Hospitals in the country); and measures for effective and prompt epidemic

26

response as a part of active monitoring and evaluation component of the new Prime Ministers program by the Ministry of Health. ii) The surveillance system would improve the ownership of the new District Health information system and will also facilitate its launch under the overall auspices of Health Management Information System. By enhancement of the scope, the number of sentinel sites will be increased. Thus all (272, having 425 hospitals, which will act as sentinel sites) National Electoral Constituencies will be covered. Under the auspices of every honorable Member of the National Assembly, the activities in a unified manner in sentinel sites in their respective electoral constituencies will be planned, executed, monitored and evaluated. Improved laboratory facilities (150 - all federal, provincial, District headquarters and major Tehsil/Taluka Hospitals would be part of the surveillance system); will also support safe blood transfusion services in all these 425 major hospitals. An intensive and sustain efforts are directed to introduce & establish a National Blood Transfusion service, linked with provincial blood transfusion services, with the prime objective of ensuring significant improvement in blood and blood products transfusion safety

iii)

iv)

v)

vi)

Development & institutionalization of Hepatitis infection control unit in each sentinel site; and deployment of full time team, comprising of: 1. Hepatitis and infection Control Officer (Total = 150) 2. Health Education & social worker (Total = 200) 3. Two laboratory Technicians (Total = 316) 4. Complete logistic support for working in the hospitals and out side in the communities to regularly work in a continuous cycle with general practitioners, dentists, barbers, tattooists and beauty parlors to advise and assist in exercising safe practices and actualizing Hepatitis prevention and control interventions.

vii) These teams will be responsible for the implementation of hepatitis prevention and control activities in their respective districts hospitals, RHCs, BHUs ; and will regularly perform outreach activities. viii) Strengthening of Federal & Provincial water quality control reference laboratories and promotion of good hygienic practices to ensure the safety of drinking water and food for prevention of hepatitis A&E.

27

ix. Sustained Behavior Change Communication and Advocacy activities by mixed media approach. x. Operational & community based research xi. Standardized Viral Hepatitis case management and counseling services at specialized levels. xii. Quality management encompassing capacity building of partners, both Public & private sectors; for the prevention and control of Viral Hepatitis. 6. By fully activating and actualizing all components of the revised Program, it is anticipated that it would yield tangible results within period of two years; a mid period prevalence survey is to be conducted. Hopefully these results would have sufficient impact to hold up this program as a role model for other developing countries affected by the scourge of Viral Hepatitis. National Viral Hepatitis Surveillance System development Purpose: The purpose is to standardize and put in place the hepatitis surveillance system i.e. guidelines/manual and instruments, in line with WHO recommendation. The guidelines and tools are supposed to be useful / applicable in urban as well as rural healthcare settings all across the country. To achieve this objective there is a need to develop this system through a participatory development process. This would improve the ownership of the new District information system and will also facilitate its launch under the overall auspices of Health Management Information System. Goal: Development of a comprehensive acute viral surveillance system (by passive reporting and active search in high prevalent areas), which is able to generate accurate viral hepatitis data to support primary and secondary prevention, education, and medical management. Objective: To measure the burden of disease; determine risk factors; identify outbreaks; monitor trends; evaluate control measures, interventions and programs; and identify infected persons for medical referral, education and counseling. Promote research activities that will assist in decreasing the incidence of viral hepatitis and benefit those with chronic hepatitis.

28

Key Components: The Hepatitis Surveillance Procedures are proposed to include:

monitoring disease incidence detection of outbreaks and determination of sources of infection and modes of transmission by epidemiological investigation

spread containment identification of contacts of case-patients for post exposure prophylaxis differentiation of types of viral hepatitis Monitoring the sequelea of hepatitis B&C infection including asymptomatic chronic infection, chronic hepatitis, cirrhosis and primary liver cancer

Number of third doses of hepatitis B vaccine (HepB3) administered to infants; and high risk individuals

Number of suspect cases of viral hepatitis Number of confirmed cases for each type of viral hepatitis

Scope of the Work: The venture is expected to include (but not limited to) the following activities:

i.

ii.

iii.

iv.

v.

A thorough review of the existing system of reporting including that of the HMIS and DEWS and the MIS units of various national and provincial health programs as well as other medical Institutes for a comprehensive situation analysis. Review of the available guidelines/standards/recommendations of WHO/CDC and other professional bodies regarding the surveillance system development for communicable disease control. Special sero-prevalence surveys as needed to measure the prevalence of hepatitis B and hepatitis C infection in the general population and in special groups such as medical staff, blood donors, pregnant women, military recruits, health care workers, certain patient groups. Epidemiological research to fill in the gaps in the available information regarding behaviors that increase the risk of transmission of viral hepatitis and effective prevention activities specific to Pakistan. Continued research into the effectiveness of treatment for viral hepatitis, measured by sustained viral response. A system to track persons being treated to evaluate treatment outcomes of specific populations would also be needed.

29

vi.

vii. viii.

ix. x.

Make a resource of data base for a baseline through consultation with Pakistan Medical Research Council & other relevant bodies. Arrange a summary of the epidemiological data, which has been developed & published and submitted in local and international journals and presented in different forums and workshops of professional bodies. Work out the information needs of the program and identify gaps. Based upon the above, suggest and devise an efficient and effective surveillance system (both hardware & software) and develop Indicators in context of viral hepatitis prevention & control; encompassing disease, pharmaceuticals, biologicals, screening & diagnostic lab equipments and reagents/consumables (should address input, process, output, outcome and impact indications). Develop a sentinel surveillance system to monitor the changes in HCV infection prevalence and genotype distribution The Surveillance system devised therein must include complete modus operandi, covering;

a.

b. c.

d.

e.

Data entry provisions at all tiers of health infrastructure, routine monthly reporting of aggregated data of viral hepatitis cases, spelling out the number of suspected and confirmed cases of each type of hepatitis; from peripheral level to intermediate & control level Zero reporting required at all levels. As the establishment of country wide surveillance will require time, there must be the provision to initiate surveillance in District Headquarter Hospitals, Provinces & Federal Hospitals by using their representatives outlined sentinel hospitals. All outbreaks are to be investigated immediately as per WHO protocol and subsequently confirmed serologically at the sentinel sites. Recording and reporting instruments are required to cover the disease, pharmaceuticals, biologicals, screening & diagnostic lab equipments and reagents/consumables includes notification form, investigation form and line listing; and protocol for mid & summative evaluation procedures.

xi.

Develop Guidelines/training manual for standardized viral hepatitis surveillance (both routine and active) including epidemic forecasting, preparedness with options of remedial measures application at different settings. Carryout field testing of the software, draft guidelines, manual and other instruments developed therein and incorporate feed backing the revised version.

xii.

30

xiii.

Conduct consensus-building workshop/s involving Pediatricians, Infectious Diseases Specialist, Gastroenterologists, Pathologists, Public Health Professionals and other relevant professionals from all over the country Develop liaison with the HMIS, District health, DEWS, NACP, EPI, Punjab Blood Transfusion services and other relevant bodies. Train the relevant staff on the surveillance system, guidelines and instruments. Establishment/launching of Hepatitis Surveillance system i.e. installation of equipment/reagents/kits and training of staff in screening activities, data entry; monthly & yearly data coalition and report formulation; transmission to provincial and federal levels; and Feedback. Establishment of screening, counseling and acute/chronic liver disease treatment facilities at Federal Provincial, District and Tehsil/Taluka level hospitals (Infrastructure already strengthened through the existing program i-e 150 sentinel sites)

xiv. xv. xvi.

xvii.

Intended Principal uses of data for decision-making:

Monitor Hep. B 3rd dose coverage by geographical area to measure areas with weak performance and take appropriate action Investigate all suspected/reported outbreaks and respond accordingly Determine the specific cause of acute viral hepatitis cases (reported routinely or during outbreaks) so that corrective measures can be taken Understand the epidemiology of hepatitis by etiological agent in terms of distribution over time, by age group and geographical area Measure the incidence (including age-specific incidence) and prevalence of HBsAg and anti-HCV Measure the proportion of cases of acute viral hepatitis, chronic liver disease, cirrhosis and primary liver cancer that are hepatitis B virus or hepatitis C virus carriers to: 1) determine the burden of the disease in the population 2) prioritize it among other diseases of public health importance 3) choose the proper strategies for its control

Anticipated Challenges:

Lack of resources to launch a comprehensive system meeting the program demands follow-up on laboratory reports of markers of viral hepatitis infection Lack of physician education regarding the need to screen patients for viral hepatitis, interpretation of diagnostic test results, differences between acute and chronic infection, and case reporting requirements,

31

Lack of laboratory diagnostic testing to distinguish between acute and chronic infection for hepatitis C, Incomplete and inaccurate case information reported, and Underreporting of viral hepatitis infections.

Strategies to overcome the challenges:

Improve viral hepatitis reporting and follow-up through the development of education programs on clinical management, case contact management, education, counseling, and the importance and responsibility of reporting, Assist the people involved in surveillance activities by developing detailed viral hepatitis surveillance guidelines, seeking assistance for surveillance officers, improving electronic reporting systems and integrating case tracking systems Assure the highest quality of data possible through regular coordination with laboratories so as to report complete case information with hepatitis test results Ensure that analysis capabilities meet all stake-holders' needs by analyzing case report information and disseminating periodic reports to stakeholders.

Framework for Establishment of Hepatitis Surveillance System: Goal 1: Have a comprehensive surveillance system that will generate accurate data on viral hepatitis to support primary and secondary prevention, education and medical management. Strategy 1: Assess the prevalence of hepatitis B & C in general population and high risk groups Year One:
o o

Conduct studies to establish the baseline of viral hepatitis in general population as well as high risk groups

Strategy 2: Improve viral hepatitis reporting and follow-up. Activities/Action Plans: Year One:
o o o o o o o

Conduct studies to establish the baseline of viral hepatitis in general population as well as high risk groups Develop education programs/materials on clinical management, contact management, education, counseling, and reporting, Develop and disseminate viral hepatitis surveillance guidelines to all levels Train the concerned medical staff on clinical management, counseling and surveillance of viral hepatitis. Adopt CDC hepatitis C testing algorithm, and Establish 50 sentinel sites across the country

32

Year Two to Five:

o o o

Launch an extensive training program of the associated staff Define roles and responsibilities of those conducting surveillance at all levels (National, regional, and local - District), o Increase electronic reporting and improve data quality, and o Work with the CDC and WHO information technology staff to strengthen and enhance reporting system with a tracking component. Strategy 3: Manage collection and dissemination of the highest quality data possible. Activities/Action Plans: Year One
o o o

Assess completeness and accuracy of reported viral hepatitis data Approach, convince and establish laboratories network to provide patient information on all laboratory test on the prescribed format.

Year Two:
o o

Develop a standard data quality-monitoring tool and train the concerned staff.

Year Three to Five:

o o

Evaluate the reported date on quality monitoring tool and distribute periodic reports on data quality to the provincial and district health departments.

Strategy 4: Share the collected data with all stakeholders and have feedback Activities/Action Plans Years One through Five: Disseminate periodic epidemiologic reports to stakeholders, Analyze case report data for development and evaluation of prevention activities, and o Provide periodic data analysis of case reports including disease incidence and trends over time. Goal 2: Promote research activities that will assist with decreasing the incidence of viral hepatitis and benefit those with chronic hepatitis. Strategy 1: Conduct epidemiologic research to better understand the dynamics of viral hepatitis in Pakistans context. Activities/Action Plans: Year One:
o o o o

33

Conduct research to assess hepatitis B vaccination coverage, identify barriers to vaccination and groups at higher risk of getting hepatitis B&C o Conduct survey to assess the awareness levels and determine the most effective education methodology. Year Two to Five: o Conduct targeted prevalence studies for hepatitis B and C. o Conduct mortality studies to assess the mortality rate among those infected with HBV and HCV. o Pursue studies to assess the risk of hepatitis B&C transmission associated with tattooing, body piercing, barbers, beauty saloons and nosocomial infection. Strategy # 2: Conduct research related to health services and clinical care. Activities/Action Plans: Year One:
o o o o

Conduct studies to assess the practices of medical management of those infected with viral hepatitis.

Year Two to Five: o Identify populations not receiving treatment for HBV and HCV, and identify the barriers. o Measure change in the management practices of the medical professionals subsequent to the launching of guidelines and training on standard case management. o Conduct research studies on chronic HCV treatment outcomes looking at sustained viral response.

34

Acknowledgements:
Author is grateful to the encouragement made by Deputy Chairman Planning Commission and Member (SS). The contribution made by Dr. Suhail Amjad of NHPU, Dr. Sharif Khan, NPM, Mr. M.F. Khattak, Mr. Qadir Bux Abbasi. Prof. Muhammad Umar and Mrs. Hamama-Tul-Bushra Khaar both Professors of Medicine, Rawalpindi Medical College Consultant Gastroenterologist and Hepatologist, are acknowledged with deep appreciation.

35

REFERENCES 1. Karamat K.A., Tariq. W. Proceedings Seminar Viral Hepatit6is. AFIP.Pak. 14 November 1998 2. ^ Gupta DN, Smetana HF (1957). "The histopathology of viral hepatitis as seen in the Delhi epidemic (1955-56)". Indian J. Med. Res. 45 (Suppl.): 10113. PMID 13438544. 3. ^ Balayan MS, Andjaparidze AG, Savinskaya SS, et al (1983). "Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route". Intervirology 20 (1): 2331. PMID 6409836. 4. ^ Reyes GR, Purdy MA, Kim JP, et al (1990). "Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis". Science 247 (4948): 13359. doi:10.1126/science.2107574. PMID 2107574. 5. ^ "00.084.0.01. Hepevirus 00.084. Unassigned - ICTVdB Index of Viruses". Retrieved on 2008-06-15. 6. ^ Satou K, Nishiura H (2007). "Transmission dynamics of hepatitis E among swine: potential impact upon human infection". BMC Vet. Res. 3: 9. doi:10.1186/1746-6148-3-9. PMID 17493260. 7. ^ Li TC, Chijiwa K, Sera N, et al (2005). "Hepatitis E virus transmission from wild boar meat". Emerging Infect. Dis. 11 (12): 195860. PMID 16485490. 8. ^ RatBehavior.org 9. ^ Shrestha MP, Scott RM, Joshi DM, et al (2007). "Safety and efficacy of a recombinant hepatitis E vaccine". N. Engl. J. Med. 356 (9): 895903. doi:10.1056/NEJMoa061847. PMID 17329696. 10. http://www.medicinenet.com/viral_hepatitis
11.http://www.hepctrust.org.uk/news/2008/April/Pakistan+_+Premier%E2%80%99+program

12.

36

Annex-A

Studies in Pakistan: The various studies carried out in Pakistan are briefly annexed as Annex-I

HEPATITIS A

In Pakistan, hepatitis A virus (HAV) is present in water supplies because of the contamination of water with faecal matter. Almost everyone acquires it during early childhood. In 1980s, a study carried out at Islamabad revealed 96.55% of the children between 7 and 9 years of ages to have been exposed to HAV in the past (seroreactive for anti-HAV IgG)(I). Zuberi et al (1983)(2). Similarly, we found all of 326 military recruits (average age 19 years) having been previously exposed to this virus(3). In 1988, it was found after testing 630 sera from the healthy young persons comprising of cadets from the Army Medical College and military recruits that 96.6% of the medical cadets and 100% of the military recruits were showing the past evidence of immunity against this virus. The minor difference was most probably due to the better socio-economical background of the cadets which would have saved a few of them form being infected with this virus(4).

As the virus is acquired during the childhood in Pakistan, we see more cases of AVH associated with HAV as compared with other viruses in cases of our pediatric population. More than half of the cases of AVH (about 60%) at this age are due to HAV(5). As our adult population is immune to HAV, we rarely see adult case of AHV with this virus. However, recently, some young adults were found to be infected with HAV and had presented with the acute viral hepatitis. They were all from the higher socio-economic stratum of the society. Therefore, it was deducted that a change in its epidemiology was lately taking place(6).

37

HEPATITIS B

The work on H BV seroepidemiology started as the test for the detection of hepatitis B Surface Antigen (HBsAg) became available. In Pakistan, Armed Forces Institute of Pathology (AFIP) Rawalpindi had a lead as in 1971, by applying counter current immuno electrophoresis (CCIP) 1.8% of local blood donors (4/214) were found to be HBV carriers(7, 8). Later on, in Karachi in 1974 and at Islamabad in 1977, 4% of blood donors were found to be the carriers(9). As the health care personnel. (HCP) are supposed to be more at danger of acquiring the infection, a well controlled study was done on HCP in 1977 in Karachi. Out of 383 HCP, 2.8% were HBsAg positive while 1.3% of the control group (out of 76 samples tested) showed this reaction (10). ln 1978, the same workers from Karachi, tested 1810 healthy subjects (1318 males and 492 females). Fifty two out of them (2.9%) were found to be the carriers. The males showed higher percentage of carrier state (3.5%) as compared with the females(1.2%)(11).

In the north of the country, the picture was somewhat similar when 1200 army personnel (recruits:800 and seasoned soldiers:400) were tested in 1978. Out of all these army personnel only 40 (3.3%) were positive for HBsAg. The carrier state was more common (4.2%) in the people of older age (at the age 41-50) (12).

In seventies, the CCIEP was the method used. However, during early 1980s, Radioimmunoassay (RIA), Enzyme Linked Immunosorbent Assay (ELISA) and reverse Passive Haemagglutination (RPHA) were used by various blood banks for the detection of HBsAg as well as antibody against HBsAg (Anti-HBs). The data was centralised and an altogether different picture emerged with these more sensitive methods of detection for HBV. In a study reported from PMRC Centre, NIH, Islamabad, 8.4% of blood donors from army, 6.9% from Red Crescent Society of Islamabad blood bank and 5.7% donors from Islamabad Polyclinic showed HBsAg carrier state. It was further reported that more males (8.13%) than females (6.7%) showed HBsAg seropositivity and out of 535 persons tested, 94 (17.6%) were anti-HBs positive(13). This showed that about one fifth of our blood donor population had already acquired immunity against HBV, mostly because of

38

the silent infection in the past, apart from those who were still carriers for the virus. During the next four years, further data was made available about the serostatus of 10,451 blood donors of the twin cities Rawalpindi/lslamabad. Eight percent (843) of these persons were found to be the carriers of HBsAg. The blood donors of the army had the highest percentage (10.7%) of HBsAg carrier rate and those from the Red Crescent Society had the lowest which was 3.89%, while the intermediate status (5.8%) was seen in case of blood donors from Polyclinic (1, 14). The difference in methodologies and different criteria of the interpretation of the results by different workers might have led to such discrepancies. In 1982, only 140 persons were studied for HBsAg positively from Peshawar. In this study 11.3% of blood donors and 15% of medical students were HBsAg positive(15).

Later, ELISA testing was resorted and the techniques were standardised with a "" better quality control for the detection of H BsAg. In 1988, in a well organised study, 60 medical students, 365 military recruits and 205 pregnant ladies were tested. Out of them, 5.3% of medical students, 10.7% of military recruits and 7.8% of pregnant ladies were HBsAg carriers, while 12.2% of medical students, 33.2% of military recruits and 33.3% of pregnant ladies were showing the evidence of past exposure to HBV, by being seropositive for antibody against HBV core antigen (anti-HBc), while 6.9% of medical students, 22.5% of military recruits and 25.4% of pregnant ladies were found to be immune to HBV (by being anti-HBs positive), respectively(4). Better socio-economic background of medical students probably has saved them from HBV exposure in the past. Military recruits who came from the poor strata of the society showed a higher percentage of exposure to HBV. One of our later studies on military recruits showed almost similar results. In this study, 9.98% of 326 persons were carriers, 30% had been exposed to the virus in the past and about 18% of them were already immune to this virus(16).

In case of Health Care Personnel (HCP), such as the operation theater staff and the laboratory workers, it was observed that the duration of stay in the profession made them more susceptible to become carriers of HBsAg. Most of them acquired this virus

39

due to their complacency in performance of their routine duties. The percentage of the carrier state remained the same (10%) when compared to the general public. The doctors were exposed to a lesser extent as compared to the medical staff (19, 20). This was mainly because of better understanding of the preventive measure by the physicians. In a community study done at Hafizabad Punjab, 4% subjects were found to be HBsAg carriers. It was observed that 40% of them had acquired the virus perinatally while 60% had been infected during their adult age. In brief, in Pakistan it is estimated that 3.6% of paediatric and 10% of adult population is HBV carrier. Seven percent of blood donors, 8% of general women, 9% of health care personnel, 31% of cases of acute viral hepatitis (AVH), 60% of chronic liver disease and primary liver cancer, 13% of patients on long term haemodialysis and 22% cases of Thalassaemia were HBsAg carriers. As the awareness for the protection against HBV was growing, it is expected that the tip of the balance regarding the prevalence was now shifting towards the hepatitis C virus (HCV) (21).

HEPATITIS C

So far, there is no clearcut picture about the seroprevalence of anti-HCV antibodies in various segments of Pakistani population. At the Armed Forces Institute of Transfusion, (AFIT) Rawalpindi, recently 689 volunteer blood donors were tested by a second generation anti-HCV gelatin particles agglutination test (Serodia). They were all healthy young male adults (19-60 years of age) and had no apparent clinical disease. They all belonged to north of the country and 33 of them were found to be seropositive i.e.4.78% (23). A study was carried out by the Aga Khan University at Hafizabad, Punjab, in 1993 to determine the HCV prevalence in the community. The anti-HCV seroprevalence was found to be 7% in the general public. It increased with the increasing age and during the seventh decade or later, it was as high as 35% of the persons tested. On a subsequent interview, it was revealed that the HCV infected persons were 3.2 times more likely to receive 10 or more injections per year compared to those who were negative for HCV. The other possible risk factors like regular shave at barbers shops,

40

dental treatment or drug abuse were not important in acquiring HVC infection in this study (26).

In another study carried out at Karachi, the seroprevalence for HCV was 6.6% in the normal population. There were 2-5 times more chances of another member of the household being infected with HCV when compared to normal household contacts(27).

The people who are kept alive on multiple transfusion and long term dialysis, have much greater risk of the acquisition of HCV. At Aga Khan Hospital, Karachi, 46% of the cases on dialysis had been found to be HCV infected (28). Most of the patient admitted in Aga Khan University Hospital were well to do persons of the society and had a better socio-economical background, as compared with the patients treated at other medical centres of the country. At Sheikh Zayed Hospital, Lahore a small group of 82 patients (18-80 years of age), attending the haemodialysis unit was studied. Out of these, 51 patients (62.2%), were seropositive for anti-HCV. There was a history of blood transfusion in 43 out of 51 sero-positive (84.3%) patients. Those who were having an ongoing HCV infection, had been on dialysis for a longer period and on an average had received more frequent transfusions as compared to those, who were seronegative for anti-HCV. The liver functions were deranged in 35% (18/51) of these cases(29).

There is a need to investigate the high risk group in general population. However, in some preliminary studies, 80% of the patients with previous cardiac bypass surgeries and 90% of the Thalassaemia major were found to be infected with this virus. On the other hand, 3 out of our 63 HIV infected patients (5%) were positive for Anti-HCV (30).

In a study conducted at Lahore, risk factors for 144 patients with ongoing HCV infection were evaluated. There was a history of multiple parental injections (needlestick) in 72 (50%) of these cases. About one quarter of them (35 cases, 24.3%) had received blood transfusion in the past. There was no apparent risk factor associated with 37 (25.7%) cases. These were labelled as endemic cases, although 5 out of them had a history of contact with a family member infected with the HCV (31). Similarly, in

41

another study the majority of HCV infected cases had a history of parental injections. However, with the passage of time when more data accumulated and there were 316 HCV infected cases of chronic liver disease, it was observed that 120 out of 316 patients (38%) had a history of previous blood transfusions and 62 (19%) had received frequent intravenous and intra-muscular injections; 4% had a family member infected with HCV and no risk factor could be found in the rest of 40% of cases (33). In most of the cases, our patients with HCV related disease had presented at a productive age, when the society is economically dependent upon their abilities and enterprises. In one of the study carried out in Karachi on 145 HCV infected cases (33), the mean age was less in cases with chronic active hepatitis (42.6+ -12.7 years) as compared with cirrhotics (51.2 + 19.2). Similarly, in another study, the age of HCV infected persons with chronic liver disease was seen to be high and more than 70% of them were in fourth (20%), fifth (30%) and sixth (21%) decades of life (34).

The ethnicity had not been studied in depth in Pakistan. However, a preliminary study done at The Pakistan Medical Research Council (PMRC) Research Centre Karachi, had shown that HCV infection was more common in Urdu speaking urban population as compared with Sindhi/Balochi speaking rural population (in which HBV and delta virus infections were more common( (35). In another study, 70.6% (223/316) patients were Punjabis, 23.10% (73/316) Pathans, 3.75% (12/312) Urdu speaking and 2.5 (8/312) were Afghan refugees in Pakistan. As we do not have a special catchment area and the majority of cases were referred from northern Punjab, central NWFP and Islamabad, it was not possible to reach to a particular conclusion regarding the higher prevalence of HCV in a particular ethnic group (34).

The findings of Zuberi about a lack of evidence for a male preponderance (35) have not been , confirmed by the other workers. Most of the workers have observed higher prevalence of HCV in case of males. We have found that males were 2.3 times more prone to have HCV infection (34). At Lahore in one study, the male to female ratio was about two to one (98 males and 46 females) (35) j and the findings of another study were not much different (males 140, females 63) (36). In 100 cases of chronic liver

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disease, we found that 43% cases of chronic hepatitis, 18% of cirrhotics and 61% patients with primary liver cancer were infected with HCV (33).

A study was done on 90 cases of chronic liver disease which were negative for HBsAg, for the evidence of HCV infection. They included cases of chronic active hepatitis and cirrhosis. All the positive reactive cases were doubly confirmed by another ELISA system. Out of these, 39 (44%) cases were having HCV infection. Five of them had multiple blood transfusions after cardiac surgery and most of them gave a history of parental exposure (33). HEPATITIS D

In Pakistan, so far very few studies have been conducted to delineate its true epidemiological situation. Until 1986, HDV was not considered to be a problem in Pakistan. However, in 1988 a study was done on 193 persons having an ongoing silent infection with HBV. Out of these, 6 (3.11%) were found to be infected with HDV. Their age ranged between 25-42 years. (37). In 1990 in southern Sindh, one series showed HDV to be the cause of about 50% of the cases of acute fulminant viral hepatitis (38). Recently, at Lahore, 150 (103 males, 47 females) having HBsAg positive status were evaluated for HDV serology. HDV infection was detected in 16.6% cases (19.4% males and 10.6% females). It was more common in third and fourth decade of life and was more common in the members of medical profession (40). It is considered that situation in Pakistan regarding the HDV infection may not be different from the neighbouring countries like Kuwait, where upto 20% of HBV carriers showed simultaneous infection with HDV (40).

HEPATITIS E

In Pakistan, the disease was reported in early 1970s in troops during their field exercise, when they were consuming the untreated river water. this was wrongly considered to be due to the HA V at that time (41).

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In our set up, hepatitis E virus (HEV) has been reported to be the cause of 77.16% adult and 29.7% paediatric cases of acute viral hepatitis (42). Many mini-epidemic of HEV have occurred at Sargodha, Mardan, Rawalpindi, Quetta and other cities. These have affected the persons residing in barracks and boarding houses of a college. The cause was the polluted water due to the contamination of the pipes of water supply passing through the drains. The outbreaks were explosive and affected the persons sharing polluted water supply. The problem could be rectified when the contamination of water supply with faecal matter was solved. No mortality was recorded in these epidemics. All the patients were negative for HBsAg, Hep-A-lgM or the evidence of recent infection with Epstein Barr Virus and Cytomegalovirus. (43, 44).

The epidemiology is peculiar in the HEV associated outbreaks. An HEV outbreak was reported from a training centre at Mardan over a short period of time. The first case occurred in August followed by 6 in September and 13 in October 1987. About 10% of the exposed personnel developed jaundice. There were scattered cases in the adjacent barracks but the maximum number of cases (21) occurred in one company of troops which had its .main water point near the polluted area (with a leaking pipe of water supply passing through a drain). All the cases were hospitalised and the average duration of their stay in hospital was 20.4 days (range 19-45). None of the patients had any residual symptoms or raised transminase levels on follow up examination The serum markers for HAV and HBV were done and no case was found to be due to recent infection with these viruses. The hepatitis E cases were confined to the area where the polluted water was being consumed. The epidemic was controlled when the pipe line was repaired and the contamination of the consumable water with the sewage was stopped.

The outbreaks of hepatitis E have also been reported from Karachi. During AugOct 1986, an outbreak was reported from a residential area of Karachi, having a common water supply by Smego et al. It was found to be due to contamination of common water supply from the main drainage. On further investigations, it became clear that this minioutbreak was a part of a larger urban epidemic, many peaks of which were observed throughout 1986. In a residential community, it is not possible to have a proper

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surveillance when isolated cases are being reported. On the other hand, in a closed community like a military camp, or a residential institution, better studies may be carried out during outbreaks of hepatitis E. In a community set up, only more explosive outbreaks of hepatitis E are noticed.

In central regions of Punjab in Pakistan, an outbreak of hepatitis-E in a College Campus at Sargodha was reported by Ticehurst et al in 1987 with 133 clinical cases. All these cases required hospitalisation and had a prolonged period of convalescence. They had a common water source for their consumption. The epidemic ended with the improvement in water supply. On testing the sera of these patients, HAV and HBV infections were excluded serologically (43). In this outbreak, virological proof was sought for HEV. Paired sera from two patients were tested for Immune Electron Microscopy (IEM) and the cases were confirmed to be due to HEV. Ten out of 85 patients showed the presence of HEV particles, when studied by Electron Microscopy (EM). These were serologically identified on IEM by using references serum obtained from the HEV infected chimpanzees. The faecal concentration of HEV appeared to be lower than those of many enteric viruses (44).

The most ideal civic facilities are provided to the residents of Islamabad, the capital of Pakistan. This is because of the fact that it was recently developed as a modern capital city, was well planned and is still sparsely populated. There is an ample supply of potable water and a good drainage system in existence. There had been no recorded outbreak of HEV in the past in this city. However, in one of our studies, we had reported about the presence of sporadic cases of hepatitis E in Islamabad area and the presence of such a reservoir of HEV was a warning sign for an impending epidemics, if the faeces of the HEV infected cases could make their way into the potable water (48). This warning turned out to be true between December 1993 and March 1994, when a massive outbreak of HEV infections affected Islamabad and created a lot of concern in general population (49). Subsequently, the cases are being recorded from Islamabad frequently.

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The HEV is gradually becoming a threat to the Pak Army personnel as the pressure is increasing over the existing drainage system with growth of the population. This is mainly because of the pressure of the population on the existing sewerage and rusting of the pipelines of old water supply system. During Dec 1994, the Lahore Garrison was badly affected with 283 cases of acute hepatitis admitted in a hospital at one time. The problem was much more complicated at Lahore, because of the continuous influx of the civilian population in the cantonment over a long period which had increased tremendously the load and pressure on the waste disposal system (50). Hepatitis E is caused by a virus called hepatitis E virus (HEV). Infection with this virus was first documented in 1955 during an outbreak in New Delhi, India. The virus particle was first visualised in 1983 but was only molecularly cloned in 1990. The incidence of hepatitis E is highest in adults between the ages of 15 and 40. Though children often contract this infection as well, they less frequently become symptomatic. Mortality rates are generally low, for Hepatitis E is a self-limiting disease, in that it usually goes away by itself and the patient recovers. Hepatitis E occasionally develops into an acute severe liver disease, and is fatal in about 2% of all cases. Clinically, it is comparable to hepatitis A, but in pregnant women the disease is more often severe and is associated with a clinical syndrome called fulminant hepatic failure. Pregnant women, especially those in the third trimester, suffer an elevated mortality rate from the disease ~20%. Hepatitis E is prevalent in most developing countries, and common in any country with a hot climate. It is widespread in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly through fecal contamination of water supplies or food; person-to-person transmission is uncommon. Outbreaks of epidemic Hepatitis E most commonly occur after heavy rainfalls and monsoons because of their disruption of water supplies. Major outbreaks have occurred in New Delhi, India (30,000 cases in 1955-1956), Burma (20,000 cases in 1976-1977), Kashmir, (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988).

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Animals as a reservoir Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs. Transmission after consumption of wild boar meat and uncooked deer meat has been reported as well. The rate of transmission to humans by this route and the public health importance of this are however still unclear. Rats also carry the virus. Recent outbreaks In 2004, there were two major outbreaks, both of them in sub-Saharan Africa. There was an outbreak in Chad in which, as of September 27 there were 1,442 reported cases and 46 deaths. In Sudan, which has been troubled with conflict recently they are also suffering from a severe Hepatitis E epidemic. As of September 28, there were 6,861 cases and 87 deaths, mainly in the West Darfur Region. Increasingly, hepatitis E is being seen in developed nations with reports of cases in the UK, US and Japan. The disease is thought to be a zoonosis in that animals are thought to be the source. Prevention Improving sanitation is the most important measure, which consists of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures and sanitary food preparation. A vaccine based on recombinant viral proteins has been developed and recently tested in a high-risk population. The vaccine appeared to be effective and safe, but further studies are needed to assess the long-term protection and the cost-effectiveness of hepatitis E vaccination.

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