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Shahab and Saqib, (2017), 1(1), 42-55 T he I nter na t io na l J o ur na l o f I n no v a tiv e R es ea rch i n B io s cie nc es S h a h a b a n d S a q ib , (2 0 1 7 ), 1 ( 1 ), 4 2 - 5 5 ht tp : // www. ij ir b .o r g Review Article Epidemiology of Hepatitis A, B, and C Nida Shahab*1 and Shahab Saqib2 1 Department of Food Technology, Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi, Pakistan 2 Quaid-e-Azam University, Islamabad * For correspondence: [email protected] ABSTRACT Hepatitis A, B, and C are viral infectious diseases that affect the liver. The clinical features, epidemiological parameters, and modes of transmission of these viruses vary extensively. Hepatitis A virus (HAV) can cause only acute hepatitis while hepatitis B virus (HBV) and hepatitis C virus (HCV) can cause both acute and chronic hepatitis. Epidemiology of HAV, HBV, and HCV will be characterized and discussed in detail in this paper. HAV is majorly transmitted via contaminated food and water. Countries with low socio-economic conditions among population have higher epidemiology of HAV in children. HBV has a universal distribution, and a large number of carriers live around the globe. HCV also has a global epidemiological distribution with highest rates of prevalence in Africa. Blood products and bodily fluids are reported as the major sources of transmission. Keywords: Hepatitis A, B, C, Epidemiology, Prevalence, Transmission, Risk factors is favored by different conditions such as lack Epidemiology of hepatitis A Hepatitis A is an infection caused by of hygienic conditions and overcrowding. The Hepatitis A Virus (HAV) and is one of the risk of infection is directly proportional to the oldest diseases known to humankind (Shepard, levels of these conditions (Guadagnino et al., Finelli & Alter, 2005). Hepatitis A has a 1997). HAV spreads from person to person via universal distribution, although there are large the fecal-oral route. People who have never geographical differences in its prevalence been in contact with the virus and who are not (Alter, factors vaccinated against it are highly susceptible to including the fecal-oral transmission and the infection. HAV has excreted abundantly in the permanent are feces and can survive in the environment for involved in its epidemiology (Fissell et al., long periods of time (Donato, Boffetta & Puoti, 2004). 1998). The infection is typically acquired by Transmission ingestion of contaminated food, water, milk, 2007). Two immunity fundamental after infection Hepatitis A is a self-limiting infection, and seafood, etc. Certain conditions of typically caused in the childhood, and its spread overcrowding, and hygienically deficit family To cite this paper: S h a h a b , N & S a q i b , S . ( 2 0 1 7 ) . E p i d e m i o l o g y o f H e p a t i t i s A , B , a n d C . T h e I n t e r n a t i o n a l J o u r n a l O f I n n o v a t i v e Research In Biosciences , 1(1), 42-55. S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5 environment also contribute to the spread of the provided for the treatment of human waste. The disease from person to person. In both seabed where crustaceans are cultivated should situations, the onset of infection can occur in the be investigated. The incidence of the disease form of large outbreaks or sporadic cases should be controlled (Rantala & Van de Laar, (Nelson et al., 2011). Occasionally, HAV can 2008). The cause of the infection should be also be acquired through anal-oral sexual determined, and interventions should be contact, via blood transfusions, blood products prescribed accordingly. The contacts of the as well as in intravenous drug users (IDUS), in index case for prophylaxis should be identified. which cases the transmission tends to be Mechanisms for detection of disease outbreaks exceptionally high (Thierfelder, Hellenbrand, and containments for the spread of the Meisel, Schreier & Dortschy, 2001). contaminations Risk groups improved to cope the endemics. High-risk groups for hepatitis A include the should be devised and Epidemiological parameters people who maintain sexual contact with On the basis of the different prevalence infected patients or have patient(s) in their rates of HAV infection, different models, family, health care personnel, people who travel profiles or epidemiological patterns have been to high endemic countries from developed established that are often overlapping and that countries, and people living in endemic regions mainly correlate the degrees of endemicity. The of hepatitis. Children and staff of day-care degree of endemicity is determined by the rates centers, workers in contact with sewage, of incidence and prevalence that are affected by patients with the chronic liver disease, IDUs the sanitary and hygienic and socio-economic who use the non-sterile material, and gay men conditions of the regions (Beutels et al., 1997). are also among high-risk groups. Additionally, In this way, different geographical areas can be persons living in refugee camps, residents in characterized according to the different levels closed institutions, people who work with non- of endemicity of HAV infection. The level of human primates, and people with alterations in endemicity is very high in developing countries the coagulation factors have also been reported with very poor health and hygiene conditions to have higher infection rates (Matos et al., (Khan et al., 2000). The infection is usually 2009). As a preventive measure, all persons acquired in childhood as an asymptomatic or included in the risk groups are to be vaccinated mild infection in these countries. In developing against HAV. countries, with economies in transition and Surveillance and control some regions of industrialized countries where The procedures for the monitoring and sanitary conditions are poor, the level of control of hepatitis A should include various endemicity is intermediate (Bell et al., 1998). In practices. The quality of drinking water should these regions, the prevalence of infection in the be monitored and appropriate devices should be child population is not too high. Paradoxically, 43 S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5 in these countries, the increase of the economic of outbreaks (Bell et al., 1998). Finally, it and health conditions can lead to a higher should be noted that due to the introduction of incidence of the disease, with infections that the vaccine against HAV in recent years, there occur in older age groups and with high rates of is going to be a reduction in the short and clinical of medium term, in some cases drastically, in the endemicity is very low in developed countries rates of the epidemiological indicators of HAV with very good health and hygiene conditions, infection. and infection rates are generally low (Mast, Epidemiology of hepatitis B evidence. Finally, the level Alter, & Margolis, 1999). In these countries, the Hepatitis B is an infectious and frequent disease can occur among high-risk groups such disease of the liver, which affects millions of as travelers to endemic areas. Hepatitis A people all over the world. There are currently epidemic occurs sporadically throughout the more than 2,000 million people who have been world with a tendency to recurring cycles. infected with HBV at some time in their life, Outbreaks are rare in developing countries and among them, nearly 350 million remain where the adults are immune. However, the chronically infected and become carriers of the increase of hygiene and sanitary problems in virus (Perz, Armstrong, Farrington, Hutin & different parts of the world entails the existence Bell, 2006). of large sectors of the population susceptible to HAV infection, and On the other hand, approximately three- the appearance of quarters of the world's population live in areas outbreaks seems inevitable when the virus is where there is a very high prevalence of HBV introduced in this population. The number of infection. In addition, each year there are about annual cases of HAV infection is estimated at 4 million of acute HBV infections, out of which 1.4 million. Also, warm seasonal peaks have 25% give rise to chronic carriers of the been observed in some countries in autumn and infection. Each year one million people in the early winter, although this seasonality is much world die from chronic active hepatitis, less pronounced in tropical or subtropical cirrhosis or hepatocellular carcinoma because regions (Khan et al., 2000). However, due to the of HBV (Rantala & Van de Laar, 2008). decline in the overall prevalence rates and the The susceptibility to HBV infection is emergence of cases related to travel to endemic generally high, except for those people who areas, the seasonal patterns are rarely observed have been vaccinated and for others who after currently. On the other hand, seven HAV having hepatitis B have become immune to the genotypes have been identified (genotypes I to infection. It has been found that the HBV VII). The distribution of the genotypes also surface antigen (HBsAg) exists in all body varies geographically, so that its determination fluids (Alter et al., 1990). constitutes a useful tool of molecular epidemiology in the investigation of the origin 44 Shahab and Saqib, (2017), 1(1), 42-55 Table 1 Level of endemicity of HAV throughout the world Degree of HAV endemicity Very high Regions in function of the Age Range of More frequent Mode of epidemiological pattern the patients Transmission East and Southeast parts of Contaminated food and Less than 5 Africa, the Middle East water, Person to person Brazilian Amazon High basin of the Person to person, outbreaks via contaminated food and water 14-May Southern and Eastern Intermediate Europe, some regions of the 24-May Middle East Low Australia, United Western Europe States, Very low Northern Europe and Japan However, only the blood, vaginal fluids, Outbreaks via contaminated food and water, Person to person May-40 Outbreaks Exposure during trips to regions of high endemicity. Unknown Sources. On the 20 studies is greatly increased (Nelson et al., menstrual blood, saliva and semen from 2011). infected patients, have been shown to be Transmission infectious. Presently, there are four documented modes The concentration of HBV in the body of transmission for the HBV, through sexual fluids is several times lower than in the blood, contact (sexually transmitted disease), from and the role of body fluid in the transmission of mother to child at birth (perinatal transmission), infection by HBV is not well defined. On the by contact with an infected person (horizontal other hand, HBV is a virus that is very resistant transmission) and parenteral exposure to blood to environmental conditions and can stay in and other body fluids (parenteral transmission). different conditions for long periods without There is a considerable variation between areas, losing its affectivity. Eight genotypes of HBV, countries, and continents in reference to the age A through H, have been identified with at which the transmission takes place (Broers et differences distribution al., 1998). Perinatal transmission is the main (Kramvis & Kew, 2007). However, unlike what route of transmission in the world for HBV happens with HCV, the influence of the from a mother to her newborn child. The genotypes in response to treatment is not clear. perinatal There seem to be differences in the evolution of mothers is rare in most developed countries, but the disease, and therefore the interest of its it occurs with great frequency and is a common determination in the molecular epidemiology mode of transmission of HBV in the areas of in geographical 45 transmission of HBsAg-positive S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5 highest endemicity and developing countries hemodialysis, acupuncture, tattoos, body (Shepard, Simard, Finelli, Fiore, & Bell, 2006). piercing and the wounds with contaminated The risk is substantially higher for children born material within the hospital practice may also to mothers with high levels of viral replication, transmit the virus (Margolis, Alter, & Hadler, 90% of whom are infected. Although the 1991). precise mechanism of perinatal transmission is On the other hand, infection after oral unknown, it is assumed that it occurs as a result ingestion of infectious material has been of exposure to the mucous membrane of blood documented, but the efficiency of transmission and infected bodily fluids. Approximately 10% in this way is low, and the oral transmission of infections can be acquired in the uterus, rarely, or almost never, contributes to the while the epidemiological evidence suggests natural acquisition of HBV. In about 35% of that occur cases the cause of the infection is not identified, approximately at the time of delivery but are not and no apparent risk factors have been related postulated for these cases that are less obvious the majority to of infections breastfeeding. Horizontal transmission is the type of transmission that forms of parenteral or occurs between family contacts and between transmission (Ott et al., 2012). children with high rates of chronic HBV Risk groups non-parenteral infection. Same as the perinatal transmission, The main groups of people who are at risk sexual transmission takes place by mucous of getting hepatitis B include the newborn membrane contact with blood and infected babies of infected mothers, children in endemic bodily fluids (Te & Jensen, 2010). Sexual areas who are interned in day-care centers, the transmission of the HBV is efficient and is family members and sexual partners of infected recognized as the reason for the spread of the persons and health care workers exposed to virus in certain risk groups such as homosexual infected blood or bodily fluids. Similarly, men and heterosexual prostitutes, as well as in patients and employees in hemodialysis centers, patients seen in outpatient consultations for IDUs who share needles without sterilization, sexually (STDS). people who use medical and dental equipment Currently, the homosexual and heterosexual without sterilization, people who perform and contact is the risk factor most frequently receive tattoos and acupuncture with non-sterile recognized in some developed countries. apparatus, people held in prisons or institutions Parenteral transmission: Transmission occurs for the disabled and recipients of blood or blood through parenteral exposure to contaminated products are also at greater risk of getting fluids. The parenteral exposure that gives rise to infected with hepatitis. Some other risk groups infection with HBV includes the transfusion of include non-immune persons living or traveling contaminated blood and blood products. The to areas endemic for hepatitis B, and sexually practice of the parenteral drug addiction, active heterosexual and homosexuals or people transmitted diseases 46 S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5 with a history of STDS (Maddrey, 2000). All around 5% of the population is infected with and especially the major risk groups are HBV. The rest of the world is part of the candidates for vaccination and checking the midfoot for the prevalence of HBV infection, success rates of them. where the 2 to 8% of the population becomes Epidemiological parameters carriers of the virus (Stuyver et al., 2000). It is HBV has a universal distribution, with high estimated that more than a third of the world's rates of carriers in developing countries with population is infected with HBV, and about 5% limitations in health care facilities. The of the same population are chronic carriers. The prevalence of chronic HBV infection varies rates of the HBsAg carrier can vary between markedly depending on the geographic location populations of different geographical areas and the different population subgroups. With from 0.1 to 20%. However, the occurrence of regards to the prevalence and geographical these rates is closely related to the incidence and distribution of hepatitis B, there is a global the age of the person at the primary infection. distribution in three areas of endemicity The rates of prevalence of the infection, the according to the prevalence of chronic HBV routes of transmission and human behavior infection as high (> 8%), intermediate (2-7%), shape the different epidemiological patterns of or low (< 2%) (Chen, Wang & Yu, 2000). Areas infection by HBV within a geographical of high endemicity include the Amazon Basin, distribution sub-Saharan Africa, Alaska, Eastern Europe, Nateras, 2007). (Dehesa-Violante & Nuñez- northern Canada and parts of Greenland, South- In areas of low endemicity, the greater East Asia, and the area of the Eastern incidence of hepatitis B is observed in Mediterranean, China and the islands of the adolescents and young adults (Franco et al., Pacific except New Zealand, Australia and 2012). In spite of the low incidence found in the Japan. In most of these areas the spread of general population, certain groups who are infection occurs in childhood, and about 70 to sexually promiscuous or who have frequent 90% of the population gets infected with HBV contact with blood or blood products, have high before the age of 40 years, and rates of chronic rates of HBV infection. On the contrary, in carriers vary between 8 and 20% of the highly endemic areas there are other different population (Custer et al., 2004). The areas of epidemiological patterns. In these regions, low endemicity include Western Europe, North hepatitis B is a disease of the newborn and America, Australia and parts of South America. children, and most of the infections occur as a In these countries, the prevalence of infection is result of maternal and neonatal transmission or higher in population groups with older age, low due to the close contact during childhood, but socioeconomic repeated the parenteral exposure to contaminated exposure to blood products such as IDU. Rates products cannot be excluded as a potential of HBV carriers here are under 0.5%, and cause. Finally, it should be noted that universal level, and with 47 S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5 vaccination measures adopted against HBV in genotypes 1, 2 and 3 have a worldwide newborns, together with the gradual decline in distribution, with type 1 (1a and 1b) being the the prevalence rates of chronic carriers of HBV most frequent (Bruggmann et al., 2014). In in endemic countries suggest that it is possible hepatitis C, the influence of the viral genotype to eradicate human hepatitis B. is more related to the pathogenesis of liver Epidemiology of Hepatitis C disease as with any epidemiological factor. Hepatitis C is an infectious disease of the Risk groups liver that is caused by HCV, a virus that was Although in 40% of the cases of hepatitis C cloned in 1989 and identified as responsible for risk factors cannot be identified, the following the majority of Hepatitis Non-A, non-B post- groups have been identified as risk factors for transfusion Health infection by HCV. The recipients of blood, Organization (WHO) estimates that about 3% blood products, and organs prior to 1992, of the world's population has been infected with patients and employees in hemodialysis centers HCV and that about 170 million people are where hepatitis C is considered as a nosocomial chronic carriers with a risk of developing infection, the hemophiliac patients, IDUs who cirrhosis carcinoma use and share contaminated material and (Lavanchy, 2011). These chronic carriers persons exposed to contaminated and non- represent a reservoir large enough for the sterile medical or dental material. Additionally, persistence of HCV. persons exposed to occupational blood, people source. and The World hepatocellular Approximately 40% of the people who are who perform and receive tattoos and infected with HCV get recovered, but the rest, acupuncture with non-sterile apparatus, the regardless of the symptoms, become chronic healthcare workers, and the newborn babies of carriers of the infection, developing cirrhosis infected mothers are also among high-risk and hepatocellular carcinoma in the 4 and 20% groups for getting infected (Ghany, Strader, of the patients, respectively. Hepatitis C is Thomas & Seeff, 2009). usually spread by the parenteral route from the Surveillance and control infected blood (Alter et al., 1999). Some people The procedures for the monitoring and acquire the infection through parenteral routes, control of hepatitis C should include the which have not been well defined, as is the case screening of blood and blood products, both of the sexual and perinatal transmission. cellular and non-cellular, in the first place. The susceptibility to HCV is general in Reliable serological and molecular biology humans since there is no vaccine available as of equipment, which have enough sensitivity and yet due to the high genetic variability of the specificity to virus. HCV has been categorized in six major contamination with pathogens such as HCV genotypes (genotypes 1 to 6) and numerous should be used for these screening processes. subtypes (designated as a, b, c, etc.). The 48 reduce the possibility of Shahab and Saqib, (2017), 1(1), 42-55 Figure 1: Global epidemiological patterns of chronic hepatitis B. Image adapted from the US Centers for Disease Control and Infection website, available at http://www.cdc.gov/globalhealth/immunization/othervpds/preventing_ hepatitisb.htm (Accessed 17 Jan., 2017) 49 Shahab and Saqib, (2017), 1(1), 42-55 Table 2 Global distribution of Hepatitis C Virus Genotypes (Petruzziello, Marigliano, Loquercio, Cozzolino & Cacciapuoti, 2016) G1 (%) 26.3 North Africa/Middle East 27.3 74.5 55.5 46.6 Total (excludes Oceania) 64.4 49.1 G2 (%) 23.7 0.8 10.2 6.5 18.6 5.5 11.0 G3 (%) 6.3 6.3 10.6 36 22.4 25.5 17.9 G4 (%) 28.1 65.3 1.7 1.2 1.0 3.7 16.8 G5 (%) 12.2 0.3 0.1 - 0.1 0.1 2.0 G6 (%) - - 0.3 1.3 7.0 0.1 1.4 Mixed 3.4 - 2.6 - 4.3 0.7 1.8 Genotypes Africa America Australia Asia Europe Secondly, universal precautions and health between 0.2 and 18% depending on the education to prevent the spread of HCV should geographical distribution. As for all parenteral be adopted, as all people who are HIV positive transmission hepatotropic virus is not known to for HCV infection are potentially infectious for occur in hepatitis C seasonal distribution (Vogt hepatitis C (Weinbaum, Sabin & Santibanez, et al., 1999). 2005). High-prevalence areas include the countries of the Far East, the Mediterranean basin and Epidemiological parameters The HCV infection has a universal certain areas of Eastern Europe and Africa. The distribution; it is estimated that about 3% of the incidence of HCV infection on a global scale is world population has hepatitis C. Only in not well known, perhaps because the acute Europe, there are approximately 4 million infection carriers. anti-HCV incidence has decreased since the transmission antibodies is high among IDUs and hemophilia of the infection from blood and blood products patients. Similarly, it is highly variable in in has been reduced almost to zero, and universal homosexual men, promiscuous heterosexuals, precautions have intensified in the medical health workers and relatives of patients with practice (Shepard et al., 2005). The prevalence of is usually asymptomatic. The HCV infection. The prevalence of HCV is very In United States, Japan and most of the low in volunteer blood donors, although before European countries, HCV infection is found the screening of anti-HCV antibodies in blood among the general population with prevalence donors, HCV was the most frequently caused between 0.5 and 2%. The rates of prevalence are transfusion of unscreened blood (Alter, 2007). as high as 10% in some regions of Africa, and In the general population, prevalence varies in Egypt the prevalence rates have been found 50 S h a h a b a n d S a q ib , (2 0 1 7 ), 1 (1 ), 4 2 - 5 5 to be even higher at around 20%. 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