Academics

Pathogen: 

Hepatitis B (HBV) and Hepatitis C (HCV) are both positive-strand RNA viruses responsible for millions of deaths around the world each year (Hepatitis C in Developing Countries, 2018) (Hepatitis B Virus in Human Diseases, 2016). In Southeast Asia there are roughly 32 million individuals infected with HCV and this, combined with the growing number of immigrants moving to Europe and North America could lead to much larger issues (Hepatitis C in Developing Countries, 2018). Six different genotypes of the hepatitis C virus have been identified, and within each of these genotypes there are subtypes that have been discovered (Hepatitis C in Developing Countries, 2018). The wide variety of genotypes and subtypes in many different regions around the world, such as Africa and the Middle East, suggest that the hepatitis C virus has been endemic and evolving in these regions for a long time (Hepatitis C in Developing Countries, 2018).  

History: 

The first historical description of Hepatitis was found on Sumerian clay tablets from roughly 3,000 BC, these tablets referred to Ahhazu, a devil that attacked the liver, which was believed to be the home of the soul at the time (Trepo, 2013). Hippocrates also described a epidemic of jaundice around 375 BC which could kill patients in 11 days (Trepo, 2013). It is estimated that roughly 16,000,000 individuals (soldiers or civilians) died due to hepatitis during the second world war. It wasn’t until after World War II that multiple serotypes (strains) of hepatitis were discovered. Following that, the HBV vaccine was developed which was also the first vaccine ever developed with the use of genetic engineering. HCV was also the first virus to be identified using the direct molecular approach. Now there is a long-term therapy for HCV consisting of daily pills for 3-6 months with an estimated cure rate of >90%. Currently, we are very close to developing a cure for hepatitis and, although it will be a challenge, we should expect to reduce global prevalence greatly once one is developed. 

Susceptible regions and demographics in Southeast Asia: 

While examining the prevalence of hepatitis B and C among individuals with mental illness, Asia, compared to other continents, was found to have a significantly higher prevalence of Hepatitis B (9.7%) compared to other continents and although they also had a high prevalence of hepatitis C (4.4%), the prevalence of hepatitis C in Northern America was much higher than all other continents at around 17.4% (Alavi, 2018). Hepatitis B is endemic in the Asia-Pacific region and in Southeast Asia, however, these regions do not have as high of a prevalence as the Saharan region of Africa does (Hepatitis B Virus in Human Diseases, 2016). A map that displays global HCV prevalence can be found in Appendix A, this can be used to observe the severe regions including Southeast Asia and the majority of Africa. There is also a wide variety of different genotypes that has spread throughout many different countries in Southeast Asia (Wasitthankasem, 2015). A figure displaying this serotype distribution throughout Southeast Asia can be found in Appendix B. Countries like China, Myanmar, Thailand, and Indonesia having some of the most genotypes of HCV within their countries (Wasitthankasem, 2015).  

The demographics that have consistently been at high risk for hepatitis B or C transmission include anyone engaging in sexual relations with an infected individual, gay men/men who have sex with men, interveinal drug users, people in contact with chronically infected individuals, healthcare workers and policemen who might come in contact with infected individuals or even infectious fluids, and hemodialysis patients (Hepatitis B Information, 2020). People who received clotting factor produced before 1987 are at risk as well as recipients of blood transfusion or organ transplants conducted prior to 1992, and lastly, people with HIV are also susceptible to Hepatitis B or C infection (Hepatitis C Questions and Answers for Health Professionals, 2020). Several of the groups at high risk mentioned above are just emerging in some of these underdeveloped countries (Hepatitis C in Developing Countries, 2018). That being said, underdeveloped countries using needles, conducting procedures such as organ transplants, or any other procedures where there is direct contact with someone’s blood need to take all precautions possible in order to reduce transmission.  

What aspects make Hepatitis B & C a successful pathogen? 

The hepatitis B and C viruses are both bloodborne pathogens that can be transmitted through contaminated body fluid coming into contact with a skin puncture or contact with the mucous membrane. The infectious fluids mentioned above include blood, semen, and saliva. Both HBV and HCV are capable for surviving outside of a host and remaining infectious for up to 7 days. The most common methods of transmission for Hepatitis B and C include sex with an infected individual, interveinal drug use/drug use involving sharing needles or syringes, being born to an infected mother, percutaneous or mucosal contact with blood from sores or cuts on an infected individual, and any exposure to sharp instruments of needles (Hepatitis B Information, 2020). There are a few less common methods of transmission; sharing personal items, such as razors or toothbrushes, that can break the skin or mucous membrane can lead to infection as well (Hepatitis B Information, 2020). Transmission can also occur as the result of unregulated tattooing or healthcare procedures that involve drawing blood, such as diabetic procedures.  

Symptoms also aid in this virus’ success, not every individual that’s infected with HBV or HCV will display symptoms; between 30% and 50% of adults have symptoms of an infection. Some of the most common symptoms comprise of fever, fatigue, loss of appetite, nausea and vomiting, abdominal pain, dark urine, clay colored stool, joint pain, and jaundice which is the discoloration of someone’s eyes, skin, and urine. When symptoms do occur, they often appear anywhere between 50 and 120 days after exposure and they can last anywhere from weeks to 6 months (Hepatitis C Questions and Answers for Health Professionals, 2020). When individuals can’t tell if their infected until long after their exposure they are at risk, the undetectable aspects of this virus make drastically influence its success as a pathogen.  

Testing for both serotypes is available but, access to healthcare is often poor in Southeast Asian countries, so accommodations should be made to allow individuals from rural regions their deserved access to healthcare. Screening for hepatitis is recommended for everyone at least once in their lives and is also recommended for pregnant mothers at some point during the course of their pregnancy (Hep C Q & A, 2020). This is done with the aim of reducing mother-to-child transmission. Screening is also highly suggested for individuals belonging various high-risk groups such as injecting drug users, people with HIV, people that have received blood transfusions or organ donations in the past, and several others. These screening tests check for antibodies to the different serotypes, other tests are then used to determine whether the virus is actually present or absent, and then even further testing can be conducted to determine the titer of virus in someone’s system (Hep C Q & A, 2020). 

The hepatitis C virus begins its life cycle once it finds a host’s hepatocytes (cells that make up the majority of liver tissue), it then attaches to specific receptors on the hepatocyte and enters the cell (Hepatitis C in Developing Countries, 2018). A diagram of the general hepatitis life cycle can be found in Appendix C, this figure displays how the virus enters a cell, what the virus does once inside the cell, and how the virus then spreads to surrounding cells. Once inside the cell the virus is exposed by lysosomes, revealing its RNA which the virus will replicate with the help of the hepatocyte (Hepatitis C in Developing Countries, 2018). This allows the hepatitis C virus to use the host’s cellular machinery to replicate its RNA and also use that RNA to code for proteins (Hepatitis C in Developing Countries, 2018). These all influence the virus’s ability to withstand and avoid attacks from the immune system which also increases the success of the pathogen. 

Once the virus has infected a cell, it will then spread via either an apical or basolateral route to another cell, this helps the virus avoid and limit its contact with the host’s immune response (Karayiannis, 2017). This allows the virus to continue its life cycle undisturbed for the most part. In addition to this, once inside the cell, the virus will become outnumbered by its sub viral particles, these sub viral particles can then be used to shield the virus from any other contact it may have with the host’s immune system (Trepo, 2013). All of these factors aid the virus in withstanding the host’s immune response which in turn aids in the overall success of the pathogen.  

Once the virus enters hepatocytes, the cells will begin to malfunction since they can no longer carry out their regular functions due to the virus using the cell’s components to manufacture its own proteins. Once these cells are infected and begin to malfunction the liver will begin to gradually lose function as the disease spreads, it’s effective at causing damage to the host since chronic cases are often asymptomatic and since symptoms don’t appear until long after exposure. This allows for the virus to make significant progress before the infection is identified, and, by the time of diagnosis it is likely that the virus has already caused significant long term health damage. This is one of the most influential factors on the pathogen’s success, it its ability to enter cells, use cells machinery to produce viral proteins, and infect other nearby cells, all while remaining undetected. This, combined with the lack of symptoms, creates a very successful pathogen capable of endemic devastation in many different regions of the world, Southeast Asia being one of these regions.  

Treatment/prevention options: 

Both hepatitis B and C are vaccine curable diseases now which greatly reduced the prevalence of cases and made the disease much more manageable (Hepatitis B Virus in Human Diseases, 2016). Around 15%-25% of infected people end up clearing the virus without any treatment, this is often due to several other factors such as antigen positivity, gender, age, genotype, and host genetic polymorphisms (Hepatitis C Questions and Answers for Health Professionals, 2020). HCV becomes chronic in around 75%-85% of cases and 10%-20% will end up developing cirrhosis in the future. If an individual clears the virus from their system then that does not make them immune to other strains (Hepatitis C Questions and Answers for Health Professionals, 2020).). There are many different prevention options such as vaccinations, screening, various methods of treatment, and other precautious measures. However, none of these methods will be successful unless there is proper communication, coordination at multiple levels, safety education for the public, better access to healthcare, and improved healthcare training and measures (Childs, 2017) Reducing prevalence of such a disease will always be difficult, that is why all of these factors are necessary, to help control the many aspects influencing prevalence. 

Vaccines: 

A study conducted in 2009 studied the effects of Hepatitis A vaccinations in China from 1990-2007 (Cui, 2009). Vaccine distribution and data from various reporting systems were reviewed and they discovered that since 1990, the incidence of Hepatitis A in China declined significantly by 90%. As the urban regions experienced a decrease in incidence the rural regions of China were experiencing a slight increase in incidence which simply means that these regions require more outreach and attention. Another finding that reinforces the efficacy of vaccines is that in 1993, on figure 1 and figure 4 in their article you can see a significant decrease in Hepatitis A prevalence following the first significant introduction of vaccine to the public. Overall, this study demonstrates the efficacy of vaccines in treating for and preventing Hepatitis, these results could most likely apply in some ways to the battle against HBV and HCV in Southeast Asia. This study also reveals a major issue that is often seen in China when treating people with infectious diseases, and this reaching the entire population or maximizing the people you can reach. This study highlighted that the rural areas require more attention to ensure that they are decreasing in prevalence at similar rates to the urban regions. It is possible that the prevalence observed in these rural regions is due to higher rates of home births, meaning women who deliver their children at home rather than a healthcare setting. This is an influential factor because these children are not receiving any vaccinations after birth like they should be. A figure that demonstrates the strong negative correlation between vaccine coverage and the percentage of perinatal chronic HBV infections can be located in Appendix E. Community coordination and education is necessary to combat and reduce mother-to-child Hepatitis transmission. These methods inform mothers of possible risks and allow them to seek friends of community members that have better healthcare access, this then allows rural families to have access to resources that would have previously been much more difficult to obtain. In another study, Compact pre-filled auto-disable injections (cPAD) were discovered to be a popular, effective, and innovative method of administration (Childs, 2018). What made these so effective is that they were small, reduced waste, simple to administer, and required less medical training. These factors allowed for cPADs to be used by mothers or others residing in rural regions with high home birth rates. This study also identified a significant decline in the number of chronic HBV infections and HBV related deaths by 76% between 1992 and 2015 following the introduction of a HepB vaccine (Fig. 1) (Childs, 2018). These findings are also in support of vaccination being a very effective method for reducing HBV prevalence and HBV related deaths. A figure that displays the effectivity of HBV vaccines can be found in Appendix D, this figure shows the drastic and significant decrease in chronic HBV prevalence that occurred as vaccine coverage increased. Vaccines have not proven to be as effective for HCV and there currently isn’t a vaccine for HCV but, there are other effective methods of disease control for HCV.  

Challenges and problems in Southeast Asia: 

A study conducted in 2015 aimed to identify and assess efficient approaches to reducing hepatitis prevalence within Southeast Asia (Wait, 2016). This study found that many countries have drastically different approaches which are unlikely to succeed. One issue that they found was improper surveillance of incidence, this leads to unreliable data which inhibits countries from understanding the true magnitude of the virus (Wait, 2016). This means that both the public and the government are unaware of the risk, this needs to change before reduction can be considered. This study also found that many of these Southeast Asian countries had limited testing facilities or difficult access to testing facilities causing an overall increase in prevalence (Wait, 2016). They also discovered that many of these countries had unreliable data (due to reasons similar to what was discussed above), little to no idea of the possible economic impact of hepatitis, and publicly funded screening programs (Wait, 2016). These factors imply that action/effort is necessary in order to effectively combat hepatitis. Also, considering the incident rates in the majority of Southeast Asian countries, it would be expected that these countries at least have some form of strategy to prevent/reduce prevalence but, surprisingly only around half of Southeast Asian countries even have a national plan (Wait, 2016). Although it may be apparent, political engagement was discovered to be scarce in Southeast Asia, this is believed to be due to poor governmental understanding of both the virus, the economic impact, and general virus data. Public awareness was also found to be very low with less than 5% of chronically infected patients being aware of their status. Screening for infected mothers is poor and vaccinations are no longer governmentally funded in many countries. Poor regulation was evident which led to higher transmission rates, especially for blood products, transfusions, and transplants. Contamination is also a major issue in many of these countries, reusing contaminated needles is endemic across Southeast Asia and more than half of all injections administered annually are considered to be unsafe due to poor sterilization procedures and other precautious measures (Wait, 2016). Despite the considerable population of injecting drug users throughout Southeast Asia, harm reduction and opioid therapies are sparse. The study concluded that Southeast Asian countries should learn from each other’s successful strategies, and they should focus on improving policies/government involvement, invest in surveillance and monitor situation, improve support for drug users and prisoners, improve vaccine coverage, and improve general healthcare access in order to successfully combat hepatitis. 

Environmental factors influencing Hepatitis prevalence: 

There are a few environmental factors that have been discovered to influence liver damage induced by HBV (Liu, 2017). Alcohol consumption, Tobacco consumption, obesity, and diabetes are known risk factors for liver damage but, recent data implicates that aflatoxins (AFB) and microcystins (MC) are also influential factors for liver damage (Liu, 2017). AFBs are used on crops typically and in 2006 it was estimated that around 5 billion individuals residing in developing countries were exposed to chronic levels of AFB via contaminated food (Liu, 2017). Around 76% of food samples provided by China were considered to be higher than the regulation limit. Once consumed, AFB will accumulate in the liver and slowly lead to health complications that can influence other liver diseases. MCs are more prevalent in water and aquatic food and induce damage to the host following consumption. It was discovered that residents from the regions studied were exposed to AFBs and MCs through the consumption of moldy food, algae contaminated aquatic food, and algae contaminated water. Water sources, seasons, and eating habits were discovered to be factors influencing exposure to AFBs and MCs. Although these toxins are not equivalent in terms of damage compared to hepatitis but, these factors put people at higher risk, and they are still detrimental to human health. For these reasons, environmental factors such as AFBs and MCs should be somewhat relevant in policies and strategies for combatting hepatitis and action should be taken out of the best interests of China’s public health.

Plans of action/successful approaches: 

One successful approach has been mothers from rural Southeast Asian communities coordinating with community members that have better access to healthcare in order to obtain a HepB-BD vaccine for their children in order to reduce mother-to-child transmission and reduce overall HBV prevalence. This approach is interesting in that the cPADs mentioned previously played a major role in the success of this approach. Mothers belonging to “home-birth” households were able to vaccinate their own children with the simplistic, waste-reducing, and efficient cPAD vaccination. This was a significant discovery and the use of these cPADs combined with the coordination of these mothers allowed them to bridge their gap to healthcare access which really is a major accomplishment. Intuitive solutions tailored to developing countries, like the one mentioned above, could end up drastically reducing global prevalence. 

Aside from vaccinations, an article that evaluated the global magnitude of hepatitis concluded on several suggestions that would benefit most struggling regions in their attempt to combat hepatitis (Averhoff, 2012). The article implied that a comprehensive and coordinated approach incorporating various aspects of prevention would be the most effective strategy. A few of the important factors were transmission prevention, injection safety within healthcare as well as communities, screening of blood/blood products, harm reduction programs, public education and awareness. The article also specified that governments must improve their surveillance, prevention measures, treatment, and their general care for infected patients. To conclude, if surveillance, coordination, communication, education, training, vaccine coverage, and effort are all drastically improved upon then it is possible that we could eventually eliminate hepatitis at some point in the future.

Appendices:  

References: 

Alavi, M., Grebely, J., Hajarizadeh, B., Amin, J., Larney, S., Law, M. G., . . . Dore, G. J. (2018). Mortality trends among people with hepatitis B and C: A population-based linkage study, 1993-2012. BMC Infectious Diseases, 18(1). doi:10.1186/s12879-018-3110-0 

This study aimed to identify mainly mortality but also morbidity rates of HBV and HCV, to do this they used specific mortality records. They determined many different mortality rates based upon many different demographics involving birth generation, country of birth, gender, and other data relating to the cases they had found. This data is helpful, especially when it comes to identifying which demographics are at highest risk or most susceptible, that can then help target regions or certain groups that need aid the most. They also used graphs to make their data easier to understand, and this pointed out trends that they found to be possibly alarming. They also focused on liver-related deaths and specific types of mortality related to HBV and HCV. Overall, their data identifies and clarifies which demographics are at most risk, what they’re most at risk for, and when risk is the highest.  

Figure 3 from this study is helpful in that it displays the types of deaths related to HBV and HCV and their prevalence among patients. Within this study there were patients from several continents with the Asia-Pacific region making up a considerable amount of the patients in the study. This figure also shows the trends of these different types of hepatitis related deaths and, show how the trends have changed over time. This figure displays the most common hepatitis-related causes of death as being liver-related mortality, followed by other-related and cancer-related deaths. Another interesting aspect of this figure is that the drug-related deaths have decreased significantly over time for both HBV and HCV.  

Averhoff, F. M., Glass, N., & Holtzman, D. (2012). Global Burden of Hepatitis C: Considerations for Healthcare Providers in the United States. Clinical Infectious Diseases, 55(suppl_1). doi: 10.1093/cid/cis361 

Childs, L., Roesel, S., & Tohme, R. A. (2018). Status and progress of hepatitis B control through vaccination in the South-East Asia Region, 1992–2015. Vaccine, 36(1), 6–14. doi: 10.1016/j.vaccine.2017.11.027 

Cui, F., Hadler, S. C., Zheng, H., Wang, F., Zhenhua, W., Yuansheng, H., … Liang, X. (2009). Hepatitis A Surveillance and Vaccine Use in China From 1990 Through 2007. Journal of Epidemiology, 19(4), 189–195. doi: 10.2188/jea.je20080087 

Figure 2 of this article is helpful because it shows how the introduction of a Hepatitis A vaccine changed the distribution of the disease in China. As the cases decreased in urban regions, the rural regions began to increase their Hepatitis A incidence. This is interesting and shows that the vaccination alone will not defeat a virus, it takes effort in multiple areas to effectively reduce an endemic disease prevalence.  

Figure 1 and figure 4 complement each other in that figure 1 displays the trend in Hepatitis A prevalence from 1990 to 2007 and figure 4 displays how much of the vaccine was introduced to the public each year in that 17-year period. It is interesting because it demonstrates how effective vaccines are, in 1993 when the first significant amount of vaccine was introduced the severe decline in prevalence can be observed on figure 1. Overall, I think these two figures just displays how effective vaccines really are when consistent effort is given.  

Hepatitis B Information. (2020, March 16). Retrieved from https://www.cdc.gov/hepatitis/hbv/index.htm 

Hepatitis B Virus in Human Diseases. (2018). Retrieved from https://books.google.com/books?hl=en&lr=&id=C_XuCgAAQBAJ&oi=fnd&pg=PA186&ots=nvKXQrQ9Ge&sig=j5Av-6o1aNzqg2jMZYBWH5zDk3Q#v=onepage&q&f=false 

Hepatitis C Questions and Answers for Health Professionals. (2020, January 13). Retrieved from https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm#section2 

Hepatitis C in Developing Countries. (2018). Retrieved from https://books.google.com/books?hl=en&lr=&id=XSmlCgAAQBAJ&oi=fnd&pg=PA3&ots=UNa1U9ciyx&sig=49NTUsdktUgwsYrBFdvdg4kkQSM#v=onepage&q&f=false 

Hughes, E., Bassi, S., Gilbody, S., Bland, M., & Martin, F. (2016). Prevalence of HIV, hepatitis B, and hepatitis C in people with severe mental illness: A systematic review and meta-analysis. The Lancet Psychiatry, 3(1), 40-48. doi:10.1016/s2215-0366(15)00357-0 

Karayiannis, P. (2017). Hepatitis B virus: virology, molecular biology, life cycle and intrahepatic spread. Hepatology International, 11(6), 500–508. doi: 10.1007/s12072-017-9829-7 

This article has a different perspective that’s useful for explaining how the Hepatitis B virus infects, enters the cells, and functions once inside a cell. This article will be discussed in a specific section of this paper and is helpful for understanding the viral life cycle, how HBV spreads, as well as the structure of the virus. 

Liu, W., Wang, L., Yang, X., Zeng, H., Zhang, R., Pu, C., … Shu, W. (2017). Environmental Microcystin Exposure Increases Liver Injury Risk Induced by Hepatitis B Virus Combined with Aflatoxin: A Cross-Sectional Study in Southwest China. Environmental Science & Technology, 51(11), 6367–6378. doi: 10.1021/acs.est.6b05404 

This article also has several figures that will be helpful when explaining how microcystin, an environmental factor, can influence and induce hepatitis and liver injury.  

Trepo, C. (2013). A brief history of hepatitis milestones. Liver International, 34, 29-37. doi:10.1111/liv.12409 

Wait, S., Kell, E., Hamid, S., Muljono, D. H., Sollano, J., Mohamed, R., … Wallace, J. (2016). Hepatitis B and hepatitis C in southeast and southern Asia: challenges for governments. The Lancet Gastroenterology & Hepatology, 1(3), 248–255. doi: 10.1016/s2468-1253(16)30031-0 

This article focuses on the challenges faced by governments when trying to control HBV and HCV across Southeast Asia. There is a specific section of this paper focusing on the results from this study because they identify areas that require the most attention. This is very helpful when addressing the problem from a governmental standpoint and could be useful for educating these susceptible regions which would hypothetically reduce the prevalence. This paper is meant to help other countries avoid the same problems and provides useful information for understanding factors influencing transmission. There is also a figure that could be useful for finding specific incidence rates throughout Southeast Asia 

Wasitthankasem, R., Vongpunsawad, S., Siripon, N., Suya, C., Chulothok, P., Chaiear, K., . . . Poovorawan, Y. (2015). Genotypic Distribution of Hepatitis C Virus in Thailand and Southeast Asia. Plos One, 10(5). doi:10.1371/journal.pone.0126764 

This source aimed to discover and understand more about the genotypic distribution of hepatitis C, which has a generally high prevalence in this region. Not only are there around 150 million individuals infected with HCV worldwide that this data could benefit but, genotypic distribution studies can benefit the situation in multiple ways. Data about genotypes can lead to more beneficial treatment regimens and this data can be used to trace transmission as well as major changes in endemic genotypic ratios. This study is valuable because their results reveal where HCV is more of an issue, reveal the countries with the most viral genetic diversity, and also reveals which genotypes are most popular where. These results can also aid the investigation of rising incidence in North America and Europe, genotypes could be compared and traced to confirm whether these viruses are being brought with individuals immigrating.  

Figure 2 in this article is helpful because it visualizes the genotypic distribution of different strains and subtypes of HCV allowing us to see the wide variety of HCV throughout Southeast Asia. This figure is also helpful for identifying the countries that require the most attention and reduction/prevention services. This figure also allows for us to see which countries may be linked through transmission networks and simplifies the genotypic variation of HCV in the Southeast Asian region.  

World Health Organization. (2016). Combating hepatitis B and C to reach elimination by 2030: advocacy brief (No. WHO/HIV/2016.04). World Health Organization.