Hepatitis News
Hepatitis C Virus in Bald Eagles
The disease is tentatively called Wisconsin River Eagle Syndrome (WRES). Symptoms include stumbling, vomiting, and seizures.
In an effort to identify the cause of WRES, scientists examined bald eagle tissues[1]. Their analyses led to the identification of Bald eagle Hepacivirus (BeHV), a novel hepacivirus-like virus. The type-virus of BeHV is the globally important human pathogen Hepatitis C Virus. Across its genome, BeHV appeared most similar to duck hepacivirus (DuHV) and generally more similar to human Hepatitis C Virus than to human pegivirus (HPgV).
At the moment of publication, the Bald eagle Hepacivirus (BeHV) was infecting about a third of the bald eagle population in the entire United States. Goldberg doesn't expect that the Bald eagle Hepacivirus is able to infect humans (personal communication, 02 December 2024).
Since 2019, no new research has been published on this subject, which is rather strange, but seems to be the effect of the Covid-19 epidemic. Scientists were called to study 'other things'. Bald eagles form a reservoir of a novel Hepatitis C-like virus that has the potential to jump species. And, remember, humans are a species too.
[1] Goldberg et al: Multidecade Mortality and a Homolog of Hepatitis C Virus in Bald Eagles (Haliaeetus leucocephalus), the National Bird of the USA in Scientific Reports - 2019
Plague may have begun wiping out Europeans long before Middle Ages
A team led by University of Copenhagen researchers in Denmark used population-scale ancient genomics to infer ancestry, social structure, and pathogen infection in 108 farmers from the Neolithic (late Stone Age) period buried in eight megalithic (large stone) graves in Sweden and a cist (small stone coffin-like box) in Denmark. They also reconstructed four six-generation pedigrees, the largest of which was made up of 38 members with a patrilineal social organization.
Plague, which is associated with bacteria-carrying fleas and rodents and can spread from person to person via respiratory droplets, killed up to half the European population, which equates to as many as 200 million people. It is characterized by lymph-node swellings, fever, muscle aches, and weakness and is caused by Yersinia pestis bacteria.
"In the period between 5,300 and 4,900 before present (BP), populations across large parts of Europe underwent a period of demographic decline," the study authors noted. "However, the cause of this so-called Neolithic decline is still debated," with experts disagreeing on whether it was caused by an agricultural crisis, climate change, war, or even an early form of the plague (Yersinia pestis).
Plague was detected in the 5,000-year-old DNA of at least 17% of the sampled population across large geographic distances. Analysis of one family revealed at least three distinct infection events over roughly 120 years and found direct genomic evidence of the practice of mating outside of a social group in a woman buried separately from her brothers.
There have been several theories involving the plague, and one of them suggested that the plague could not (yet) have caused an epidemic, but that assumption no longer holds.
Genomic analysis also showed ancestral genomic variation and virulence factors in Yersinia pseudotuberculosis, a gram-negative bacterium similar to Yersina pestis. The two pathogens are believed to have diverged before the first human plague outbreaks about 6,000 years ago.
"There have been several theories involving the plague, and one of them suggested that the plague could not have caused an epidemic, but that assumption no longer holds," lead author Frederik Seersholm, said in a news release. "We cannot yet prove that this was exactly how it happened. But the fact that we can now show that it could have happened this way is rather significant."
[1] Seersholm et al: Repeated plague infections across six generations of Neolithic Farmers in Nature - 2024
Hepatitis E Virus in Sperm
Because Hepatitis E Virus has been linked to fatal pregnancy complications and reports of male infertility in the developing world, researchers explored its infectivity in pigs, whose reproductive anatomy closely resembles that of humans[1].
After inoculating pigs with Hepatitis E Virus, the team found the virus circulated in blood and was shed in feces, meaning that the pigs were infected, but they had no clinical symptoms. Asymptomatic cases are also common in humans. Results also showed Hepatitis E Virus was present on the head of sperm cells, and that these same viral particles could infect human liver cells in culture and begin replicating.
Sexually transmitted organisms are those able to find safe haven in testicles, where they are protected by a blood-testis barrier that immune cells cannot cross. In addition to pregnancy and reproductive disorders linked to Hepatitis E Virus, there are signs it can also lead to pancreatic and neurological disorders in humans. Historically, clinical infections – even in pregnant people – have been assumed to be traced to fecal-oral transmission.
Using fluorescence microscopy in this new study to examine pig semen 84 days after inoculation with Hepatitis E Virus, the authors detected viral particles associated with at least 19% of sperm cells collected from the infected swine.
The study also showed that Hepatitis E Virus’ presence correlated with damaged sperm – potentially altering their structure and decreasing their ability to move through seminal fluid. That said, the researchers can’t yet say that these changes directly translate into fertility problems, though the link between an Hepatitis E Virus infection and human infertility suggests this could be the case.
There are implications for the swine industry, as well. Most commercial pig litters are produced by artificial insemination, with donor sperm distributed broadly from large breeder facilities.
[1] Yadav et al: Infectious hepatitis E virus is associated with the mature sperm head. In PLoS Pathogens – 2024. See here.
Adenoviruses and Hepatitis
Although these viruses are called Adenoviruses they actually belong to the genus Mastadenovirus (within the the family Adenoviridae). Currently, there are 88 human known adenoviruses (HAdVs) in seven species (Human adenovirus A to G).
An infection with an Adenovirus (or an Mastadenovirus) commonly results in a respiratory tract infection. Typical symptoms range from just of a common cold, such as nasal congestion, coryza, and cough, to difficulty breathing as in pneumonia. Other general symptoms can include fever, fatigue, muscle aches, headache, abdominal pain, and swollen neck glands. Very young children may just have an earache. However, some people may have no symptoms at all.
Human Adenovirus type 7 (HAdV-7) is known to cause a more severe disease than other types[2]. It is a strain that's known to cause respiratory symptoms and spread among people living in close quarters, including military recruits. HAdV-7 has also been tied to cases of severe pneumonia and death in infants in South America.
Recently, researchers of the Centers for Disease Control and Prevention (CDC) described cases of eight US children who died of acute hepatitis of unknown cause - half of whom tested positive for adenovirus - between October 2021 and June 2023.
A total of 392 pediatric hepatitis cases of unknown origin were reported during the period. Of the eight who died, two had weakened immune systems, and one of the four who tested positive for adenovirus had no underlying medical conditions. Two children required a liver transplant.
Before these cases, adenovirus had been associated with hepatitis only in people with impaired immune systems. Another 1,010 similar cases were later reported by other countries.
A vaccine against adenovirus strains 4 and 7 is approved by the U.S. Food and Drug Administration, but it is available only for members of the US military.
[1] Almendares et al: Deaths Associated with Pediatric Hepatitis of Unknown Etiology, United States, October 2021–June 2023 in Emerging Infectious Diseases -2024. See here.
[2] Fu et al: Human adenovirus type 7 infection causes a more severe disease than type 3 in BMC Infectious Diseases - 2019
Capuchin Monkey Hepatitis B Virus
Researchers found antibodies that were specific of Capuchin Monkey Hepatitis B Virus in five animals and high concentrations Capuchin Monkey Hepatitis B Virus in one animal. A non-inflammatory, probably chronic infection was seen in all animals.
Further testing revealed that Capuchin Monkey Hepatitis B Virus is related to Woolly Monkey Hepatitis B Virus, which in turn was already known to be closely related to (Human) Hepatitis B Virus (hHBV). Infection-determining Capuchin Monkey Hepatitis B Virus surface peptides bound to the human Hepatitis B Virus receptor (human sodium taurocholate co-transporting polypeptide), but preferentially interacted with the capuchin monkey receptor homologue.
The researchers established that neither Capuchin Monkey Hepatitis B Virus nor Woolly Monkey Hepatitis B Virus was the likely ancestor of the divergent human Hepatitis B Virus genotypes F/H found in American natives.
All known hepatitis B virus genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent Woolly Monkey Hepatitis B Virus forms another orthohepadnavirus species. The evolutionary origins of human Hepatitis B Virus are unclear. They speculate that there are two possible routes. One via the migration of Paleolithic hunter-gatherers during the last ice age when the Bering Strait between Asia and the Americas was frozen (between circa 24,000 and 17,000 BC). The other via the so-called Polynesian expansion, where seafarers travelled the Pacific Ocean and likely reached the american continent (between circa 700 and 1756 AD).
[1] Breno Frederico de Carvalho Dominguez Souza et al: A novel hepatitis B virus species discovered in capuchin monkeys sheds new light on the evolution of primate hepadnaviruses in Journal of Hepatology – 2018. See here.
Syphilitic hepatitis
Syphilis can virtually affect any organ of the human body. Syphilitic hepatitis, also called 'luetic jaundice', is a rare manifestation of syphilis signifying spirochete dissemination to the liver. It was first recognized in 1585[1] and was initially reported in the literature by Harn in 1943[2]. The actual incidence of syphilitic hepatitis is uncertain. However, it occurs in 0.2 to 38% of patients with a history of syphilis diagnosis[3][4].
Syphilitic hepatitis is usually defined as a cholestatic pattern of liver enzyme elevation with serological treponemal evidence in the absence of other causes of hepatic dysfunction, and improvement after appropriate antimicrobial therapy[5].
Involvement of the liver can occur at any stage of the disease, although most cases have been reported to occur during the early stages of syphilis[6].
Due to the recent increase in the incidence of primary and secondary syphilis, it is imperative that clinicians should consider syphilis in the differential diagnosis of patients with liver dysfunction and elevated liver function tests (LFTs) of unclear etiology[5].
[1] Tolia et al: The great impostor: transaminitis masking the coinfection of syphilis and human immunodeficiency virus in Case Report - 2017. See here.
[2] Subedi et al: Syphilitic hepatitis as a manifestation of secondary syphilis in Baylor University Medical Center Proceedings - 2021.
[3] Mezzano et al: Syphilitic hepatitis. reporte de una serie de casos in Revista Médica de Chile - 2019. See here.
[4] Pizzarossa, Rebella: Hepatitis in patients with syphilis: an overlooked association in BMJ Case Reports - 2019.
here.
[6] Huang: A systematic literature review of syphilitic hepatitis in adults in Journal of Clinical and Translational Hepatology - 2018. See here.
Hepatitis E Virus in Chad
Of the 385 reported cases, more than half were male (n=215; 57%). Cases aged less than 10 years (n=90; 23.4%) and 21-30 years (n=89; 23.1%) accounted for the largest proportion of cases.
Heavy rain in Chad since June 2021 have greatly impacted the Tandjile region and by October 2021, approximately 161,000 people were affected. Floodwaters caused substantial infrastructural damage in a setting that already has pre-existing water, sanitation and hygiene (WASH) challenges such as a poor access to safe drinking water and high rates of open defecation.
The last known outbreak of Hepatitis E Virus in Chad began in August 2016 and lasted for 17 months before the Ministry of Health declared the end of the outbreak in February 2018. A total of 1874 suspected Hepatitis E Virus cases and 23 associated deaths were reported. The area affected in this outbreak was located in the Salamat region, just over 700 km north east of the current outbreak.
Source.
Hepatitis E Virus in South Sudan
[This is South Sudan as it should be] |
In 2021, the number of Hepatitis E cases have risen significantly in the country, increasing from 564 reported during the triennium 2018-2020, to 1143 suspected cases with five deaths in 2021 (as of 29 November). In last two years (2020-2021), a total of 1420 suspected cases were reported, of which 47 have been laboratory confirmed by polymerase chain reaction (PCR) at the Uganda Virus Research Institute (UVRI).
The current 2021 outbreak is occurring in Unity State, with cases mainly being reported from Bentiu IDP camp. This led the Ministry of Health (MoH) to declare a Hepatitis E outbreak in Bentiu internally displaced people (IDP) camp in August 2021. A proportion of cases (323; 28.3%) has been reported from outside the camp, in Bentiu and Rubkona towns, suggesting ongoing transmission in the surrounding community. Males aged 15-44 years are being reported as the most affected group, followed by male children 1-4 years, and females aged 15-44 years. There are no cases currently hospitalized, with clinical management implemented in outpatient departments (OPD).
Bentiu IDP camp hosts over 107,000 people and is divided into five sectors. Hepatitis E cases are reported from all sectors, highlighting widespread transmission.
Unity State, is also affected by a flood that has caused a massive displacement and the development of new IDP sites, adding 30,000 more IDPs hosted in the Bentiu IDP camp.
Hepatitis B Virus in Bedbugs
[Common bed bug - Image: El Grafo] |
The common bed bug (Cimex lectularius) is the species best adapted to human environments. It is found in temperate climates throughout the world. Other species include the tropical bed bug (Cimex hemipterus), found in tropical regions, which also infests poultry and bats, and Leptocimex boueti, found in the tropics of West Africa and South America, which infests humans and bats. The western bat bug (Cimex pilosellus) and the bat bug (Cimex pipistrella) primarily infest bats, while the Mexican chicken bug (Haematosiphon inodora), a species of North America, primarily infests poultry.
So, there are quite a few species of bed bugs that live close to humans and have a nightly feast on our blood. Well, since our blood can be infected with all sorts of viruses, we can ask the question if bedbugs can become infected too (and potentially spreading the infection to others).
The answer to that vexing question is: yes.
The tropical bed bugs were collected from the bedding in the huts of village dwellers in Senegal, West Africa[1]. Hepatitis-B surface antigen (HBSAg) was detected in unengorged nymph and adult bedbugs in each of the first three collections. The results were the highest field infection-rates of hepatitis-B virus reported in any insect species. The bedbug must be considered a potential vector of hepatitis-B virus, the scientists report.
Also, in South-Africa, scientist found that transmission of Hepatitis B Virus was possible via (I) contamination of a person when crushing infective bugs, (II) contamination from infected faeces, and (III) infection by bite due to regurgitation or interrupted feeding[2].
In other research, scientists could find Hepatitis B in bedbugs, but not Hepatitis C[3].
[1] Wills et al: Hepatitis-B virus in bedbugs (Cimex hemipterus) from Senegal in Lancet – 1977
[2] Jupp et al: The mechanical transmission of hepatitis B virus by the common bedbug (Cimex lectularius L.) in South Africa in South African Medical Journal - 1983
[3] Silverman et al: Assessment of hepatitis B virus DNA and hepatitis C virus RNA in the common bedbug (Cimex lectularius L.) and kissing bug (Rodnius prolixus) in American Journal of Gastroenterology – 2001
Hepatitis D Virus: The search for its origins
The origins of Hepatitis D Virus have long been a mystery. Having an animal origin has seemed unlikely because the ancestor satellite would either need to bring along its old helper or switch to a new and unfamiliar helper in humans. Both options add a degree of difficulty that normal viruses don't have to deal with.
Recently, studies have discovered relatives of Hepatitis D, known as Deltaviruses, in a diverse range of animals including fish, amphibians and termites. This suggests the possibility that Hepatitis D-like satellites could jump between animals more easily than thought[1].
Hepatitis D Virus is the only satellite known to cause illness in humans. Hepatitis D Virus exploits the Hepatitis B Virus, to enter and exit cells, and in the process causes the most severe form of viral hepatitis in 20 million people worldwide.
A recent study discovered new, close animal relatives of Hepatitis D, meaning that it is a zoonotic disease[2]. The virus passed from animals to humans and then slowly travelled around the world. As a result, hepatitis D can now be found on all continents.
All new Deltaviruses found—along with one recently discovered in rats from Panama – came from the Americas[3]. This was unexpected because Hepatitis D was previously thought to have originated somewhere in Africa.
So, the arrival of Hepatitis B (a compatible human helper for Hepatitis D) to the Americas via human migration might have facilitated Hepatitis D's leap into humans.
Deltaviruses have made jumps between non-human mammals. One Deltavirus from a lesser dog-like bat from Mexico was most similar to Deltaviruses from spiny rats in Panama[3]. Meanwhile, two different Deltaviruses were discovered in common vampire bats from Peru that were not closely related to one another or the other bat Deltavirus. Multiple non-human mammal jumps show that this host-leaping habit is a rule rather than an exception for Deltavirus evolution.
Exactly which helpers are used by the new animal-infecting deltaviruses is still a mystery, but viruses related to Hepatitis C Virus are emerging as strong candidates after being found in bat and rodent hosts along with Deltaviruses. Regardless, the absence of Hepatitis B-related helpers revealed another piece of the Hepatitis D origin puzzle: somewhere along the journey into humans, the forebear of Hepatitis D switched helpers, acquiring the modern association with Hepatitis B.
[1] Chang et al: Novel hepatitis D-like agents in vertebrates and invertebrates in Virus Evolution - 2019
[2] Bergner et al: Diversification of mammalian deltaviruses by host shifting in PNAS – 2021
[3] Paraskevopoulou et al: Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus in PNAS - 2020
Hepatitis B Virus in Tibetan Frogs
In addition to exogenous Hepatitis B viruses, a number of endogenous sequences (eHBV), in the form of endogenous viral elements (EVEs), have been identified in animal genomes. Hepatitis B e-viruses have been documented in turtles, crocodiles and snakes. Endogenous viruses are sequences with a viral origin that are included in a genome. About 8 percent of our genome is composed of sequences with viral origin.
In 2016 scientists reported the first amphibian Hepatitis B Virus genome: the Tibetan Frog Hepatitis B Virus (TFHBV)[1]. This indicates that the evolutionary history of the Hepatitis B viruses is more complex than previously realized and combines both virus-host codivergence over millions of years and host species jumping.
The High Himalaya frog (Nanorana parkeri) is also known as Xizang Plateau frog, Parker's slow frog, mountain slow frog or Tibetan frog, is Tibet and in Nepal, although it is expected to be found in neighbouring Bhutan and northern parts of India too.
It is a medium-sized frog. Both males and females grow to a maximum snout–vent length of about five centimeters. This frog is commonly found on high-altitude grasslands, forests, shrubs, lakes, ponds, marshes, streams and rivers in the Tibetan Plateau at elevations between 2,850 and 5,000 meters above sea level. It an explosive breeder in streams and marshes.
As a result of these findings, hepadnaviruses have now been grouped into five genera: Parahepadnavirus, Metahepadnavirus, Herpetohepadnavirus, Avihepadnavirus, and Orthohepadnavirus[2].
[1] Dill et all: Distinct Viral Lineages from Fish and Amphibians Reveal the Complex Evolutionary History of Hepadnaviruses in Journal of Virology - 2016
[2] Magnius et al: ICTV Virus Taxonomy Profile: Hepadnaviridae in Journal of General Virology - 2020. See here.
Hepatitis E Virus in Yellow-necked Mouse
The role of wild rodents and small mammals in the epidemiology of Hepatitis E Virus has been a subject of considerable debate. Time for a study, scientists decided.
A study was conducted to investigate the potential presence of Hepatitis E Virus in small rodents collected within their natural habitats and to detect if they can be potential reservoirs of the virus[2].
A total of 483 small rodents were captured using snap traps placed at a number of regions in Croatia. Sampling was undertaken in 2008 and repeated from 2010 to 2014. Liver samples were subsequently tested for the presence of Hepatitis E Virus.
Hepatitis E Virus was detected in only one liver sample from Yellow-necked Mouse (Apodemus flavicollis) collected near Zagreb in 2014.
According to the sequence analysis, the isolate has shown to be a member of Orthohepevirus A species, genotype HEV-3. The genotyping results confirmed grouping into subtype 3a.The detected Hepatitis E Virus strain showed to be genetically highly related to strains found in humans and/or domestic pigs and wild boars from Croatia.
The findings indicates that wild small mammals do play a possible role in the epidemiology of HEV-3 infection and therefore should be taken under consideration as potential reservoirs or/and transmitters of the disease. However, further investigation is needed to recognize their potential for maintaining the infection in natural conditions.
[1] Smith et al: Proposed reference sequences for Hepatitis E virus subtypes in Journal of General Virology – 2016. See here. [2]
Prpić et al: First evidence of hepatitis E virus infection in a small mammal (yellow-necked mouse) from Croatia in PloS One – 2019. See here.
Hepatitis D Virus in Snakes
Mother Nature always manages to surprise us, because recently a Hepatitis D Virus was discovered in birds[1]. Spurred on by this discovery scientists recently identified a novel Hepatitis D Virus in boa contrictors (Boa constrictor) and named it snake Hepatitis D Virus (shortened to SHDV)[2]. The scientists also detected snake Hepatitis D Virus RNA in a water python (Liasis mackloti savuensis) in the same snake colony, potentially indicating vertical and horizontal transmission.
Sequence comparison showed the snake Hepatitis D Virus antigen (sHDAg) to be 55% and 37% identical to its human and avian counterparts. However, the scientists were unable to detect accompanying Hepatitis B viruses, suggesting that snake Hepatitis D Virus could be a satellite virus of an (at the moment) unknown enveloped virus.
The identification of Hepatitis D Viruses in distantly related species other than humans indicates that the previously suggested hypotheses on the origins of Hepatitis D Viruses need to be updated.
[1] Wille et al: A divergent hepatitis D-like agent in birds in bioRxiv – 2018
[2] Hetzel et al: Identification of a Novel Deltavirus in Boa Constrictors in mBio - 2019
Hepatitis B Virus in Maxwell’s Duikers
Viral copy numbers in the blood of these dead Maxwell's Duikers were in the range known from humans with active chronic infections leading to liver damage, suggesting this virus could be pathogenic in duikers, though many orthohepadnaviruses appear to be apathogenic in other hosts.
Analysis placed the virus as a divergent member of the mammalian clade of orthohepadnaviruses, though its relationship to other orthohepadnaviruses remains uncertain. This represents the first orthohepadnavirus described in an artiodactyl (or even-toed ungulate), an order of mammals that includes pigs, peccaries, hippopotamuses, camels, chevrotains, deer, giraffes, pronghorn, antelopes, sheep, goats, and cattle. . The scientists have tentatively named this virus Taï Forest hepadnavirus.
The Taï Forest hepadnavirus is closely related to Hepatitis B Virus in woodchucks, the Hepatitis B Virus in arctic squirrels and Hepatitis B Virus in ground squirrels. These North American virusses now have a novel African family member.
[1] Gogarten et al: A Novel Orthohepadnavirus Identified in a Dead Maxwell’s Duiker (Philantomba maxwellii) in Taï National Park, Côte d’Ivoire in Virusses – 2019. See here.
Hepatitis B Virus sheds light on ancient human population movements into Australia
Unique strains of Hepatitis B Virus are endemic among modern-day Australian Aboriginals (Hepatitis B Virus/C4)[1] and Indigenous Melanesians (Hepatitis B Virus/C3)[2]. Australian researchers have used current Hepatitis B Virus genome sequences to deduce ancient human population movements into Australia, adding weight to the theory that the mainland Aboriginal population separated from other early humans at least 59,000 years ago and possibly entered the country near the Tiwi Islands[3].
Chronic Hepatitis B Virus infection is endemic in Australian Aboriginal and Torres Strait Islander people and is an important cause of morbidity and mortality due to liver disease and liver cancer.
The research team collected Hepatitis B Virus samples from people living in over 30 communities across the Northern Territories and found Hepatitis B Virus isolated from Aboriginal Australians is a unique strain, known as HBV/C4, not found anywhere else in the world.
The researchers found that the precursor of the modern Hepatitis B Virus/C4 virus entered Australia over 51,000 years ago, and then separated into two groups; one centred in the northwest region, and a second in the central/eastern region of the Northern Territories. Strikingly, the two groups share a similar geographical distribution to the two main divisions of Aboriginal Australian languages spoken in Australia today.
The analysis also suggested that Hepatitis B Virus/C3 was carried into Melanesia by Indigenous Melanesians who migrated through New Guinea north of the highlands.
[1] Littlejohn et al: Molecular virology of hepatitis B virus, sub-genotype C4 in northern Australian Indigenous populations in Journal of Medical Virology - 2014
[2] Utsumi et al: Molecular epidemiological study of hepatitis B virus infection in two different ethnic populations from the Solomon Islands in Journal of Medical Virology - 2007
[3] Yuen et al: Tracing Ancient Human Migrations into Sahul Using Hepatitis B Virus Genomes in Molecular Biology and Evolution – 2019
Hepatitis B Virus treatment: the challenge
While vaccination is highly efficacious in preventing infection, vaccine coverage is incomplete and ongoing mother-to-child transmission contributes to the continued propagation of the disease. Although current Hepatitis B treatments effectively suppress viral replication, they are typically not curative. There is therefore a high unmet need for curative Hepatitis B Virus therapies.
However, research has shown that Hepatitis B Virus has a far higher mutation rate than previously thought. In a surprisingly short period of time, the virus effectively takes over the human cell's replication machinery in order to proliferate billions of viruses per day with every possible mutation represented[2]. With modern sequencing, these mutant viral strains, sometimes called 'quasispecies', can be precisely characterized.
You understand the problem: if a treatment is curative today, it might not be so tomorrow.
[1] WHO: Factsheet Hepatitis B. See here.
[2] Lin et al: New insights into the evolutionary rate of hepatitis B virus at different biological scales in Journal of Virology – 2015
Hepatitis A Virus in Marsupials
Only recently, highly diverse nonprimate hepatoviruses were discovered, suggesting that the ancestors of Hepatitis A Virus may have evolved in mammals other than primates prior to their introduction into humans. Additionally, the unique structural properties of Hepatitis A virusses, resembling those found in ancestral insect viruses, suggest that it is an ancient picornavirus[2].
The expanded genus Hepatovirus now includes at least 16 putative virus species. The majority of novel hepatoviruses were obtained from bats and rodents.
Now, scientists have discovered a novel marsupial Hepatitis A Virus in Brazilian common (or big-eared) opossum (Didelphis aurita)[3]. That is a potential problem, since opossums are commonly hunted and consumed as wild game by resource-limited (read: poor) Brazilian communities.
Because the family containing marsupial Hepatitis A Virus shares a common ancestor with human Human Hepatitis A Virus, it may hypothetically retain the ability to infect humans.
The results of this research strongly suggest that the species barriers toward Hepatitis A Virus infection seem penetrable.
[1] Cristina, Costa-Mattioli: Genetic variability and molecular evolution of hepatitis A virus in Virus Research - 2007
[2] Wang et al: Hepatitis A virus and the origins of picornaviruses in Nature - 2015
[x] de Oliveira Carneiro et al: A Novel Marsupial Hepatitis A Virus Corroborates Complex Evolutionary Patterns Shaping the Genus Hepatovirus in Journal of virology - 2018. See here.
Hepatitis B Virus in Crocodilians
Endogenous viral elements (EVEs) are entire or fragmented viral genomes that have been integrated into the genome of their hosts in a sometimes distant past. They are therefore vertically inherited in a stable manner[2]. These elements can be seen as the genetic ‘fossils’ of which can be detected in whole genome sequence data millions of years later. Endogenization of viruses is not rare; in fact, it appears to be a recurrent and on-going process[3].
The scientists searched the recent saltwater crocodile, gharial, and American alligator draft genome assemblies using whole viral genomes of the duck Hepatitis B Virus and the Mesozoic endogenic Zebra finch Hepatitis B Virus (eZHBV) and identified two endogenous crocodilian Hepatitis B viruses (eCRHBVs): eCRHBV1 and eCRHBV2.
eCRHBV1 is present in all crocodilians except alligators and is 63.8–102.6 Millon Years (MY) old, which means that it is of Cretaceous origin. The second, eCRHBV2 is exclusively shared between saltwater and dwarf crocodiles: its endogenization thus occurred during the Paleogene in the ancestor of Crocodylidae (30.7–63.8 MYA).
So, the Hepatitis B Virus has been on the planet for millions of years. No wonder, then, that it has become so versatile. It changes, mutates and jumps species without any problem. As the Greek philosopher Heraclitus already said in the 4th century BC: There is nothing permanent except change.
[1] Suh et al: Early Mesozoic Coexistence of Amniotes and Hepadnaviridae in PloS Genetics - 2014
[2] Katzourakis et al: Endogenous viral elements in animal genomes in PLoS Genetics – 2010
[3] Holmes: The Evolution of Endogenous Viral Elements in Cell Host & Microbe – 2011
The Seasonality of Hepatitis
Micaela Elvira Martinez, an assistant professor of Environmental Health Sciences, collected information from the World Health Organization, the U.S. Centers for Disease Control and Prevention, and peer-reviewed publications to create a calendar of epidemics for 69 infectious diseases. A given year will see outbreaks of flu in the winter, chickenpox in the spring, and gonorrhea and polio in the summer -- to name a few of the best described seasonal outbreaks.
She found seasonality occurs not just in acute infectious diseases like Influenza but also chronic infectious diseases like Hepatitis, which depending on geography, flares up with greater regularity certain times of the year[1].
The paper describes several drivers of seasonality in infectious diseases: (a) vector seasonality, (b) seasonality in nonhuman animal host (i.e., livestock, other domestic animals, or wildlife), (c) seasonal climate (e.g., temperature, precipitation, etc.), (d) seasonal nonclimatic abiotic environment (e.g., water salinity), (e) seasonal co-infection, (f) seasonal exposure and/or behavior and/or contact rate, (g) seasonal biotic environment (e.g., algal density in waterbodies), (h) seasonal flare-up/symptoms and/or remission/latency, (i) observed seasonal incidence with no hypotheses regarding drivers.
Let's see what Martinez' paper has to say about Hepatitis:
- Hepatitis A (Acute): seasonal drivers are (f) and (i) – Dry season (in Brasil)[2][3]
- Hepatitis B (Chronic): seasonal driver is (h) – Seasonality is observed with elevated levels in spring and summer and/or autumn in some parts of the world, whereas there is lack of seasonality in other parts of the world [3][4]
- Hepatitis C (Acute and Chronic): seasonal driver is (f) - Seasonality observed in some countries and absent in others; spring and/or summer peaks in Egypt, China, and Mexico while there is a winter peak in India[3]
- Hepatitis E (Acute): seasonal driver is (c) - Waterborne outbreaks occur during the rainy season or following flooding (in China)[5]
"Seasonality is a powerful and universal feature of infectious diseases, although the scientific community has largely ignored it for the majority of infections," says Martinez. "Much work is needed to understand the forces driving disease seasonality and understand how we can leverage seasonality to design interventions to prevent outbreaks and treat chronic infections."
[1] Micaela Elvira Martinez: The calendar of epidemics: Seasonal cycles of infectious diseases in PLoS Pathogens - 2018. See here.
[2] Bensabatb et al: Epidemiological and Serological Studies of Acute Viral Hepatitis in Brazil's Amazon Basin in Bulletin of the Pan American Health Organisation - 1987
[3] Fares: Seasonality of Hepatitis: A Review Update in Journal of Family Medicine and Primary Care - 2015. See here.
[4] Zhang et al: Effect of Seasonal Variation on the Clinical Course of Chronic Hepatitis B in Journal of Gastroenterology - 2006
[5] Zhuang et al: Epidemiology of Hepatitis E in China in Gastroenterologia Japonica - 1991
A Novel Genotype of Hepatitis B Virus: J
You might think that nine different genotypes are more than enough, but nature has decided otherwise. A novel genotype (J) was recovered from an 88-year-old patient from the Ryukyu Islands in Japan who had a history of 'residing' in Borneo during the World War II[1].
It was divergent from nine human (A to I) and four ape (chimpanzee, gorilla, gibbon and orangutan) Hepatitis B Virus genotypes. After further research it was found that this Hepatitis B Virus was genetically closer to gibbon and orangutan genotypes that other human genotypes. It was surmised that the man was infected during the Japanese occupation of in the Dutch East Indies during the World War II.
So, the scientists thought, if one person was infected by an ape and the Hepaptis B Virus adapted (read: mutated) itself to humans, there must be many more undetected infections. People and apes are often inhabiting the same environments.
[1] Tetematsu et al: A Genetic Variant of Hepatitis B Virus Divergent from Known Human and Ape Genotypes Isolated from a Japanese Patient and Provisionally Assigned to New Genotype J in Journal of Virology – 2009. See here.
Human Papillomavirus (HPV) linked to sex with Neanderthals
Although over 200 types of the virus exist, just two — HPV16 and HPV18 — account for about 70 percent of all cervical cancers. HPV16 infection can also lead to anal cancer and cancers that develop in the throat, at the base of the tongue and the tonsils.
"There is not a more carcinogenic agent that causes cancer in humans than HPV, especially HPV16," said Robert Burk, who led the research.
As a medical geneticist Burk wanted to understand the genetics that drive the development of cancer. But there wasn’t a clear path to study how HPV contributes to the disease. So, he and his team began collecting as much information about the virus as possible.
In research published last year, Burk and colleagues analyzed the genetic sequences of HPV16 viruses from thousands of individuals and found that few women shared an identical form of the virus. It’s an indication that the virus has a knotty evolutionary past, and understanding might help shed light on why it can go on to cause cancer in some cases and not in others[2].
"It became clear that trying to study the viral genome and its association with cancer had to be viewed through the eyes of evolution," Burk said.
So, in the new study, Burk started with some of human’s closest evolutionary relatives, monkeys. The researchers isolated papillomaviruses from the oral, perianal and genital areas of squirrel and rhesus monkeys. When the scientists then compared the virus genomes, they found that the viruses that were most similar to each other came from the same parts of the body, meaning before papillomaviruses took up residence as cancer-causing parasites in humans, they first adapted to particular places in the body. The viruses then evolved within these niches for at least 40 million years.
To find out how the highly pathogenic HPV16 type of the virus evolved, the team then compared more than 200 complete HPV16 virus genomes and over 3,500 partial sequences isolated from around the world. When the researchers analyzed the virus’ evolutionary tree, they discovered that an ancient version of the virus split off onto its own evolutionary trajectory at about the same time modern humans separated from Neanderthals around 618,000 years ago. This version later evolved into four sub-types of HPV16 in Eurasian populations (ABCD lineages). The timing coincides with a split in Neanderthal populations that spread through Eurasia around 100 thousand years ago.
The finding suggests “genetic [versions] associated with cervix cancer in Northern European women appear to trace back to [the transfer of] Neanderthal genes through sexual intercourse between modern humans and archaic hominids,” Burk said. But it also “starts to provide an explanation for the differential carcinogenic potential of HPV16.”
[1] Chen et al: Niche adaptation and viral transmission of human papillomaviruses from archaic hominins to modern humans in PLoS Pathogens - 2018
[2] Mirabello et al: HPV16 E7 Genetic Conservation Is Critical to Carcinogenesis in Cell - 2017
Hepatitis E Virus in Rats
Following the now accepted scheme, Hepatitis E Virus in rats is called Hepatitis E Virus C-1, the first virus in the Orthohepevirus C sub-family. HEV-C1 strains can be divided into three genetic groups (G1, G2 and G3)[2].
So, Hepatitis E Virus has been found to infect rats. The question remained if this virus could infect humans. Test in laboratories suggested that it could, but now the first couple of human cases of rat Hepatitis E Virus have been reported.
[28sep18] The BBC reported: First human case of rat hepatitis found in Hong Kong
A 56-year-old man from Hong Kong has developed the world's first human case of rat hepatitis E. Researchers say it is unclear how the man contracted the virus, but refuse bins outside his home were infested with rats.
Doctors discovered the case when tests on the man showed abnormal liver function following a liver transplant. Further tests showed that he was carrying a strain of hepatitis "highly divergent" from the strain that affects humans, researchers from the University of Hong Kong said.
[21nov18] Outbreak News Today reported: Hong Kong reports 2nd human case of Rat Hepatitis E The Department of Health confirmed that the second patient was a retiree with underlying illnesses and a suppressed immune system.
[05nov20] ... and another human case of Rat Hepatitis E in a male patient reported in Hong Kong. See here.
[1] Smith et al: Consensus proposals for classification of the family Hepeviridae in Journal of General Virology – 2014
[2] Obana et al: Epizootiological study of rodent-borne hepatitis E virus HEV-C1 in small mammals in Hanoi, Vietnam in Journal of Veterinary Medical Science - 2017
[3] Rivero-Juarez et al: Orthohepevirus C infection as an emerging cause of acute hepatitis in Spain: first report in Europe in Journal of Hepatology - 2022
Domestic Cat Hepatitis B Virus
A novel Hepatitis B Virus was discovered in a domestic cat from Australia[1]. In 2016, a seven year-old male-neutered domestic shorthair cat was presented for vomiting and weight loss. Diagnosed with Feline Immunodeficiency Virus (FIV), the cat was eventually euthanized.
To identify potential viral pathogens infecting domestic cats scientists performed high-throughput transcriptome sequencing of tissues from cats infected with Feline Immunodeficiency Virus (FIV).
During that investigation several cats, that had previously died as a result of FIV, also seemed infected with a virus. The virus itself was elusive and it showed only 73–94% amino acid identity with known Hepatitis B viruses. This suggested the presence of a novel virus that was divergent from currently known Hepatitis B viruses. Such a large genetic distance merits assignment of a new species within the genus Orthohepadnavirus, which was tentatively named Domestic Cat Hepadnavirus or Domestic Cat Hepatitis B Virus.
Further research revealed that it exhibited no close phylogenetic relationship to any other known Hepatitis B virusses.
[1] Aghazadeh et al: A Novel Hepadnavirus Identified in an Immunocompromised Domestic Cat in Australia in Virusses – 2018. See here.
Immune system does not recover despite cured Hepatitis C Virus infection
Infection with Hepatitis C Virus turns almost always chronic and poses a major health problem around the world. The infection can lead to cirrhosis and cancer of the liver when the immune system fails to fight the virus. Eventually the immune system becomes exhausted. Since a couple of years, however, most patients with Hepatitis C Virus can now be cured in a matter of a few weeks with revolutionary new medications.
The study included 40 patients with chronic Hepatitis C Virus infection whom researchers followed before, during and after treatment with these new medications to investigate impact on the composition and diversity of the immune system. Diversity is vital to the ability of the immune system to fight infections. Of particular importance are natural killer cells, a type of white blood cells. The researchers used flow cytometry and a new measurement method to derive the composition of the immune system, as well as the appearance of natural killer cells and their function in the blood.
“Researchers in the field previously focused on analysing individual components but were unable to draw any comprehensive conclusions,” says Niklas Björkström, who led the study. “The immune system is extraordinarily complex, incorporating a large number of interacting parts. We adapted new methods in order to assess and analyse that complexity in a fresh manner.”
The results showed that the overall composition of the immune system was affected by the chronic infection, with significantly reduced diversity among the natural killer cells. Many of the changes remained long after the virus had been eliminated by means of medication. Researchers have not yet determined the long-term implications but are currently exploring whether patients have a harder time fighting future infection.
Strunz et al: Chronic hepatitis C virus infection irreversibly impacts human NK cell repertoire diversity in Nature Communications - 2018
Hepatitis B Virus and Genghis Khan
Now, scientists found evidence that Mongol warriors from the steppe carried an early form of Hepatitis B Virus. Sequencing 304 genomes from the skeletons of people who lived on the steppe during the Iron and Bronze Ages (from about 2500 BC until 1200 AD), they found that twenty-five of the samples had DNA from Hepatitis B Virus in their bones[1].
That means that Hepatitis B Virus on the ancient steppes may have been as prevalent as it is in some of the most heavily impacted areas of the world today.
What the researchers found was that Hepatitis B Virus was circulating on the Eurasian steppes for thousands of years. One of the stains found is now extinct, having apparently faded out of existence sometime in the last 4,500 years. And one of the nine major genotypes circulating today appears to be the product of an ancient recombination between two strains of the Hepatitis B Virus.
[Novel genotypes A, B, C, D, E, F, G, H] |
[Genotypes of Bronze Age and Iron Age] |
One modern strain, genotype A, was previously thought to have emerged in Africa and spread to the Americas and India within the last few centuries via the slave trade. But the researchers found some ancestral strains of type A in people living on the steppe as early as 4,300 years ago: some from the Sintasha culture in what is now southwest Russia, and one in a person from the Scythian culture in what is now Hungary.
That, suggests that it's the other way around, that it came from Europe, but it was introduced to South Asian populations historically recently.
[1] Mühlemann et al: Ancient hepatitis B viruses from the Bronze Age to the Medieval period in Nature – 2018
Stone Age and Medieval Hepatitis B Virus decoded
[Skeletal remains of HBV positive individual from the Stone Age site of Karsdorf (Germany). The individual was a male who died ataround 25-30 years. – Credit: Nicole Nicklisch] |
For this study, the researchers analyzed samples from the teeth of 53 skeletons excavated from Neolithic and medieval sites in Germany[1]. The remains dated from around 5000 BC to 1200 AD. The researchers screened all samples for viral pathogens and detected ancient Hepatitis B Virus in three of the individuals. Full Hepatitis B Virus genomes were recovered from these samples, two of which were from the Neolithic period, dating to about 7000 and 5000 years ago, and one from the medieval period[2]. The Neolithic genomes represent the by far oldest virus genomes reconstructed to date.
Interestingly, the ancient virus genomes appear to represent distinct lineages that have no close relatives today and possibly went extinct. The two Neolithic genomes, although recovered from individuals that lived 2000 years apart, were relatively similar to each other in comparison with modern strains, and were in fact more closely related to modern strains of Hepatitis B Virus found in Chimpanzees and Gorillas. In contrast, the medieval Hepatitis B Virus genome is more similar to modern strains, but still represents a separate lineage. This is the case even when it is compared to two previously published Hepatitis B Virus genomes recovered from mummies dating to the 16th century. The Hepatitis B Virus strains found in these mummies are closely related to modern strains, suggesting a surprising lack of change in the virus over the last 500 years.
These findings point to a complicated history for the virus, which may have involved multiple cross-species transmission events.
[1] Ben Krause-Kyora et al: Neolithic and Medieval virus genomes reveal complex evolution of Hepatitis B in eLife – 2018
[2] Patterson Ross et al: The paradox of HBV evolution as revealed from a 16th century mummy in PloS Pathogens - 2018
Hepatitis A Virus in Molluscs
One of the places you might venture into quite frequently when you have diarrhoea is the toilet. In several countries faeces still is led untreated into the sea. So, the question is therefore, is Hepatitis A Virus able to infect (edible) molluscs.
Scientists studied of a total of 352 samples, including four bivalve mollusc species, the Mediterranean mussel (Mytilus galloprovincialis), the European razor clam (Solen vagina), the striped venus clam (Venus gallina) and the abrupt wedge shell (Donax trunculus). Hepatitis A Virus was detected in 77 samples[1]. All of these molluscs are consumed in the Mediterranean.
If you like to eat your molluscs raw, you should be aware that you could become infected with Hepatitis A Virus.
[1] Suffredini et al: Occurrence and Trend of Hepatitis A Virus in Bivalve Molluscs Production Areas Following a Contamination Event in Food and Environmental Virology - 2017
Hepatitis E Virus in Namibia
[The number of patients seen with acute clinical jaundice in Windhoek district by week, from September 2017 to 8 January 2018 (n = 237)] |
Although infections with Hepatitis A, B and C are common in Namibia, Hepatitis E is rarely diagnosed in the country. As a result, the country has limited capacity for hepatitis E laboratory diagnosis. Additionally, the majority of hepatitis E cases have been reported from informal settlements within the capital district, Windhoek, where living conditions are poor. These areas are overcrowded, have limited access to safe drinking water, sanitation and hygiene.
Moreover, the holiday season will likely increase the movement of people within the country. All of these could be major contributing factors to this outbreak.
Additionally, during the rainy season, people often use rainwater or other surface water for drinking and domestic uses. This likely increases the risk of hepatitis E infection. Therefore, the above-mentioned factors might lead to the propagation of the cases from this area to other informal settlements and its distribution to other towns or districts, with similar poor environmental health conditions. Thus, the overall risk is assessed as high at the national level and low at regional and global levels.
Hepatitis B Virus in 16thC Mummified Child
Previous scientific analysis of the 16th century (radiocarbon dating is AD1569±60) remains suggested the child was infected with Variola virus, or smallpox[2]. In fact, this was the oldest evidence for the presence of smallpox in Medieval remains and a critical time stamp for its origins.
Using advanced sequencing techniques, researchers now suggest otherwise: the child was actually infected with Hepatitis B Virus. Interestingly, children infected with Hepatitis B Virus infections can develop a facial rash, known as Gianotti-Crosti syndrome. This may have been misidentified as smallpox and illustrates the difficulties of identifying infectious disease in the past.
“The data emphasizes the importance of molecular approaches to help identify the presence of key pathogens in the past, enabling us to better constrain the time they may have infected humans,” explains Hendrik Poinar, an evolutionary geneticist. “The more we understand about the behaviour of past pandemics and outbreaks, the greater our understanding of how modern pathogens might work and spread, and this information will ultimately help in their control,” says Poinar.
Using small tissue samples of skin and bone, scientists were able to tease out tiny fragments of DNA and then stitch together pieces of genetic information to create a much more complete picture.
While viruses often evolve very rapidly - sometimes in just days - researchers suggest that this ancient strain of Hepatitis B Virus has changed little over the last 450 years and that the evolution of this virus is complex.
The team found a close relationship between the ancient and modern strains of Hepatitis B Virus, but both are missing what is known as temporal structure. In other words, there is no measurable rate of evolution throughout the 450-year period which separates the mummy sample from modern samples.
[1] Patterson Ross et al: The paradox of HBV evolution as revealed from a 16th century mummy in PloS Pathogens - 2018
[2] Marennikova et al: Smallpox diagnosed 400 years later: results of skin lesions examination of 16th century Italian mummy in Journal of Hygiene, Epidemiology, Microbiology and Immunology - 1990