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Contents
The flu, or influenza, is a highly contagious viral infection that mainly affects the respiratory system. Its usually a seasonal illness, with yearly outbreaks killing hundreds of thousands of people around the world. Though rare, completely new versions of the virus may infect people and spread quickly, resulting in pandemics (an infection that spreads throughout the world) with death tolls in the millions. Symptoms of the flu include sudden onset fever, coughing, sneezing, a runny nose, and severe malaise, though it can also include vomiting, diarrhea and nausea. Influenza has plagued humankind for centuries and, given its highly variable nature, may continue to do so for centuries to come.
Influenza is a viral respiratory infection that causes symptoms similar to, but more severe than, the common cold. Flu symptoms can include sudden onset fever, cough, runny or stuffy nose and severe malaise (feeling unwell).
The flu can also sometimes cause vomiting, diarrhea and nausea, (particularly in young children), but the flu is primarily a respiratory disease and not a stomach or intestinal disease.
Symptoms develop 1 to 4 days after contracting the virus. Most people recover within 2 weeks without medical treatment, but the flu can cause serious complications, including pneumonia, bronchitis and sinus and ear infections.
The flu season typically lasts from late fall to spring. Each year, flu epidemics cause 3 to 5 million cases of severe illness and about 290,000 to 650,000 deaths around the globe, according to the World Health Organization (WHO).
During recent years in the United States, between 12,000 and 56,000 people have died annually from the flu, according to the Centers for Disease Control and Prevention (CDC).
Influenza has likely been around for millennia, though its cause was only identified relatively recently.
One of the earliest reports of an influenza-like illness comes from Hippocrates, who described a highly contagious disease from northern Greece (ca. 410 B.C.).
The word influenza, however, wasnt used to describe a disease until many centuries later. In 1357, people called an epidemic in Florence, Italy influenza di freddo, which translates to cold influence, referring to the diseases possible cause.
In 1414, French chroniclers used similar terms to describe an epidemic that affected up to 100,000 people in Paris. They said it originated from vent puant et tout plein de froidure, or a smelly and cold wind.
The term influenza became commonplace to describe the disease, at least in Britain, in the mid-1700s. At the time, it was thought that the influence of the cold (influenza di freddo), along with astrological influences or the conjunction of stars and planets (influenza di stelle), caused the disease.
In 1892, Dr. Richard Pfeiffer isolated an unknown bacterium from the sputum of his sickest flu patients, and he concluded that the bacteria caused influenza. He called it Pfeiffers bacillus, orHaemophilus influenzae.
Scientists later discovered thatH. influenzaecauses many types of infectionsincluding pneumonia and meningitisbut not influenza.
Researchers finally isolated the virus that causes flu from pigs in 1931, and from humans in 1933.
Influenza viruses, which are part of the Orthomyxoviridae family of viruses, cause the flu.
Four types of the virus exist: A and B, which are responsible for seasonal flu epidemics in people; C, which is relatively rare, causes a mild respiratory illness, and is not thought to cause epidemics; and D, which primarily infects cattle and isnt known to affect people.
Influenza A virus, which also infects including birds, swine, horses, and other animals, is further divided into subtypes based on two antigens (proteins) on the viruss surface: hemagglutinin (H), of which there 18 subtypes, and neuraminidase (N), of which there 11 subtypes.
The specific virus is recognized by these antigens. For example, H1N1 refers to influenza A virus with hemagglutinin subtype 1 and neuraminidase subtype 1, and H3N2 refers to influenza A virus with hemagglutinin subtype 3 and neuraminidase subtype 2.
Influenza B, on the other hand, is recognized by lineages and strains. The influenza B viruses commonly seen in people belong to one of two lineages: B/Yamagata or B/Victoria.
Influenza is a constantly evolving virus. It quickly goes through mutations that slightly alter the properties of its H and N antigens.
Due to these changes, acquiring immunity (either by getting sick or vaccinated with a flu shot) to an influenza subtype such as H1N1 one year will not necessarily mean a person is immune to a slightly different virus circulating in subsequent years.
But since the strain produced by this antigenic drift is still similar to older strains, the immune systems of some people will still recognize and properly respond to the virus.
In other cases, however, the virus can undergo major changes to the antigens such that most people dont have an immunity to the new virus, resulting in pandemics rather than epidemics.
This antigenic shift can occur if an influenza A subtype in an animal jumps directly into humans.
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It can also occur if an intermediate host such as a pigwhich is susceptible to avian, human, and swine influenzabecomes simultaneously infected by influenza viruses from two different species and the viruses exchange genetic information to acquire completely new antigens, a process called genetic reassortment.
The flu spreads several ways: through airborne coughs or sneezes, through touching contaminated surfaces like doorknobs or keyboards, through contact like handshakes or hugs and from saliva shared through drinks or kissing. If you become sick, consider working or studying from home while recovering, as going to work or school can spread the disease to others.
The elderly, young children, pregnant women, people with chronic disease and those with compromised immune systems are more likely to get the flu. The CDC says the flu vaccine is the most effective way to prevent the flu, though it is not foolproof. Avoiding close contact with sick individuals, covering coughs and sneezes, and washing your hands often can help prevent the flu. Once someone has contracted the flu, doctors can prescribe antiviral medication to shorten the illness and decrease symptoms.
Pinpointing pandemics from historical reports is challenging given the lack of accurate and consistent records, but epidemiologists generally agree that the 1580 influenza outbreak is the earliest known pandemic.
The 1580 pandemic began in Asia during the summer, and then spread to Africa and Europe. Within six months, influenza had spread from southern Europe all the way to the northern European countries, and the infection subsequently reached the Americas. The actual death toll is unknown, but 8,000 deaths occurred in Rome alone.
Nearly 150 years later, another influenza pandemic arose. It began in 1729 in Russia and spread throughout Europe within 6 months and all the world within three years. King Louis XV was reportedly infected and stated that the disease spread like a foolish little girl, or follette in French.
Only 40 years later, in 1781, another pandemic struck. It arose in China, spread to Russia, and then encompassed Europe and North America over the next year. At its peak, the infection struck 30,000 people each day in St. Petersburg and affected two-thirds of the population in Rome.
The pandemic of 18301833 began in China, and then spread by ships to the Philippines, India and Indonesia, and finally across Russia and into Europe, which experienced two recurrences over the span of the pandemic.
Outbreaks appeared in North America from 18311832. Before it ended, the pandemic may have affected 20 to 25 percent of the worlds population.
The first modern flu pandemic occurred in 1889 in Russia, and its sometimes known as the Russian flu. It reached the American continent just 70 days after it began and ultimately affected approximately 40 percent of the worlds population.
The flu pandemic of 1918 is sometimes known as the mother of all pandemics. The so-calledSpanish flu pandemicwas the deadliest in history, affecting one-third of the worlds population and killing up to 50 million people.
The Spanish flu, the first known pandemic to involve the H1N1 virus, came in several waves and killed its victims quickly, often within a matter of hours or days. More U.S. soldiers in World War I died from the flu than from battle.
The 20th century saw two other flu pandemics: the 1957 Asian flu (caused by H2N2), which killed 1.1 million people worldwide, and the Hong Kong flu of 1968 (H3N2), which killed 1 million people worldwide. Both of these flu strains arose from a genetic reassortment between a human and an avian virus.
In 2009, a new influenza A H1N1 virus emerged in North America and spread throughout the world. The swine flu pandemic primarily affected children and young adults who had no immunity to the new virus, while nearly one-third of people over the age of 60 had antibodies against the virus due to prior exposure to a similar H1N1 virus strain.
Compared with previous pandemics, the 2009 swine flu was relatively mild, despite killing up to 203,000 people worldwide.
Shortly after scientists identified the influenza A virus, researchers began work on creating a flu vaccine, with the first clinical trials commencing in the mid-1930s.
Given the high death toll of World War I soldiers to the flu, the U.S. military was highly interested in a flu vaccine. During World War II, U.S. soldiers were part of field tests on the safety and efficacy of the new vaccine.
But during these 19421945 tests, scientists discovered influenza type B, necessitating a new bivalent vaccine that protects against both H1N1 and the influenza B virus.
After the Asian flu pandemic arose in 1957, a new vaccine protecting against H2N2 was developed. WHO monitored the circulating influenza virus strains in various countries to determine which flu vaccine would be needed in an upcoming season.
During the 1978 pandemic, scientists developed the first trivalent flu vaccine, which protected against one strain of influenza A/H1N1, one strain of influenza virus A/H3N2 and a type B virus. Most U.S.-licensed seasonal flu vaccines since then have been trivalent.
In 2012, the first quadrivalent flu vaccine that protects against an additional influenza B virus was approved for use.
Scientists at WHO and its collaborating centers determine which strains to vaccinate against based on how the viruses have mutated in the past year and how they are spreading, with different vaccines needed for the Northern and Southern hemisphere.
But given the uncertainties involved in these estimates, vaccine effectiveness can vary widelythe 20042005 vaccine was only 10 percent effective in the United States, while the 2010-2011 vaccine was 60 percent effective, according to the CDC.
The 20182019 flu vaccine was 29 percent effective against Influenza A and B and 44 percent effective in preventing influenza A (H1N1) viruses in the United States.
Lina B. (2008). History of Influenza Pandemics. In: Raoult D., Drancourt M. (eds)Paleomicrobiology. Springer, Berlin, Heidelberg.Potter, C.W. (2001). A history of influenza.Journal of Applied Microbiology.Sophie Valtat et al. (2011). Age distribution of cases and deaths during the 1889 influenza pandemic.Vaccine.U.S. Flu VE Data for 2018-2019. CDC.Lone Simonsen et al. (2013). Global Mortality Estimates for the 2009 Influenza Pandemic from the GLaMOR Project: A Modeling Study.PLOS ONE.Barberis, I. et al. History and Evolution of Influenza Control through Vaccination: From the First Monovalent Vaccine to Universal Vaccines.Journal of Preventive Medicine and Hygiene57.3 (2016): E115E120. Print.Paules et al. (2018). Chasing Seasonal InfluenzaThe Need for a Universal Influenza Vaccine. The New England Journal of Medicine.Seasonal Influenza Vaccine Effectiveness, 2005-2018;CDC.The Flu Vaccine Is Working Better Than Expected, C.D.C. Finds;NYTimes.Seasonal Influenza, More Information;CDC.How the Flu Virus Can Change: Drift and Shift;CDC.Estimating Seasonal Influenza-Associated Deaths in the United States.CDC.
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OverviewWhat is mpox?
Mpox is a rare disease caused by the mpox virus. It leads to rash and flu-like symptoms. Like the better-known virus that causes smallpox, its a member of the family called orthopoxvirus.
Mpox was discovered in 1958 when two outbreaks of a pox-like disease occurred in groups of monkeys being used for research. Its spread mainly through human contact with infected rodents, but can sometimes be spread through skin-to-skin contact with a person who is infected. There are two known types (clades) of mpox virus one that originated in Central Africa and one that originated in West Africa. The current world outbreak (2022) is caused by the less severe West African clade.
Mpox is rare. But the number of cases is increasing in Africa, as well as in regions that havent seen these infections before.
For decades, mpox was mostly been seen in Africa. However, its occasionally found in other countries, including the United States. In the spring of 2003, the first outbreak of mpox outside of Africa occurred in the U.S. A shipment of infected animals from Ghana was imported into Texas. The infected rodents spread the virus to pet prairie dogs, which then infected 47 people in the Midwest.
As international travel becomes more common, viruses that were once fairly confined to certain locations can more easily spread around the world. In the summer of 2021, a case of mpox was found in a U.S. resident who had traveled from Nigeria to the United States. Then, 2022 brought outbreaks to regions outside of Africa, including Europe, the Americas and Australia.
Anyone can get mpox. In Africa, most cases are among children under 15 years old. Outside of Africa, the disease appears to be more common in men who have sex with men, but there are numerous cases in people who dont fall into that category.
After exposure, it may be several days to a few weeks before you develop symptoms. Early signs of mpox include flu-like symptoms, including:
After a few days, a rash often develops. The rash starts as flat, red bumps, which can be painful. Those bumps turn into blisters, which fill with pus. Eventually, the blisters crust over and fall off the whole process can last two weeks to four weeks. You can also get sores in your mouth, vagina or anus.
Not everyone with mpox develops all the symptoms. In fact, in the current (2022) outbreak, many cases arent following the usual pattern of symptoms. This atypical presentation includes only a few lesions, no swollen lymph nodes, less fever and other signs of illness. You can have it and not know it. Even if you dont show many signs of infection, you can spread still spread it to others through prolonged close contact.
Mpox is spread when you come into contact with an animal or a person infected with the virus. Animal-to-person transmission occurs through broken skin, like from bites or scratches, or through direct contact with an infected animals blood, bodily fluids or pox lesions (sores).
Mpox can spread from person to person, but its less common. Person-to-person spread (transmission) occurs when you come in contact with the sores, scabs, respiratory droplets or oral fluids of a person who is infected, usually through close, intimate situations like cuddling, kissing or sex. Research is ongoing, but researchers arent sure if the virus is transmitted through semen or vaginal fluids.
You can also get mpox by coming into contact with recently contaminated materials like clothing, bedding and other linens used by a person who is infected or an infected animal.
Because mpox is rare, a healthcare provider may first suspect other rash illnesses, such as measles or chickenpox. But swollen lymph nodes usually distinguish mpox from other poxes.
To diagnose mpox, your healthcare provider takes a tissue sample from an open sore (lesion). Then, they send it to a lab for polymerase chain reaction (PCR) testing (genetic fingerprinting). You may also need to give a blood sample to check for the mpox virus or antibodies your immune system makes in defense of it.
Mpox is usually a self-limited disease with symptoms lasting from two weeks to four weeks. Most people with mpox get better on their own without treatment. Following diagnosis, your healthcare provider will monitor your condition and try to relieve your symptoms, prevent dehydration and give you antibiotics to treat secondary bacterial infections if they develop.
Theres not currently an approved antiviral treatment for mpox. Antiviral drugs may help, but they havent been studied as a treatment for mpox. Several investigational antivirals with activity against mpox are available, but only as part of a research study.
A smallpox vaccine provides protection against mpox, but its use is currently limited to clinical trials. Prevention depends on decreasing human contact with infected animals and limiting person-to-person spread. The best way to help prevent the spread of mpox virus is to:
Mpox normally takes about two weeks to four weeks to run its course. If youre exposed to mpox, your provider will monitor you until the rash resolves.
The less severe West African clade is causing the current world outbreak (2022). No one has died from this outbreak to date. But mpox can lead to other problems (complications) like pneumonia and infections in your brain (encephalitis) or eyes, which can be fatal.
If have mpox symptoms, there are over-the-counter medications that can help you feel better, including:
Call your healthcare provider if you:
Seek medical care if you develop the following symptoms:
Although they both cause skin rashes, different viruses cause mpox and chickenpox. Mpox is an orthopoxvirus, while chickenpox is a herpes virus. Both viruses can be spread through skin-to-skin or prolonged face-to-face contact, but chickenpox is very contagious and spreads more easily than mpox. People with mpox are more likely to have swollen lymph nodes than people with chickenpox.
The rashes act differently, too. While the chickenpox rash can appear in waves, mpox sores develop at the same time. Chickenpox symptoms including the rash tend to get better within two weeks, while it takes two weeks to four weeks for mpox to resolve.
Smallpox and mpox are both part of the orthopoxvirus family, so theyre caused by similar but distinct viruses. Thanks to effective vaccines, smallpox was eradicated (is no longer a circulating disease) by 1980. Smallpox was very contagious and spread more easily than mpox. Mpox symptoms are similar to smallpox, but milder.
A note from Cleveland Clinic
The last two years have been incredibly challenging the COVID-19 pandemic changed so much about the way we lived and worked. Now, just as were starting to ease back into regular life, were hearing media stories about mpox as an emerging threat. But mpox is a rare disease. Its spread through close contact, like kissing and sex though were still learning about how mpox spreads in humans. The best way to protect yourself is to avoid contact with people who are infected, wash your hands frequently and wear a face mask in crowded, indoor spaces. Early symptoms of mpox are flu-like and include fever, chills and body aches. After a few days, a rash will begin to develop. See a healthcare provider if you develop symptoms.
--Preclinical studies show that ASC10-A, the active metabolite of double prodrug ASC10, has potent antiviral activities against both monkeypox and SARS-CoV-2 viruses
--Ascletis has received the Notice of Issuance from the United States Patent and Trademark Office (USPTO) for the patent application of ASC10 and its derivatives, and their uses to treat multiple virus infections
HANGZHOU and SHAOXING, China, Jan. 26, 2023 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") announces that the China National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application of ASC10 for monkeypox indication.
ASC10 is an oral double prodrug. After oral administration, both ASC10 and single prodrug molnupiravir are rapidly and completely converted in vivo into the same active metabolite ASC10-A, also known as -D-N4-hydroxycytidine (NHC) or EIDD-1931.
Preclinical studies show that ASC10-A has broad spectrum antiviral activities including potent activities against both monkeypox and SARS-CoV-2 viruses. Ascletis has received the Notice of Issuance from the United States Patent and Trademark Office (USPTO) for the patent application of ASC10 and its derivatives, and their uses to treat multiple virus infections including SARS-CoV-2, monkeypox virus and respiratory syncytial virus (RSV). Ascletis is the first Chinese biotech company which has been granted a patent by the USPTO for its in-house developed oral viral polymerase inhibitor and its derivatives.
Monkeypox virus is an orthopoxvirus that causes a disease with symptoms similar to smallpox[1]. As of January 25, 2023, over 85,106[2] confirmed cases have been reported globally and monkeypox virus has spread in 110 countries[2] according to data from World Health Organization (WHO).
Data from in vitro antiviral cellular assay with infectious monkeypox virus, a study sponsored by Ascletis and conducted at IIT Research Institute (IITRI) of Illinois Institute of Technology in Chicago, U.S., showed that ASC10-A has potent antiviral activity against monkeypox virus, suggesting that ASC10 has the potential to be an effective treatment of monkeypox virus infection. In August 2022, researchers from National Institute of Infectious Diseases, Tokyo, Japantested 132 drugs and the results showed that molnupiravir (active metabolite ASC10-A) and other two drugs have potent cellular antiviral activity in the infectious monkeypox virus assay[3]. The rest of 129 drugs such as remdesivir, favipiravir, sofosbuvir and ribavirin, etc. do not have antiviral activities against monkeypox virus[3].
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"I'm very glad that the IND application of ASC10 for monkeypox bas been approved by China NMPA, which further validates Ascletis' in-house R&D capabilities on viral diseases. Currently, there is no approved treatment for monkeypox in the world. We hope that ASC10 will make a contribution to the control of monkeypox globally." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.
[1] https://www.who.int/health-topics/monkeypox/#tab=tab_1
[2] https://worldhealthorg.shinyapps.io/mpx_global/
[3] Daisuke Akazawa, Hirofumi Ohashi, Takayuki Hishiki, et al. Potential anti-monkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments. bioRxiv preprint. https://doi.org/10.1101/2022.08.02.502485
About Ascletis
Ascletis is an innovative R&D driven biotech listed on the Hong Kong Stock Exchange (1672.HK), covering the entire value chain from discovery and development to manufacturing and commercialization. Led by a management team with deep expertise and a proven track record, Ascletis focuses on three therapeutic areas with unmet medical needs from a global perspective: viral diseases, non-alcoholic steatohepatitis (NASH) and oncology. Through excellent execution, Ascletis rapidly advances its drug pipeline with an aim of leading in global competition. To date, Ascletis has three marketed products, i.e. ritonavir tablets, GANOVO and ASCLEVIR, and 22 drug candidates in its R&D pipeline. The most advanced drug candidates include ASC22 (HBV functional cure), ASC10 and ASC11(oral small molecules for COVID-19 treatment), ASC40 (recurrent glioblastoma), ASC42 (PBC, primary biliary cholangitis), and ASC40 (acne).
For more information, please visit www.ascletis.com.
SOURCE Ascletis Pharma Inc.
