Jul
25
2020

The Immune System Changes With Age

When we are young, we do not think about our immune system, but the immune system changes with age. When we are older than age 60, we notice that we may be taking longer to recover from a flu.

How does the immune system work?

There are two parts to the immune system, the innate immune system and the adaptive immune system. The innate immune system works to protect us from bacteria, viruses, toxins and fungi from the time we are born. The adaptive immune system uses B lymphocytes from the bone marrow to produce antibodies against viruses. This provides often lifelong immunity against this specific virus, but takes 3 to 5 days to kick in. Vaccinations can also trigger antibody production to protect us from viruses in the future. Both the adaptive and the innate immune system work together closely.

What are the ingredients for a fully functioning immune system?

The immune system consists of various immune organs that are distributed throughout the body. The bone marrow produces lymphocytes, granulocytes, macrophages, eosinophils and basophils. The adenoids in the back of the nasal passages and the tonsils in the back of the throat contain a lot of lymphocytes that are ready to protect us from colds and flus. We have lymph nodes throughout the body and they are connected with lymphatic vessels. The lymph nodes filter the lymph fluid that travels in the lymphatic vessels.

Other sites of lymphocyte production

The small intestine contains the Peyer’s patches, a collection of lymphocytes that protect our gut from invading bacteria or viruses. The spleen is located in the left abdominal cavity under the diaphragm. It removes old red blood cells and provides lymphocytes for the immune system. The thymus gland is located between the breast bone and the trachea. It changes bone marrow derived lymphocytes (B cells) into T lymphocytes that can process antigens from viruses and pass them on to the adaptive immune system for a full antibody response.

Cellular interactions between various players of the immune system

Back in the 1970’s it was already known that there were bone marrow derived B lymphocytes and thymus processed T lymphocytes. We knew then that B cells were involved in antibody production (adaptive immunity). T lymphocytes were thought to turn into killer T lymphocytes to kill cancer cells. But some T cells were T helper cells to process antigen and present it to B lymphocytes for antibody production.

More research since then refined what we know about the cells of the immune system.

Natural killer cells (NK cells)

Natural killer cells (NK cells) are part of the innate immune system. They attack cancer cells and cells that are infected by viruses. It takes about 3 days for their full action to develop. NK cells utilize the cell surface histocompatibility complex to decide whether to destroy a cell or not. T cell lymphocytes do not have the ability to do that. In the Covid-19 coronavirus situation NK cells play an important role to combat the disease right away.

Monocytes

They are large white blood cells that can differentiate further into macrophages and dendritic cells. Monocytes are part of the innate immunity, but they have an antigen presenting capability, which makes them also part of the adaptive immunity.

Memory T cells

The immune system learns to adapt to viruses and bacteria that we have come in contact with. The reason for the memory of the immune cells are the memory T cells. They replicate like stem cells, which keeps a clone of T lymphocytes, T helper cells and cytotoxic T killer cells in the background. They circulate through the body including the lymph glands and the spleen.

Immunosenescence as we age

There are several factors that come together, which age our immune system. The term for this is “immunosenescence“. There are genetic differences and differences due to the sex hormones. Estrogens increase the response of the immune system. In contrast, progesterone and androgens (including testosterone) decrease the immune response. This may be the reason why women tend to live longer than men.

As we age there are more and more memory T cells (both cytotoxic T cells and T helper cells). This weakens the formation of the natural killer cells (NK cells) of the innate immune system. Even the initiation of the adaptive immune system can be slower when we age and also the response to the flu vaccine. In addition, this can pave the way to autoimmune diseases.

The immune system changes with age: Evidence of immunosenescence

The following 3 factors show whether a person has immunosenescence:

  • The immune system has difficulties to respond to new viruses/bacteria or to vaccines
  • Accumulation of memory T cells crowding out cells of the rest of the immune system
  • Low-grade inflammation that is chronic and persists (“inflamm-aging”)

The process of immunosenescence starts with the involution of the thymus gland around the time of puberty. At that time the sex hormone secretion is highest. At the same time a growth factor from the bone marrow and the thymus gland decreases. It has the name interleukin-7 (IL-7). The end result is a slow decrease of the innate immune system with age and a more substantial weakening of the adaptive immune system due to a lack of naïve T and B cells. 

Chronic viruses can weaken the immune system further

The varicella herpes zoster virus causes chickenpox. In some people the chickenpox virus can persist, but the immune system actively keeps it controlled. In the 60’s or 70’s when the immune system is weakened from aging, there can be a flare-up as shingles, a localized form of the chickenpox virus.

Another virus, the human cytomegalovirus can cause a chronic infection that often persists lifelong. In this case the immune system is chronically weakened because of a massive accumulation of T memory cells, which keeps the human cytomegalovirus infection at bay.

What we need when the immune system changes with age 

Vitamin A

Both the innate and adaptive immunity depend on vitamin A and its metabolites. The skin cells and mucosal cells function as a barrier, which is important for the innate immunity. The skin/mucosal lining of the eye, the respiratory tract, the gastrointestinal and genitourinary tracts help the innate immunity to keep viruses and bacteria out of the body. Vitamin A is important to support macrophages, neutrophils and natural killer (NK) cells. In addition, vitamin A supports the adaptive immune system, namely T and B lymphocytes, so that the body can produce specific antibodies against viruses.

I do not take vitamin A supplements as I eat diversified foods like spinach, vegetables, poultry, Brussels sprout, fish and dairy products that contain vitamin A and carotenoids.

Vitamin C

This vitamin is a powerful antioxidant. It can neutralize reactive oxygen species, which are produced when the immune cells fight viruses and bacteria. Neutrophils, lymphocytes and phagocytes are all supported by vitamin C. Vitamin C and E co-operate in their antioxidant functions. Vitamin C is essential for a strong antibody response with bacterial or viral infections. I take 1000 mg of vitamin C once daily.

Vitamin D

The immune system is very dependent on vitamin D as the immune cells all contain vitamin D receptors. People who have less than 10 ng/mL of vitamin D in the blood are vitamin D deficient. They have much higher death rates when they get infected with the Covid-19 coronavirus.

Vitamin D regulates the expression of target genes. At the center is the vitamin D receptor, which is a nuclear transcription factor. Together with the retinoic X receptor (from vitamin A) the vitamin D receptor binds small sequences of DNA. They have the name “vitamin D response elements” and are capable of initiating a cascade of molecular interactions. The result is a modulation of specific genes. Researchers identified thousands of vitamin D response elements that regulate between 100 and 1250 genes.

You need enough vitamin D for your immune system

When enough vitamin D is present in the blood (more than 30 ng/mL) the immune system releases the peptides cathelicidins and defensins, which effectively destroy bacteria and viruses.

Vitamin D has mainly an inhibitory function regarding adaptive immunity. It inhibits antibody production from B cells and also dampens the effect of T cells. Researchers reported that vitamin D3 is useful in the treatment of autoimmune diseases.

I am a slow absorber of vitamin D3 as repeat blood vitamin D levels showed. I need 10,000 IU of vitamin D3 daily to get a blood level of 50-80 ng/mL (=125-200 nmol/L). This is the higher range of normal. Everybody is different. Ask your physician to check your blood level of vitamin D. Toxic vitamin D blood levels are only starting above 150 ng/mL (= 375 nmol/L).

Vitamin E

This is a vitamin that is fat soluble and helps the body to maintain its cell membranes. But researchers found that vitamin E also stimulates the T cell-mediated immune response. This is particularly important for the aging person to prevent respiratory tract infections. I take 125 mg of Annatto tocotrienols per day (this is the most potent form of vitamin E).

Vitamin B6

This vitamin is important for antibody production by B cells. Vitamin B6 regulates the metabolism of amino acids, which in turn form proteins. Antibodies and cytokines require vitamin B6. The T helper immune cells that initiate an adaptive immune response depend on vitamin B6 as well. I take a multi B complex vitamin (Mega B 50) twice per day, so I supplement with a total of 100 mg of vitamin B6 daily.

Folate

Folic acid is a coenzyme for the metabolism of nucleic acids and amino acids. Studies in humans and animals have shown that folate deficiency leads to increased susceptibility to infections. People with folate deficiency develop a megaloblastic anemia with immune weakness that leads to chronic infections. With my B complex supplement I get 2 mg of folic acid daily.

Vitamin B12

Methylation pathways depend on vitamin B12 as a coenzyme. Vitamin B12 is also involved as a coenzyme in the production of energy from fats and proteins. In addition, hemoglobin synthesis depends on vitamin B12. Patients with vitamin B12 deficiency develop pernicious anemia. These patients also have a weak immune system due to natural killer cell activity suppression and because circulating lymphocyte numbers are significantly decreased.

Treatment with cyanocobalamin reverses the immune weakness rapidly and treats pernicious anemia at the same time. I take 50 micrograms twice per day as part of the Mega-B50 multivitamin tablet. But I also inject 1000 micrograms of vitamin B12 every 6 months subcutaneously to be sure it is absorbed into the body. In older age the intrinsic factor from the stomach lining, which is required for absorption of vitamin B12 in the small intestine, can be missing, leading to vitamin B12 deficiency despite swallowing supplements.

Minerals required for a good immune response

Researchers identified five minerals that are essential for a strong immune system. They are zinc, iron, selenium, copper and magnesium.

Zinc

Zinc is important for a normal function of the innate and adaptive immune system. As zinc cannot be stored in the body, taking regular zinc supplements (30 to 50 mg daily) is important. I take 50 mg of amino acid chelated zinc daily.

Iron

Iron is important for cell oxygen transport and storage, DNA synthesis and for mounting an effective immune response. In particular it is the T cell differentiation and proliferation where iron is needed. Iron deficient people get a lot of infections because the immune system is paralyzed. I eat one spinach salad or steamed spinach daily, which gives me enough iron supply per day.

Selenium

Selenium is a trace mineral that is important for a normal immune response and for cancer prevention. When selenium is missing, both the adaptive and innate immune system are suffering. In this case viruses are more virulent. With selenium supplementation cell-mediated immunity is improved and the immune response to viruses is more potent. I take 200 micrograms of selenium per day.

Copper

Deficiency in copper results in a very low neutrophil blood count and causes susceptibility to infections. Copper is a trace mineral that participates in several enzymatic reactions. It is important for the innate immune response to bacterial infections. A well-balanced Mediterranean diet contains enough copper, which is why I do not supplement with extra copper.

Magnesium

An important cofactor for vitamin D in the body is magnesium. Magnesium participates in many enzymatic reactions. Between vitamin D and magnesium, the immune system is strengthened. I take 150 mg of magnesium citrate twice per day. By the way, magnesium also helps us to get a restful sleep, if we take it at bedtime.

Other dietary factors that strengthen the immune system

Polyunsaturated omega-3 fatty acids are essential for the body and help to modulate the immune system. I take 1800 mg of omega-3 (EPA/DHA) twice per day. I also like to eat fish and seafood at least 3 times per week.

Probiotics benefit both the innate and the adaptive immune system. They strengthen the epithelial gut barrier, which is an important innate immune defence. Probiotics also lower the risk for Clostridium difficile gut infections. I take one probiotic every morning.

The Immune System Changes With Age

The Immune System Changes With Age

Conclusion

The immune system consists of different organs like the bone marrow, the spleen, lymph glands, Peyer’s patches in the gut, the thymus gland and more. There is the innate immune system, which responds immediately to a virus like the Covid-19 coronavirus. The adaptive immune response involves antibody production against, for instance, the measle virus or the mumps virus. With the aging process the immune system slows down (immunosenescence). This involves an accumulation of memory T cells and a depletion of natural killer cells (NK cells). This means that the innate immunity is getting weaker as we age and chronic inflammation occurs more often. This is the reason why people above the age of 65 get more severe symptoms from the Covid-19 coronavirus. They are also more affected by influenza-type illnesses.

Take supplements to strengthen the immune system

I reviewed the cofactors of a healthy immune system in some detail. It is important that you pay attention to these, particularly the vitamin D3 intake. With a strong immune system, we can survive viral infections better, including the current Covid-19 coronavirus. Future research will likely detect how to reactivate a sluggish immune system in older people. This way vaccination responses following flu injections will become more reliable in seniors.

Mar
21
2020

Coping with Covid-19 Coronavirus

Recently the topic of coping with Covid-19 Coronavirus is at the forefront of our thinking. Coronaviruses are a group of viruses that lead to severe respiratory distress. The first known coronavirus appeared in 2003 and was called Severe Acute Respiratory Syndrome (SARS). It originated in China. The second one was called Middle East Respiratory Syndrome (MERS), which began in Saudi Arabia in 2012. Covid-19 Coronavirus started in December 2019 in Wuhan, China.

The Wuhan market in Wuhan, China

This link contains a walk-around in the Wuhan market, where’re all kinds of animal parts are sold for the peculiar taste of Chinese connoisseurs. Unfortunately, it may be the mix of infected animal parts and crowds of humans that can lead to endemics like SARS or Covid-19 Coronavirus.

Covid-19 Coronavirus is a variation of a general flu virus. Coronavirus attaches to the mucous membranes of the nasal cavity, the sinus cavities and the pharynx. It sets up an inflammatory reaction of the mucous membrane cells. The cold-like symptoms in the head occur around the 5th day of infection, but sometimes there is a longer incubation and the cold-like symptoms occur only around day 10. A high fever and a cough are next. Next it affects the mucous membranes of the voice box, the trachea, the bronchial tubes and finally of the alveoli (the tiny air sacs of the lungs).

Viral pneumonia causes mortality

It is this inflammation of the alveoli, which can make a person dangerously sick. If the virus is stronger than your immune system, you can get viral pneumonia. With this condition there are a lot of secretions that must be coughed up or else there is not enough surface in the lungs to absorb oxygen. You can literally drown in your own secretions. It is the inflammation in the lungs, called viral pneumonia, which kills many patients.

Antiviral medication

Regular antibiotics will not help for a viral flu, whether this is the influenza virus or the Covid-19 Coronavirus. But antiviral medication like oseltamivir (Tamiflu), zanamivir (Relenza), or peramivir (Rapivab) might help. Despite these efforts the death rate of the ordinary influenza virus infection is about 0.13 %, as the Centers for Disease Control have calculated. In comparison, SARS had a mortality rate of 7.5 to 10% and MERS a mortality rate of 35%. The present new variation of a coronavirus has a mortality around 3.7% in China and 1.9%, outside of China according to the WHO.

Interception of the multiplication of Covid-19 coronavirus

Why wait until the virus has traveled from the top (nose, sinuses) to the bottom (lungs)? There is a mega vitamin D3 dose therapy that became popular when the SARS epidemic was around. It was originally developed for influenza.

Recently I came down with a cold, when I remembered that you can fight the cold or flu with mega vitamin D3 doses. The cold did not fit into my plans. I was three days before singing as a lead singer in a local church and I needed my voice. I felt a burning in the back of my throat and knew I was coming down with a cold. Next I felt congested in my nose and sinuses.

Experience of the mega vitamin D3 therapy

I braced myself for the cold affecting my voice box and taking my voice away. But on the second day of the cold/flu I took 50,000 IU of vitamin D3. The following day the congestion was still confined to my nose and sinuses only. But it did not go further down into my throat or chest. I continued my dose of 50,000 vitamin D3 for the second day and a 3rd dose on the 3rd day. The mega vitamin D3 doses saved my voice. My cold/flu never progressed any further; it simply stopped.

Slow and fast absorbers of vitamin D3

I know that I am a slow absorber of vitamin D3 and normally need 10,000 IU daily to get into the normal range of 25-hydroxy vitamin D using a blood test. My cold symptoms settled down, there was no sign of laryngitis, where you sound scratchy. I also did not get a cough, which based on my past experience, would have lingered on for weeks. Other people who are fast absorbers get effective 25-hydroxy vitamin D blood levels with daily doses of only 4,000 IU or 5,000 IU. However, for the mega dose vitamin D3 therapy these subtle differences don’t matter. The whopping dose of vitamin D3 leads to a high 25-hydroxy vitamin D levels that last about 2 months.

Mechanism of stimulation of the immune system by mega vitamin D3 therapy

Taking high doses of vitamin D3 releases cathelicidin and defensins. These are polypeptides that have antibacterial and antiviral properties. The vitamin D antimicrobial pathway is described in this link. Vitamin D stimulates the immune system (B cells and T cells), which can suppress viral and bacterial infections. Dr. Thornburg describes that an adult should treat a cold/flu within 24 to 36 hours after onset with 50,000 IU of vitamin D3 once daily for 3 days. He also lists pediatric doses. A 30 lb child would receive 1/5th of the adult dose or 10,000 IU once a day for three days.

Following this treatment, the patient resumes the previous vitamin D3 maintenance dose.

Opinion of conventional medicine

The Mega vitamin D3 therapy approach is not part of conventional medicine. Here is a publication that states that Vitamin D, Vitamin C, Zinc, and Echinacea in combination can be useful in the treatment of the common cold. But the section that describes the use of vitamin D seems to be very conservative. It does not even mention the importance of measuring the vitamin D blood levels.

25-hydroxy vitamin D blood level

Without a 25-hydroxy vitamin D levels the physician cannot determine whether or not you have adequate vitamin D blood levels. The normal level is considered to be 25-80 ng/mL. Many physicians say a level of 50-80 ng/mL is better (higher end of normal). This blood test will measure the sum of vitamin D from oral vitamin D3 and from sun-induced vitamin D. This test also reveals whether a person is a fast or a slow absorber. What counts is that a person taking vitamin D3 gets the blood level into the therapeutic range.

Vitamin D Toxicity 

Are there toxic levels of vitamin D? Whenever the topic of mega dose vitamin D3 is mentioned, conventional medicine will warn that vitamin D toxicity could develop including kidney stones and “bone pain, drowsiness, continuous headaches, irregular heartbeat, loss of appetite, muscle and joint pains.” In these cases of toxicity the researchers did not indicate what the level of 25-hydroxy vitamin D level was. Other publications have established that the original recommended dose of vitamin D3 by the Food and Nutrition Board of 2000 IU per day was way too low.

According to this publication based on many other papers 10,000 IU per day or more should be considered the new recommendation.

Vitamin D3 Mega dose

Dr. Schwalfenberg stated: “This is a 1-time 50,000 IU dose of vitamin D3 or 10, 000 IU 3 times daily for 2 to 3 days. The results are dramatic, with complete resolution of symptoms in 48 to 72 hours. One-time doses of vitamin D at this level have been used safely and have never been shown to be toxic.” The half-life of 25-hydroxy-vitamin D3 is 15.1 days. This means that the transient elevation of 25-hydroxy-vitamin D3 will last only 5 half-lives or 75.5 days. After that time (2 1/2 months) the body has eliminated the mega dose of vitamin D3.

Community-based measures to reduce spread of Covid-19

There are several measures that help to stop the spread of Codi-19 Coronavirus. As our hands are often transmitting flu bugs to our eyes or mouth, it is important to wash our hands frequently with soap and water. And do not touch your face!

Coughing, sneezing

Cough or sneeze into your bent elbow, not your hands or into a Kleenex.

Cleaning your home

Frequently clean toilet seats, light switches, door knobs and bedside tables. These are the items that are most frequently touched. Phones, computers and other devices should be wiped down with alcohol prep wipes (70% alcohol).

Social distancing

When Covid-19 Coronavirus is spreading in a community, it is important that people avoid large gatherings. This often includes school closures and closures of theatres, sports facilities etc. Droplets can fall up to 2 meters (6 ½ feet) from the mouth of an infected person. It makes sense that an infected person wears a mask to retain larger droplets with viruses, but the virus is small enough to directly penetrate a regular mask. The recommendation right now is that people who are self-isolating, but have no symptoms do not wear a mask. Masks are in short supply worldwide.

Self-quarantining

Many countries also recommend that all overseas travellers who come back home should voluntarily self-quarantine themselves for 14 days and watch for symptoms. The main two symptoms are a high fever and a persistent cough. Take your temperature once or twice daily when in self-quarantine. Make sure you have a friend bring you food items and whatever you need from a grocery store. If you are on regular medicine, talk to your pharmacist how this can be home delivered or picked up by a friend.

Vaccine development against Covid-19 Coronavirus

Vaccines against Covid-19 Coronavirus are still one year or more away from mass production. In April 2020 one of the vaccine manufacturer, Moderna will start testing on humans in the US. But it will take until next year before this vaccine will be available to everybody.

Another approach to help patients with Covid-19 Coronavirus infection is a plasma-derived hyperimmunoglobulin therapy.  Antibodies from patients who recently recovered from a Coronavirus infection are the basis for this treatment. Takeda, Japan’s largest drug manufacturer, announced on March 4, 2020 that it would develop a hyperimmunoglobulin against Covid-19 Coronavirus.  Recently recovered patients have specific antibodies in their blood, which the company can recover from their plasma. When physicians inject the recovery plasma into patients with a positive test against Covid-19 Coronavirus, their recovery accelerates and the course of the infection is much milder. This new therapy was dubbed “TAK-888”. However, testing requires still many more month of further research to ensure it is safe.

Why does Italy have high Corona death rates?

In the March 18, 2020 issue of the German Magazine stern.de this question was posed. There are 31,500 Italians with the Coronavirus infection so far. 2503 people died from the Covid-19 Coronavirus. This translates into a mortality rate of around 8%, which is more than double of average rate of in other countries. For comparison, here are the death rates in other countries: China 4%, South Korea 1% and Germany 0.26%. Why these tremendous differences?

Low testing rates

Scientists believe that the policy in Italy to only test patients with symptoms suppresses the number of reported infected patients. This leads to unreported cases and falsely reporting higher Corona death rates. In South Korea where mortality rates are low, physicians did 3692 tests for Covid-19 per a million people up to March 8, 2020. In contrast, health professionals in Italy did only 826 Corona tests per million people. This leads to underreporting of infected people, causes more transmissions and higher death rates. Dr. Jeffrey Shaman, an epidemiologist at Columbia University said: “If we have 3,500 confirmed cases in the U.S., you might be looking at 35,000 in reality”.

Physicians in the US do not test enough people for Covid-19, and like in Italy this will lead to much higher infection rates as assumed to occur in the beginning.

Seniors are at higher risk for mortality from Covid-19 Coronavirus

According a report from the UN in 2015 there were 28.6% of the Italian population were 60 years or older. In South Korea 18.5% of People were older than 60 at the same time. Seniors have other underlying diseases like type 2 diabetes, emphysema, heart disease and others. When patients with these conditions get Covid-19 Coronavirus, the mortality is higher. Children and people below the age of 60 may have clinically undetectable disease, and only a Covid-19 test would show it, if they were positive.

Coping with Covid-19 Coronavirus

Coping with Covid-19 Coronavirus

Conclusion

Vitamin D3 has long recognition as a stimulant of the immune system. We now know that high doses of vitamin D3 release two polypeptides, cathelicidin and defensins. They have antibacterial and antiviral actions. Several physicians have developed a mega vitamin D3 approach when a cold or flu just starts to hit you. An adult should then take 50,000 IU of vitamin D3 daily for 3 days. In many cases it will cut the cold/flu short within 48 to 72 hours. Dr. Schwalfenberg said that “one-time doses of vitamin D at this level have been used safely and have never been shown to be toxic.”

Inflammation from Covid-19 Coronavirus

Any flu virus, including the coronavirus varieties, cause a lot of inflammation. When the inflammation reaches the lungs (inflammation of the air sacs or alveoli) a lot of patients die because they cannot get enough air. But with the use of mega vitamin D3 doses we have a powerful tool to prevent the further spread of the virus. If you take this on the first or second day of the flu, you can prevent the further spread of the coronavirus into the lungs. The reason is the release of cathelicidin and defensins from the action of vitamin D3. These polypeptides have antibacterial and antiviral properties.

Vaccine development

Vaccine development is still a year away from being available. In the meantime, high dose vitamin D3 therapy is available and is cheap.

Most importantly, help stop the spread by being meticulous about your hygiene, as mentioned before. Also, adjust your life style by staying away from larger crowds. You will not hang out in bars and clubs, and instead of going out for meals, prepare your own or arrange for food delivery. Panic never helped in crisis situations; common sense does!

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Dec
07
2019

The Use Of Oncolytic Viruses For Cancer Treatment

In the first place, preliminary experiments indicate that the use of oncolytic viruses for cancer treatment may become a reality. There are several lines of research that point to the fact that oncolytic viruses can make a difference in treating incurable cancer patients.

Notably, Canadian researchers had reported in 2011 that oncolytic viruses created by genetically modifying smallpox vaccine viruses would enter tumor cells of patients, but not damage normal cells. Specifically, a high percentage of the end stage patients responded with tumor regression.

Shortly after Mayo Clinic physicians were desperate when two patients with end stage multiple myeloma, a vicious bone tumor, did not respond to chemotherapy. Significantly, they tried something unconventional: high doses of the measles vaccine in an attempt to stimulate the immune system. Here is an overview from 2014 that shows that many different cancers respond to various immunological approaches.

Study from Holland regarding end stage melanoma patients

Here is a small human study involving end-stage melanoma patients treated with the oncolytic virus T-VEC combined with pembrolizumab (Keytruda). It is important to realize that Keytruda helps to reactivate a T-cell response to the cancer cells. In this case the cancer cells absorb the oncolytic virus (T-VEC), but it leaves normal cells alone. Inside the cancer cells the oncolytic virus multiplies and destroys the cancer cells. In this 2017 study 21 patients with terminal, nonresectable melanoma received treatment with T-VEC and Keytruda. Specifically, 62% of the patients showed an objective response to the treatment. Moreover, 33% fulfilled the criteria of an immune-related response. In the past terminal patients like these had a 0% response to radiotherapy or chemotherapy.

History of research about oncolytic viruses

To begin with, in 1912 rabies virus treatment against cervical carcinoma was a first attempt to treat cancer. Researchers conducted many experiments between 1950 and 1970 with wild type or naturally attenuated viruses. This included, for example, hepatitis A and B viruses. In 1991 cancer researchers developed the concept of genetically engineered oncolytic viruses. Today cancer researchers know that the protection mechanisms in most cancer cells have deficiencies. This involves the interferon‐beta signal pathway. Having said this, there is an opportunity to let oncolytic viruses destroy cancer cells, while normal cells stay unaffected. An oncolytic virus that cancer experts use in human cancers is the genetically engineered herpes simplex virus type I (HSV‐1). Others that cancer researchers developed have strange names like T‐Vec, G47∆, JX594, CG0070 and Reolysin.

Various cancers that researchers treated with oncolytic viruses

Here are a few examples of cancers where researchers used oncolytic viruses to exert a significant therapeutic effect.

Glioblastoma

Glioblastoma is a deadly form of a brain tumor, which has a high rate of mortality. Researchers have investigated new avenues to treat this cancer. Researchers tested the genetically engineered dendritic vaccine. Initial clinical trials showed significant effectiveness compared to non-treated controls. In a large phase 3 clinical trial 331 patients with newly diagnosed glioblastoma received treatment at the time of neurosurgery with dendritic cell vaccine. 30.2% of the patients were still alive and doing well after 3 1/3 years. Without the added vaccination procedure all of these patients would have died in the past because of the aggressiveness of the glioblastoma.

Multiple myeloma

Researchers could cure multiple myeloma and other cancers by using the measles vaccine. Here is a report by the popular press about two women who had multiple myeloma. One woman got cured by high doses of a measles vaccine. The other women experienced some relief, but did not survive.

This publication explains that oncolytic viral therapy of cancer is a lot more complicated than originally thought.

Prostate cancer

Researchers found that vaccines against prostate cancer were effective with the combination of oncolytic virus therapy with regular anti-cancer treatments. But oncolytic virus therapy alone has a poorer prognosis than a combination of chemotherapy or radiotherapy with oncolytic virus therapy.

Cervical cancer

The high-risk HPV16 strain most often causes cervical cancer. The HPV (human papilloma virus) vaccine targets patients with previous exposure to HPV16. However, researchers have noticed that in some cases a phenomenon called the “HPV immune escape” has allowed in some vaccinated women to still develop cervical cancer. Now a group of researchers are investigating how the vaccine could be improved by finding out how the immune system is being tricked in these cases by the HPV virus to bypass the antibodies of the vaccine.

Pancreatic cancer

This cancer is very difficult to detect in the early stages, and as a result the outlook for chemotherapy or radiotherapy is extremely poor. Researchers have used several approaches as an alternative to conventional therapy. Immunotherapy is an option. Mayo clinic researchers have already announced that the measles vaccine approach will likely be applicable to pancreatic cancer treatment as well in the near future. However, other clinical trials are on the way to use alternative vaccination procedures.

Neuroblastoma, glioma and melanoma

This link shows that the FDA has accepted engineered oncolytic herpes virus (engineered to secrete GM-CSF) as a treatment against melanoma. Other approaches with engineered bacteria can affect neuroblastoma and glioma.

Survival data using oncolytic viruses for cancer treatment

Cancer researchers have completed a number of smaller clinical trials at this point. One of them describes end stage melanoma (stage III and IV) where the only treatment was with the oncolytic virus T‐Vec. The overall response rate compared to the control, which was only 5.7%, the experimental group with T-Vec was 26.4%. This is considered a good response rate given that we are dealing with end stage melanoma patients.

Mechanism of how oncolytic viruses stimulate the immune system to overcome various cancers

As mentioned above oncolytic viruses multiply in the cancer, once they have been incorporated. This leads to cancer cell death. It exposes the dead cancer tissue to the immune system. What helps in the process is that inhibitory proteins from the cancer cells that used to inhibit the immune system are no longer provided by the dead cancer cells. The end result is that the immune system mounts a formidable response against the cancer cells through killer T cells. This immune response also affects remote metastases of the same histological cancer type. This review article summarizes how oncolytic viruses work for cancer cell destruction and how this method can be combined with other treatment modalities.

The Use Of Oncolytic Viruses For Cancer Treatment

The Use Of Oncolytic Viruses For Cancer Treatment

Conclusion

Currently various cancer centers are involved with clinical trials in humans to test the power of oncolytic viruses. What cancer researchers have learnt is that oncolytic viruses are a useful tool to kill cancer cells. But the immune system of cancer patients is in a suppressed state. Pembrolizumab (Keytruda) is a medication that will stimulate the immune system by stimulating killer T cells to destroy cancer cells. The combined effect of killing cancer cells with oncolytic viruses and stimulating the immune system is the big news. This has been the breakthrough that cancer researchers have been waiting for. Now several clinical trials are on the way where survival rates for cancer patients given the new combination therapy are assessed.

Oncolytic virus therapy here to stay

It is a treatment which is no longer a thought model with animal experiments. Well known medical centers are using it in patients, and as the results become more obvious, it will very likely become a new treatment modality for cancer.

Jan
31
2013

Staying Healthy During Exotic Travel

A study of 82,825 ill travelers from Europe, North America, Israel, Japan, Australia and New Zealand was published who were interested in staying healthy during exotic travel. They had traveled the world between June 1996 and August 2011. The data was based on the GeoSentinel surveillance network database. There were 3,655 patients (4.4%) who were seriously sick with one of 13 tropical diseases. There were 13 deaths (=0.4%), 10 of which were from malaria. Two died from melioidosis. This is an infectious disease caused by a bacterium found in soil in Southeast Asia (including Thailand, Laos, southern China, Singapore, Malaysia, Burma and Vietnam), Taiwan and northern Australia. One person died from severe dengue. The interesting fact is that there was not a single case of Ebola virus, although this is a highly publicized and lethal illness in Africa. The majority of travelers sustained malaria and typhoid.

The tropical diseases were either due to viral illnesses, bacterial infections or protozoan infections.

Frequent viral illnesses encountered by visitors to Asia were dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS); avian influenza, Lassa fever as well as other tropical hemorrhagic fevers, Japanese encephalitis including other tropical encephalitis cases, Rift Valley fever and yellow fever.

This is a list of the bacterial infections that were reported: Anthrax, Carrion’s disease (=Bartonella bacilliformis), epidemic typhus, leptospirosis, melioidosis, murine typhus, paratyphoid fever, plague, relapsing fever, scrub typhus, spotted fever group rickettsioses and typhoid fever.

An interesting side-note is that even in familiar places like Hawaii leptospirosis is re-emerging as this link shows. So, it is important for visitors to Kauai and the Big Island of Hawaii (Waipio valley) to refrain from swimming in streams or natural ponds and to not expose your face to cascading waterfalls as leptospirosis can enter through the eyes, the nose, the mouth and scratches on the skin.

Finally, the following protozoan infections were found frequently: East African sleeping sickness, falciparum malaria and Plasmodium knowlesi malaria.

Staying Healthy During Exotic Travel

Staying Healthy During Exotic Travel

Each travel region has its special infection characteristics. With travel to Central America infectious diseases ranked in decreasing frequency like this: typhoid fever, leptospirosis, falciparum malaria and paratyphoid fever. In the Caribbean falciparum malaria was followed by typhoid fever, leptospirosis and paratyphoid fever. In South America the highest on the list was again falciparum malaria, followed by typhoid fever, paratyphoid fever and leptospirosis. In Sub Saharan Africa the highest number of falciparum malaria cases were registered (2633 of them), followed by 42 cases of typhoid fever, paratyphoid fever and leptospirosis. In the Middle East only one case of falciparum malaria, one case of typhoid fever and 2 cases of paratyphoid fever were reported. In contrast there were many more infections reported in South Central Asia (India): 286 cases of typhoid fever, followed by parathyroid fever, falciparum malaria and leptospirosis. All of the cases of typhoid fever and parathyroid fever in India were adequately treated with antibiotics and no deaths resulted from that. This is an example where no vaccine is available for prevention, but swift medical treatment could help immediately when an infection had occurred.

In South East Asia (Malaysia, Philippines, Indonesia) leptospirosis was on top, followed by typhoid fever, falciparum malaria and parathyroid fever. North East Asia (Korea, Mongolia), had only 3 cases of typhoid fever and 1 case of paratyphoid fever. Oceania (Polynesia) reported 26 cases of falciparum malaria, followed by paratyphoid fever and typhoid fever.

Several interesting observations were made with regard to this study.

  1. Most patients with travel acquired tropical illnesses presented within less than 17 days at the doctor’s office at home and 91% of them had developed a fever.
  2. The spectrum of the tropical disease that was diagnosed and treated varied according to the geographic destination where the traveler had been, which is consistent with the observations mentioned above (different distribution of tropical diseases depending on which area was traveled). Visitors to West Africa had a high rate of falciparum malaria, visitors to India sustained largely enteric fevers; and leptospirosis,  scrub typhus and murine typhus were the dominant tropical diseases for visitors to South East Asia.
  3. Males were found to be less diligent in using chemoprophylaxis for malaria prior to their travel than females. Overall only a minority had attended a travel clinic prior to their travel for immunizations and chemoprophylaxis for preventable tropical disease such as malaria.
  4. Other global life-threatening diseases like meningitis, other forms of septicemia, severe bacterial pneumonia and legionnaires also have to be considered as they occurred in roughly 30% of returning travelers.
  5. Malaria was the largest percentage of the tropical diseases that travelers brought home and 67% of all cases were male patients. They were mostly visiting West Africa where they acquired malaria (typically from Nigeria,  Ghana and the Ivory Coast). As mentioned they accounted for 10 of the 13 deaths.

The authors recommend that travelers should prepare themselves for trips to the tropics and subtropics, preferable visiting one of the travelers’ clinics. The recommended procedures should be followed meticulously. Not all of the diseases can be prevented, but if the traveler turns sick, they should seek medical advice as soon as possible in the country where they travel as these physicians often have special expertise in these tropical diseases.

One of the comments of the study was that often people visit relatives and friends in an area where tropical disease exists without any chemoprophylaxis or vaccinations beforehand. The visitors were under the impression that prior living in the area as a child would still protect them now during the travel as an adult, which is not the case. This can be prevented by visiting a travel clinic well before the planned trip, so there is enough time for vaccinations and possible blood tests.  

More information on:

1. Traveler’s diarrhea:  http://nethealthbook.com/infectious-disease/parasites/travelers-diarrhea/

2. Parasites: http://nethealthbook.com/infectious-disease/parasites/