Why Did Swine Flu Kill Healthy Adults?

One of the most intriguing questions about the swine flu epidemic last year was why most of the deaths occurred in healthy young adults. Why were the very young and the very old generally spared?

A recent paper in Nature Medicine provides a clue, according to a news article in Science magazine. The gist of it is that the immune system of most adults is not very effective against first exposure to the H1N1-type virus. Unable to kill the virus initially with just a normal first immune response, the immune system in some patients mounted an all-out “do or die” effort to kill the virus. The result was a severe inflammatory reaction in the lungs that ultimately killed the patient instead of the virus.

The theory of a hyperactive but ineffective immune system would explain why the very young and the very old were spared by swine flu. The very young do not have a fully developed immune system with which to mount even a normal immune response, much less an exaggerated one. And many older persons may have had at least some effective antibodies against H1N1 by virtue of having been exposed to the previous H1N1 strain that was around until the late 1950’s.

Vaginal Gel is Effective Against HIV

Finally, there’s an HIV prevention method that’s controlled by women. This is especially important for women who are not in a mutually monogamous relationship and who cannot convince their men to use a condom. (In Africa, over 60% of HIV-infected persons are women who contracted the disease via heterosexual sex.)

In a study published last week in Science, nearly 900 sexually active women in a high-risk area in South Africa were supplied with either a vaginal gel containing the antiviral drug tenofovir, or just the gel alone as a control, over a thirty-month period. Women who received the drug were 39% less likely to become infected with HIV, compared to women in the control group.

Why wasn’t the treatment 100% effective? Part of the reason may be that some study participants may not have used the gel properly and consistently. Among women who used the gel as advised (both before and after sex) more than 80% of the time, the reduction in HIV infections was 54%. When the gel was used less than half the time the reduction in infections was only 28%. No one should be surprised; after all condoms, too, only work if you use them!

AIDS researchers are cheering. Although prevention wasn’t perfect, they’ve proved that pre-exposure prophylaxis controlled by women is at least partially effective. The next step will be to find more potent drugs or a more effective delivery method – perhaps a vaginal ring that releases the drug over longer periods of time.

By the way, would you like to know how the researchers monitored compliance to the study protocol (participant’s actual use of the gels)? They counted the used gel applicators returned by the women in the study and compared that number to the 181,340 gel applicators they gave out. Obviously the researchers suspected in advance that compliance might be a problem. You have to admire the researchers’ advance planning and their willingness to do what was necessary to improve the validity of their results.

The Benefits of Human Breast Milk

Colonization of the human infants’ gastrointestinal tract by bacteria occurs only after birth. It is known that human breast milk encourages colonization of the newborn’s gut by beneficial bacteria and discourages colonization by harmful ones, but how exactly does it do that? An article in the Proceedings of the National Academy of Sciences provides a tantalizing glimpse into the likely mechanisms.

About 4-12% of the macronutrient composition of human milk consists of a structurally diverse group of complex sugars called oligosaccharides. These oligosaccharides are indigestible by the infant, and so for many years scientists thought they had no function. It turns out that they are digestible by a particular group of beneficial bacteria called bifidobacteria. The presence of these oligosaccharides in human milk gives the bifidobacteria a nutritional advantage over less desirable bacteria in the human infant’s gut. In other words, these oligosaccharides are produced in human milk specifically to provide nutrients to beneficial bacteria, rather than to nourish the infant.

Some of these oligosaccharides have another interesting property; they bind to certain harmful bacteria, thus preventing them from attaching to the epithelial cells lining the gut. Researchers think that these oligosaccharides may flush out harmful bacteria during that very vulnerable time in early life when the infant’s immune system has not yet developed fully.

Oral Immunotherapy for Food Allergies

Some people have food allergies so severe that even the slightest contact with the food can lead to a life-threatening allergic response. A rare but potentially fatal allergic response to peanuts, for example, is why most airlines no longer serve peanuts on their flights. Other sufferers are equally allergic to milk or to eggs, commonly used as ingredients in many food products and recipes. Is there anything that can be done for people with life-threatening food allergies aside from having them try to avoid the food?

Current research efforts are focused on oral immunotherapy (OIT). OIT consists of exposing the patient to miniscule quantities of the allergen in a supervised research setting (under close medical supervision), and then if an allergic reaction fails to occur or remains mild, slowly increasing the dose over days or months to “desensitize” the patient.

Researchers caution that the technique is not yet ready for widespread clinical use, however. The risk of an adverse reaction to the first dose is fairly high, and little is known about the safety of OIT when done at home under a variety of conditions. In addition, it is not known how long desensitization lasts if/when regular desensitizing dosing is ended. There is a danger that desensitized patients might develop a false sense of security once they become partially desensitized or quit their therapy altogether.

Nevertheless, OIT might become a useful therapy for severe food allergies in the future, once we better understand how to perform it safely. For sufferers of truly severe food allergies, the risks associated with desensitization would have to be balanced against the risk of accidental exposure to the allergen and perhaps even death.

Bacterial Resistance to Antibiotics

The prevailing thought has always been that bacterial resistance to antibiotics comes about by a process of natural selection. When antibiotics kill most but not all of a bacterial population, the bacteria that survive are those that were most resistant to the antibiotic. These resistant bacteria then flourish, passing their resistance genes on to other bacteria and outcompeting their more vulnerable kin. The more times an antibiotic is used, then, the more likely it becomes that the surviving bacteria will be resistant to it.

But now researchers have found another mechanism for bacterial resistance to antibiotics. It turns out that antibiotics induce the formation of toxic molecules within bacteria called reactive oxygen species, or free radicals, that help kill the bacteria. But if the concentration of antibiotic is below the threshold for killing the bacteria outright, the free radicals cause mutations in the bacteria, some of which by random chance may confer drug resistance. In other words, antibiotics speed up the process of bacterial evolution in the surviving bacteria.

The finding opens a new avenue for research – finding molecules that prevent this bacterial mutagenesis, thus perhaps delaying the development of antibiotic resistance.

H1N1 Flu Deaths Update

The Centers for Disease Control and Prevention estimated this week that between 7,000 and 14,000 people have died of swine flu in the U.S. through mid-November, out of the 34-67 million people who had the swine flu so far.

Deaths caused by the flu are notoriously hard to estimate because most people are not tested for the flu when they have it and because people may die of a combination of causes, including the flu. The usual estimate is that the regular seasonal flu causes about 30,000 deaths each flu season (the winter months), so these latest swine flu numbers aren’t too bad. In fact they’re well below the government’s estimate back in August of 30,000 to 90,000 deaths from swine flu this season.

The big question is what will happen in January/February – will swine flu reassert itself in a third wave, as happened in the pandemics of 1918 and 1957? Will the H1N1 virus change to become more lethal, or more resistant to the vaccine? If either of these things happens the situation could change quickly. Most people in the U.S. are not yet immune to the swine flu because they have not had it yet and they have not been vaccinated against it.

Apparently many people think the danger is passed. We’ll hope they’re right. But if you still haven’t gotten your swine flu shot, it’s not too late. The vaccine supply seems to be pretty good these days.

Prion-like Activity in Neurodegenerative Disorders

Could misfolded human proteins with prion-like activity contribute to the progression of certain chronic diseases such as Alzheimer’s, Parkinsons, and Huntington’s disease? A common feature of all three of these diseases is the presence of abnormal accumulations of certain misfolded proteins in or around nerve cells in the brain. Eventually these protein accumulations become so extensive that they choke off nerve cell function.

No one is saying that these diseases are infectious, like mad cow disease. But according to the latest thinking, once an endogenous protein "goes rogue" and misfolds, it might then cause nearby normal proteins to misfold as well. Once the process starts it could become self-propagating, from one region of the brain to the next.

The Spleen Stores Monocytes

Shortly after severe tissue damage such as that caused by a heart attack or an infection, the number of monocytes, the white blood cells that eventually mature into macrophages, increases dramatically in the blood. These new monocytes appear too quickly to have been newly produced from stem cells in bone marrow. So where do they come from?

Apparently they come from the spleen. The spleen stores up to ten times as many monocytes as there are in the bloodstream at any one time. When a tissue is injured the spleen releases its stored monocytes, which then migrate to the site of injury, develop into macrophages, and participate in the cleanup and repair process. It’s a pretty efficient use of resources, when you think about it - a virtual army of monocytes is kept on standby, ready to be deployed when needed.

Swine Flu Takes Hold in Argentina

Swine flu just won’t go away. A recent a sharp uptick in the number of deaths from swine flu in Argentina has moved that country into third place for the most swine flu deaths, after Mexico and the United states. And the timing couldn’t be worse; it’s winter in South America, the season when influenza viruses typically spread the easiest. Of special concern is that the death rate in Argentina (1.6%) is more than three times the world average.

We need to keep an eye on this pesky bug. Who knows what it could do in North America NEXT flu season? For the latest information on swine flu (also now called Pandemic H1N1), see the World Health Organization website.

The Pandemic of 2009

The World Health Organization has officially declared a pandemic as a result of the rapid worldwide spread of Influenza A (H1N1), formerly known as swine flu. But that does NOT mean that a lot of people will die. By definition, a pandemic is simply a widespread outbreak of a new human flu virus that spreads rapidly from human to human, causing human illness.

Some flu pandemics cause only mild symptoms and few deaths – others can be quite deadly. The best-known pandemics of the last century were the deadly Spanish flu of 1918 (20-40 million deaths), and the milder Asian flu of 1957 (1-4 million deaths) and Hong Kong flu of 1968 (also 1-4 million deaths). In contrast, the milder seasonal flu that many of us get nearly every year kills “only” about a quarter of a million people each year.

Pandemics are of concern to public health officials (and the public!) because the virus spreads so quickly and because the consequences of the spread cannot always be predicted in advance. Fortunately, it now appears that this pandemic will be no more deadly than the typical seasonal flu that many of us get nearly every year. Most people who become infected with Influenza A (H1N1) are recovering without the need for medical care. But it could have been otherwise, and that’s why health officials were so concerned at first and why they are still watching it closely.

The other flu we worry about is avian flu (see Human Biology 5th ed., pp. 540-541). Avian flu is VERY deadly in the few cases in which it has been caught from birds, but human-to-human transmission is still exceedingly rare.

What to Call Swine Flu

What should be the proper name for swine flu, now that we know that people are catching it from infected people, and not from swine? The World Health Organization has stopped calling it swine flu in favor of “influenza A (H1N1)”. But that name also applies to one of three strains of seasonal flu and to the deadly 1918-1919 Spanish flu (which didn’t even originate in Spain!) The U.S. Centers for Disease Control (CDC) calls it both “novel influenza A (H1N1)” and “H1N1 flu (swine flu)” on its website. Of course the Mexican government objects to calling it “Mexican flu”.

An article on what to call this virus appears this week in Science.

Swine flu

It first appeared in Mexico in March. Popularly called swine flu, the H1N1 virus turns out to have a strange mixture of viral genes; 48% of its genes are from swine flu viruses, 34% are from avian flu viruses, and 17% are from human flu viruses. A key feature of the H1N1 virus is that it can be transmitted from human to human. By yesterday, swine flu had infected nearly 2,400 people, mostly in Mexico and the United States, killing 44. Where it came from, how far it will spread, and whether it will cause a pandemic remain unanswered questions. The World Health Organization’s influenza pandemic alert is currently at phase 5, just below a phase 6 full-alert.

There have been plenty of reports in the popular press about swine flu, some true, some not. For example, initial reports of a very high death rate from swine flu had to be revised downward once it was determined that many of the deaths attributed to swine flu were not caused by H1N1. Still, a death rate of nearly 2 % in healthy adults is quite high for any flu virus. Two percent of the world’s population is how many million people???

For authoritative updates about swine flu, try the news section of a magazine such as Science (see this week’s report) or the website of the World Health Organization.

A Way to Cure HIV Infection?

Modern HIV treatment drugs suppress an active HIV infection well enough that an HIV-infected person can live a relatively normal life. But they don’t cure an HIV infection because some viruses lie dormant inside living cells, out of reach of suppressive drug therapy. For that reason, high-cost suppressive therapy needs to be continued throughout the life of the patient, just so the drug is present whenever viruses do come out of hiding. What is needed is a way to get rid of the latent viruses lying dormant inside cells, once and for all.

A new approach is anti-latent therapy – therapy designed to prevent dormant viruses from staying dormant and hidden. The idea is to force any remaining dormant viruses to become active again so that they can be targeted and killed by suppressive therapy. A combination of anti-latent therapy and suppressive therapy just might wipe out an HIV infection completely. At least, that’s the idea.

Measles is on the Rise

According to the Centers for Disease Control and Prevention (CDC), there were more cases of measles in the U.S. in the first 7 months of 2008 than at any comparable time in the past 12 years. There have also been measles outbreaks in Switzerland, Italy, Israel, and Britain in recent years. The most likely reason is that an increasing number of children have not been vaccinated against the disease because some parents believe that vaccinations cause autism. Health officials contend that there is no connection between vaccinations and autism, but many parents remain unconvinced.

Measles is highly contagious, so it is no surprise that it may be among the first vaccine-preventable diseases to reappear when vaccination rates decline. Fortunately, measles is not very virulent; most patients are treated at home and recover without any long-term consequences. But if the return of measles is an early indication of lower vaccination rates, it may only be a matter of time before other vaccine-preventable diseases return as well. And that has health officials worried.

How do you feel about childhood vaccinations?

Your Bacterial Friends

How many bacteria normally live on or in your body, and what are they doing there? The government wants to know, with the goal of better understanding their roles in health and disease. So last year NIH launched the Human Microbiome Project. The early results show that bacteria and other microbes colonizing human tissues outnumber the body’s cells by ten to one! Over 600 different bacteria have been identified in such places as the vagina, belly button, nose, mouth, and digestive tract, not to mention all over the skin. And would it surprise you to know that there are more bacteria in your belly button than between your toes? Different bacteria influence our ability to fight infections, digest nutrients, and produce vitamins, plus there may be many other functions that we don’t even know about yet.

See the brief news article on this subject in Science magazine (“Bacteria are Picky About Their Homes on Human Skin”, Science May 23, 2008, p. 1001.)

My Mother's Cells Within Me

Nearly all of us harbor cells that come from a close relative. The phenomenon, called microchimerism, occurs because the placenta is not a perfect barrier to formed cells - sometimes maternal cells make their way into the fetus, and vice versa. Apparently some of these cells live indefinitely in their new host, which is surprising since foreign cells are usually attacked and killed.

Scientists are still working out what the foreign cells may be doing in their host. In some cases they may differentiate into fully functional tissue cells in the host. For example, genetically female heart cells (presumably from the mother) have been found in males. In other cases these foreign cells may trigger immune disorders later in life, when the immune system of the host finally recognizes and attacks the foreign cells. Diseases that may have a microchimerism link include several autoimmune inflammatory diseases of connective tissue (scleroderma, lupus erythematosus, and rheumatoid arthritis), and perhaps even Type 1 diabetes, a disease characterized by poor regulation of blood sugar.

Reference: Nelson, J.Lee. Your Cells are My Cells. Scientific American Feb. 2008, pp. 72-79.

AIDS proteins

The AIDS virus can only make about 15 proteins on its own. In order to reproduce, it must rely on its ability to force its human host cell to make all of the other proteins it needs. And with the use of a new genetic screen, researchers at Harvard University have identified at least 273 of these human proteins. Knowing precisely which human proteins the virus needs may lead to techniques for growing the virus in the laboratory for research purposes, or ways to block one or more of these key proteins in humans without disrupting the human body very much.

Instructors who are especially interested in how viruses reproduce may wish to read the full research article (Science online January 10; "Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen") and comment on its findings in class. The article itself is too difficult for entry-level students.

The Immune System and Cancer

The July 2007 issue of Scientific American has an informative article on the role of the immune system in the development and spread of cancer. (A Malignant Flame. Scientific American July 2007, pp. 60-67). The article describes how our thinking has changed over the past decade or so.

It turns out that although the immune system sometimes helps to prevent the development and spread of cancer, at other times the immune system actually contributes to cancer development. This is particularly true of the non-specific immune defense mechanisms (they call it the “innate” immune system). The next generation of anti-cancer drugs may include some anti-inflammatory therapies, as well as traditional chemotherapies. Instructors with a special interest in cancer may wish to incorporate information in the article into their discussion of Chapter 18 – Cancer – in Human Biology, 5th ed.

The article points out that the immune system is also increasingly being implicated as a possible player in a whole host of chronic diseases, including heart disease, diabetes, Alzheimer’s disease, and schizophrenia and depression. More information is likely to be forthcoming on the role of the immune system in these diseases in the years to come.