Colds and Flu: Variations on a Theme

    You wake up one morning with a scratchy tickle at the back of your throat. It’s nothing, you think, but by the evening you’re worried. What are you coming down with now? In all likelihood, it’s just a cold. The sore throat will persist for a few days, along with a runny nose and stuffy head. You may develop a cough. About a week after the scratchy throat began you begin to forget about the cold and by ten days it is a memory. Your body has met a small bit of protein-coated RNA called a virus, and defeated it. 

The difference between a cold symptoms and flu symptoms

    The next month another bit of protein-coated RNA called an orthomyxovirus finds its way into your nose. This time the story is very different. At noon, you are feeling well. By 4PM you have been felled. Getting up from your desk feels like climbing Mount Everest. You cannot get warm – even under a pile of blankets. Then come the muscle aches, as if you’d run a marathon. This time there is no hope of sticking to a routine – you have the flu. The worst of the symptoms fade after a week, but fatigue and lack of energy may persist for several more. Rest, time and patience eventually lead you back to health. Next year, you think, you will get that flu shot. 

The viruses that cause the problems

    The viruses that caused these two illnesses are superficially similar. They are little protein bags full of bits of RNA– technically not living things, but able to commandeer the machinery of living cells to reproduce themselves. Carried in droplets spewed into the air by coughs and sneezes of infected people, they are directly inhaled or carried into the nose and mouth on fingers from surfaces where those droplets landed. Specialized proteins on viral surfaces attach them to the cells in the upper airways. These proteins (H, or hemagglutinin and N, or neuraminidase) and their numbered subtypes (1, 2, or3) give flu viruses their unimaginative names. Swine flu virus becomes H1N1.   

    For reasons not yet understood, the body’s response to the attack of cold viruses is not as severe as it is to flu viruses. Once inside cells, flu viruses elicit a flood of proteins called interferons, which are the source of fever, muscle aches and profound fatigue. The viruses rapidly go about the business of making more of themselves, sending them out to infect more cells and generating a new wave of symptoms. In the meantime, white blood cells begin to produce antibodies that target viral surface proteins and prevent them from locking onto more cells. Eventually the tide of the battle turns and no more cells are infected. The rest of the illness -the recovery phase – involves cleanup of the remnants of the fight. 

Why flu shots don’t always work
    Flu shots use mixes of several different flu virus types to stimulate the body to make antibodies to those viral surface proteins in advance of “catching” the flu. If and when the virus invades, the antibodies are in place, ready to block the initial attachment to cells in the upper airways. Because the flu viruses that travel the world vary over time, each year’s flu vaccine is a composite of some of the currently circulating strains and may or may not be a good match to the virus that ultimately shows up.  

    Immunization is recommended for children (older than 6 months), the elderly, people in the health and teaching professions, those living in nursing homes and dormitories, and for all age groups who are at risk for flu complications, namely those with other respiratory problems, cardiac disease, diabetes and immune system impairments (including those induced by treatment of other diseases like cancer). Most adults in good health have the immune wherewithal to recover from flu and colds without complications or medical intervention. 

Complications of the flu

    The complications of the flu and of colds are similar. Both infections affect the upper airways, causing swelling and inflammation of the linings of the nose, throat and sinuses and blocking narrow passageways within. Earaches and pain in the forehead or the face develop but often resolve with simple measures like propping head up while sleeping, and taking an anti-inflammatory medication like aspirin or Advil. Unremitting pain, with or without fever, may indicate secondary bacterial infection of the ears or sinuses – the only reason for the prescription of an antibiotic during a cold. 

    Pneumonia is the most serious flu complication. Pneumonia means that the lungs’ spongy structures where carbon dioxide is exchanged for oxygen are swollen and filled with inflammatory debris. Reappearance of fever and fatigue after the flu has begun to improve may be the first sign of pneumonia. Other symptoms are chills, chest pain, shortness of breath, and dry or productive cough. Sometimes the pneumonia is caused by bacteria, but more often by the original virus or another. Pneumonia caused by bacteria, at least outside hospitals, is much less common. Prompt medical attention is in order because oxygen levels may be low. Medical attention should also be sought for other delayed symptoms like change in mental status, particularly in babies and the elderly. Occasionally diarrhea and vomiting are part of the flu and may produce dehydration.       

Why hydration is important

     Dehydration is also a result of fever, the metabolic equivalent of exercising in a warm environment. Dehydration stresses already inflamed airways. The easiest way to keep track of hydration status is to look at your urine – the darker the color, the drier you are. Aim for almost clear urine by drinking plenty of water.  

Managing fever

    Fever, while distressing, is part of the body’s defense against cold and flu viruses, which thrive in the relatively cooler temperatures of the upper airways. Some of the fever related discomfort can be relieved with a bath. Aspirin is not to be used in children with the flu because of a rare complication called Reyes syndrome, a liver failure. Tylenol is safe for them.

  What about anti-viral drugs for the flu

     Antiviral drugs (Tamiflu, Relenza. Symmetrel, and Flumadine) drugs are only effective if begun in the first 24-36 hours after symptoms begin. They lessen the duration of symptoms by about a day. Widespread use will produce increasing numbers of drug resistant strains of viruses.  

    New flu viruses appear regularly and prompt anxious comparisons to devastating epidemics of the past. Worrying about them doesn’t help. Taking care of what you can do for yourself and your contacts (see below) is your best option. 
                                                                      Useful actions to prevent colds and flu

  • Maintain good health habits throughout the year: adequate sleep and exercise, nutritious diet, no smoking, modest alcohol use.
  • Cover your nose and mouth with a disposable tissue when you cough or sneeze, with the crook of your elbow in the absence of a tissue.
  • Wash your hands with soap and water or an alcohol based cleanser after coughing or sneezing, before eating, and after being out in public.
  • Keep your hands away from your eyes, nose and mouth.
  • During flu outbreaks avoid crowded, closed environments when possible and wash hands when you come home.
  • Remember that your flu is infectious for up to 7 days and try to avoid infecting others.
  • Get a flu shot if you are in a high risk group.

Sickle Cell Anemia: Side Effect of the Battle with Malaria

One of the milestones in the history of molecular biology and genetic diseases occurred in 1949, when Lines Pauling ( 1901-1994; 1953 Nobel Prize in Chemistry) discovered that  sickle cell anemia, an inherited blood disorder,  was caused by a single change in the structure of a single protein in hemoglobin, the complex molecule which carries oxygen in everyone’s red blood cells. For the first time, a hereditary disease was shown to be the result of a miniscule change in DNA that leads cells to make slightly different proteins. In sickle cell anemia, the tiny substitution in the hemoglobin protein changes the way the molecule shapes itself three-dimensionally and this change causes all of the misery and illness associated with sickle cell anemia (also known as sickle cell disease).

Hemoglobin fails to stack and fold itself normally

Hemoglobin molecules carry oxygen from the lungs to the rest of the body, and pick up carbon dioxide to be expelled on the next pass through the lungs. Hemoglobin molecules are stacked neatly inside red blood cells which, under a microscope, look like plump, oval discs, flattened in their mid-sections. To hold and release oxygen and carbon dioxide, the hemoglobin molecules change their shapes, folding and unfolding in response to changes in the acidity of the blood. In sickle cell disease, hemoglobin does not stack neatly or fold correctly, and it distorts the shape of the red blood cells, damaging their membranes. Instead of flattened ovals, red blood cells containing sickle cell hemoglobin assume odd and spiky shapes which are reminiscent of sickles.

Abnormally shaped red  blood cells cause trouble

Distorted, sickled red blood cells are shorter-lived than normal red blood cells, causing anemia , or low red blood cell counts, with symptoms of fatigue, weakness and shortness of breath. The abnormally shaped cells also get stuck in small blood vessels of many organs, causing pain and organ damage, and symptoms like strokes, abdominal pain, joint pain and swelling. Episodes of pain and other symptoms are called sickle cell crises, last for about a week, and often require hospitalization and narcotics. The spleen can become severely damaged and non-functional in patients with sickle cell disease. The spleen is an important part of the immune system and, without it, sickle cell patients can be subject to life threatening infections. They require prophylactic antibiotics and careful attention to immunizations. Sickle cell crises are triggered by stress, dehydration, infections and illness and the damage they cause can shorten life. Modern diagnosis and treatment have raised life expectancy of sickle cell patients to over age fifty, an improvement of almost a decade compared to the past.  Some babies with sickle cell disease have been successfully treated with bone marrow transplants.

A  common genetic trait

In certain parts of the world, 10-40% of the population carry one copy of the mutated gene that codes for the abnormal hemoglobin of sickle cell anemia. Those carriers are said to have sickle cell trait, and they do not suffer from sickle cell disease, which appears only if two copies of the gene are present. But since children get half their genes from each parent, if two carriers of the sickle cell trait get together and have children, the odds are that 25% of their children will be born with two copies of the gene and have sickle cell disease, 25% will have normal hemoglobin, and fifty percent will carry a single copy of the gene, without symptoms.  These are the same odds that are associated with other recessive traits, such as blue eyes or red hair, that require two copies of a given gene for expression of the trait carried by the gene.

The trait has an upside – in malaria infections

Why would a genetic trait be so common when it can lead to a disease that causes illness and premature death? The geography associated with sickle cell trait provides one answer.  Sickle cell trait is common in groups of people who come from the belt of the earth around the equator where malaria is or was at one time endemic:  sub-Saharan Africa, India, the Mediterranean and Arabian Gulf countries, and Central and South America. What is the relationship between malaria and sickle cell trait? The malaria parasite lives in red blood cells, which are full of hemoglobin. The parasite feeds on hemoglobin as a necessary part of its lifecycle. But something about the hemoglobin produced by the abnormal gene makes carriers of the sickle cell trait less likely to succumb to malaria in infancy and less subject to severe malarial symptoms at older ages. The sickle cell trait thus confers a survival advantage on people from malarial regions of the earth, and it has persisted in the population despite the disadvantage it produces when a child inherits two copies of the sickle cell gene.  Paradoxically, two copies of the gene do not protect against malarial symptoms because the infection triggers sickle cell crises.

Sickle cell disease affects as many as one in 400-500 of African Americans in the United States, and about 1 in 36,000 Hispanic Americans.  About 90,000-100,000 people in the US have the disease.  The sickle cell trait is present in one out of every 12 African Americans and one of every 100 Hispanic Americans.  In France sickle cell disease is now the leading genetic disease because of emigration from Africa and the Caribbean. Over a long period of time, as these populations live and reproduce in regions where malaria is not a significant threat, the trait may disappear since it will no longer be conferring a survival advantage.  In the meantime, researchers hope to better understand how sickle cell hemoglobin tames the malaria parasite and to use the knowledge in the battle against this ancient disease.

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