Fighting Tuberculosis in the Wilderness

             If South Africa has a soul, it was surely in the room with the members of the Western Cape, South African National Tuberculosis Association - SANTA - at the Wilderness Hotel as they opened their annual general meeting by spontaneously singing hymn after hymn of joy, praise, and glory to God. Coming together from both the high and low veld of Western Cape, the volunteers of SANTA are dedicated to their work of helping individuals, families and communities overcome the persistent danger of a TB epidemic that continues to threaten the people of South Africa, neighboring countries, and the world. Although South Africa now has the highest rate of active TB in Africa and one of the higher rates of multi-drug resistant TB in the world, this worldwide pandemic is  currently spreading fastest in the nations of the former Soviet Union where disease control measures are underfunded and less focused.    

            The Western Cape TB association invited several speakers to address their annual meeting including senior HIV/TB doctors, researchers and representatives of the South African Ministry of Health. They asked me to talk about selenium. It was quite a journey from Johannesburg to Wilderness, over 1200 kilometers. After driving to Bloemfontein for an evening stopover, and then through the great Karoo semidesert, we passed through Oudtshoorn, the ostrich capital of South Africa at the edge of the highveld. From there we descended through one of the undiscovered natural wonders of South Africa, a narrow canyon cut through red rock by a gushing stream, with rust colored canyon walls rising two to three hundred meters straight up on either side. After a few kilometers driving through this amazing geological feature, the N-12 emerged into an expansive mountain valley, the highway winding steeply down, seemingly forever, to the coastal town of George. The incredible vistas reminded me of descending from the Alps on my first visit to Switzerland as a teenager. 

            After so many hours on the road, my driver and I finally arrived at the affordable guest house situated high on the hill above Wilderness. Looking down from our elevated viewpoint I observed a pristine strand of white sand stretching six kilometers along the Indian Ocean with line after line of waves rolling in to gently break on the shore. I momentarily dreamed how wonderful it would be to surf those gorgeous, continuous waves. That was until I heard there were treacherous crosscurrents prevailing along this stretch of coast. Beside the mammalian porpoises and whales plying the waters, the pentacle of the marine food chain, the Great White Shark, also trolls these chilly seas. It was much safer at a surf-spot breaking at a small bay near George, a dozen kilometers south. I am old now but can still dream of my hay-day as a beachboy.     

Breaking the trance, one might say tuberculosis is indeed the great white shark of diseases, forever trolling the planet. TB has been in humans for between ten and thirty thousand years. Over the last ten millennia it is estimated that one out of every seven people who have lived on Earth has died as a result of TB. In the 19^th and early 20th centuries tuberculosis raged out of control. Until German scientist Robert Kock discovered in 1882 that TB is caused by small bacteria - a mycobacterium – doctors thought “bad air” caused this contagious lung disease. The discovery of “germs” by Robert Kock and the French scientist Louis Pasteur in the 1880s caused a revolution in medical science. The Germ Theory of Disease opened the door to the eventual discovery of antibiotics, and later anti-viral medicines that keep people healthy and alive today.   

            According to the World Health Organization (WHO) in their Global TB Report 2018, approximately 1.7 billion people, or 23% of the world’s population is infected with TB. Like HIV, TB is not evenly distributed around the globe. Suppressed by the immune system, tuberculosis remains latent in most who are infected. The vast majority of those living with TB bacteria in their lungs will never experience active disease. However various factors contribute to the development of active TB, including any other disease that puts stress on, or depresses the immune system. According to the WHO report, the five major factors that cause latent TB to activate include malnutrition, HIV, diabetes, smoking and alcohol abuse. Occupational hazards, such as working in the mining industry, can contribute. Overcrowded conditions in prisons and dusty, smoky, overcrowded townships or slums also affect TB rates.         

Today more than ten million people worldwide experience active TB each year. The good news is that over 80% of cases are cured with drug treatment – 82% in South Africa. Unfortunately, in some cases the tuberculosis bacillus has developed resistance to drugs that have been used to treat it for the last seventy years. Multi-drug resistant TB (MDR-TB) is much harder to treat, but still, the cure rate is between 55% and 75%. That leaves 1.6 million deaths worldwide from TB each year, making TB the tenth leading cause of death in the world. Approximately 19% of all those that die of TB are HIV positive. With death rates from HIV falling due to the advent of anti-retroviral therapy (ART), the annual global death toll from tuberculosis surpassed that from HIV a few years ago.

In 1993 the World Health Organization announced the fight against tuberculosis is a “global emergency”. Through an intensive international effort, today active TB rates worldwide are gradually falling at the rate of 2% per annum. Because of the recent widespread adoption of ART therapy for those with HIV, TB rates in Eastern and Southern Africa are falling much faster than that, decreasing in the range of 5% to 8% per year. Eswatini (Swaziland) had done the best job in the region because over 90% of it’s HIV patients now receive ARVs. Following in the wake of the surge of HIV disease in Southern Africa in the 1990s and 2000s, a tsunami of TB slammed across the region in the early 2000s. TB contributed to almost 50% of the HIV deaths in Southern Africa. Only the efforts of various ministries of health, in concert with the Global Fund for HIV, TB and Malaria have been able to beat back this wave of disease. Together they have made huge progress. However, compared to the tremendous success in Eswatini, other countries are trying to catch up. In the next decade Lesotho and South Africa face the greatest challenge.       

As one reviews the myriad charts and statistics included in the 270 pages of the WHO Global TB Report 2018 and reads chapter after chapter describing how the world should tackle this disease following the UN’s plans for monitoring, preventing and funding the necessary tasks that go into gaining the upper hand against such a massive global health problem; one should take a step back to gain greater perspective. That includes understanding the relevant biology, microbiology and immunology of how immune suppression caused by HIV interacts with tuberculosis opportunistic infection.      

In HIV disease, CD4 white blood cells, the generals of the immune system army, decline causing immune deficiency. Different opportunistic infections appear at different levels of immune suppression. Active TB usually occurs after CD4 counts fall below 150. Scientists have determined that a person is thirteen times more likely to have active TB if their CD4 count is below 135 than if it is above that level. While those with HIV are sometimes given the drug co-trimoxizole to help prevent TB when their CD4 count is low, most do not receive this prophylactic treatment.

Not surprisingly, another mycobacterium, the pneumonia bacteria that latently exists in most people’s lungs is also one of the top three co-factors causing death in HIV disease. What do TB and pneumonia mycobacteria cells have in common with the HIV virus? What do all three have in common with the cells of the human body they infect? What is their common denominator?

Every cell in the human body contains selenium. Cells require selenium for their structural integrity because selenium molecules help hold them together like nails hold a wooden house together. However, selenium is also the keystone element for both the immune system and the antioxidant system that helps keep cells healthy. Surprisingly, in the past few years scientists have discovered that there are more bacterial cells in the human body than there are human cells expressing human DNA. Most bacteria in humans are harmless. Many play an important role in health, including the “flora” that inhabit the gut and help break down food particles so they can be absorbed by the intestines. Other helpful bacteria inhabit the skin, the body’s largest organ. These friendly bacteria help the body’s skin prevent other, more harmful bacteria from colonizing it. However, just like every human cell, every bacterial cell also needs the protective influence of selenium molecules. Many, probably most viruses need selenium too. Where do bacteria and viruses acquire the selenium they require? They take it from the human organs and cells they infect. Bacterial cells infect organs and tissues and compete with the body for its selenium resources. Viruses infect cells and likewise attack cellular selenium supplies.

When the influenza-A virus infects the lungs, within three days the level of selenium in the cells lining the lungs falls by 40%. That makes those cells sick. It makes the lungs sick and more vulnerable. And that makes the person sick. When Ebola infects people, it depletes selenium from the body extremely rapidly. The circulatory and immune systems jam up and 90% of those infected die, usually in about two weeks. Various hepatitis viruses infect the liver – and no wonder. The liver is the most concentrated large source of selenium in the body – a great place for viruses to mine selenium. Of course the slow acting HIV virus also genetically encodes selenium. It needs selenium to form its protective envelop coat.  As a lentivirus or “slow virus”, HIV slowly drains selenium from the body and CD4 counts gradually fall. Not surprisingly, like all cells of the body, both tuberculosis and pneumonia mycobacterial cells need selenium to survive and reproduce. Like HIV, Ebola and various hepatitis viruses; TB and pneumonia also invade the body in search of the essential trace element they need to survive and replicate. That is what Nature is all about – survival. Survival of those that can acquire the vital selenium resources that are needed for life and quasi-life forms, like viruses, to exist.     

            As one selenium expert explained: if a person has enough selenium in the body, they will be healthy. If not, they will tend not to be healthy. Unfortunately, half the people across Southern Africa are nutritionally deficient in selenium due to the low levels of selenium in the soil their food is grown in.

            It is well established that selenium supplements increase CD4 count. That means that for HIV patients whose CD4 counts are below 600, in most cases their CD4 count will increase by approximately 200 points if they use the correct dose of selenium – between 200 and 600 micrograms (mcg) per day. Depending on the level of immune depression, HIV patients should consider using 600mcg when the CD4 count is below 100; 400mcg when the CD4 count is between 100 and 400, and at least 200mcg when the CD4 count is above 400. This is not a substitute for ARV treatment. Instead it is the icing on the cake of ARV therapy.  

            In the Western Cape when I heard about the treacherous currents hidden below the idyllic waves off Wilderness beach, it reminded me of the time I almost drowned while bodysurfing in Southern California. I was riding the waves in a small cove where I frequently bodysurfed. Due to a storm system offshore, that day the waves were especially large, causing an unseen rip tide. As I struggled to swim back to shore the enraged, hungry waves twice took me under. Gasping for air and unable to fight them any longer, I yelled out for the lifeguard to save me. That strong swimmer came to my rescue and pulled me to safety where I collapsed exhausted on the beach, slowly regaining my breath.

            That thought reminded me of my grandmother. I never met my grandmother because she died of TB in 1947, just a year before the cure for TB was discovered - four years before I was born. My mother told me about her mother. She had TB – which drained selenium from her body and lungs. Then she caught influenza. That also drained selenium from her lungs. Influenza on top of tuberculosis, both weakened her lungs’ immune defenses and allowed the suppressed, latent mycobacteria lurking in her lungs to multiply and present as frank pneumonia. Shortly after developing pneumonia she passed away. My grandmother suffered three waves of disease. All three attacked her selenium supply and thus the integrity of her immune system – especially in the lungs. After three successive waves of selenium depletion, she was gone.

            If there was a killer disease that drained the human body of water, governments would snap into action and supply water to all the sick people who needed it. Most people and governments understand water. Selenium is just as essential to life as water. But selenium is a mere trace mineral. Although it is absolutely essential to life, it exists in minute quantities, invisible to the eye. Unfortunately, most people, governments and even physicians do not understand selenium. That is a deadly shame. That failure of governments and even the WHO to appreciate the central role selenium plays in immune health and disease pathogenesis results in thousands, indeed hundreds of thousands of people with HIV and TB dying much sooner than they would if health authorities understood and applied proven selenium science to help patients stay healthy. This hard science exists. But there seems to be no one willing to translate arcane science into action. That is why I call on governments not to ignore science, but rather to embrace it for the benefit of the people they claim to serve - their citizens.

            This basic science has been published in medical journals, but more needs to be done. The research that scientists and governments need to conduct include testing to see if selenium can help prevent latent TB from becoming active TB. Since selenium supplements significantly increase CD4 count, it certainly should. Shockingly, this has never been adequately tested in a clinical trial to confirm this expected medical benefit. Secondly, the standard course of TB treatment takes six, frequently unpleasant months to complete. Could adding selenium to the current drug combination used to treat TB shorten the period to cure active TB to four months or even three months; or perhaps reduce drug side-effects? It might. This should be examined in a properly constituted clinical trial. Finally, multidrug resistant TB is very difficult to treat with many people dying from it. Could using high-dose selenium in addition to current MDR-TB medications improve survival rates? Only a well-designed, controlled clinical trial can provide the answer. All three of these studies are begging to be conducted. How long will governments and research universities procrastinate before they answer these important scientific questions?  

            When the Liberian Ministry of Health tested high-dose selenium in Ebola patients during the 2014 epidemic in West Africa it cut the mortality rate by about 43%. If selenium can accomplish that against Ebola, what might it achieve against tuberculosis? Why has it not been tested yet? How long must we wait? 

But will governments who do not even inform HIV patients about the dramatic, proven benefits of adding selenium to ARVs in fighting HIV disease conduct this research? Probably not. Inaction is always easier than action. No one asks questions if governments do nothing about a situation people are not even aware of. But the cost of inertia and inaction is great. Too many people die. Too many families lose loved ones. Too many communities unnecessarily lose productive citizens to these two pandemics. Where are the experts that should be drawing attention to this yawning gap in research?

And where is the soul of Southern Africa? It is singing hymns of praise and glory to God in the Wilderness. Meanwhile the brain of Southern Africa should be conducting medical research. That could save innumerable lives and billions of rand of taxpayer’s money by confirming more effective, cost-efficient ways to improve the health of all people in Southern Africa and help bring these two epidemics to an end – sooner rather than later. I pray that enlightened people will help make that happen. At least I can dream.