Posts Tagged ‘infectious disease’

There's Silver in Them There Pills

Wednesday, December 25th, 2013

Like most medically-trained people (and hopefully many of the rest of us), I've been highly concerned about the rise of drug-resistant microorganisms, bacteria that can't be treated with our standard antibiotics. A recent article in The Wall Street Journal with the intriguing title "Antibiotics of the Future" offered considerable hope, but let look at some background on the subject first.

The WSJ article said that two million patients each year in the United States develop infections that doctors can't combat with our normal antibiotics; earlier in the year, the CDC in a report titled "Antibiotic Resistance Threats in the United States 2013" estimated that at least 23,000 of them die. They divide the microorganisms, all bacteria except for Candida (a fungus), into three groups: those whose threat levels are considered urgent, serious or concerning. The three in the urgent category include Clostridium difficile, which causes severe, life-threatening diarrhea, often in patients who have been hospitalized and are already on antibiotics, and leads to a quarter-million infections, 14,000 deaths and a billion dollars in medical expenses yearly. Then there are the carbapenem-resistant Enterobacteriaceae,  abbreviated as CRE (the carbapenems are powerful antibiotics considered the "drugs of last resort," used when all other old and modern antimicrobials fail or are thought to be likely to fail; Eneterobacteriaceae are bacteria that are part of the normal gut flora.)

CRE infections most often happen in patients getting treatment for other serious conditions. They may be on a respirator, have a long-term catheter in their bladder or have been on other antibiotics. One estimate says there are 9,000 CRE infections a year and they cause at least 600 deaths. Patients in intensive care units not infrequently have IV catheters placed in large veins in the neck, chest or groin to allow hospital personnel to give medications and draw blood sample for a prolonged period of time. If these get infected they can cause a bloodstream infection (sepsis is the medical term). About half of all hospital patients who get CRE that goes on to cause a bloodstream infection die.

The third infectious urgent threat level is the bacteria, Neisseria gonorrhoeae, that causes the STD gonorrhea. The CDC estimates more than 800,000 cases occur yearly in the United States and 30% of these are resistant to some antibiotic, but almost all can be treated, at this time, with a two-drug cocktail. Gonorrhea causes severe reproductive system complications and the CDC says it "disproportionally affects sexual, racial and ethnic minorities."

Then there is MRSA, methicillin-resistant Staphylococcus aureus. This bug is classified as serious, not urgent, yet there are roughly 80,000 severe MRSA cases a year and over 11,000 of these patients die. Most major MRSA cases are seen in healthcare setting among patients with weakened immune systems (e.g., those on hemodialysis or receiving cancer therapy) but less serious MRSA  can case problems in otherwise healthy people, including athletes who share towels or razors, children in day-care and members of the military in cramped quarters. Some of these infections, usually of the skin, can become severe and life-threatening.

The CDC piece, except for Candida, excludes non-bacterial diseases, but I received a reader comment a while back from a person whose website ( has a post on Deadly Viruses.  Like parasitic diseases, e.g., malaria, viruses through the ages have killed simply enormous numbers of people. Now we're facing a future when bacterial illnesses could overtake their status as the prime infectious threats to mankind.

An article in the December 23, 2013 online version of the New York Times described an increased death rate among dolphins, with many dying of viral disease. A number of them also showed evidence of antibiotic resistant bacteria, presumably from environmental contamination. Dolphins have been termed the modern equivalent of the canary in the coal mine, a biological early warning system analogous to the times when miners used to carry caged canaries while at work; if there was any methane or carbon monoxide in the mine, the canary would die before the levels of the gas reached those hazardous to humans.

The New England Journal of Medicine in January, 2013published an article titled "The Future of Antibiotics and Resistance." The lead author, Dr. Brad Spelberg, works where I did my research fellowship. He and two colleagues mention that antibiotic-resistant bacteria are considered, in a major yearly publication by the World Economic Forum  (WEF), to be a leading risk to human health.

The World Economic Forum's (WEF) 2013 publication on Global Risks analyzed fifty possibilities (e.g., economic disparity, religious fanaticism, rising greenhouse gas emissions, terrorism, water supply crises), examining their likelihood over the next decade, the impact if they actually happen and how interconnected they were to each other.  It used those to generate analyses of three major risk cases: one was on the threats to economic/environmental systems, a second on so-called 'digital wildfires" from misinformation, and  The Dangers of Hubris on Human Health, devoted to antibiotic-resistant bacteria.

In a study done in Europe, 50% of French patients experiencing a flu-like syndrome (FLS) expected their physician to prescribe an antibiotic; FLS may be caused by influenza virus or other viruses and antibiotics are not of any use against these viral diseases. The WEF piece mentioned an article reporting 98% of Chinese children seen in a Beijing pediatric hospital for common colds were given antibiotics.

Huge quantities of antibiotics are being used for animals as well.  Animals being raised for their meat are often given antibiotics as growth promoters. A 1950 article in Science News announced results from Lederle Laboratories that lacing the hog feed with trace amounts of an antibiotic could increase the yield of meat by a half. Then in 1977 the FDA sent out a notice that it would withdraw approval of non-medical use of penicillin and tetracyclines, but no hearings on the subject followed that non-binding pronouncement.

A Federal District judge finally ordered those FDA hearings in 2012, but an article online less than two weeks ago said only suggestions to the animal-growing industry have resulted. In 2009, more than 3,000,000 kilograms of antibiotics were given to US patients; in 2010, 13,000,000 kilograms were used for animals.

Back to the Wall Street Journal article: it mentions four new approaches to treatment of these deadly bugs. The two I found most intriguing were research to befuddle the bacteria by working against the signaling chemicals they use to become infectious and using silver to increase the ease with which antibiotics enter the microbes.

There's a way to go before these concepts are translated into bedside medicine, but there is more than a glimmer of hope on the horizon.


Cholera: Part 1 background and history

Sunday, February 24th, 2013

An 1882 monument to victims of cholera

Cholera is an infectious illness, found only in humans, caused by a bacteria in contaminated water, leading to severe diarrhea and dehydration and capable of killing its victims in a matter of hours if untreated. When I read about the disease for the second time in decades (the first time was after a 21st-century epidemic in Haiti), I was amazed at how quickly a victim can lose 10% or more of their body weight in severe cases; e.g., eight quarts between my normal bedtime and when I usually wake up. Many people who ingest the bacteria don't develop any symptoms, but if they do and lack modern re-hydration therapy, their chance of dying is 40-60%.

In all likelihood it is an ancient disease with writings from the lifespan of Buddha  (563-583 BCE) and from the time of Hippocrates (460-377 BCE) revealing diseases that presumably were  cholera. It has, over the last several hundred years, been a major killer of mankind, causing millions of deaths in the 19th century.   Those numbers place it among the deadliest of infectious illnesses, in the company of smallpox, the Spanish flu, bubonic plague, AIDS and malaria.

A CBC News article online with the title "Cholera's Seven Pandemics," starts with a major outbreak in India near the Ganges River delta. Between 1817 and 1823 there were 10,000 deaths among the British soldiers stationed in that country, estimates of hundreds of thousands of fatal cases among native Indians and 100,000 dying in Java in the year 1820. The second pandemic began in 1829, again in India, and spread to Russia, Finland, Poland, England, Ireland, Canada, the U.S. and Latin America, before another outbreak in England and Wales that killed 52,000 over two years. The sixth pandemic killed more than 800,000 people in India alone and, over the next 24 years swept over parts of Europe, Russia, northern Africa and the Middle East.

The National Library of Medicine's website entry on cholera associates it with crowding, poor sanitation, famine and war. India has remained a source as the disease is endemic (ever present) there. People get cholera by eating or drinking either contaminated food or water; the medical term is the fecal-oral route.

In the summer of 1854 London was the epicenter of a deadly outbreak. Dr. John Snow, a famous British physician born March 15th, 1813, had been noted as a pioneer in anesthesiology, using chloroform to assist in Queen Victoria's delivery of her eighth child in 1853.

Then, as documented in the book, The Ghost Map by Steven Johnson, Snow turned his investigative talents and keen mind to cholera, becoming in the process the modern father of epidemiology.

London's population had grown immensely and its sewage system was antiquated. In addition to basements filled with excrement, cesspools and drainage into water sources were rampant. A major concept of disease causation was the miasma theory. The term means "bad air" and the assumption was illness was caused by the presence in the air of a miasma, a ill-smelling vapour containing suspended particles of decaying matter .

Snow, on the other hand, felt cholera was caused by something ingested, most likely by drinking water contaminated by waste products.

In a painstaking and extremely clever investigation, Snow had, in a prior cholera outbreak in 1849 which was responsible for a dozen deaths in flats in a slum area, shown that two separate  sets of milieu had markedly differing death rates. All environmental parameters were essentially identical in the two groups with one exception; where they obtained their water. The group who suffered a much higher rate of illness got theirs from a company whose river source was in the same area where many sewers emptied.

Vibrio cholerae, the cholera bacteria

Five years later a much larger cholera epidemic provided an opportunity to more closely examine the water sources of the victims. One particular pump, seemingly providing clear water, proved to be the culprit. The Broad Street pump's output was examined by a Snow's colleague, a skilled microscopist Dr. Arthur Hassall, and found to contain what Hassall believed to be decomposed organic matter with oval-shaped tiny life-forms felt to be feeding on that organic substance. Snow was not aware then of the 1854 work of an Italian scientist, Filippo Pacini, who had examined the intestines of patients dying from cholera in Florence and found a comma-shaped bacillus he termed a Vibrio.

The proponents of the miasma theory did not yield easily, but Snow's map of the location of deaths from cholera eventually let his hypothesis of a water-borne illness prevail.  Then an assistant curate (church figure in charge of a parish) named Henry Whitehead who had read Snow's papers on the epidemic eventually found the index (first) case, a baby Lewis. As a result, the Broad Street pump was excavated and a direct connection to a cesspool was found.

The juxtaposition of Snow's scientific data and Whitehead's work as a beloved neighborhood figure led to the local Vestry Committee's report endorsing the water-as-culprit theory.

The city subsequently launched a major project to carry waste and surface water away from Central London.





Five years later, he