Archive for the ‘infectious diseases’ Category

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

Tuberculosis Part one: How long has it plagued us?

Saturday, June 23rd, 2012

I was reading an article in The Wall Street Journal this morning about "Untreatable tuberculosis in India" and decided to explore the background data before writing about what we're facing now.

I have a personal acquaintance with TB; when I returned to Air Force Active Duty status in 1977, I got a TB skin test. Much to my surprise it was positive.

I'm glad my chest x-ray didn't look like this

My chest x-ray was normal; I had none of the symptoms of active TB: chronic cough with blood-tinged sputum, night sweats, fever and weight loss. So I didn't have active disease and could be treated with only one drug; the infectious disease specialist told me I would take a medicine called isoniazid (INH) for a year.

I found out that about a third of the entire world population has been infected with the human variant of TB, Mycobacterium tuberculosis. In the US, 5-10% of the population will have a positive skin test; in other parts of the world, especially in some Asian and African countries, up to 80% will test positive.

Around the world new TB infection are estimated to occur at the rate of one per second, nine million cases a year with 95% of those living in developing countries. The vast majority of those remain asymptomatic. Of those who have a normal immune system, roughly 5-10% will ever develop active disease. But if you have HIV you have at least a 30% chance of moving on to symptomatic disease & x-ray-positive TB; other studies place the risk even higher, at 10% per year.

Now that milk is pasteurized, most of us in the US don't have to worry about the bovine strain of TB. But that isn't true everywhere, so beware of drinking unpasteaurized milk when you travel abroad.

A detailed online history of TB from the New Jersey Medical School commented that 2-3 million people die of the infection every year; the vast majority of those lived in developing countries. The ancient Greeks called the disease phthisis. It's been with us for millennia; ~4,500-year-old spinal column bits and pieces from mummies in Egypt  were the earliest evidence of human infection that I had been familiar with, but I found an article that doubled that estimate. Bones from an ancient site off the coast of Israel, estimated to be 9,000 years old, not only had the characteristic signs of TB, but also had DNA and bacterial cell wall lipids that could be analyzed by modern techniques.

One of his ancestors had evidence of the earliest TB we're aware of

Researchers from England commented that the tuberculosis we see today came from a human strain of the bacteria, not from a bovine origin. They also said that the DNA was subtly different from that of TB organisms today and felt this meant there has been a very long linkage between this infection and people. But the very earliest animal to have clearcut evidence of TB was a long-horned 17,000-year-old bison with skeletal remains showing the disease.

TB outbreaks still occur in the US. The June 20, 2012 edition of JAMA has a CDC report of cases which occurred in a homeless shelter in Illinois. The majority of the 28 patents involved (82%) had a history of excess alcohol use  and many had longer stays in the men's section of the shelter and socialized in two bars in the area.

The risk factors seen in developing countries: lower socio-economic status and overcrowding, seem to me to have played a role in this US series of patients. Alcohol over-usage has been implicated as a risk factor for TB,  perhaps from repeated prolong close contacts in bars and perhaps from effects on the immune system.

I'll get back to the current issues with TB in my next post.




The 1918 flu virus and its descendants: Part 2 Rediscovering the culprit

Sunday, May 13th, 2012

many other major pandemics were associated with rodents, but not the 1918 flu

I re-read my last post a day after writing it and amended the first line, since I found it misleading. It was the worst flu pandemic ever, but I knew that smallpox, the Black Plague, AIDS, malaria and perhaps even typhus each have caused nearly as many or even more deaths over a period of years. I eventually found a rather strange, non-medical website with the "7 Worst Killer Plagues in history," and confirmed my belief that no other bacteria or virus had wreaked as much havoc in brief span of time as the 1918-1919 H1N1 influenza virus.

I wanted to find out what happened to that highly pathogenic organism and, after searching the web, realized the PBS article on the "Spanish flu" was a good place to start. It mentions that the influenza virus was not identified until 1933 and that the actual genetic identity of the particular strain involved in that pandemic (as opposed to the basic type...H1N1) was not identified for many years. The influenza virus responsible for the 1918-1919 pandemic has had many descendants, none as deadly as their ancestor.

In 1950, Johan V Hultin, a graduate student starting his doctoral studies in microbiology, got a clue from a visiting professor who suggested hunting for the virus in bodies buried 32 years prior in the permafrost of the Arctic. Hultin and his faculty advisor traveled to Alaska where flu among the Inuits had been especially deadly with 50 to 100% death rates in five villages.

early days in the Far North

Gold miners, under contract with the Territorial government, had served as grave diggers in 1918-1919 and tissue samples were recovered from four bodies exhumed in 1951. Pathology slides fit with viral lung damage and, in some cases, secondary bacterial pneumonia. But tissue cultures from the samples did not cause disease in ferrets and no influenza virus was recovered.

It wasn't until 1995 that science had advanced enough to for researchers to start the work necessary to identify the virus's unique features. Jeffrey Taubenberger, a molecular pathologist then working at the Armed Forces Institute of Pathology (AFIP), began a ten-plus-year-long project starting with autopsy tissues from the time of the pandemic that had been preserved in the National Tissue Repository. His project was stimulated by a paper published in the journal Science in February, 1995, in which preserved tissue samples from the famous British scientist John Dalton (often called the father of modern atomic theory) were examined. Dalton was color-blind and had donated his eyes at his death in 1844 to determine the cause of the defect; his DNA was studied 150 years later and the resultant publication gave Taubenberger the impetus to do the same with the flu virus.

Hultin read the first paper from Taubenberger's group, wrote to him and eventually went back to Alaska to exhume more flu victims. One was an obese woman whose lungs had the findings of acute viral infection. Samples of these permafrost-preserved tissue had RNA incredibly similar to those obtained from the AFIP National Tissue repository.

And so began an amazing chapter in the history of virology.

Rabies and pet care

Tuesday, April 17th, 2012

make sure your dog's rabies vaccination is up to date

We got an older dog, a thirty-pound Tibetan terrier, eight months ago after not having a pet in the home for three years. He's had all his immunizations, but he's due for a repeat rabies shot in June. We plan to travel via car with him for the month of October and want to cross the Canadian border to see Vancouver. So we asked friends who have two much larger dogs and live in Washington State if they've been able to take their dogs into Canada.

"It's no problem as long as you bring proof that his rabies vaccination is current," my friend Bob said.

We joined the Rocky Mountain Tibetan Terrier Association and got their newsletter. One section was on preventing dog attacks, both outside the home and at home. The information came from the American Veterinary Association. More than 60% of dog bite victims are children; they need to learn not to play rough with family pets. One comment said, "Never put your face directly in front of a dog--even in play."

'Guilty as charged,' I thought. Yoda and I play and he often licks my face. I don't plan to change my behavior, but I will mention the ideas to the parents of his favorite kid, who is now one and a half years old. I do think the recommendation makes sense, for children in particular.

bats may carry the disease

So why is this important? I found an NIH National Library of Medicine article on rabies which said  that deadly viral infection is spread by infected animals. In the US the number of cases has fallen dramatically and most bites from rabid animals involve non-canines: bats, raccoons, foxes and skunks as well as cats are mentioned. We spend over $300 million a year on rabies prevention with the vast majority of that going to pet immunizations.

Worldwide rabies statistics are quite different:  over 90% of human exposure to rabies and over 99% of deaths are due to rabid dogs. Many developing countries, in spite of some having programs to vaccinate dogs and get rid of strays, can't afford a complete program.

If your child or anyone else is bitten by a non-vaccinated animal, then immediate medical care is absolutely crucial. The CDC has an online helpful description of appropriate wound care and rabies post-exposure vaccinations. Let's be clear: if your child or you are bitten, even by a beloved pet of yours that has had its shots, see your doctor right then or go to an ER. Animal bites can cause many complications outside of rabies.

Why is this so important? Well, I just read an article about a  survivor from clinical rabies, an eight-year-old girl from a non-urban area on the West Coast. That's exceedingly rare!

Yes, that's true; rabies is uniformly fatal...unless it's prevented. In the US, there have been only three people who got rabies and survived. So urgent treatment with a series of shots of both human rabies immune globulin and rabies vaccine is critical.

Don't delay; save a life.


Influenza H5N1 HPAI research: lots of viewpoints

Friday, March 16th, 2012

When experts disagree, who should we believe?

Shortly after I wrote my post on the dangers of H5N1 HPAI, my weekly copy of JAMA, AKA the Journal of the American Medical Association, arrived containing a commentary titled "International Debate Erupts over Research on Potentially Dangerous Flu Strains." The pros and cons of release of the two groups' research were discussed and the rationale for publishing the methods and details was explained.

One expert in the field had a balanced view. He felt release of the details of the recent research on H5N1 HPAI might be extremely useful to  those who evaluate which strains of influenza are about to pose a real threat to humans and could potentially cause epidemics. Doing so might provide lead time for other scientists who work on vaccines to prevent wider spread of the particular strain of flu.

But in a January, 2012 online discussion of the controversy the head of a university Center for Biosecurity felt the lives of hundreds of millions of people could be at risk if such an engineered virus strain were to be released, even accidentally. He feels that continued research would require the level of biosecurity utilized with other dire agents such as smallpox.

The first infectious disease specialist countered with the concept that H5N1 HPAI wasn't an especially likely pick for those interested in bioterroism. It's certainly not a selective weapon and its use would require considerable expertise.

The second expert noted there had been no data that such a strain of flu would ever develop naturally, outside the lab, and we had to return to the concept of weighing potential harm versus good.

Now the original researchers have stated that the new viral subtype isn't as deadly as feared; it hasn't killed the ferrets being used as laboratory substitutes for humans and has proven to be controllable with vaccines and antiviral medications. Because of ethical limitations it hasn't been tried on human subjects and they don't know whether it even could be spread among humans.

And which of these is the worst?

I think we're treading very close to the edge here. I don't look forward to widespread beneficial effects of complete publication of the ongoing lab research results. And I do fear the possibility of groups who don't care if they kill off a third of everyone, including their own followers. Accidental release of a lab-engineered organism into the human population could also happen, even if unlikely.

Another online article said the work on the mutant form of H5N1 had been performed in BS-3 labs, used for studying agents that can cause serious or lethal disease, but do not ordinarily spread among humans and have existing preventives or treatments.

A GAO 2009 report counted 400 accidents at BS-3 labs in the previous decade. Scientists argued that the H5N1 HPAI studies must be moved to BS-4 labs with one professor stating, "An escape would still produce the worst pandemic in history." Yet between 1978 and 1999, over 1,200 people acquired deadly microbes from BS-4 laboratories, the biosafety-4 level facilities that normally deal with infectious agents that have no known preventive measures or treatment.

Scandia National Laboratory's International Biological Threat Reduction program directed by Ren Salerno has a worldwide ongoing effort to prevent laboratory accidents, but there are varying standards for biosafety and at least 18 BS-4 labs outside of the US as of 2011.

So I'm still worried.


Viral diseases old and new: Let's just begin with the flu

Sunday, March 4th, 2012

A cause for alarm and action

Two days ago I began a post on zoonoses, diseases that spread from animals to humans. As usual, my interest led me from one fairly-limited topic to more-generalized subjects and I eventually decide to write a multi-post discussion of viral diseases that either have caused massive, widespread epidemics (AKA pandemics) or could potentially lead to them.

The number of deaths they have resulted in is staggering. HIV/AIDS has killed over 25 million of us in the past 30 years; the Black Plague over a 330-year period killed 75 million and smallpox is estimated to have caused over 300 million deaths over the centuries.

But let's start with influenza, the virus that we read about year after year as a worldwide threat. In the fall my wife and I get flu shots; we got used to doing so when we were both on active duty as Air Force medical staff personnel. It was routine; I didn't pay a lot of attention to what this year's shot contained and only vaguely kept up with anything written about the flu itself.

Then so-called "bird flu" came along and  the world geared up for a terrible pandemic.Usually the kind of influenza virus found in birds doesn't infect humans. But one unusual strain, called H5N1 (I'll explain what that means later) killed a six-year-old boy in Thailand in 2003. Of the people who caught this virus, 60 % died.

Most of us have heard about the Spanish flu, a major pandemic that infected a third of everyone living in 1918-1919 and caused 20 to 40 million deaths worldwide. Yet only 3% of those whom the virus infected died from it.

The so-called Asian flu pandemic in 1956-1958 causes 2 million deaths; the Hong Kong flu in 1968-1969 killed 1 million and the yearly seasonal flu results in anywhere from 5 to 15% of us getting ill; 250,000 to 500,000 die as a result. But these flu strains actually only resulted in a death ratio of less than 0.1%.

As it turned out, there was very little person to person spread of the avian flu. If there had been the results could have been catastrophic.

But the pigs had nothing to worry about; we did!

One of the outcomes of the avian H5N1 outbreak was fortuitous. When the "Swine flu" pandemic occurred in 2009-2010, the public health establishment and the medical community were considerably better prepared. The CDC summary is worth reading as it documents the steps taken to contain the virus; actually this was a flu strain that was transmitted from person to person and wasn't present in US pig herds.

The virus itself had genes from four different influenza virus sources, two from pigs, one from birds and one from a human flu virus. The CDC widely distributed kits to labs enabling them to identify the new viral strain. They and the World Health Organization (WHO) kept tabs on the numbers of cases of the new disease and WHO announced a global pandemic in June, 2009 .

A vaccine was developed with unusual speed and a preliminary target group of higher-risk individuals was identified; this consisted of 159 million people in the US. Vaccine safety was tested in various groups and the vaccine itself was administered starting in early October; by late December 2009 enough had been produced to allow vaccination of anyone wishing it.

The final results were impressive; less than two-thirds of a million people caught the virus and the death rate was 0.03%



What else can a strep infection lead to?

Saturday, December 24th, 2011

tiny bacteria can lead to huge consequences

I wash my hands more frequently these days, not as a sign of OCD, but just from common sense. Familiar bacteria, ones that some of us carry and that our school-age kids may encounter several times a year, can rarely cause horrendous, life-threatening problems. WebMD has a short review of one of these diseases, one that physicians call necrotizing fasciitis (NF), but most non-medical folk know of as "Flesh-eating Strep."

I had read about this complication of the same bacteria that can cause strep throat, but prior to moving to Fort Collins in 1999, had never known of someone who developed it. Then, shortly after arriving here we joined the Newcomers Club. We met lots of people who came to the "Choice City" after retiring and heard of one who subsequently lost a spouse to the disease.

After that I paid a lot more attention to the entity. As I read considerably more about NF, I realized that streptococcal infections weren't its only cause, but I'll focus on strep today.

NF isn't the only major complication caused by Group A streptococci (GAS). There's a toxin-caused deadly illness called toxic shock syndrome. This has been around in the medical literature for about three decades. I became aware of it in December 1980 when the New England Journal of Medicine published an article describing 38 cases of this dire syndrome where patients, usually women who were menstruating and using tampons, developed high fever, low blood pressure and multi-organ failure, as well as sloughing off the skin of their palms and soles. The causative agent often was staph and blood cultures were often positive for staphylococci.

Yet half of the cases in a 2010 review did not involve menstruating women, in fact a quarter of the patents were men. Over the past thirty years, tampons have been improved so that the number of cases invoking their use has gone down markedly.

But the syndrome is still around and other bacteria, especially GAS, have been involved. Many of the patents who developed strep-associated toxic shock syndrome (STSS) had underlying chronic diseases (e.g., diabetes, cancer or alcoholism) or had recent surgical procedures. Some researchers have implicated a specific toxin in strep TSS.

When GAS bacteria find their way into areas where they are rarely seen, they can cause diseases much more severe than the usual strep throat or skin infections. These illnesses are called "invasive group A streptococcal disease."

It's estimated that an average of 10,000 cases of invasive GAS disease with a mortality rate over 10% happen in our country every year. Necrotizing fasciitis and STTS are even more likely to be lethal. A fifth to a quarter of those who develop NF die and half of those who have STTS.

Remember most of the millions of cases of strep infections that occur yearly here are relatively mild, but even those are nothing to be ignored. Good hand washing technique is crucial and I've provided you a link to the Mayo Clinic's article on thus subject.

The CDC article stresses that anyone who develops an infected wound, particularly if they also have a fever, should see a physician immediately. You may save your life if you do so.