Control of Tuberculosis: An Agent Carter & Captain America Size Task

The popular culture infectious diseases references continue.

On last night's premiere of ABC's new 1940s-era show, Marvel's Agent Carter a character who sneezes exclaims that she likely has tuberculosis. (For those of who might not know, in the Marvel universe, Agent Carter was an associate of Captain America.) 

In the 1940s tuberculosis was a serious fear in the US and pre-streptomycin (1944) there was no effective treatment available. Despite this, deaths had been declining due to improving socioeconomic and health conditions in the US. However, in 1945 the incidence rate was still was at an alarming 87 per 100,000. For comparison, it was 3 per 100,000 in 2013--a 96% reduction.

Though, as I've written before, there are vulnerabilities in our control of tuberculosis including drug resistance and the fact that the bulk of tuberculosis cases in the US occur in foreign-born individuals, who may present special challenges with respect to case identification, contact tracing, and treatment. 

With those caveats, a 96% reduction in tuberculosis cases in 70 years, in the absence of a vaccine program, was a Captain America seized feat.

Flu in 2015: Just the Facts

Right now the infectious disease in the headlines is one that deserves a lot of attention and is always at  the top of my list of infectious disease threats: influenza. 

Why?

We are in the beginnings of what will be a rough influenza season. About a week ago, we hit the epidemic threshold when 6.9% of all deaths reported were due to pneumonia and influenza, prompting the CDC to declare an epidemic. In Allegheny County (PA), where I live, there have been 2 deaths reported with close to 2000 cases reported. Pediatric deaths this season number 21 nationally. 

The season is particularly rough because of two factors:

1. The dominant strain is H3N2: Of the several strains of influenza that circulate, H3N2 seasons tend to be more severe likely due to the inherent virulence of the strain with severe cases occurring in the very young and the very old.

2. The vaccine mismatch: Each year viral strains predicted to be dominant are placed in the (now) 4-strain vaccine. This year the H3N2 included is a mismatch and not fully protected against what is the dominant strain. What happened was a new "drifted" variant of H3N2 emerged too late to be included in this year's vaccine.

It's important to note that when you read about numbers of cases confirmed at the county, state, or national level these numbers are only the tip of the iceberg as many physicians don't test formally for influenza because they make the diagnosis clinically and hospitals use tests of varying accuracy (false negatives occur with rapid tests). Chances are if you have symptoms such as fever, muscle aches, and cough you have influenza. Note, influenza doesn't cause gastrointestinal symptoms such as vomiting or diarrhea; it is a pet peeve of mine to see viral gastroenteritis labeled "flu".

What to do?

All is not lost though. There have been rough H3N2 dominated seasons with vaccine mismatch before. There are several things that should be helpful to minimize the impact.

1. Get a vaccination: Though the vaccine is mismatched there will likely be some protection afforded. You may still get the flu, but it could be less severe and less likely to require a visit to the hospital.

2. Low-tech social distancing: If you're sick with the flu, don't go to work; if you're children are sick, keep them out of school. Also, cough into the crook of your elbow not your hands (which you should wash a lot).

A children's nursery rhyme about influenza ("in flew Enza")

3. High risk groups should not try and wait it out. If you're pregnant, immunosuppressed, have underlying health conditions you should not try and wait for the virus to pass. You should see a healthcare provider who may prescribe an antiviral (see #3 below)

3. Doctors should prescribe antivirals: Doctors notoriously under prescribe antivirals for influenza. This is unfortunate as these medications can lessen the severity of influenza symptoms and their duration. There is some concern about shortages, but they are not widespread and people should be able to find drugs like Tamiflu but it may take some looking.

The traditional peak of the flu season is next month, in February, so expect for the season to worsen before it improves.

You can take solace in the fact that next year's vaccine will contain the mismatched strain missing from this year's strain. A larger point to understand about flu vaccines is that because of the genetics of the virus  coupled to our vaccine technology we have to change vaccines frequently and changes can't happen on the fly because of the long lead time to make the vaccine. The scenario occurring this season is something that we will always remain at risk of until a universal flu vaccine--one which doesn't have to be changed seasonally--is developed. That would be something more valuable than the Holy Grail.

Why Did 5000 Chickens Almost Cross the Road?

Remember avian influenza? The deadly version of flu that passes from poultry to humans and has caused outbreaks in many nations, most notably China. While we were dealing with Ebola panic and now a severe seasonal influenza outbreak, these viruses continued to spread (despite the lack of headlines).

The latest version of avian influenza to generate concern is H7N9 which has infected about 500 people since March of 2013, killing one-third. Taiwan has had 4 imported cases. The virus is spread to humans through direct and indirect contact with poultry. Limited human-to-human spread may also occur.

Because of the connection with poultry, control measures are centered around delimiting exposure to potentially infected birds. This often involves closing markets, culling, and inspections. 

An ongoing dilemma in Hong Kong involved a plan to inspect all local chickens at a small checkpoint while the market is disinfected after a culling of close to 20000 birds because of the potential for H7N9's presence given imports from a mainland farm tested positive for the virus. This arrangement was not found to the liking of the farmers who believe it will prove too onerous for them to conduct business.

Their response was to threaten to release 5000 live chickens into the busiest streets of Hong Kong. Not only would that action cause a major calamity but if any of the birds are harboring H7N9 (or other avian influenza viruses that can infect humans) could potentially widen exposure which is traditionally restricted to market-goers. They have since rescinded the threat. 

This incident illustrates why infectious diseases are so important. In just this one snapshot, you see economics, commerce, trade, government, and healthcare all intermingled. The ripple effect of certain infectious disease can be far-reaching and touch on virtually all aspects of modern civilization. 

Sir William Osler once remarked that to know syphilis--which has the ability to cause disease in every organ system--is to know medicine; similarly, to know infectious disease is to know the world.

Consumption: A Disease For All Seasons, not Just a Winter's Tale

We often talk colloquially about a disease consuming an individual. Examples include AIDS, cancer, or, quite literally flesh-eating bacteria. However, there is one disease that actually has the original claim to that moniker: tuberculosis. 

Consumption was the name of the condition that eventually became known as tuberculosis and its first mentions reach back to the times of Hippocrates and Herodotus. Indeed the Hippocratic corpus distinctively describes consumption (phthisis in Greek) as being nearly always fatal and consisting of symptoms recognizable to a physician practicing over 2000 years later. The disease, in an era without antibiotics and proper nutrition, could be a death sentence and as the infection progress patients would literally waste away as the disease consumed them.

In the developed world, tuberculosis has faded from the mind of the general public and in the US we are now at an all time low with cases falling below 10,000 with 65% of cases occurring in those born outside the US--a statistic often misused by anti-immigration advocates. Because certain types of tuberculosis are transmitted from person-to-person through the air it is one of the instances in which legitimate quarantine orders are issued in the US for non-compliant patients.

A recent movie--in which I had to suspend disbelief about a flying horse, cessation of aging, and Lucifer--reminded me that anti-immigration sentiment over tuberculosis is nothing new. In the supernatural film Winter's Tale a couple arriving in late 19th century America is summarily deported when a "pulmonary" problem is detected on their screening immigration physical examination and later in the film a character dies of it. The pulmonary problem was tuberculosis.

If one reads historical accounts of how immigration and infectious diseases interacted--such as Howard Markel's When Germs Travel--you will learn that fear of tuberculosis led to a very unscientific process of looking for and excluding those with a physical appearance thought to be conducive to tuberculosis infection--ignoring the fact that the disease had stricken many individuals including the famous and the beautiful.

Tuberculosis was, for a time, the reigning king of infectious disease killers before being replaced by HIV and it has not lost its appetite for blood. Now armed with drug resistance genes, tuberculosis control will remain an important task for the foreseeable future.

HIV: You're Still the One

Infectious disease physicians often tell those who are diagnosed with HIV in the modern era that they will likely live a normal life span if they are placed on and are adherent to antiretroviral therapy. My career started just as this modern era dawned but I wasn't too far removed from the bad old days of HIV to not have some experience with it. 

As a resident, I recall about a dozen patients with undiagnosed HIV presenting to the hospital with shortness of breath and subsequently diagnosed with Pneumocystis pneumonia. Some of these patients ended up in the ICU and on mechanical ventilator. During my fellowship in infectious disease, by contrast, I think I only saw one relatively mild case of Pneumocystis. 

A few weeks ago, however, I had the unfortunate opportunity to relive this experience when a patient was admitted to the hospital with a severe pneumonia requiring mechanical ventilation and round-the-clock care in the ICU. This patient was not known to be HIV positive but I soon discovered that the virus and Pneumocystis were responsible for the dire conditions of the patient. 

According to current statistics, 86% of those with HIV know their status leaving 14% unaware of their diagnosis. My patient was one of the 14%. Being aware of one's diagnosis is no guarantee, however, that viral suppression will occur. In fact, 70% of those with HIV in the US have not achieved viral suppression, despite the high potency of antiretroviral therapy indicated other factors are at play. 

Individuals with Pneumocystis pneumonia who require a ventilator have a 60% mortality rate--a startlingly high mortality rate that often necessitates starting anti-HIV therapy in the ICU without counseling, without a genotype, and with no assurance that the patient will be compliant. But, in such situations anything that will help the patient leave the hospital alive is welcomed. 

My patient, thankfully, was one of the 40% that survive but served to remind me that in the midst of Ebola, MERS, and avian influenza, HIV remains an ominous foe.