NEWSBYCRAIG KIEBLER

(photo credit: Aussiegal)

Editor's Note: Craig commented on my surveillance post to remind us that disease notification is not the only way we track outbreaks. His additions were important enough that I am giving them their own post.

The current surveillance situation is a little broader than Notifiable Diseases and depends on the methodology used for the surveillance as well as the end purpose of the surveillance.

Most of what you've discussed would fall into a 'direct reporting' capacity used by the national health infrastructure.  Separately, there have been attempts at indirect, Syndromic Surveillance - basically looking for indirect indicators of disease in the population.  By and large, this has not proven to be effective.  Other systems use a methodology of looking at social/societal disruption associated with an outbreak of disease - such things as cancellation of sporting events, festivals, or school closures.  This methodology may not be 'disease specific'; however, it has proven to be fairly sensitive.  A downside is that one must understand and take cultural perspectives, expectations, and practices into account.

Another point of debate in the biosurveillance community is that regarding purpose of the surveillance system.  Traditional monitoring tends to lean toward a true epidemiological approach - it is slow, but you generally get a high degree of specificity.  Alternatively, one can take the 'tip off' approach, effectively trading specificity of detection with much more rapid (and sensitive) indication.  You might detect that something is happening and have vague descriptions of disease signs, but not a true clinical description.

Each methodology and purpose has its strengths and weaknesses, and use of the various systems is not mutually exclusive.  The questions become:  How is each system's reporting used most effectively?  How do we make decisions from the gathered data? How do we effectively communicate our conclusions? How do we integrate our surveillance and response methodologies?

TB is an insidious disease that can infect people without causing obvious disease - in fact, in an otherwise healthy person, only 5-10% of infected people show signs of the disease.  These are the individuals that can spread the disease through aerosol, requiring only a small infectious dose.  However, those persons who are infected may experience changes to their immune status at some point in life and progress to the fulminant form of TB - a weakened immune system is responsible for the high prevalence of TB in HIV infected persons.  As already described, TB tends to affect the poor, with less access to antimicrobials.  Add to this the fact that some protocols require treatment of up to two years and you get a situation where continued propagation of the disease is nearly inevitable.  The other ‘heads of Ghidorah' are the emergence of multi-drug resistant (MDR) and extremely drug resistant (XDR) strains of TB, thereby further diminishing our arsenal for combating the disease.  The emergence of such strains has become an even more important global health concern as exemplified in 2007 when an American lawyer contracted XDR TB abroad, with resulting chaos surrounding quarantine procedures and personal rights.

Our Ghidorah also has a secret weapon.  The World Health Organization lists Mycobacterium bovis (Bovine TB) on its list of ‘Seven Neglected Endemic Zoonoses'.  Bovine TB can infect cattle, goats, sheep, cats, dogs, pigs, buffalo, badgers, possums, deer, elk, bison, horses, foxes, hares, ferrets, antelope, camels, llamas, alpacas, non-human primates, and yes...humans.  The global burden of disease is unknown, but it can cause disease that is indistinguishable from Mycobacterium tuberculosis (Human TB).  Additionally, it can be spread by aerosol from animals to humans or humans to animals, by drinking blood or unpasteurized milk from an infected animal, or through direct inoculation.  Research has also shown the capacity for human-to-human transmission.  Ingestion of the organisms can cause a myriad of other conditions, such as cervical lymphadenitis, urinary or reproductive tract lesions, bone or joint infections and infections of the brain.  Like M. tuberculosis, infection with HIV increases the risk and speeds progression of Bovine TB.

Bovine TB may not be as much of a problem in developed countries; however, when we look at socio-economic risk factors in poorer nations, it becomes more of a problem.  In the same areas that do not have regular access to treatment, we often see a larger number of individuals reliant on livestock for their individual consumption and/or for their livelihoods.  Additionally, many of these areas do not regularly pasteurize dairy products, some households co-habitate with their livestock, and some local customs entail drinking of animal blood - all risk factors for transmission of the disease.  In those cattle that have been diagnosed with Bovine TB in many developing nations, we also see a reluctance to cull the animals because they are the primary wealth of the owners.  So, we have another form of TB, of which the global disease burden is unknown, and where social and cultural risk factors for the disease converge in areas that have high HIV burdens and very limited access to diagnostics and treatment.

Much like Ghidorah, TB is a ‘monster' that has many heads and multiple forms and has a predilection for the countryside - represented here as people living in locations and conditions where they do not have access to diagnostics and treatment.  Increases in travel, global burden of HIV infection, and lack of health infrastructure in areas that need it most, all conspire to make TB a continuing risk to global health.

Sorry, smallpox...I think you can continue to be confined to your cage.

When I was a kid I remember watching the Saturday morning Monster Matinee.  Each weekend movies would show battles between Godzilla, Mothra, Rodan, and a myriad of others.  For some reason I always enjoyed these movies, as cheesy as they were.  Being a visual person, I tend to make associations between information and experiences.  In this case, while thinking of a showdown between smallpox and tuberculosis, I couldn't help but also think of the Monster Matinee - a little strange I know, but it helps me form associations.

Each monster had special abilities and some showed a predilection for geographical locations, such as with Godzilla and Tokyo.  Mothra had silken sprays and could form gale-forced winds with her wings, Godzilla crushed things underfoot and could breath fire, Rodan had an incredibly strong beak and atomic breath.  Where am I going with this?  Just like the creatures in the Monster Matinee, diseases of global concern each have characteristics that make them unique and formidable; characteristics that we continually try to counter or exploit in treatment and control.  Smallpox and tuberculosis (TB) are (or have been in the past) global ‘monsters', each with their own nasty idiosyncrasies that have been a scourge to human-kind.

As others have described, smallpox has been around for a long time; however, we were able to develop an efficacious vaccine and control methodology, resulting in the last naturally occurring case of smallpox documented in 1977.  While some have questioned the security of the smallpox repositories (especially in Russia and given reports of biowarfare testing in the 1980's), we have the tools and methodology that have proven effective if we are faced with a resurgence of naturally-occurring smallpox.  Yes, people would be disfigured and deaths would occur during the time interval it would take to ramp-up vaccine production and put concentric vaccination strategies into effect; however, it would be controllable.

When I think of TB, however, I think of a less well-known Matinee Monster, the three-headed, fire-breathing dragon Ghidorah.  In the movie, Ghidorah sneaks to earth and starts to raze the countryside.  It takes all of the efforts of three other monsters, Godzilla, Mothra, and Rodan to fight him.  Again, let me explain how Ghidorah symbolizes TB in my mind.

(photo credit: L_J)

"As the race started, Hare sprinted ahead while Tortoise lumbered along at a steady pace.  Hare, seeing that he was far ahead of Tortoise, decided to take a quick nap before resuming the race.  As Hare slept, Tortoise passed him and finished the race.  When Hare awoke he could not believe the situation, to which Tortoise stated, "Slow and steady wins the race."

The Race

The incidence of Dengue fever (DF) is expanding globally, due to the extension of the mosquito vector's habitat, as well as increasing urbanization in endemic regions - DF is now considered endemic in more than 100 countries, many of them with sub-optimal or limited health care infrastructure.  Additionally, DF has at times caused explosive outbreaks regularly leading to infection rates of 40-50% - many of those affected are children. The World Health Organization (WHO) estimates that 2.5 billion people are now at risk of Dengue infection and that there are 50 million infections globally every year.

In comparison, of the viral hepatitis types, it is estimated that 360 million people are chronically infected with Hepatitis B globally and that more than 2 billion people have been infected at some point in their lives.  WHO estimates that 180 million people are currently infected with Hepatitis C globally, of which 130 million are chronic carriers.  Further, WHO assesses that up to 76% of all liver cancer cases are due to chronic HepC infection.  Additionally, there has been a growing trend of concurrent HepB infection and HepC co-infection in HIV-patients, as well as concern around transmission of HepB and HepC among IV drug users.

Much like our Tortoise, Hepatitis infection tends to be an insidious disease that can cause acute debilitation, and more importantly, long-term life-threatening liver disease.  Most individuals chronically infected don't know they carry the virus, yet are still able to transmit the disease.  This, coupled with the prevalence of viral hepatitis in developing countries with limited availability of HepB vaccine and health infrastructure, concurrent HIV infections and lack of sanitation, all lead to a global health crisis.  Dengue, our quick and elusive Hare, is responsible for ever-increasing global morbidity and mortality.  However, its acute onset and progression, requirement for a mosquito vector, limited vector habitat range, and low incidence of progression to the more lethal DHF and DSS forms, make DF less of a pandemic concern.

So, even though our Hare (DF) is characterized by rapid and sometimes explosive outbreaks leading to high morbidity rates, in the end, the high global prevalence and slow, steady, progressive nature of Hepatitis wins this race.

(photo credit: minds-eye)

When I began thinking of this disease pairing, it brought to mind a story many of us learned in our childhood.  I'd like to share that story again with you now:

"Once upon a time there was a hare, who bragged to anyone who would listen about how fast he could run.  He took great pride in his speed, often showing off his skill and teasing those who were slower than him.  During one of his bragging fits, Hare began to make fun of one of the slowest animals, Tortoise.  Well, Hare bragged that he was the fastest in the world and challenged Tortoise to a race.  Tortoise, who was sick of hearing Hare brag, accepted the challenge."

The Hare

Dengue fever (DF) is an arthropod-borne disease caused by one of four related viruses (DEN-1, DEN-2, DEN-3, DEN-4).  The disease is found in tropical and sub-tropical regions based on the habitat of its vector, the Aedes mosquito.  Humans are the primary hosts of the disease.  Infection by one virus does not confer cross-immunity to the other viruses, but it does provide lifelong immunity to that particular strain; therefore, a person can theoretically be infected four separate times (e.g. one time with each form of the virus).  Individuals who are infected with Dengue develop acute onset of high fever, head and muscle pain, nausea, vomiting and rash, 3-14 days after being bitten by an infected Aedes mosquito.

Dengue hemorrhagic fever (DHF) is a life-threatening complication of DF infection, which causes hemorrhage and circulatory dysfunction; in severe cases, this can progress to Dengue Shock Syndrome (DSS), characterized by serious shock and sometimes death.  While classical DF infection is rarely fatal, individuals progressing to DHF and DSS experience mortality rates as high as 2.5% and 10%, respectively.

The Tortoise

Hepatitis is a condition characterized by inflammation of the liver.  As such, there are many causes of hepatitis (e.g. bacteria, viruses, toxins, etc.).  For our purposes, I've decided to limit our ‘Tortoise' to the five viral Hepatitis types: A, B, C, D, and E.  Hepatitis A and E are acute liver diseases transmitted by fecal ingestion, contaminated water or food, and person-to-person contact (HepA).  There is a vaccine available for HepA, but not HepE.

Hepatitis B and C cause chronic infection that can subsequently lead to liver disease or liver cancer.  Both can be transmitted through contact with infected body fluids, sexual contact, and from mother to child during birth.  While there is a vaccine for HepB, there is not one for HepC due to the extreme variability of the virus allowing it to evade the immune system.   Hepatitis D requires concurrent infection with HepB; however, when this condition is met, it can cause acute, full-blown hepatitis or chronic-active hepatitis, potentially leading to cirrhosis.

Hepatitis can cause a myriad of symptoms (e.g. jaundice, vomiting, nausea, fatigue, etc.) and in its chronic form, can lead to severe liver disease (causing a variety of life-threatening symptoms) and liver cancer.  The insidious nature of various forms of the disease assist with continued transmission, as does lack of availability to vaccines in poorer countries.