Author: Kendall Penndorf

You would have to live under the proverbial public health rock to have missed news of the UN’s landmark proclamation to combat antimicrobial resistance (AMR).  “Superbugs” or antimicrobial resistant bacteria, fungi, viruses, and parasites are a global health concern poised to claim many more lives.  How does AMR happen?

Among the most prescribed drugs in medicine, antibiotics are not appropriate to treat many illnesses and infections including the common cold, influenza, most sore throats, and ear infections.  According to the Centers for Disease Control and Prevention, up to half of all illnesses for which antibiotics are prescribed are not bacterial in nature and thus unresponsive to antibiotics.

Over-prescription of antibiotics is one cause for AMR, as is our food system’s use of antibiotics for livestock to promote growth and prevent infection.  The cost associated with developing new antibiotics is prohibitive.  Unlike medication to manage chronic diseases, antibiotics are meant to be used sparingly which does not recoup the estimated $1 billion spent to develop a new drug.  As a result, the majority of leading pharmaceutical companies no longer develop new antibiotics.

Regular and timely vaccinations are integral to reducing dependency on antibiotics and thus antimicrobial resistance.  The use of vaccines has significantly decreased the prevalence of the world’s deadliest and most preventable diseases, including diphtheria and pertussis.  Even with the increased availability of vaccines, UNICEF reports that 24 million children – roughly 20% of children born each year – do not receive all vaccines recommended in the first year of life.

Europe and the United States have seen a resurgence of vaccine-preventable diseases including pertussis, better known as whooping cough.   Why are diseases we associate with our grandparents’ generation, reappearing in countries with the means to eradicate them?

After publication of a famously fraudulent report that linked routine childhood vaccinations to autism, vaccination rates plummeted in some developed countries.  Vaccine hesitancy, or delay or refusal of available vaccines, led to non-medical exemptions (NMEs) which allow parents to opt out of immunizations for religious, philosophical, or personal reasons.  Children with and without current immunizations then mingle at all the usual spots: daycare, school, and public facilities.

One of the most amazing attributes of vaccines is their ability to protect us regardless of whether we’ve been immunized.  Herd immunity, or the benefit to the community if most citizens are properly immunized, protects children too young to be immunized and those with compromised immune systems.  If the ratio of immunized individuals drops below 95%, the risk to those groups increases.

Vaccine compliance is just one way to reduce reliance on antibiotics and halt antimicrobial resistance.  Sadly, lack of access to vaccines in the developing world is the number one issue impacting compliance.  By comparison, vaccine hesitancy and NMEs fall squarely into the “First World Problems” category.

What can the United States and Europe do to increase vaccinations among constituents?  An article in the New England Journal of Medicine found that while NMEs have increased in the US, states with stricter exemption criteria had fewer NMEs.  WHO’s Europe regional office published the Guide to Tailoring Immunization Programmes (TIP) in an effort to educate parents and providers.

To see which vaccine-preventable diseases are trending in your area, check out this fabulous interactive map from the Council on Foreign Relations.

You’ve likely heard of lab rats, but detection rats technology?  APOPO, a Belgian non-profit, with headquarters in Tanzania, breeds, trains, and implements landmine and tuberculosis detection rats in Africa and Asia.  Equipped with exceptional noses, African Giant Pouched rats have helped clear over 26 million square meters of land, including nearly 100 thousand landmines destroyed in Mozambique, Angola, Cambodia, Thailand, and Vietnam.  Once ravaged by civil and international wars, these lands are now suitable for community use.

Tuberculosis (TB) kills over a million people annually.  In countries such as Tanzania and Mozambique, prevalence of tuberculosis is high while detection and treatment are low.  This discrepancy is attributable to a lack of diagnostic equipment, trained staff, and lagging infrastructure and utilities.  A trained tuberculosis detection rat – otherwise known as a HeroRAT – can screen 100 samples in 20 minutes.  The same task would take a trained technician 4 days.  In Tanzania alone, over 8 thousand positive TB samples that were missed by technicians were identified by HeroRATS.

Could programs like APOPO fundamentally change the way we think about rats and their role in public health?  To find out, we must first take a look back at our long, intertwined history, past traditional research laboratories, and into a future where rats may well be our colleagues.

Wherever people make a home, rats are sure to follow. Inveterate opportunists, rats make good use of our infrastructure and food system with enviable aplomb.  What works for rats hasn’t always proved advantageous for humans.  Take for instance the Bubonic Plague of the 14^th century.  Long blamed for the disease that raised black, fetid boils and led to the swift demise of two-thirds of Europe’s population, rats are still synonymous with scourge, despite mounting evidence that implicates gerbils for harboring the fleas that carried the Plague.  An even more compelling argument suggests that at its most virulent, the Plague spread human-to-human.  This theory is supported by records that show that deaths increased in the winter months, a time when most rodent populations would dwindle considerably.

The story of rats next takes us to the laboratory of University of Wisconsin professor, E. V. McCollum. The year is 1908 and McCollum has just purchased 12 albino rats to further his research on nutrition.  Though he has been studying cows for some time, McCollum feels rats will be superior due to the ease of housing, feeding, breeding, and disposal.  McCollum might not yet realize that his will be the first of many rat colonies established for research.  The first experiment involves splitting the rats into two groups and feeding them different diets.  For a time, all rats will develop normally, until one group ceases to grow.   McCollum postulates the existence of a factor present in some foods that promotes extended growth.  He calls this “factor A,” known today as Vitamin A.

McCollum’s next success would come at Johns Hopkins University’s newly established Department of Chemical Hygiene, later renamed the Bloomberg School of Public Health.  McCollum and colleagues used diet to induce Rickets in rats.  Rickets, a disease that causes crippling bone deformities, was common among the children of tenement-dwellers in urban centers.  Believed to be caused by diet and environment, McCollum prescribed over 300 diets to his Rickets rats and found that those supplemented with cod-liver oil improved.  He also found that rats that had daily sun exposure fared better than those left in the dark.  McCollum named this new discovery Vitamin D.

Advents in technology revealed increasingly subtle yet deeply profound insights into human physiology.  DNA sequencing and genetic engineering allow scientists to simulate human diseases in rats, including cancer, Alzheimer’s Disease, cardiovascular disease, and diabetes.  Modern medicine owes much of what it knows about the etiology and treatment of these diseases to laboratory rats. One reason for rats’ success as research subjects in human disease is the genetic and physiological similarities we share, so similar in fact that it is not surprising to learn that all mammalian life plausibly shares a single, rat-like ancestor .

Recent studies venture past the scientific and into the silly.  Rats exposed to the psychoactive ingredient of marijuana are less likely to perform a complex task in favor of a simple task with a smaller reward.  The rat’s ability to complete the harder task is not affected, just his willingness to exert cognitive effort.  Sound familiar?

Ever wonder if rats laugh when tickled?  Dr. Jaak Panksepp thinks they do and has video to prove it!  Panksepp, a neuroscientist at Bowling Green State University, finds that young rats laugh when tickled and will seek out a tickling hand over a still one.  He also learned that rats read environmental cues when it comes to laughter.  Just as you or I wouldn’t laugh at a funeral, a young rat won’t laugh under a bright light or with the odor of cat urine in the air.

Science might ultimately prove that rats are better people than us.  Scientists wanted to know if rats would help another rat in distress, thus displaying empathy and altruism.  One experiment trapped one rat in a clear tube to determine if the other rat would free it by opening a door with its nose.  In a riskier experiment, rats on a dry platform were tasked with opening a door for a rat frantically treading water on the other side.  Even when enticed by treats, rats overwhelmingly chose to help friends and strangers alike.

When it comes to rats, there is much more than meets the eye.  Are they simply a tool to be confined to the laboratory, or might we find them suited to a diverse range of tasks, such as with APOPO?  If science has shown that rats laugh, are good Samaritans, and exhibit free will, might we need to reexamine our relationship inside and outside the lab?

Watch this Ted Talk by APOPO founder, Bart Weetjens: How I Taught Rats to Sniff Out Landmines.

From American Cheese to Vitamin A, check out 100 Objects That Shaped Public Health (and yes, rats made the list!)

 

2015 saw a twenty-fold increase of microcephaly in Brazilian newborns.  A WHO report states with scientific consensus that the Zika virus is the cause for microcephaly and Guillain-Barre syndrome, while further neurological disorders are potentially linked.  An article published by the Journal of the American Medical Association seeks to uncover what we might learn about Zika as this cohort of babies age and what similarities can be found in the Thalidomide crisis of the 1960s.

Hailed as the ‘worst man-made peacetime disaster in history,’ thalidomide was manufactured and marketed by a German pharmaceutical company as a safe and effective sleeping pill and anti-nausea drug for pregnant women.  Thalidomide was widely available in the late 1950s and early 1960s in the United States, Europe, Australia, and parts of Asia resulting in the birth of as many as 20,000 babies with crippling deformities.  Thalidomide was banned in 1962.

For most, the story ends there.  Now, 60 years later, there are only a few thousand thalidomide survivors – known as thalidomiders – left.  They’ve taken to the Internet to share their stories which you can read here, here, and here.  Amidst stories of institutionalization and acceptance is a common theme: healthcare costs associated with a debilitating condition.  Many suffer from chronic joint ailments that make day-to-day living more difficult as they age.

What can researchers learn from thalidomide?  Like the Zika virus itself, much is left to be discovered.

In many ways, thalidomide survivors thrived.  They married, became parents, had careers, and hobbies.  Microcephaly doesn’t hold such promise for the future.  According to the National Institute of Neurological Disorders and Strokes, microcephaly associated with Zika is likely to be severe and require lifelong intensive care.

The healthcare costs of thalidomide is hard to quantify.  Mostly of normal intelligence, thalidomiders attended mainstream schools.  Many developed ingenious adaptations to overcome the vagaries of everyday life.  There is no way to know how much money will be needed to care for children with special needs caused by Zika.  Globally children with special needs are the most vulnerable population.  They have less access to healthcare and education and face more discrimination and violence than peers.

With so much focus on microcephaly, how might Zika influence the developing brains of healthy infants and children?  Studying differences in outcomes of typical children and those with microcephaly will be key to developing treatment methods.  Does Zika have the potential to cause more damage than thalidomide?  Just ask a pediatric neurologist:

“Depending on the rapidity with which an effective vaccine can be developed and distributed effectively, the ability to marshal resources to do appropriate science, and large-scale prevention efforts, Zika has the potential to be much worse and to have an impact that continues over a much longer period of time.”

Interested in learning more about thalidomide?  Check out this great video from The New York Times Retro Report: