The Toxin-Based Diseases Common in North America during the 1600-1700s

July 5, 2019

When the pilgrims landed at Plymouth Rock in 1620, they did not arrive alone. Their arrival predated the discovery of microbes and the germ theory of disease, but these dangerous pathogens tagged along, nevertheless. These new diseases threatened the survival of all people in North America. Although Native American populations were equipped to deal with native diseases, European contact exposed them to foreign diseases for which they had no existing immunity or knowledge of treatment. Inside the colonies, dehydration and malnutrition weakened immunity, while poor sanitation and high levels of exposure increased morbidity. Across the board, illness became an unpredictable, yet inevitable part of life. 
 
Unfortunately, disease has nonspecific effects on skeletal remains and Native American perspectives from this era were poorly documented, so much of our knowledge about disease in North America during the 1600s-1700s comes from the written records of the European settlers. Therefore, our resources for understanding the true impact that foreign pathogens had on the lives of indigenous North American people are significantly limited. Furthermore, because there was no knowledge of the underlying cause, spread, or prevention of disease, people could only speculate about what was making them sick. For the most part, diseases were classified based on observable symptoms.
 
The following is a brief survey of 5 bacterial pathogens, and their exotoxins, that were common during the European colonial expansion into North America. Notably, diphtheria, pertussis, and typhoid fever are thought to have accompanied the Europeans to the new continent, while dysentery and Streptococcus (scarlet fever) are regarded as diseases that were endemic to North America.   
 

"The Plague Among Children" 

Diphtheria and scarlet fever were significant causes of childhood death during the European colonial expansion. Sore throats were common, and diphtheria and scarlet fever were not recognized as separate diseases until the late 1800s. Whooping cough was another prominent childhood disease, however, it was less threatening to childhood survival than other pathogens of the time. 
 
1. Diphtheria: Corynebacterium diphtheria.  Diphtheria caused over 1,000 deaths amongst the colonists between 1735-1736 alone. In New Hampshire, 90% of those deaths occurred in children under the age of 10. Numbers continued to rise over the next 4 years, wreaking havoc and earning diphtheria the title of “Plague Among Children” from Noah Webster. Colonial records indicate that the disease had many other names including cynanche, angina, canker, bladders, rattles, and throat distemper.
 
Diphtheria is a bacterial infection that primarily affects the upper respiratory tract of its victims. It is caused by the gram-positive, rod-shaped bacterium Corynebacterium diphtheria and transmitted through coughs and sneezes of the infected.
 
Characteristic gray pseudomembrane caused by diphtheria.

Diphtheria toxin: Diphtheria pathogenesis is dependent upon the presence and secretion of an exotoxin – diphtheria toxin. Exotoxins are uniquely capable of acting locally and globally (far from the site of bacterial colonization). They cause damage to host cells by either destroying them directly or disrupting normal metabolic activity. 
 
Diphtheria toxin inhibits protein synthesis by catalyzing the transfer of NAD+ to inactivate an elongation factor (eEF-2) that is required for translation. As a result, healthy tissue in the back of the nose and throat is destroyed. Within a couple of days, dead tissue buildup creates a thick gray coating at the back of the throat or nose. In severe cases, this characteristic pseudomembrane may cause airway obstruction and lead to suffocation. Prior to vaccination, the only available treatment was tracheotomy to allow patients to breathe again. Additional symptoms of diphtheria include weakness, fever, sore throat, and swollen neck.
 
2. Scarlet Fever: Streptococcus pyogenes. Scarlet fever is caused by the gram-positive group A streptococcus (GAS) bacteria (S. pyogenes). It is spread through close contact and produces symptoms, including sore throat, high fever, enlarged tonsils, headache, and rash, that overlap a variety of other diseases. As a result, scarlet fever was often confused with smallpox, measles, and diphtheria, during the European colonial expansion. The infection was classified as a frontier disease because it did not pop up in urban centers.
 
The classic body rash of scarlet fever.

Erythogenic toxin: Today we know that the development of scarlet fever relies upon the secretion of erythogenic (rash-causing) toxins. Many erythogenic toxins have been identified to date, but S. pyogenes SpeA, SpeB, and SpeC are the exotoxins that have been most extensively studied and characterized. SpeA and SpeC induce inflammation, stimulate cytokine production, and activate T-cells in a non-specific manner, while SpeB degrades extracellular matrix proteins, cytokines, and immunoglobins. As a result, erythogenic toxins cause damage to plasma membranes of blood capillaries under the skin and produce the characteristic red rash on the body and tongue (strawberry tongue) associated with scarlet fever.
 
Strawberry tongue, a symptom indicative of scarlet fever.

3. Whooping Cough: Bordetella pertussis. Another upper respiratory infection common amongst children during the European colonial expansion was whooping cough. This highly contagious disease is characterized by a continual cough that is accompanied by a high-pitched crowing sound during inhalation, discharge of mucus, and possible vomiting. Complications include pneumonia, asphyxia, convulsions, and brain damage, but overall, the disease was a minor threat to survival compared to other microbial diseases of the time. Although we are not certain of the impact of pertussis on indigenous survival, it is reasonable to hypothesize that this disease was a greater threat to Native American people since the pathogen was likely not endemic to North America pre-European settlement. 
 
Pertussis toxin: Whooping cough is caused by the gram-negative bacterium Bordetella pertussis. This encapsulated coccobacillus also relies on an exotoxin – pertussis toxin – to cause disease. The pertussis toxin paralyzes the cilia of respiratory epithelial cells and inhibits the host’s ability to eliminate pulmonary secretions. Additionally, the pertussis toxin interferes with intracellular communication and leads to increased cAMP concentrations inside of host cells. As a result, insulin is released and hypoglycemia may occur. It is unknown whether this toxin is directly involved in the frequent, violent coughing associated with the disease.
 

“The Bloody Flux"

4. Dysentery: Shigella dysenteriae. Dysentery, also known as the bloody flux and camp fever, was a very common and significant concern to both Europe and North America. The disease is caused by the gram-negative bacterium Shigella dysenteriae and spreads rapidly in unsanitary conditions where food and water are contaminated by human waste. Soldier’s camps and immigrant ships were ideal breeding grounds for such conditions, making dysentery a recurring, debilitating, and often fatal threat.
 
Dysentery is a gastrointestinal disease. Symptoms include bloody or mucusy diarrhea, stomach cramps, pain, nausea, vomiting, and fever. During this time, there were no antibiotics. Patients simply had to allow the disease to run its course, and many died from severe dehydration before the infection was cleared from their systems. Those who did survive were left weak and susceptible to future infection.  
 
Shiga-toxin: S. dysenteriae is another pathogen that relies on secretion of an exotoxin – Shiga-toxin – to compromise its host. Shiga-toxin inhibits protein synthesis by damaging ribosomal RNA. It is effective against small blood vessels in the gut, kidneys and lungs. Uptake of the Shiga-toxin by these tissue types leads to breakdown in the lining of blood vessels. Depending on which organs are affected, hemorrhaging, bloody diarrhea, kidney failure, or pulmonary edema may result. 
 
Notably, some serogroups of E.coli, including O157:H7, produce exotoxins that are similar, if not identical, to Shiga-toxin. These are called verotoxins (Stx1/Stx2) or Shiga-like-toxins (SLT), and are often associated with hemolytic uremic syndrome. 
 

“Burning Fever” 

5. Typhoid Fever: Salmonella enterica serovar Typhi (S. Typhi). Typhoid fever became one of the first epidemics to cause an outbreak among the European colonists. Between 1607-1624, 85% of the population at the James River in VA died from a typhoid epidemic. The World Health Organization estimates the death toll was > 6,000 during this time. To the Native Americans, typhoid fever was a  “virgin soil disease,” meaning no prior immunity to these bacteria existed. Therefore, primary exposure to these pathogens resulted in large scale outbreaks within indigenous communities as well. Typhoid fever was known by many names including slow fever, nervous fever, continued fever, burning fever, long fever, and bilious fever.
 
Typhoid fever is caused by a gram-negative rod, S. Typhi; and once again, poor sanitation, infected water, and overcrowding contribute to the spread of this disease. Infection presents as fever, body aches, loss of appetite, headache, cough, and restlessness. As the disease progresses, delirium, severe constipation, dehydration and death may occur. If the patient survives infection, the typical duration of typhoid fever is 3 weeks.
  
CDC rendering of Salmonella

Typhoid toxin – The pathogenesis of S. Typhi remains poorly understood; however, we do know that the typhoid serovars of S. enterica are unique in their ability to produce typhoid toxin. How this endotoxin contributes to  disease is not yet clear, but the immune system and central nervous system are the suspected targets of typhoid toxin.
 
The 1600s-1700s was a period of change and uncertainty in North America. Few factors threatened survival as much as the microbial pathogens that infiltrated the continent. Unfortunately, ignorance of the diseases they were bringing did not prevent the devastation these pathogens wreaked as they spread throughout the pilgrim’s colonies and the indigenous population of North America. This is a brief survey of some of the major toxin-based bacteria of the time. It is amazing to recognize that sanitation, vaccination, and antibiotics have made all 5 of these pathogens preventable or treatable in our world today.
 
 

Author: Ashley Hagen, M.S.

Ashley Hagen, M.S.
Ashley Hagen is a science communications specialist at ASM.