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Why does botulinum toxin seem to be more dangerous to humans than to other mammals?

Why does botulinum toxin seem to be more dangerous to humans than to other mammals?


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Various mammals seem to get away with eating parts of carcasses that we would prefer to not even touch, and that we assume will make us sick.
Because of that, I assume botulinum toxin is more dangerous to humans than many animals.

Is that right so far - can they handle more of some toxins compared to us?
Or are they better in avoiding harmful substances based on more suited olfactory sense?
Or are we just more afraid?

Assuming the differences exist - what is the cause for it?
Are there plausible explanations in terms of evolutionary pressure?


Because of that, I assume botulinum toxin is more dangerous to humans than many animals.

Couldn't find too many examples but, there are some things to consider (according to [1]):

  • there are seven distinct types of toxin with variable action among animals
  • different dose / effect intensity ratio between toxin types
  • toxins A, B, E and F cause disease in humans
  • toxin C and D are more common to birds, cattle, horses

And here are some numbers:

  • cattle median lethal dose: 0.388 ng /kg [2] of C type toxin
  • mouse median lethal dose ( 12.88 times more than cattle): 5 ng/kg [2] of C type toxin
  • human median lethal dose: 1 ng/kg [1] of A type toxin

When it comes to carcasses toxicity, there are some papers to consider:

  • Smith GR, Turner A. Factors affecting the toxicity of rotting carcasses containing Clostridium botulinum type C. Epidemiol. Infect. 1987 Jun;98(3):345-51. PubMed PMID: 3297745. - Persistent toxicity at 20 and 37 degrees Celsius even for a long time. No toxicity at 16 degrees Celsius
  • Smith GR, Turner A, Till D. Factors affecting the toxicity of rotting carcasses containing Clostridium botulinum type E. Epidemiol. Infect. 1988 Jun;100(3):399-405. PubMed PMID: 3288491. - Maximal toxicity at 30 degrees Celsius that is lost in time.

are they better in avoiding harmful substances based on more suited olfactory sense?

Not if we are talking about nonproteolytic B, E and F type bacteria. Indeed, Clostridium botulinum, proteolytic type A, B and F types produce odor [3].

Or are we just more afraid?

I don't see how fear could (significantly) influence pharmacodynamics and pharmacokinetics of the toxin.


References:

  1. CIDRAP - Center for Infectious Disease Research and Policy. Botulism. Available from http://www.cidrap.umn.edu/infectious-disease-topics/botulism
  2. Moeller RB, Puschner B, Walker RL, Rocke T, Galey FD, Cullor JS, Ardans AA. Determination of the median toxic dose of type C botulinum toxin in lactating dairy cows. J. Vet. Diagn. Invest. 2003 Nov;15(6):523-6. PubMed PMID: 14667014.
  3. P. Kendall. Botulism. Colorado State University Extension. Available from http://www.ext.colostate.edu/pubs/foodnut/09305.html

You seem to not understand how botulism works. It is impossible for vultures (or anybody else) to get botulism from a carcass.

First, you have spores. They are ubiquitous in nature, and you have probably eaten lots of them. They are especially common on vegetables growing around/in dirt, like garlic. The spores are

  • indestructible when using common cooking methods
  • dormant under normal food storage conditions
  • not dangerous to humans above 1 year of age. They remain dormant in the human body and get excreted without causing anything.

Then, you have botulinum bacteria colonies. To get a colony going, you need to take some spores and cut off the oxygen supply. For example, storing raw garlic in oil provides both a possible contamination route and a perfect growth environment.

The bacteria themselves are - easy to kill off with heat - not prone to establishing a colony in your body.

The problem with the bacteria: Once there has been a colony, it starts producing the toxin. This toxin is very poisonous even in minute amounts, and stays around to harm you even after you have killed the bacteria which produced it (e.g. with acid). It is not especially heat stable, certainly not as stable as the spores.

So, the way you get botulism is:

  • Start out with food contaminated by the spores (meat is rarely such food, vegetables are more common. Of course, cross contamination in your kitchen is possible.)
  • Cut off all oxygen supply for some time. A colony forms.
  • Sterilizing the food by placing it in boiling water for some time doesn't matter, the spores will survive it easily. (This is why industrial food is canned at much higher temperatures, and safe home canning recipes are quite acidic).
  • eat the food after it has been stored with the colony inside.

So, vultures don't have any special resistance to botulism toxin, they just don't come in contact with it.

On a side note, there are quite a few other pathogens which are common in meat, and vultures are probably more resistant to them than humans. But it is normal for bacteria to be able to only make one species, or a small range of species sick. Just ask the poor medical researchers trying to heal human disease in mouse models - there are huge differences.


Who's Protecting Whom From Deadly Toxin?

Botulism bacteria, or Clostridium botulinum, grow in poorly preserved canned foods, especially meat and fish. The microbe's toxin could be lethal as a bioweapon. Dr. Phil Luton/Science Photo Library/Corbis hide caption

Botulism bacteria, or Clostridium botulinum, grow in poorly preserved canned foods, especially meat and fish. The microbe's toxin could be lethal as a bioweapon.

Dr. Phil Luton/Science Photo Library/Corbis

Questions are swirling around a science journal's decision last year to publish a description of a newly discovered botulinum toxin while omitting key genetic details that researchers would normally disclose.

The unusual case highlights important unresolved issues in how to balance scientific openness with the worry that biological information could potentially be misused.

Shots - Health News

Why Scientists Held Back Details On A Unique Botulinum Toxin

NPR has learned that the scientist at the center of this controversy has not been sharing materials and information with other botulinum toxin researchers — and for two years, he ignored entreaties from federal officials who wanted the microbe so that they could test vaccines and antitoxins.

The scientist kept the genetic sequence secret, but federal officials did not recommend doing so.

Some experts who have concerns about how potentially dangerous discoveries are dealt with in biology say this situation shows that it's still unclear what kinds of findings should be withheld from the public, who should make those decisions, and how to ensure that legitimate researchers will get access to the information so that science can advance and protect public health.

A Dangerous New Toxin

Botulinum toxin, produced by bacteria, is the most poisonous substance known. For that reason it has long been considered a potential bioweapon. The federal government even stockpiles antitoxins against the known toxin types, in case of a terrorist attack.

So it was big news last October when scientists announced that they'd discovered the first new form of botulinum toxin in more than 40 years — a toxin they called "type H" that they said could not be neutralized by the available treatments.

Scientists led by Stephen Arnon at the California Department of Public Health made the surprise find in a clinical sample from a baby who had been sick with infant botulism.

Editors for the Journal of Infectious Diseases agreed to Arnon's request that the papers not include the genetic sequence for the novel toxin because of fears it could provide a recipe for a bioweapon.

In an editorial, the journal editors noted that Arnon had consulted with experts at multiple federal government agencies before publishing.

In a statement provided to NPR Monday, the California Department of Public Health made it clear that federal officials had not asked Arnon to withhold the genetic data.

"While the Department indicated to the media that this decision was made at the behest of federal agencies, we now know that this is not the case," the agency's director, Ron Chapman, said in the statement. "The Department is committed to accuracy in all of its communications with the public and regrets the error."

NPR asked to speak with Arnon, but a spokesman for the public health department said Arnon would not be available for an interview.

NPR sent detailed questions to the agency and Arnon on April 16. As of 5 p.m. Monday, California time, we'd received no response to those questions.

A Meeting With Government Officials

On May 29, 2012, Arnon met to discuss this newly discovered toxin with representatives of government agencies including the National Institutes of Health, Centers for Disease Control and Prevention, Department of Defense and Federal Bureau of Investigation.

"It is my understanding that there was no recommendation from that committee to withhold the sequence," says Robert Tauxe, deputy director of the division of foodborne, waterborne and environmental diseases at the CDC.

But there was one thing that federal officials did want: the microbial strain that made the toxin.

"Sitting around the table, I think this was the request of everybody from the government . 'Can you provide us with the strain?' " says Leonard Smith of the U.S. Army Medical Research Institute of Infectious Diseases.

He explains that officials wanted the strain to evaluate whether stockpiled therapies or vaccines in development would work against the toxin. "And I think that started the problem," says Smith. "Because Dr. Arnon was very reluctant to release it."

Internal emails obtained by NPR under the California Public Records Act reveal the frustration of government officials as their requests resulted in no action.

"It's time for us to revisit the issue of making available your novel [botulinum] strain for USG [U.S. government] evaluation," Michael Kurilla, director of the Office of BioDefense Research Affairs at the NIH, wrote to Arnon in September 2012. "At this point, I have exhausted my internal resources to constructively engage with you on this topic. . If you are prepared to share your strain (and I do mean a live strain, rather than an extract), then let us proceed. On the other hand, if we are merely to continue with unproductive conversations and more letter writing, I will simply declare defeat on my part to address what may represent a potentially serious vulnerability to a biothreat agent that had been previously considered adequately addressed."

The CDC first requested that Arnon send them the strain in 2011, an agency spokesman told NPR. The agency did not receive it until January 2014.

Now that CDC researchers finally do have access to the strain, important work can begin, says Tauxe.

"The bottom line for us is, there's a lot more science to be done still," says Tauxe, "with questions that are still open about just how does this toxin differ from the standard known seven toxin types. . Will the existing antitoxin that we have here in the United States protect against it, or not?"

"I wish we had received the information two years ago, 2 1/2 years ago. We could have had a jump on things," says USAMRIID's Smith. "Later is better than never."

'Google Botulinum And Iran'

And it wasn't just key government agencies that Arnon shut out from working on the novel toxin. Other botulinum experts say they also tried to obtain the strain, after the scientific papers describing it were published in October.

Researcher Andreas Rummel of Hannover Medical School in Germany says he repeatedly asked Arnon, both by email and at a scientific conference in Annapolis, to share the sequence with his lab and others that study botulinum toxin.

"And he basically pointed out that I should go to Google and make a search for Iran and botulinum neurotoxin," says Rummel, saying that the implication was that the information could not be shared because of fears that scientists in Iran could use the information to produce a bioweapon.

Rummel says he also had a long phone call with Arnon, and that Arnon referred him to Web pages of think tanks in Washington, D.C., that referred to the possible production of botulinum toxin as a bioweapon in Iran.

"He was not willing to provide any even partial sequence of the strain. At least the release of a partial sequence would have helped to improve diagnostics worldwide," says Rummel, noting that without this information, laboratory tests would not be able to identify any patients sickened with this toxin.

Asked if Arnon's fears about misuse of the information were warranted, Smith at USAMRIID replied, "I don't know."

"I think that was a judgment call on Dr. Arnon's part," says Smith, who describes himself as a friend of Arnon. "I'm not going to say either way whether he was right or wrong. In his conviction, he felt that the way he handled this was the way it needed to be. He didn't want to be accused of putting information out there that could come back and harm the United States, and I have to respect his conviction and judgment on that."

But Rummel doubts that just knowing the genetic sequence would let someone make a dangerous new weapon. The sequence would only allow scientists to produce a naked neurotoxin that would not be surrounded by various proteins that normally stabilize it.

"I cannot see that this, from the technical scientific point of view, will pose any threat," Rummel says.

Because Arnon did not publish the full genetic sequence, he notes, botulinum scientists have been unable to verify Arnon's work.

"The question for me is, is this really a new serotype or not?" says Rummel, noting that it could just be a hybrid of already known toxin types.

A Letter Goes Unanswered

That question was echoed by another researcher whose requests for access to the strain or genetic sequence have been denied.

Eric Johnson of the University of Wisconsin, Madison, has studied botulinum toxin for 30 years. He says at the moment, it's not possible to know whether Arnon really has discovered a novel toxin.

In a recently published letter to the editors of the Journal of Infectious Diseases, Johnson wrote that "there are significant scientific concerns in the studies in that certain of the strategies and experiments performed were not decisive and definitive to define a new serotype of botulinum neurotoxin."

"It is impossible to critically evaluate the novelty of a declared new serotype or potentially significant discovery when other laboratories do not have access to the materials and information," Johnson wrote.

"The specialty of my lab is purifying toxins," Johnson told NPR. "If we had the nucleic acid we could clone the gene and express it and purify it and definitively study its characteristics."

Editors of the Journal of Infectious Diseases said they sent Johnson's letter to Arnon at the California Department of Public Health and that he informed the journal that "the California Department of Public Health elected not to submit a reply."

The journal editors, however, did respond to Johnson's letter, saying that when they accepted the manuscript with the sequence information withheld, the purpose was not to keep reputable scientists from obtaining useful information. They expected that the strains and data would be shared.

David Hooper of Massachusetts General Hospital, one of the journal's editors, said that the journal had not been involved in the consultations with the government. The plan to publish without the genetic information had been Arnon's idea.

"I think we made our best judgment," Hooper told NPR.

But one outside expert who reviewed the research paper for the journal prior to publication advised against withholding the gene sequence, saying it would be "unprecedented" for the journal to publish a paper about a new gene and not provide the sequence. "Indeed, this paper provides little value for medicine, public health or biodefense efforts if the gene sequences are not provided," the reviewer wrote.

This reviewer did agree that "the risk of nefarious use of the gene sequence outweighs its immediate release" but urged that the authors simply wait a year or two and publish the full information — after countermeasures against the toxin were developed.

Keeping the Genetic Information Secret

Federal officials generally seem to have supported publication of the research findings.

One letter to Arnon says the government supported his submitting "any and all manuscripts" regarding this novel finding for publication.

"While we appreciate that you recognized the potentially sensitive nature of these findings and solicited our input prior to submission, representatives from the intelligence, public health and scientific communities who have reviewed the available information believe these results dealing specifically with the discovery, isolation, identification, and characterization of this novel strain of C. botulinum should be published," senior science adviser George Korch of the Department of Health and Human Services wrote to Arnon in January 2013. "It was never our intention to prevent public dissemination of the discovery of this novel strain. In fact, I am aware of an endorsement for publication from the Centers for Disease Control and Prevention from over one year ago."

In December 2013, Arnon was quoted by a newspaper, The Sacramento Bee, as saying that "the recommendations from the federal government were clear on the potential risks of publishing the gene sequence." The story was picked up by the AP and other news outlets.

But after that story appeared, Arnon wrote an email to the editors of the Journal of Infectious Diseases and a communications consultant. He wrote that the newspaper's quote was "bogus" and not something that he had ever said or written. The federal government never made recommendations on the potential risks of publishing the gene sequence, he said.

"I would appreciate any and all of you making clear to whomever may inquire that the federal government did not 'recommend' to CDPH that CDPH withhold the toxin gene sequence," Arnon wrote.

Emails show that Arnon worried about keeping the genetic information secret.

In a letter to the editors of the journal, he noted that anyone could request the genetic sequence under California's Public Records Act.

Arnon encouraged the journal's editors to write an editorial supporting the decision to not release the sequence, noting that if legal questions about public access arose, "it would be very valuable to have the leading journal in infectious diseases clearly state that presently not releasing the sequence is the right and proper course to take."

In another letter to the journal editors, he noted his concern that computer hackers would attempt to get the sequence information. He said his team had prepared for that by deleting emails that might contain sensitive information and making sure that no sequence information was stored on computer hard drives.

Journal Editors Making Ad Hoc Decisions

One editor of a scientific journal says that the questions about information-sharing raised by this discovery will come up again and again in the future as researchers make other finds that raise potential security issues, and that the federal government needs to figure out how to provide guidance.

Similar issues arose in 2012 concerning the publication of research detailing the genetic steps that could potentially make a bird flu virus transmissible through the air between humans. Papers describing that work were eventually published in full, after a long and heated debate among scientists, government officials, and security experts.

"Editors are running into more and more papers in which there are concerns. And this is being handled ad hoc inside the journals," says Arturo Casadevall of Albert Einstein College of Medicine, who edits the journal mBio and serves on the National Science Advisory Board for Biosecurity, which advises the government on research that could be potentially misused.

He notes that ultimate responsibility does fall on the scientists and the journals. "The problem is lack of sufficient expertise," says Casadevall.

Where Do We Go From Here?

He and several other journal editors are now calling for the government to set up a national board that would evaluate scientific papers for potential security risks and make recommendations about whether information should be made public or kept secret.

He says, however, that if research is identified as being too sensitive for public release, it's unclear how to ensure that scientists who need to know will get access.

"This is an area where the jury's still out. Basically we have never faced these problems before in science and what we need is discussion and to come to a consensus on how these things are going to be handled," says Casadevall. "But right now, that doesn't exist."


Introduction

Clostridium botulinum and botulism, the disease it causes, have been known to man for centuries 1 . Botulism is a severe neuroparalytic disease caused by the action of botulinum neurotoxins (BoNTs) produced by anaerobic spore-forming C. botulinum and some of its close relatives 2 . The BoNTs are regarded as the most potent toxins known to mankind 3 . If left untreated, a severe case of botulism leads to death of the patient due to paralysis of respiratory muscles. Although the disease has been known to man since ancient time, Muller in 1870 coined the name 𠆋otulism’ for the newly described disease 4 . Following the advent of microbiology in the late 19 th century, the causative organism was isolated from contaminated meat and recognized as an anaerobic bacillus 5 . Cultivation of the bacillus and its subsequent introduction into animals leading to development of the symptoms of botulism has been reported 6 .

One of the most fascinating aspects in the field of botulinum toxin research in recent years has been application of the most potent toxin in treatment of neurological disorders. It has become the first biological toxin which is licensed as drug for treatment of human diseases. As of January 2008, two BoNT serotypes (A and B) are approved for clinical use in the United States by Food and Drug Administration (FDA). Subsequently, the neurotoxin has become a household name as clients line up at local gyms, parties, and spas for Botox injections, in order to temporarily rid themselves of wrinkles and sweaty armpits. This review provides updated information on warfare potential and medical uses of botulinum neurotoxin.


The most toxic substances for the body

By means of different tests, we can determine the toxicity of a substance, whether it’s liquid, gaseous or a solid. If you want to know which substances are most toxic to the body, keep reading:

1. Mercury

For a long time now, manufacturers have stopped producing thermometers that contain mercury. This is because mercury is a toxic substance and exposure to this element can cause irreparable damage to the kidneys and brain. Contact with mercury for pregnant women is prohibited, as it is the cause of hearing, vision and memory problems in the fetus.

2. Arsenic

If a person inhales arsenic, the body’s circulatory system absorbs it. The extent to which it is absorbed depends upon the solubility (the level to which it has been dissolved in the oxygen that we breathe). The size of the arsenic particles and whether the substance has been diluted or not, also has an impact on the level of toxicity.

When arsenic is present in food, the intestine absorbs it quickly, where it rapidly reaches the blood stream. Arsenic that has been ingested is mostly eliminated through urine, but this still leaves traces inside the body. This heavy metal can cause multi-organ failure, cardiac and respiratory problems.

3. Lead

Until fairly recently, lead was being used in household paint, pipework and even in dentistry. When ingested, the human body can’t excrete this metal and it becomes harmful in a short period of time. Symptoms of lead poisoning can include brain damage, memory loss, abdominal pain and even infertility.

4. Botulinum toxin

Commonly referred to as Botox, and widely used in the aesthetic industry, this is one of the most toxic substances that exists. Botox is often injected to improve the appearance of wrinkles and to increase the size of the lips. Botulinum neurotoxins can cause muscle paralysis and it has the ability to ‘stick’ to viruses and bacteria and makes them more resistant to medications.

5. Cyanide

Although several plants naturally produce cyanide, (bamboo, sorghum, and cassava), when high concentrations of this compound enter our body, cyanide can cause death. Liquid or gaseous cyanide can enter the body through ingestion, inhalation or contact with mucous membranes (eyes, nose) and skin.

6. Toluene

Toluene is another substance that is very toxic to the body and we can find this in various objects that we have at home: plastic bottles, paints, cosmetics, adhesives, nylon, perfumes… And the list goes on.

Inhaling toluene can be dangerous to our health, so it’s necessary to take certain precautions. For example, always wear a mask when painting, avoid breathing in car fumes and wear latex gloves when using cleaning products. Also present in nail polishes and makeup, be sure to check the ingredients of cosmetics and avoid using products that contain this substance.

7. PCBs

This synthetic chemical was very popular in certain commercial industries because of its two main characteristics: stability and non-flammability. Although nowadays there are few products on the market containing this chemical, it’s still in use. PCBs are often found in paints (that are made from oil), coal, plastics and food crops.

Latest research reveals that traces of PCBs have also been found in fish, such as salmon and even in several aquatic mammals. To prevent this chemical from entering your body, only consume organic products and wash all foods thoroughly before eating them.

8. Tetrodotoxin

Not all toxic substances are produced in laboratories, many are also found naturally in our environment. Tetrodotoxin is the most noxious element that an animal can produce. We can find this substance in the famous ‘pufferfish’ or ‘fugu’.

The fugu is an expensive culinary delicacy that requires expert chefs to handle and prepare it. Without the correct preparation technique, this dish can cause poisoning and even death. A single puffer fish contains enough toxins to kill 30 people. The tetrodotoxin compound is 1,000 times deadlier than cyanide, and 100 times more deadly than the venom of a black widow spider.


Micro Exam 4

No matter the cause, it results in these typical symptoms: photophobia (sensitivity to light), headache, painful or stiff neck, fever, and usually an increased number of white blood cells in the CSF.

often associated with epidemic forms of meningitis.

This organism causes the most serious form of acute meningitis, and it is responsible for about 25% of all meningitis cases.

Most cases occur in young children, since vaccination of otherwise healthy children against this disease is not recommended until age 11

The portal of entry for this pathogen is the upper respiratory tract.

The bacterium passes into surrounding blood vessels, rapidly penetrating the meninges and producing symptoms of meningitis.

The most serious complications of meningococcal infection are due to meningococcemia, which can accompany meningitis but can also occur on its own. The pathogen releases endotoxin within the bloodstream, which acts as a potent white blood cell stimulator.

The pathogen has a natural ability to avoid destruction through its production of IgA protease and the presence of a capsule.

The scene is set for transmission when carriers live in close quarters with nonimmune individuals, as may be expected in families, day care facilities, college dormitories, and military barracks

this pathogen is the most frequent cause of community-acquired meningitis and often causes a severe form of the disease.

It does not cause the petechiae associated with meningococcal meningitis, and that difference is useful diagnostically.

Pneumococcal meningitis is most likely to occur in patients with underlying susceptibility, such as patients with alcoholism, patients with sickle-cell disease, and those with absent or defective spleen function. Up to 25% of pneumococcal meningitis patients will also develop pneumococcal pneumonia.

Routine vaccination with one of two subunit vaccines (both contain capsular polysaccharide conjugated to a protein) is recommended for all children, beginning at age 2 months, with the recommendation of a follow-up booster dose

Cells do not produce capsules or endospores and have from one to four flagella.

is not fastidious and is resistant to cold, heat, salt, pH extremes, and bile. It grows inside host cells and can move directly from an infected host cell to an adjacent healthy cell.

The death rate is around 20%. Pregnant women are especially susceptible to infection, which can be transmitted to the infant prenatally when the microbe crosses the placenta or postnatally through the birth canal. Intrauterine infections are systemic and usually result in premature abortion and fetal death.

Most cases are associated with ingesting contaminated dairy products, poultry, and meat.

It is sometimes classified as a meningoencephalitis (inflammation of both brain and meninges).

Headache is the most common symptom, but nausea and neck stiffness are very common. This fungus is a widespread resident of human habitats. It has a spherical to ovoid shape, with small, constricted buds and a large capsule that is important in its pathogenesis

Masses of dried yeast cells are readily scattered into the air and dust. Its role as an opportunist is supported by evidence that healthy humans have strong resistance to it and that clinically obvious infection occurs primarily in debilitated patients

By far the highest rates of cryptococcal meningitis occur among patients with AIDS. This meningitis is frequently fatal. Other conditions that predispose individuals to infection are steroid treatment, diabetes, and cancer. It is not considered communicable among humans

The morphology is very distinctive. At 25°C, it forms a moist white to brown colony with abundant, branching, septate hyphae. These hyphae fragment into thick-walled, blocklike arthroconidia (arthrospores) at maturity.

On special media incubated at 37°C to 40°C, an arthrospore germinates into the parasitic phase, a small, spherical cell called a spherule that can be found in infected tissues as well. This structure swells into a giant sporangium that cleaves internally to form numerous endospores that look like bacterial endospores but lack their resistance traits.

But many other viruses also gain access to the central nervous system on occasion. An initial infection with herpes simplex type 2 is sometimes known to cause meningitis other herpesviruses, such as HHV-6, HHV-7, and HHV-3 (the chickenpox virus), can infect the meninges as well.

Arboviruses, arenaviruses, and adenoviruses have also been identified as causative agents of meningitis and it is recognized that HIV infection may manifest as meningitis even when the virus is controlled in the rest of the body.

Viral meningitis is generally milder than bacterial or fungal meningitis, and it is usually resolved within 2 weeks. The mortality rate is less than 1%.

20% of them die, even with aggressive antibiotic treatment, and those who survive often have brain damage.

It has been implicated in outbreaks of neonatal and infant meningitis transmitted through contaminated powdered infant formula. Although cases of Cronobacter meningitis are rare, mortality rates can reach 40%.

It can form a rounded, thick-walled cyst that is resistant to temperature extremes and mild chlorination.

Most cases of infection reported worldwide occur in people who have been swimming in warm, natural bodies of freshwater.

Infection can begin when amoebas are forced into human nasal passages as a result of swimming, diving, or other aquatic activities. The amoeba infects the olfactory epithelium and utilizes the olfactory nerve to travel to the brain.

It differs from Naegleria in its portal of entry it invades broken skin, the conjunctiva, and occasionally the lungs and urogenital epithelia.

Peak incidence of infection typically occurs when the arthropod is actively feeding and reproducing, usually from late spring through early fall. Warm-blooded vertebrates also maintain the virus during the cold and dry seasons.

Humans can serve as dead-end, accidental hosts, as in equine encephalitis, or they can be a maintenance reservoir, as in yellow fever

________________________ encephalitis begins with an arthropod bite, releasing the virus into the bloodstream, where it will travel to nearby lymphoid tissues for replication

The patient's history of travel to endemic areas or contact with vectors, along with serum analysis, helps with the diagnosis.

Most of the control safeguards for ________________ disease are aimed at the arthropod vectors.

All encephalitis cases are treated with acyclovir, in case they are caused by this virus, against which acyclovir is effective.

The virus is found throughout North America but until recently was rarely seen in humans.

The usual pattern is sporadic, but epidemics can occur in humans and horses.

Seroprevalence of this polyomavirus nears 80% in many parts of the United States and Europe, though most infections are asymptomatic.

In patients with immune dysfunction, especially in those with AIDS, this pathogen can cause a condition called progressive multifocal leukoencephalopathy.

Infection in the fetus and in immunodeficient people, especially those with AIDS, is severe and often fatal.

Although infection in otherwise healthy people is generally unnoticed, recent data tells us it can have profound effects on their brain and the responses it controls

It seems that people with a history of this infection are more likely to display thrill-seeking behaviors and other significant changes in their brains.

most cases are asymptomatic or marked by mild symptoms such as sore throat, lymph node enlargement, and low-grade fever.

In patients whose immunity is suppressed by infection, cancer, or drugs, the outlook may be grim. The infection causes a more chronic or subacute form of encephalitis than do most viruses, often producing extensive brain lesions and fatal disruptions of the heart and lungs.

Symptoms of all forms include altered behavior, dementia, memory loss, impaired senses, delirium, and premature senility. Uncontrollable muscle contractions continue until death, which usually occurs within 1 year of diagnosis.

It is thought that 10% to 15% of CJD cases are due to an inherited mutation within a single gene. These are termed familial or hereditary CJD

a protein called PrPC that spontaneously transforms into a nonfunctional form in CJD. This altered protein (PrPSC), which he termed a prion, triggers damage in the brain and other areas of the central nervous system. The PrPSC actually becomes catalytic and able to spontaneously convert other normal human PrPC proteins into the abnormal form. This becomes a self-propagating chain reaction that creates a massive accumulation of PrPSC, leading to plaques, spongiform damage (that is, holes in the brain), and severe loss of brain function.

It is distributed nearly worldwide, except for perhaps two dozen countries that have remained rabies-free by practicing rigorous animal control.

The average incubation period is 1 to 2 months or more, depending on the wound site, its severity, and the inoculation dose

"furious" - the first acute signs of neurological involvement are periods of agitation, disorientation, seizures, and twitching. Spasms in the neck and pharyngeal muscles lead to severe pain upon swallowing, leading to a symptom known as hydrophobia (fear of water). Throughout this phase, the patient is fully coherent and alert.

"dumb" - a patient is not hyperactive but is paralyzed, disoriented, and stuporous.

Being neurotropic, the virus infiltrates the motor neurons of the anterior horn of the spinal cord, although it can also attack spinal ganglia, cranial nerves, and motor nuclei.

Depending on the level of damage to motor neurons, paralysis of the muscles of the legs, abdomen, back, intercostals, diaphragm, pectoral girdle, and bladder can result.

In rare cases of bulbar __________________, the brain stem, medulla, or even cranial nerves are affected. This situation leads to loss of control of cardiorespiratory regulatory centers, requiring mechanical respirators

The etiologic agent, Clostridium tetani, is a common resident of soil and the gastrointestinal tracts of animals. It is a gram-positive, endospore-forming rod. The endospores it produces often swell the vegetative cell but are only produced under anaerobic conditions.

C. tetani releases a powerful neurotoxin, tetanospasmin, that binds to target sites on peripheral motor neurons, on the spinal cord and brain, and in the sympathetic nervous system. The toxin acts by blocking the inhibition of muscle contraction.

Without inhibition of contraction, the muscles contract uncontrollably, resulting in spastic paralysis. The first symptoms are clenching of the jaw, followed in succession by extreme arching of the back, flexion of the arms, and extension of the legs

Lockjaw confers the bizarre appearance of risus sardonicus (sardonic grin), which looks eerily as though the person is smiling. Death most often occurs due to paralysis of the respiratory muscles and respiratory arrest.

As the vegetative cells grow, various metabolic products are released into the infection site, including the tetanospasmin toxin. The toxin spreads to nearby motor nerve endings in the injured tissue, binds to them, and travels via axons to the ventral horns of the spinal cord

Endospores usually enter the body through accidental puncture wounds, burns, umbilical stumps, frostbite, and crushed body parts

Neonatal ____________ still kills 60,000 newborns each year. A majority of infections in these countries are a direct result of unhygienic practices during childbirth, including the use of dung, ashes, or mud to arrest bleeding or for religious purposes during this process.

Clostridium botulinum, like Clostridium tetani, is an endospore-forming anaerobe that does its damage through the release of an exotoxin.

Until recent times, it was relatively common and frequently fatal, but modern techniques of food preservation and medical treatment have reduced both its incidence and its fatality rate.

a common cause of death in livestock that have grazed on contaminated food and in aquatic birds that have eaten decayed vegetation.

There are three major forms, distinguished by their means of transmission and the population they affect. These are food-borne (in children and adults), infant, and wound. Food-borne in children and adults is an intoxication resulting from the ingestion of preformed toxin the other two types are infections that are followed by the entrance of an exotoxin called botulinum toxin

The effect of botulinum is to prevent the release of acetylcholine, the neurotransmitter that initiates the signal for muscle contraction.

The usual time before onset of symptoms is 12 to 72 hours, depending on the size of the dose.

Neuromuscular symptoms first affect the muscles of the head and include double vision, difficulty in swallowing, and dizziness, but there is no sensory or mental lapse. Later symptoms are descending muscular paralysis and respiratory compromise. In the past, death resulted from respiratory arrest, but mechanical respirators have reduced the fatality rate to about 10%.

Trypanosoma brucei is a flagellated protozoan, an obligate parasite that is spread by a blood-sucking insect called the tsetse fly, which serves as its intermediate host. It shares a complicated life cycle with other hemoflagellates.

T. brucei gambiense is found in west and central Africa, is associated with chronic disease, and accounts for over 95% of total reported cases

T. brucei rhodesiense is found in eastern and southern Africa.

occurs only in sub-Saharan Africa

Most of the time it refers to an infection of the valves of the heart, often the mitral or aortic valves

Two variations of infectious endocarditis have been described: acute and subacute. Each has distinct groups of possible causative agents, most of which are bacterial organisms

Symptoms include fever, anemia, abnormal heartbeat, and sometimes symptoms similar to myocardial infarction. Shortness of breath is a common symptom additionally, chills may develop.

most often caused by Staphylococcus aureus

Most commonly caused by bacteria of low pathogenicity, often originating in the oral cavity.
- Alpha-hemolytic streptococci, such as Streptococcus sanguinis, S. oralis, and S. mutans, are most often responsible, although normal biota from the skin and other bacteria can also colonize abnormal valves and lead to this condition

Gram-negative bacteria multiplying in the blood release large amounts of endotoxin into the bloodstream, stimulating a massive inflammatory response mediated by a host of cytokines. This response invariably leads to a drastic drop in blood pressure, a condition called endotoxic shock. Gram-positive bacteria can instigate a similar cascade of events when fragments of their cell walls are released into the blood.

Fever is a prominent feature. The patient appears very ill and may have an altered mental state, shaking chills, and gastrointestinal symptoms. Often an increased breathing rate is exhibited, accompanied by respiratory alkalosis.

Low blood pressure is a hallmark of this condition and is caused by the inflammatory response to infectious agents in the bloodstream, which leads to a loss of fluid. This condition is the most dangerous feature of the disease, often culminating in death.

hosts spread the disease to other mammals, called amplifying hosts, that become infected with the bacterium and experience massive die-offs during epidemics.

caused by a facultative intracellular gram-negative bacterium called Francisella tularensis

abundantly distributed through numerous animal reservoirs and vectors in northern Europe, Asia, and North America but not in the tropics. This disease is noteworthy for its complex epidemiology and spectrum of symptoms.

Although rabbits and rodents (muskrats and ground squirrels) are the chief reservoirs, other wild animals (skunks, beavers, foxes, opossums) and some domestic animals are implicated as well.

slow-acting, but it often evolves into a progressive syndrome that mimics neuromuscular and rheumatoid conditions. An early symptom in 70% of cases is a rash at the site of a tick bite. The lesion, called erythema migrans, can look like a bull's-eye, with a raised, erythematous (reddish) ring that gradually spreads outward and a pale central region

Other early symptoms are fever, headache, stiff neck, and dizziness. If not treated or if treated too late, the disease can advance to the second stage, during which cardiac and neurological symptoms, such as facial palsy, can develop. After several weeks or months, a crippling polyarthritis can attack joints. Some people acquire chronic neurological complications that are severely disabling.

Culture of the organism is not useful.

The symptoms are sore throat, high fever, and cervical lymphadenopathy, which develop after a long incubation period (30 to 50 days). Many patients also have a gray-white exudate in the throat, a skin rash, and enlarged spleen and liver. A notable sign is sudden leukocytosis, consisting initially of infected B cells and later T cells. Fatigue is a hallmark of the disease.

infection during the teen years results in disease about 25% of the time, whereas infection before or after this period is usually asymptomatic

Direct oral contact and contamination with saliva are the principal modes of transmission, although transfer through blood transfusions, sexual contact, and organ transplants is possible.

Bacillus anthracis is a gram-positive, endospore-forming rod that is among the largest of all bacterial pathogens.

a facultative parasite that undergoes its cycle of vegetative growth and sporulation in the soil. Animals become infected while grazing on grass contaminated with endospores.

The main virulence factor of B. anthracis is what is referred to as a "tripartite" toxin

also called "breakbone fever" because of the severe pain it can induce in muscles and joints (it does not actually cause fractures).

The illness is endemic to Southeast Asia and India, and several epidemics have occurred in South America and Central America, the Caribbean, and Mexico.

Although it typically presents as a mild infection, a new form of disease called dengue hemorrhagic fever (DHF) has emerged that causes high rates of morbidity and mortality in endemic areas.

Dengue shock syndrome (DSS) can develop in DHF patients exhibiting life-threatening hypotension.

Symptoms are similar to dengue fever with the additional complication of severe joint pain, sometimes lasting for years, and occasional neurological impairment.

contains tiny, aerobic gram-negative coccobacilli

enters through damaged skin or via mucous membranes of the digestive tract, conjunctiva, and respiratory tract.

It is associated predominantly with occupational contact in slaughterhouses, livestock handling, and the veterinary profession. Infection takes place through contact with blood, urine, and placentas and through consumption of raw milk and cheese. Human-to-human transmission is rare, but brucellosis is considered the most common laboratory-acquired infection.

The patient's history can be very helpful in diagnosis, as are serological tests of the patient's blood and blood culture of the pathogen. In areas where Brucella is endemic, serology is of limited use because significant proportions of the population already display antibodies to the bacterium. Blood culture is the gold standard. PCR-based testing is available but not yet reliable enough.

Humans acquire infection largely by means of environmental contamination and airborne spread. Birth products such as placentas of infected domestic animals contain large numbers of bacteria. Other sources of infectious material include urine, feces, milk, and airborne particles from infected animals

The signs and symptoms include an acute febrile state resulting in headache, muscle pain, and rigors. Most patients recover rapidly with no lasting effects, but about 5% of older, chronically ill patients can die.

It produces symptoms similar to those of to Ehrlichia and Anaplasma. It is also carried by ticks.

caused by a bacterium called Rickettsia rickettsii, which is transmitted by hard ticks such as the wood tick (Dermacentor andersoni), the American dog tick (D. variabilis, among others), and the Lone Star tick (Amblyomma americanum). The dog tick is probably most responsible for transmission to humans because it is the major vector in the southeastern United States.

it can cloak itself in host proteins, disguising itself from the immune system. It can also induce autoimmunity, so that the same immune cells trained to recognize it begin to react with host tissues, causing the symptoms of late-stage Chagas disease.

Once the trypanosomes are transmitted by a group of insects called the triatomines, they multiply in muscle and blood cells

The disease manifestations are divided into acute and chronic phases. Soon after infection, the acute phase begins symptoms are relatively nondescript and range from mild to severe fever, nausea, and fatigue. A swelling called a "chagoma" at the site of the bug bite may be present. If the bug bite is close to the eyes, a distinct condition called Romana's sign, swelling of the eyelids, may appear. The acute phase lasts for weeks or months after which the condition becomes chronic and virtually asymptomatic for a period of years or indefinitely.

spread primarily by the female Anopheles mosquito and occasionally by shared hypodermic needles and blood transfusions.

the first symptoms are malaise, fatigue, vague aches, and nausea with or without diarrhea, followed by bouts of chills, fever, and sweating.

These symptoms occur at 48- or 72-hour intervals, as a result of the synchronous rupturing of red blood cells. The interval, length, and regularity of symptoms reflect the type of malaria

Patients with falciparum ____________, the most virulent type, often manifest persistent fever, cough, and weakness for weeks without relief.

Complications are hemolytic anemia from lysed blood cells and organ enlargement and rupture due to cellular debris that accumulates in the spleen, liver, and kidneys.

One of the most serious complications of falciparum _________________ is termed cerebral ___________. In this condition, small blood vessels in the brain become obstructed due to the increased ability of red blood cells (RBCs) to adhere to vessel walls (a condition called cytoadherence induced by the infecting protozoan).

Plasmodium also metabolizes glucose at a very high rate, leading to hypoglycemia in the human host. The damage to RBCs results in anemia

They are named "retroviruses" because they reverse the usual order of transcription. They contain an unusual enzyme called reverse transcriptase (RT) that catalyzes the replication of double-stranded DNA from single-stranded RNA.

There are two major types of HIV—namely HIV-1, which is the dominant form in most of the world, and HIV-2.
Genetic sequencing of HIV-1 shows that it is most related to simian immunodeficiency viruses in chimpanzees, while HIV-2 evolved from related viruses in sooty mangabeys, a type of monkey found in Africa.
Both highlight the evidence that HIV in humans was derived from a zoonotic primate virus.

sneezing, scratchy throat, and runny nose (rhinorrhea) usually begin 2 or 3 days after infection. Generally is not accompanied by fever, although children can experience low fevers (less than 102°F).

Note that people with asthma and other underlying respiratory conditions (COPD) often suffer more severe symptoms triggered by this.

caused by one of over 200 different kinds of viruses. The particular virus is almost never identified, and the symptoms and handling of the infection are the same no matter which of the viruses is responsible.

most common type of virus leading to this is the group called rhinoviruses, of which there are 99 serotypes. Coronaviruses and adenoviruses are also major causes. Most viruses causing this never lead to any serious consequences, but some of them can be serious for some patients. The respiratory syncytial virus (RSV) causes colds in most people, but in some, especially infants, infection with this virus can lead to more serious respiratory tract symptoms

do not have many virulence mechanisms

transmitted by droplet contact, but indirect transmission may be more common, such as when a healthy person touches a fomite and then touches one of his or her own vulnerable surfaces, such as the mouth, nose, or an eye. In some cases, the viruses can remain airborne in droplet nuclei and aerosols and can be transmitted via the respiratory route.

The infectious agents that may be responsible for the condition include a variety of viruses or bacteria and, less commonly, fungi.

Infections of the sinuses often follow a bout with the common cold. The inflammatory symptoms of a cold produce a large amount of fluid and mucus, and when trapped in the sinuses, these secretions provide an excellent growth medium for bacteria or fungi. This is why it is common for patients suffering from the common cold to then develop sinusitis caused by bacteria or fungi.

typically experiences nasal congestion, pressure above the nose or in the forehead, and sometimes the feeling of a headache or a toothache. Facial swelling and tenderness are common. Discharge from the nose and mouth appears opaque and may have a green or yellow color in the case of bacterial infections. Viral infections are less likely to produce colored discharge. Discharge caused by an allergy is usually clear, and the symptoms may be accompanied by itchy, watery eyes.

Viral infection is probably the most common cause

Many cases are caused by Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Corynebacterium tuberculostearicum, and Haemophilus influenzae. The causative organism is usually not identified, but treatment is begun empirically, based on the symptoms. (not a communicable disease.)

Viral infections of the upper respiratory tract lead to inflammation of the eustachian tubes and the buildup of fluid in the middle ear, which can lead to bacterial multiplication in those fluids.

Bacteria can migrate along the eustachian tube from the upper respiratory tract. When bacteria encounter mucus and fluid buildup in the middle ear, they multiply rapidly. Their presence increases the inflammatory response, leading to pus production and continued fluid secretion. This fluid is referred to as effusion.

accompanied by a sensation of fullness or pain in the ear and loss of hearing. Younger children may exhibit irritability, fussiness, and difficulty in sleeping, eating, or hearing. Severe or untreated infections can lead to rupture of the eardrum because of pressure of pus buildup, or to internal breakthrough of these infected fluids, which can lead to more serious conditions such as mastoiditis, meningitis, or intracranial abscess.

most common cause is Streptococcus pneumoniae

Viral sore throats are generally mild and sometimes lead to hoarseness. Sore throats caused by bacteria are generally more painful than those caused by viruses, and they are more likely to be accompanied by fever, headache, and nausea.

Clinical signs of a sore throat are reddened mucosa, swollen tonsils, and sometimes white packets of inflammatory products visible on the walls of the throat, especially in streptococcal disease. The mucous membranes may be swollen, affecting speech and swallowing. Often results in foul-smelling breath. The incubation period for most sore throats is generally 2 to 5 days.

most serious cases are caused by Streptococcus pyogenes. Specialized polysaccharides on the surface of the cell wall help to protect the bacterium from being dissolved by the lysozyme of the host. Lipoteichoic acid (LTA) contributes to the adherence of S. pyogenes to epithelial cells in the pharynx. A spiky surface Page 621projection called M protein contributes to virulence by resisting phagocytosis and possibly by contributing to adherence. A capsule made of hyaluronic acid (HA) is formed by most S. pyogenes strains. It probably contributes to the bacterium's adhesiveness.

characterized by a sandpaper-like rash, most often on the neck, chest, elbows, and inner surfaces of the thighs. High fever accompanies the rash.

It most often affects school-age children and was a source of great suffering in the United States in the early part of the 20th century. In epidemic form, the disease can have a fatality rate of up to 95%. Most cases seen today are mild. They are easily recognizable and amenable to antibiotic therapy. Because of the fear elicited by the name "scarlet fever," the disease is often called "scarlatina" in North America.

It is characterized by nephritis (appearing as swelling in the hands and feet and low urine output), blood in the urine, increased blood pressure, and occasionally heart failure.

caused by an exotoxin manufactured by Corynebacterium diphtheriae, a non-endospore-forming, gram-positive, club-shaped bacterium.

The symptoms are experienced initially in the upper respiratory tract. At first the patient experiences a sore throat, lack of appetite, and low-grade fever. The most striking symptom of this disease is the characteristic membrane, usually referred to as a pseudomembrane, that forms on the tonsils or pharynx.

The membrane is formed by the bacteria and consists of bacterial cells, fibrin, lymphocytes, and dead tissue cells and may be quite extensive. It adheres to tissues and cannot easily be removed. It may eventually completely block respiration. The patient may or may not recover after this crisis.

The disease worsens in the second (paroxysmal) stage, which is characterized by severe and uncontrollable coughing (a paroxysm is a convulsive attack).

The common name for the disease comes from the sound a patient makes as he tries to grab a breath between uncontrollable bouts of coughing. The violent coughing spasms can result in burst blood vessels in the eyes or even vomiting. In the worst cases, seizures result from small hemorrhages in the brain.

As in any disease, the convalescent period is the time when numbers of bacteria are decreasing and no longer cause ongoing symptoms. But the active stages of the disease damage the cilia on respiratory tract epithelial cells, and complete recovery of these surfaces requires weeks or even months. During this time, other microorganisms can more easily colonize and cause secondary infection.

Bordetella pertussis is a very small, gram-negative rod. Sometimes it looks like a coccobacillus. It is strictly aerobic and fastidious, having specific nutritional requirements for successful culture.

It is absolutely essential for the bacterium to attach firmly to the epithelial cells of the mouth and throat, and it does so using specific adhesive molecular structures on its surface. One of these structures is called filamentous hemagglutinin (FHA). It is a fibrous structure that surrounds the bacterium like a capsule and is secreted in soluble form. In that form, it can act as a bridge between the bacterium and the epithelial cell.

The two most important exotoxins are pertussis toxin and tracheal cytotoxin. Pertussis toxin triggers excessive amounts of cyclic AMP to accumulate in affected cells. This results in copious production of mucus and a variety of other effects in the respiratory tract and the immune system.

Children 6 months of age or younger, as well as premature babies, are especially susceptible to serious disease caused by this virus. RSV is the most prevalent cause of respiratory infection in the newborn age group, and nearly all children have experienced it by age 2. An estimated 100,000 children are hospitalized with RSV disease each year in the United States. The mortality rate is highest for children with complications such as prematurity, congenital disease, and immunodeficiency. Infection in older children and adults usually manifests as a cold.

The first symptoms are fever that lasts for approximately 3 days, rhinitis, pharyngitis, and otitis. More serious infections progress to the bronchial tree and lung parenchyma, giving rise to symptoms of croup, which include acute bouts of coughing, wheezing, dyspnea, and rales. This condition is often called "croup" and bronchiolitis be aware that both of these terms are clinical descriptions of diseases caused by a variety of viruses (in addition to RSV) and sometimes bacteria.

The virus is highly contagious and is transmitted through droplet contact but also through fomite contamination.

can leave patients vulnerable to secondary infections, often bacterial. Influenza infection often leads to a pneumonia that can cause rapid death, even in young, healthy adults.

Patients with emphysema or cardiopulmonary disease, along with very young, elderly, or pregnant patients, are more susceptible to serious complications.

All cases are caused by one of three influenza viruses: A, B, or C. They belong to the family Orthomyxoviridae

binds primarily to ciliated cells of the respiratory mucosa

In general, humans are rather easily infected with the bacterium but are resistant to the disease. Estimates project that only about 5%-10% of infected people actually develop a clinical case of tuberculosis. The majority of TB cases are contained in the lungs, even though disseminated TB bacteria can give rise to tuberculosis in any organ of the body. Clinical tuberculosis is divided into primary tuberculosis, secondary (reactivation or reinfection) tuberculosis, and disseminated tuberculosis.

transmitted almost exclusively by fine droplets of respiratory mucus suspended in the air.

In the IGRA test, a patient's blood is drawn and incubated in test kits that detect the presence of T cells that react with M. tuberculosis antigens. If they have been so sensitized, they will release interferon-gamma (IFN-γ) after binding the antigens. High levels of IFN-γ trigger a positive response. The advantage of these tests is that no return visit is required.

Bacteria and a wide variety of viruses can cause this

kills more children than any other infectious disease in the world today

often simply called the pneumococcus, is a small, gram-positive, flattened coccus that often appears in pairs, lined up end to end. It is alpha-hemolytic on blood agar

Infection can occur when the bacterium is inhaled into deep areas of the lung or by transfer of the bacterium between two people via respiratory droplets

The polysaccharide capsule of the bacterium prevents efficient phagocytosis, apparently by blocking the attachment of complement, with the result that the fluids of inflammation are continuously released into the lungs.

As the infection and inflammation spread rapidly through the lung, the patient can actually "drown" in his or her own secretions. If this mixture of exudates, cells, and bacteria solidifies in the air spaces, a condition known as consolidation occurs.

Systemic complications of pneumonia are pleuritis and endocarditis, but pneumococcal bacteremia and meningitis are the greatest danger to the patient

Mycoplasmas are among the smallest known self-replicating microorganisms. They naturally lack a cell wall and are therefore irregularly shaped. They may resemble cocci, filaments, doughnuts, clubs, or helices. They are free-living but fastidious, requiring complex medium to grow in the lab.

widely distributed in aqueous habitats as diverse as tap water, cooling towers, spas, ponds, and other freshwaters

The organism is endemically distributed on all continents except Australia. Its highest rates of incidence occur in the eastern and central regions of the United States, especially in the Ohio Valley

In people with intact immune defenses, it is usually held in check by lung phagocytes and lymphocytes, but in those with deficient immune systems, it multiplies intracellularly and extracellularly. The massive numbers of fungi adhere tenaciously to the lung pneumocytes and cause an inflammatory condition. The lung epithelial cells slough off, and a foamy exudate builds up.

Symptoms are nonspecific and include cough, fever, shallow respiration, and cyanosis

caused by MRSA strains of Staphylococcus aureus, as well as nonresistant strains

Soon, a severe pulmonary edema occurs and causes acute respiratory distress (acute respiratory distress syndrome [ARDS] has many microbial and nonmicrobial causes this is only one of them).

The acute lung symptoms appear to be due to the presence of large amounts of this antigen, which becomes disseminated throughout the bloodstream (including the capillaries surrounding the alveoli of the lung).

Massive amounts of fluid leave the blood vessels and flood the alveolar spaces in response to the inflammatory stimulus, causing severe breathing difficulties and a drop in blood pressure. The propensity to cause a massive inflammatory response could be considered a virulence factor for this organism.

The process involves the dissolution of solid tooth surface due to the metabolic action of bacteria.

The symptoms are often not noticeable but range from minor disruption in the outer (enamel) surface of the tooth to complete destruction of the enamel and then destruction of deeper layers

Deeper lesions can result in infection to the soft tissue inside the tooth, called the pulp, which contains blood vessels and nerves. These deeper infections lead to pain, referred to as a "toothache."

Two representatives of oral alpha-hemolytic streptococci, Streptococcus mutans and Streptococcus sobrinus, seem to be the main causes

A specific condition called early childhood caries may also be caused by a newly identified species, Scardovia wiggsiae. Note that in the absence of dietary carbohydrates, bacteria do not cause decay.

Teeth become vulnerable to caries as soon as they appear in the mouth at around 6 months of age.

initial stage is gingivitis, the signs of which are swelling, loss of normal contour, patches of redness, and increased bleeding of the gingiva.

Spaces or pockets of varying depth also develop between the tooth and the gingiva. If this condition persists, a more serious disease called periodontitis results. This is the natural extension of the disease into the periodontal membrane and cementum.

The deeper involvement increases the size of the pockets and can cause bone resorption severe enough to loosen the tooth in its socket. If the condition is allowed to progress, the tooth can be lost

plaque accumulating in the gingival sulcus cause abrasions in the delicate gingival membrane, and the chronic trauma causes a pronounced inflammatory reaction.

with high numbers of the bacteria associated with periodontitis also have thicker carotid arteries and increased rates of cardiovascular disease, further supporting the systemic effects of oral inflammation.

After an average incubation period of 2 to 3 weeks, symptoms of fever, nasal discharge, muscle pain, and malaise develop.

These may be followed by inflammation of the salivary glands (especially the parotids), producing the classic gopherlike swelling of the cheeks on one or both sides. Swelling of the gland is called parotitis, and it can cause considerable discomfort.

Viral multiplication in salivary glands is followed by invasion of other organs, especially the testes, ovaries, thyroid gland, pancreas, meninges, heart, and kidney. Despite the invasion of multiple organs, the prognosis of most infections is complete, uncomplicated recovery with permanent immunity.

experienced as sharp or burning pain emanating from the abdomen.

caused by Helicobacter pylori, a curved, gram-negative rod

transmitted from person to person by the oral-oral or fecal-oral route. It seems to be acquired early in life mainly through what is called "familial transfer"—the microbe is acquired from family members, especially from infected mothers to their children.

Gastric or peptic ulcers are actual lesions in either the mucosa of the stomach (gastric ulcers) or in the uppermost portion of the small intestine (duodenal ulcers). Severe ulcers can be accompanied by bloody stools, vomiting, or both. The symptoms are often worse at night, after eating, or under conditions of psychological stress.

These bacteria are normal intestinal biota in cattle, poultry, rodents, and reptiles, and each (including domesticated pets) has been documented as a source of infection in humans.

Animal products such as meat and milk can be readily contaminated during slaughter, collection, and processing. Inherent risks are involved in eating poorly cooked chicken or unpasteurized fresh or dried milk, ice cream, and cheese.

these bacteria are gram-negative, straight rods, nonmotile and non-endospore-forming. They do not produce urease or hydrogen sulfide, traits that help in their identification.

They are primarily human parasites, though they can infect apes

Although Shigella dysenteriae causes the most severe form of dysentery, it is uncommon in the United States and occurs primarily in the Eastern Hemisphere.
-- produces a heat-labile exotoxin called shiga toxin, which seems to be responsible for the more serious damage to the intestine as well as any systemic effects, including injury to nerve cell

In the past decade, the prevalent agents in the United States have been Shigella sonnei and Shigella flexneri, which cause approximately 20,000 to 25,000 cases each year, half of them in children.

frequent, watery stools fever and often intense abdominal pain. Nausea and vomiting are common. Stools often contain obvious blood and even more often are found to have occult (not visible to the naked eye) blood. Diarrhea containing blood is also called dysentery. Mucus from the GI tract will also be present in the stools.

invades the villus cells of the large intestine rather than the small intestine. In addition, it is not as invasive as Salmonella and does not perforate the intestine or invade the blood. It enters the intestinal mucosa by means of lymphoid cells in Peyer's patches. Once in the mucosa, Shigella instigates an inflammatory response that causes extensive tissue destruction. The release of endotoxin causes fever

the agent of a spectrum of conditions, ranging from mild gastroenteritis with fever to bloody diarrhea.

About 10% of patients develop hemolytic uremic syndrome (HUS), a severe hemolytic anemia that can cause kidney damage and failure. Neurological symptoms such as blindness, seizure, and stroke (and long-term debilitation) are also possible. These serious manifestations are most likely to occur in children younger than age 5 and in elderly people.

efface (rub out or destroy) enterocytes, which are gut epithelial cells. The net effect is a lesion in the gut (effacement), usually in the large intestine. The microvilli are lost from the gut epithelium, and the lesions produce bloody diarrhea.

The most common mode of transmission is the ingestion of contaminated and undercooked beef, although other foods and beverages can be contaminated as well. Ground beef is more dangerous than steaks or other cuts of meat

Other farm products may also become contaminated by cattle feces. Products that are eaten raw, such as lettuce, vegetables, and apples used in unpasteurized cider, are particularly problematic.

slender, curved or spiral, gram-negative bacteria propelled by polar flagella at one or both poles, often appearing in S-shaped or gull-winged pairs

causes more diarrhea than Salmonella and Shigella combined

Campylobacter jejuni is the most common cause of diarrhea, although there are other pathogenic species.

tend to be microaerophilic inhabitants of the intestinal tract, genitourinary tract, and oral cavity of humans and animals

Transmission of this pathogen takes place via the ingestion of contaminated beverages and food, especially water, milk, meat, and chicken. Recent studies suggest that C. jejuni is much more resistant to heating temperatures during the cooking process than was previously estimated, increasing the need for proper food handling.

a gram-positive, endospore-forming rod found as normal biota in the intestine.

It was once considered relatively harmless but now is known to cause a condition called pseudomembranous colitis, also known as antibiotic-associated colitis.

In many cases, this infection is precipitated by therapy with broad-spectrum antibiotics. It is a major cause of diarrhea in hospitals, although community-acquired infections have been on the rise in the last few years.

it is able to superinfect the large intestine when drugs have disrupted the normal biota. It produces two enterotoxins, toxins A and B, that cause areas of necrosis in the wall of the intestine.

comma-shaped rods with a single polar flagellum. They belong to the family Vibrionaceae.

A freshly isolated specimen contains quick, darting cells that slightly resemble a comma

After an incubation period of a few hours to a few days, symptoms begin abruptly with vomiting, followed by copious watery feces called secretory diarrhea.

The intestinal contents are lost very quickly, leaving only secreted fluids. This voided fluid contains flecks of mucus—hence, the description "rice-water stool."

Fluid losses of nearly 1 liter per hour have been reported in severe cases, and an untreated patient can lose up to 50% of body weight during the course of this disease.

The diarrhea causes loss of blood volume, acidosis from bicarbonate loss, and potassium depletion, which manifest in muscle cramps, severe thirst, flaccid skin, sunken eyes, and—in young children—coma and convulsions. Secondary circulatory consequences can include hypotension, tachycardia, cyanosis, and collapse from shock within 18 to 24 hours.

The virulence of V. cholerae lies mainly in the action of an enterotoxin called cholera toxin (CT), which disrupts the normal physiology of intestinal cells. When this toxin binds to specific intestinal receptors, a secondary signaling system is activated. Under the influence of this system, the cells shed large amounts of electrolytes into the intestine, an event accompanied by profuse water loss.

It was recently discovered that V. cholerae uses quorum sensing to regulate the precise expression of its virulence factors, making proteins used in this process potential targets for drug therapy.

can be readily isolated and identified in the laboratory from stool samples. Direct dark-field microscopic observation reveals characteristic curved cells with brisk, darting motility as confirmatory evidence.

an intestinal protozoan of the apicomplexan type that infects a variety of mammals, birds, and reptiles

The organism's life cycle includes a hardy intestinal oocyst as well as a tissue phase. Humans accidentally ingest the oocysts with water or food that has been contaminated by feces from infected animals. The oocyst "excysts" once it reaches the intestines and releases sporozoites that attach to the epithelium of the small intestine

The organism penetrates the intestinal cells and lives intracellularly within them. It undergoes asexual and sexual reproduction in these cells and produces more oocysts, which are released into the gut lumen, excreted from the host, and after a short time become infective again. The oocysts are highly infectious and extremely resistant to treatment with chlorine and other disinfectants.

a member of the Reovirus group, which consists of an unusual double-stranded RNA genome with both an inner and an outer capsid.

Diagnosis is not always performed, as it is treated symptomatically.

Stool samples from infected persons contain large amounts of virus, which is readily visible using electron microscopy

The virus gets its name from its physical appearance, which is said to resemble a "spoked wheel." A rapid antigen test for stool specimens is commonly used in clinical settings, and an ELISA test is available.

transmitted by the fecal-oral route, including through contaminated food, water, and fomites. For this reason, disease is most prevalent in areas of the world with poor sanitation

The effects of infection vary with the age, nutritional state, general health, and living conditions of the patient. Babies from 6 to 24 months of age lacking maternal antibodies have the greatest risk for fatal disease. These children present symptoms of watery diarrhea, fever, vomiting, dehydration, and shock. The intestinal mucosa can be damaged in a way that chronically compromises nutrition, and long-term or repeated infections can retard growth. Newborns seem to be protected by maternal antibodies. Adults can also acquire this infection, but it is generally mild and self-limiting.

the most common cause of food-borne illness in the United States.

Transmission is fecal-oral or via contamination of food and water. Viruses generally cause a profuse, watery diarrhea of 3 to 5 days duration. Severe vomiting is a feature of the disease, especially in the early phases. Mild fever is often seen

associated with eating foods such as custards, sauces, cream pastries, processed meats, chicken salad, or ham that have been contaminated by handling and then left unrefrigerated for a few hours.

Because of the high salt tolerance of S. aureus, even foods containing salt as a preservative are not exempt. The toxins produced by the multiplying bacteria do not noticeably alter the food's taste or smell.

The exotoxin (which is an enterotoxin, meaning that it acts on the enteric, or gastrointestinal, system) is heat-stable inactivation requires 100°C for at least 30 minutes. Thus, heating the food after toxin production may not prevent disease.

the organism is a sporulating gram-positive bacterium that is naturally present in soil. As a result, it is a common resident on vegetables and other products in close contact with soil.

It produces two exotoxins, one of which causes a diarrheal-type disease and the other of which causes an emetic, or vomiting, disease.

The type of disease that takes place is influenced by the type of food that is contaminated by the bacterium.

Emetic - most frequently linked to fried rice, especially when it has been cooked and kept warm for long periods of time. These conditions are apparently ideal for the expression of the low-molecular-weight, heat-stable exotoxin having an emetic effect.

sporulating gram-positive bacterium that causes intestinal symptoms

Those most frequently implicated in disease are animal flesh (meat, fish) and vegetables such as beans that have not been cooked thoroughly enough to destroy endospores.

When these foods are cooled, endospores germinate and the germinated cells multiply, especially if the food is left unrefrigerated.

Most of us are familiar with diseases that present a constellation of bowel syndromes, such as irritable bowel syndrome and ulcerative colitis.

When the presence of an infectious agent is ruled out by a negative stool culture or other tests, these conditions are suspected.

Its presence appears to stimulate secretion of large amounts of mucus in the gut, which may be part of its role in causing chronic diarrhea. The bacterium also seems capable of exerting toxic effects on the gut epithelium, although the mechanisms are not well understood.

Its mode of transmission is fecal-oral—though not through the ingestion of cysts themselves

Four pairs of flagella emerge from the ventral surface, which is concave and acts as a suction cup for attachment to a substrate. Giardia cysts are small and compact, and they contain four nuclei.

Typical symptoms include diarrhea of long duration, abdominal pain, and flatulence. Stools have a greasy, malodorous quality. Fever is usually not present.

Ingested cysts enter the duodenum, germinate, and travel to the jejunum to feed and multiply. Some trophozoites remain on the surface, while others invade the deeper crypts to varying degrees. Superficial invasion by trophozoites causes damage to the epithelial cells, edema, and infiltration by white blood cells, but these effects are reversible.

The presence of the protozoan leads to malabsorption (especially of fat) in the digestive tract and can cause significant weight loss.

The protozoan has been isolated from the intestines of beavers, cattle, coyotes, cats, and human carriers, but the precise reservoir is unclear.

Cysts are usually ingested with water and food or swallowed after close contact with infected people or contaminated objects. Infection can occur with a dose of only 10 to 100 cysts

This phase is marked by dysentery (bloody, mucus-filled stools), abdominal pain, fever, diarrhea, and weight loss.

The most life-threatening manifestations of intestinal infection are hemorrhage, perforation, appendicitis, and tumorlike growths called amebomas. Lesions in the mucosa of the colon have a characteristic flasklike shape.

Extraintestinal infection occurs when amoebas invade the viscera of the peritoneal cavity. The most common site of invasion is the liver. Here, abscesses containing necrotic tissue and trophozoites develop and cause amoebic hepatitis.

Another, rarer complication is pulmonary amoebiasis. Other infrequent targets of infection are the spleen, adrenals, kidney, skin, and brain. Severe forms of the disease result in about a 10% fatality rate.

Amoebiasis begins when viable cysts are swallowed and arrive in the small intestine, where the alkaline pH and digestive juices of this environment stimulate excystment. Each cyst releases four trophozoites, which are swept into the cecum and large intestine. There, the trophozoites attach by fine pseudopods, multiply, actively move about, and feed

harbored by chronic carriers whose intestines favor the encystment stage of the life cycle. Cyst formation cannot occur in active dysentery because the feces are so rapidly flushed from the body, but after recuperation, cysts are continuously shed in feces.

Humans are the primary hosts of E. histolytica. Infection is usually acquired by ingesting food or drink contaminated with cysts released by an asymptomatic carrier.

an inflammatory disease marked by necrosis of hepatocytes and a response by mononuclear white blood cells that swells and disrupts the liver architecture.

far milder and shorter-term than the other forms.

accompanied by vague, flulike symptoms. Darkened urine is often seen in this and other hepatitises. Jaundice is present in only about 10% of the cases.

generally of low virulence. Most of the pathogenic effects are thought to be the result of host response to the presence of virus in the liver

spread through the fecal-oral route (and is sometimes known as infectious hepatitis)

Most of these are a result of close institutional contact, unhygienic food handling, consumption of shellfish, sexual transmission, or travel to other countries.

Diagnosis of the disease is aided by detection of anti-HAV IgM antibodies produced early in the infection and by tests to identify HA antigen or virus directly in stool samples.

In addition to the direct damage to liver cells, the spectrum of hepatitis disease may include fever, chills, malaise, anorexia, abdominal discomfort, diarrhea, and nausea. Rashes may appear and arthritis may occur

known to be a cause of hepatocellular carcinoma

Some patients are coinfected with a particle called the delta agent, sometimes also called a hepatitis D virus. This agent seems to be a defective RNA virus that cannot produce infection unless a cell is also infected with HBV.

Even a minute amount of blood (a millionth of a milliliter) can transmit infection. The abundance of circulating virions is so high and the minimal dose so low that such simple practices as sharing a toothbrush or a razor can transmit the infection.

also been detected in semen and vaginal secretions, and it can be transmitted by these fluids.

Growing concerns about virus spread through donated organs and tissue are prompting increased testing prior to surgery. Spread of the virus by means of close contact in families or institutions is also well documented.

risk is highest among people living under crowded conditions, drug addicts, the sexually promiscuous, and those in certain occupations, including people who conduct medical procedures involving blood or blood products.

an RNA virus in the Flaviviridae family

much more likely to become chronic

The virus's core protein seems to play a role in the suppression of cell-mediated immunity as well as in the production of various cytokines. The protein may also be responsible for altering mitochondrial activity in HCV-infected cells

It is the most common worm disease of children in temperate zones.

Freshly deposited eggs have a sticky coating that causes them to lodge beneath the fingernails and to adhere to fomites. Upon drying, the eggs become airborne and settle in house dust. Eggs are ingested from contaminated food or drink and from self-inoculation from one's own fingers. Eggs hatch in the small intestine and release larvae that migrate to the large intestine. There the larvae mature into adult worms and mate.

Trichuriasis has its highest incidence in areas of the tropics and subtropics that have poor sanitation.

Embryonic eggs deposited in the soil are not immediately infective and continue development for 3 to 6 weeks in this habitat. Ingested eggs hatch in the small intestine, where the larvae attach, penetrate the outer wall, and go through several molts.

The mature adults move to the large intestine and gain a hold with their long, thin heads, while the thicker tail dangles free in the intestinal lumen.

Following sexual maturation and fertilization, the females eventually lay 3,000 to 5,000 eggs daily into the bowel. The entire cycle requires about 90 days, and untreated infection can last up to 2 years.

Humans are its definitive host.

It develops in the intestine and can cause long-term symptoms. It can be transmitted in raw food such as sushi and sashimi made from salmon. (Reputable sushi restaurants employ authentic sushi chefs who are trained to carefully examine fish for larvae and other signs of infection.)

It must also be recognized that transmission of this pathogen can occur in the United States through the consumption of undercooked or lightly smoked trout, perch, or pike—all very common fish to the American freshwater sport fisherman.

As is the case with most tapeworms, symptoms are minor and usually vague and include possible abdominal discomfort or nausea.

The tapeworm seems to have the ability to absorb and use vitamin B12, making it unavailable to its human host. Anemia is therefore sometimes reported with this infection.

H. nana, known as the dwarf tapeworm because it is only 15 to 40 mm in length

spends its larval and adult stages in humans and releases embryonic eggs in feces, which are then spread to other humans through food, drink, or contaminated objects placed in the mouth.

The eggs thrive in warm, moist soils and resist cold and chemical disinfectants, but they are sensitive to sunlight, high temperatures, and drying.

After ingested eggs hatch in the human intestine, the larvae embark upon an odyssey in the tissues. First, they penetrate the intestinal wall and enter the lymphatic and circulatory systems. They are swept into the heart and eventually arrive at the capillaries of the lungs. From this point, the larvae migrate up the respiratory tree to the glottis. Worms entering the throat are swallowed and returned to the small intestine, where they reach adulthood and reproduce, producing up to 200,000 fertilized eggs a day.

Even as adults, male and female worms are not attached to the intestine and retain some of their exploratory ways. They are known to invade the biliary channels of the liver and gallbladder, and on occasion the worms emerge from the nose and mouth.

This helminth is a tapeworm. Adult worms are usually around 5 meters long and have a scolex with hooklets and suckers to attach to the intestine.

Disease caused by T. solium (the pig tapeworm) is distributed worldwide but is mainly concentrated in areas where humans live in close proximity with pigs or eat undercooked pork.

In pigs, the eggs hatch in the small intestine and the released larvae migrate throughout the organs. Ultimately, they encyst in the muscles, becoming cysticerci, young tapeworms that are the infective stage for humans.

When humans ingest a live cysticercus in pork, the coat is digested and the organism is flushed into the intestine, where it firmly attaches by the scolex and develops into an adult tapeworm.

Infection with T. solium can take another form when humans ingest the tapeworm eggs rather than cysticerci. Although humans are not the usual intermediate hosts, the eggs can still hatch in the intestine, releasing tapeworm larvae that migrate to all tissues. They form bladderlike sacs throughout the body that can cause serious damage.

They complete their sexual development in mammals such as humans, cats, dogs, and swine. Their intermediate development occurs in snail and fish hosts.

Humans ingest metacercariae in inadequately cooked or raw freshwater fish

Larvae hatch and crawl into the bile duct, where they mature and shed eggs into the intestinal tract. Feces containing eggs are passed into standing water that harbors the intermediate snail host. The cycle is complete when infected snails release cercariae that invade fish living in the same water.

Periodic outbreaks in temperate regions of Europe and South America are associated with eating wild watercress.

The life cycle is very complex, involving the mammal as the definitive host, the release of eggs in the feces, the hatching of eggs in the water into miracidia, invasion of freshwater snails, development and release of cercariae, encystment of metacercariae on a water plant, and ingestion of the cyst by a mammalian host eating the plant.

The life cycle of this nematode is spent entirely within the body of a mammalian host such as a pig, bear, cat, dog, or rat. In nature, the parasite is maintained in an encapsulated (encysted) larval form in the muscles of these animal reservoirs and is transmitted when other animals prey upon them.

The disease cannot be transmitted from one human to another except in the case of cannibalism.

The cyst envelope is digested in the stomach and small intestine, which liberates the larvae. After burrowing into the intestinal mucosa, the larvae reach adulthood and mate. The larvae that result from this union penetrate the intestine and enter the lymphatic channels and blood. All tissues are at risk for invasion, but final development occurs when the coiled larvae are encysted in the skeletal muscle. At maturity, the cyst is about 1 mm long and can be observed by careful inspection of meat. Although larvae can deteriorate over time, they have also been known to survive for years.

The disease is caused by the blood flukes Schistosoma mansoni and S. japonicum, species that are morphologically and geographically distinct but share similar life cycles, transmission methods, and general disease manifestations.

one of the few infectious agents that can invade intact skin.

The first symptoms of infection are itchiness in the area where the worm enters the body, followed by fever, chills, diarrhea, and cough. The most severe consequences, associated with chronic infection, are hepatomegaly, liver disease, and splenomegaly.

Schistosomes are trematodes, or flukes, but they are more cylindrical than flat. They are often called blood flukes

Once inside the host, it coats its outer surface with proteins from the host's bloodstream, basically "cloaking" itself from the host defense system. This coat reduces its surface antigenicity and allows it to remain in the host indefinitely.

The cycle begins when infected humans release eggs into irrigated fields or ponds, either by deliberate fertilization with excreta or by defecating or urinating directly into the water.

The egg hatches in the water and gives off an actively swimming ciliated larva called a miracidium, which instinctively swims to a snail and burrows into a vulnerable site, shedding its ciliated covering in the process. In the body of the snail, the miracidium multiplies into a larger, fork-tailed swimming larva called a cercaria. Cercariae are given off by the thousands into the water by infected snails.

Upon contact with a human wading or bathing in water, cercariae attach themselves to the skin by ventral suckers and penetrate into hair follicles. They pass into small blood and lymphatic vessels and are carried to the liver. Here, the schistosomes achieve sexual maturity, and the male and female worms remain permanently entwined to facilitate mating. In time, the pair migrates to and lodges in small blood vessels at specific sites. Schistosoma mansoni and S. japonicum end up in the mesenteric venules of the small intestine. While attached to these intravascular sites, the worms feed upon blood, and the female lays eggs that are eventually voided in feces or urine.

Cystitis is a disease of sudden onset. Symptoms include pain, frequent urges to urinate even when the bladder is empty, and burning pain accompanying urination (called dysuria). The urine can be cloudy due to the presence of bacteria and white blood cells. It may have an orange tinge from the presence of red blood cells (hematuria). Low-grade fever and nausea are frequently present.

If back pain is present and fever is high, it is an indication that the kidneys may also be involved (pyelonephritis). Pyelonephritis is a serious infection that can result in permanent damage to the kidneys if improperly or inadequately treated.

If only the bladder is involved, the condition is sometimes called acute uncomplicated UTI.

When they occur in health care facilities, they are almost always a result of catheterization

In 95% of UTIs, the cause is bacteria that are normal biota in the gastrointestinal tract. Escherichia coli is by far the most common of these, accounting for approximately 80% of community-acquired urinary tract infections. Staphylococcus saprophyticus and Enterococcus are also common culprits

caused by Leptospira interrogans

There are nearly 200 different serotypes of this species distributed among various animal groups, which accounts for extreme variations in the disease manifestations in humans.

During the early—leptospiremic—phase, the pathogen appears in the blood and cerebrospinal fluid. Symptoms are sudden high fever, chills, headache, muscle aches, conjunctivitis, and vomiting.

During the second—immune—phase, the blood infection is cleared by natural defenses. This period is marked by milder fever headache due to leptospiral meningitis and Weil's syndrome, a cluster of symptoms characterized by kidney invasion, hepatic disease, jaundice, anemia, and neurological disturbances.

Long-term disability and even death can result from damage to the kidneys and liver, but they occur primarily with the most virulent strains and in elderly persons.

the first symptoms of infestation are itchiness in the area where the helminth enters the body, followed by fever, chills, diarrhea, and cough. Urinary tract symptoms occur at a later date. Remember that adult flukes can live for many years and, by eluding the immune defenses, cause chronic infection.

The urinary manifestations occur if a host is infected with Schistosoma haematobium.

able to invade intact skin and attach to vascular endothelium

The vaginal condition caused by this fungus is known as a yeast infection.

The yeast is easily detectable on a wet prep or a Gram stain of material obtained during a pelvic exam

In otherwise healthy people, the fungus is not invasive and limits itself to this surface infection. However, infections of the bloodstream do occur and have high mortality rates. They do not normally stem from vaginal infections with the fungus, however, and are seen most frequently in hospitalized patients.

AIDS patients are also at risk of developing systemic infections.

Trichomonads are considered asymptomatic infectious agents rather than normal biota because of evidence that some people experience long-term negative effects.

Many cases are asymptomatic, and men seldom have symptoms. Women often have vaginitis symptoms, which can include a white to green, frothy discharge

Chronic infection can make a person more susceptible to other infections, including HIV. Also, women who become infected during pregnancy are predisposed to premature labor and low birth weight infants. Chronic infection may also lead to infertility.

can lead to complications such as pelvic inflammatory disease (PID), infertility, and, more rarely, ectopic pregnancies. Babies born to some mothers with this have low birthweights.

not considered to be sexually transmitted, but very common in sexually active women

The acute form is virtually always caused by bacterial infection. The bacteria are usually normal biota from the intestinal tract or may have caused a previous urinary tract infection.

The chronic form is also often caused by bacteria. Researchers have found that the chronic form, often unresponsive to antibiotic treatment, can be caused by mixed biofilms of bacteria in the prostate.

In the male, infection of the urethra elicits urethritis, painful urination and a yellowish discharge, although a relatively large number of cases are asymptomatic. In most cases, infection is limited to the distal urogenital tract, but it can spread from the urethra to the prostate gland and epididymis

In the female, it is likely that both the urinary and genital tracts will be infected during sexual intercourse. A mucopurulent (containing mucus and pus) or bloody vaginal discharge occurs in about half of the cases, along with painful urination if the urethra is affected. Major complications occur when the infection ascends to higher reproductive structures such as the uterus and fallopian tubes. One disease resulting from this progression is salpingitis (inflammation of the fallopian tubes) may be isolated, or it may also include inflammation of other parts of the upper reproductive tract (pelvic inflammatory disease (PID)). The buildup of scar tissue from PID can block the fallopian tubes, causing sterility or ectopic pregnancies

Children born to gonococcus carriers are also in danger of being infected as they pass through the birth canal. Because of the potential harm to the fetus, physicians usually screen pregnant mothers for its presence.

C. trachomatis is a very small, gram-negative bacterium. It lives inside host cells as an obligate intracellular parasite.

ability to grow intracellularly contributes to its virulence because it escapes certain aspects of the host's immune response. Also, the bacterium has a unique cell wall that apparently prevents the phagosome from fusing with the lysosome inside phagocytes.

majority of cases are asymptomatic

Males - the bacterium causes an inflammation of the urethra. The symptoms mimic gonorrhea—namely, discharge and painful urination. Untreated infections may lead to epididymitis.

Females - cervicitis, a discharge, and often salpingitis. Pelvic inflammatory disease is a frequent sequela of female Chlamydia infection. A woman is even more likely to experience PID as a result of a Chlamydia infection than as a result of gonorrhea.

Infection with this microorganism is usually detected initially using a rapid technique such as PCR or ELISA. Direct fluorescent antibody detection is also used. Serology is not always reliable.

Brought into direct contact with mucous membranes or abraded skin, T. pallidum binds avidly by its hooked tip to the epithelium

PRIMARY - The earliest indication is the appearance of a hard chancre at the site of entry of the pathogen. A chancre appears after an incubation period that varies from 9 days to 3 months. The chancre begins as a small, red, hard bump that enlarges and breaks down, leaving a shallow crater with firm margins.

SECONDARY - About 3 weeks to 6 months after the chancre heals, the secondary stage appears. By then, many systems of the body have been invaded, and the signs and symptoms are more profuse and intense. Initial symptoms are fever, headache, and sore throat, followed by lymphadenopathy and a peculiar red or brown rash that breaks out on all skin surfaces, including the palms of the hands and the soles of the feet. A person's hair often falls out.

LATENCY & TERTIARY - about 30% of infections enter a highly varied latent period that can last for 20 years or longer. During latency, although antibodies to the bacterium are readily detected, the bacterium itself is not.

The final stage of the disease (tertiary) is relatively rare today because of widespread use of antibiotics. Cardiovascular syphilis results from damage to the small arteries in the aortic wall. As the fibers in the wall weaken, the aorta is subject to distension and fatal rupture. In one form of tertiary syphilis, painful, swollen tumors called gummas develop in tissues such as the liver, skin, bone, and cartilage

This ulcerative disease usually begins as a soft papule, or bump, at the point of contact. It develops into a "soft chancre" (in contrast to the hard syphilis chancre), which is very painful in men but may be unnoticed in women.

Inguinal lymph nodes can become very swollen and tender.

It is very common in the tropics and subtropics and is becoming more common in the United States.

transmitted exclusively through direct contact and is considered a sexually transmitted infection.

After initial infection, a person may notice no symptoms.

Alternatively, herpes can cause the appearance of single or multiple vesicles on the genitalia, perineum, thigh, and buttocks. The vesicles are small and are filled with a clear fluid. They are intensely painful to the touch. The appearance of lesions the first time one gets them can be accompanied by malaise, anorexia, fever, and bilateral swelling and tenderness in the groin. Occasionally, central nervous system symptoms such as meningitis or encephalitis can develop.

Thus, initial infection can be either completely asymptomatic or serious enough to require hospitalization.

After recovery from initial infection, a person may have recurrent episodes of lesions.

In most cases, patients remain asymptomatic or experience recurrent "surface" infections indefinitely.

Very rarely, complications can occur. Every year, one or two persons per million with chronic herpes infections develop encephalitis. The virus disseminates along nerve pathways to the brain (although it can also infect the spinal cord). The effects on the central nervous system begin with headache and stiff neck and can progress to mental disturbances and coma. The fatality rate in untreated encephalitis cases is 70%, although treatment with acyclovir is effective.

Patients with underlying immunodeficiency are more prone to severe, disseminated herpes infection than are immunocompetent patients. Of greatest concern are patients receiving organ grafts, cancer patients on immunosuppressive therapy, those with congenital immunodeficiencies, and AIDS patients.

Recent data suggest that people with HSV-1 are more prone to Alzheimer's disease, particularly if they carry a particular variant of a particular gene

in the neonate and the fetus Page 717(figure 23.17), HSV infections are very destructive and can be fatal. Most cases occur when infants are contaminated by the mother's reproductive tract immediately before or during birth, but they have also been traced to hand transmission from the mother's lesions to the baby

HSV-1 is thought of as a virus that infects the oral mucosa, resulting in "cold sores" or "fever blisters," and HSV-2 is thought of as the genital virus. In reality, either virus can infect either region, depending on the type of contact that transmits the infectious agent.

a group of nonenveloped DNA viruses belonging to the Papovaviridae family.

There are more than 100 different types of HPV. Some types are specific for the mucous membranes others invade the skin.

Some of these viruses are the cause of plantar warts, which often occur on the soles of the feet. Other HPVs cause the common or "seed" warts and flat warts.

Symptoms, if present, may manifest as warts—outgrowths of tissue on the genitals.

In females, these growths can occur on the vulva and in and around the vagina.

In males, the warts can occur in or on the penis and the scrotum.

In both sexes, the warts can appear in or on the anus and even on the skin around the groin, such as the area between the thigh and the pelvis. The warts themselves range from tiny, flat, inconspicuous bumps to extensively branching, cauliflower-like masses called condyloma acuminata. The warts are unsightly and can be obstructive, but they do not generally lead to more serious symptoms.

Certain types of the virus infect cells on the female cervix. This infection may be "silent," or it may lead to abnormal cell changes in the cervix. Some of these cell changes can eventually result in malignancies of the cervix.

The vast majority of cervical cancers are caused by HPV infection. (It is possible that chronic infections with other microorganisms cause a very small percentage of cervical malignancies.)

The major virulence factors for cancer-causing HPVs are oncogenes, which code for proteins that interfere with normal host cell function, resulting in uncontrolled growth.


Further Reading:

  1. Molecules of Death, Waring, Stenton, Mitchell
  2. Chemical Warfare Agents, Romano, Lukey, Salem
  3. Chemical Warfare Agents, Marrs, Maynard, Sidell

If you have something the size of a mosquito, then you are, naturally, limited by the payload that a mosquito can carry. A mosquito has a total mass of roughly 1-2 milligrams. The median lethal dose (MLD) of Ricin, injected, to a human is 22 micrograms per kilogram of human. So, a lethal dose of Ricin for an average human would require 1.78 milligrams. Your electronic mosquito would need to be rather large to carry around this much.

However, Ricin is FAR from the most lethal substance to humans. Reading a quick list online showed at least 7 compounds that are lethal in smaller doses than Ricin. At the very top of the list is Botulinum Toxin. Botulinum Toxin is the most spectacularly lethal neurotoxin we have ever encountered. it has an estimated Median Lethal Dose of merely 1.3-2.1 nanograms per kilogram. Mass of an average person is 62 kilograms, so a lethal dose of Botulinum Toxin is only 130.2 nanograms. Or, for more clarity, 0.0000001302 grams. This is certainly small enough to be delivered by a mosquito-sized deliver system, and could easily be delivered in a much higher dose.

For a bit of clarification. median lethal dose represents the amount necessary to kill 50% of the test targets. So you are going to want to up the dosage of this toxin to make sure you get everyone. but since the amount delivered is measured in nanograms, this isn't a problem for your delivery method. The problem is that while botulinum toxin is spectacularly lethal, it doesn't do so quickly when administered in a 'lethal dose.' It takes several days before the symptoms become fatal, and there are effective anti-toxins against it.

Polonium-210 is another option for you (It has a similar MLD), if you want to kill them with radiation poisoning instead of neurotoxin. but again, it's slow. Probably not within two days if you stick to the actual MLD levels

It's simply a matter of volume. there are too many neural cells for a tiny amount of poison to tear up quickly. There is a way to speed things up, and that is to have your mosquito precision-target where it delivers the poison. Delivering the poison as close to the spinal cord and brainstem as possible. So if you want this to work quickly, you need to massively overdose them on it.

So, how much could a mosquito deliver? A mosquito that eats until it is full can harvest 0.01 milliliters of water. As 1 milliliter of water weighs 1 gram, we can compute that a mosquito can carry an additional 0.01 grams of matter and still fly well. Remembering that the MLD of botulinum toxin is 130.2 nanograms, we can compute that a single mosquito could carry 7,680,915.5 times the MLD of botulinum toxin.


Contents

C. botulinum is a Gram-positive, rod-shaped, spore-forming bacterium. It is an obligate anaerobe, meaning that oxygen is poisonous to the cells. However, C. botulinum tolerates traces of oxygen due to the enzyme superoxide dismutase, which is an important antioxidant defense in nearly all cells exposed to oxygen. [5] C. botulinum is able to produce the neurotoxin only during sporulation, which can happen only in an anaerobic environment. C. botulinum is divided into four distinct phenotypic groups (I-IV) and is also classified into seven serotypes (A–G) based on the antigenicity of the botulinum toxin produced. [6] [7]

Groups Edit

Physiological differences and genome sequencing at 16S rRNA level support the subdivision of the C. botulinum species into groups I-IV. [8]

Groups of C. botulinum [8] [9]
Group Serotypes
I (Proteolytic) All type A and proteolytic strains of types B and F
II (Non proteolytic) All type E and nonproteolytic strains of types B and F
III Type C and D
IV Type G

One of the fundamental differences between group I and group II is that C. botulinum group I can lyse native proteins like coagulated egg white, cooked meat particles, whereas group II cannot. [9] However, group II can ferment various carbohydrates like sucrose, mannose. And both of them can degrade the derived protein, gelatin. [9] Human botulism is predominantly caused by group I or II C. botulinum. [9] Group III organisms mainly cause diseases in animals. [9] Group IV C. botulinum has not been shown to cause human or animal disease. [9]

Botulinum toxin Edit

Neurotoxin production is the unifying feature of the species. Eight types of toxins have been identified that are allocated a letter (A–H), several of which can cause disease in humans. They are resistant to degradation by enzymes found in the gastrointestinal tract. This allows for ingested toxin to be absorbed from the intestines into the bloodstream. [3] However, all types of botulinum toxin are rapidly destroyed by heating to 100 °C for 15 minutes (900 seconds). Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium Clostridium botulinum. C. botulinum elaborates eight antigenically distinguishable exotoxins (A, B, C1, C2, D, E, F and G). [ citation needed ]

Most strains produce one type of neurotoxin, but strains producing multiple toxins have been described. C. botulinum producing B and F toxin types have been isolated from human botulism cases in New Mexico and California. [10] The toxin type has been designated Bf as the type B toxin was found in excess to the type F. Similarly, strains producing Ab and Af toxins have been reported. [ citation needed ]

Evidence indicates the neurotoxin genes have been the subject of horizontal gene transfer, possibly from a viral (bacteriophage) source. This theory is supported by the presence of integration sites flanking the toxin in some strains of C. botulinum. However, these integrations sites are degraded (except for the C and D types), indicating that the C. botulinum acquired the toxin genes quite far in the evolutionary past. Nevertheless, further transfers still happen via the plasmids and other mobile elements the genes are located on. [11]

Botulinum toxin types Edit

Only botulinum toxin types A, B, E, F and H cause disease in humans. Types A, B, and E are associated with food-borne illness, with type E specifically associated with fish products. Type C produces limber-neck in birds and type D causes botulism in other mammals. No disease is associated with type G. [12] The "gold standard" for determining toxin type is a mouse bioassay, but the genes for types A, B, E, and F can now be readily differentiated using quantitative PCR. [13] As no antitoxin to type H is yet available, discovered in 2013 and by far the deadliest, details are kept under shroud. [14]

A few strains from organisms genetically identified as other Clostridium species have caused human botulism: C. butyricum has produced type E toxin [15] and C. baratii had produced type F toxin. [16] [17] The ability of C. botulinum to naturally transfer neurotoxin genes to other clostridia is concerning, especially in the food industry, where preservation systems are designed to destroy or inhibit only C. botulinum but not other Clostridium species. [ citation needed ]

Phenotypic groups of Clostridium botulinum
Properties Group I Group II Group III Group IV
Toxin Types A, B, F B, E, F C, D G
Proteolysis + weak
Saccharolysis +
Disease host human human animal
Toxin gene chromosome/plasmid chromosome/plasmid bacteriophage plasmid
Close relatives C. sporogenes
C. putrificum
C. butyricum
C. beijerinickii
C. haemolyticum
C. novyi type A
C. subterminale
C. haemolyticum

Laboratory isolation Edit

In the laboratory, C. botulinum is usually isolated in tryptose sulfite cycloserine (TSC) growth medium in an anaerobic environment with less than 2% oxygen. This can be achieved by several commercial kits that use a chemical reaction to replace O2 with CO2. C. botulinum is a lipase-positive microorganism that grows between pH of 4.8 and 7.0 and cannot use lactose as a primary carbon source, characteristics important for biochemical identification. [18]

C. botulinum was first recognized and isolated in 1895 by Emile van Ermengem from home-cured ham implicated in a botulism outbreak. [19] The isolate was originally named Bacillus botulinus, after the Latin word for sausage, botulus. ("Sausage poisoning" was a common problem in 18th- and 19th-century Germany, and was most likely caused by botulism.) [20] However, isolates from subsequent outbreaks were always found to be anaerobic spore formers, so Ida A. Bengtson proposed that the organism be placed into the genus Clostridium, as the genus Bacillus was restricted to aerobic spore-forming rods. [21]

Since 1959, all species producing the botulinum neurotoxins (types A–G) have been designated C. botulinum. Substantial phenotypic and genotypic evidence exists to demonstrate heterogeneity within the species. This has led to the reclassification of C. botulinum type G strains as a new species, C. argentinense. [22]

Group I C. botulinum strains that do not produce a botulin toxin are referred to as C. sporogenes. [23]

The complete genome of C. botulinum has been sequenced at Wellcome Trust Sanger Institute in 2007. [24]

Foodborne botulism Edit

"Signs and symptoms of foodborne botulism typically begin between 18 and 36 hours after the toxin gets into your body, but can range from a few hours to several days, depending on the amount of toxin ingested." [25]

  • Double vision
  • Blurred vision
  • Dropping eyelids
  • Nausea, vomiting, and abdominal cramps
  • Slurred speech
  • Trouble breathing
  • Difficulty in swallowing
  • Dry mouth
  • Muscle weakness
  • Constipation
  • Reduced or absent deep tendon reactions, such as in the knee

Wound botulism Edit

Most people who develop wound botulism inject drugs several times a day, so it's difficult to determine how long it takes for signs and symptoms to develop after the toxin enters the body. Most common in people who inject black tar heroin, wound botulism signs and symptoms include: [25]

  • Difficulty swallowing or speaking
  • Facial weakness on both sides of the face
  • Blurred or double vision
  • Dropping eyelids
  • Trouble breathing
  • Paralysis

Infant botulism Edit

If infant botulism is related to food, such as honey, problems generally begin within 18 to 36 hours after the toxin enters the baby's body. Signs and symptoms include:

  • Constipation (often the first sign)
  • Floppy movements due to muscle weakness and trouble controlling the head
  • Weak cry
  • Irritability
  • Drooling
  • Dropping eyelids
  • Tiredness
  • Difficulty sucking or feeding
  • Paralysis [25]

Beneficial effects of botulinum toxin Edit

Purified botulinum toxin is diluted by a physician for treatment:

  • Congenital pelvic tilt
  • Spasmodic dysphasia (the inability of the muscles of the larynx)
  • Achalasia (esophageal stricture)
  • Strabismus (crossed eyes)
  • Paralysis of the facial muscles
  • Failure of the cervix
  • Blinking frequently
  • Anti-cancer drug delivery [26]

Adult intestinal toxemia Edit

A very rare form of botulism that occurs by the same route as infant botulism but is among adults. Occurs rarely and sporadically. Signs and symptoms include:

  • Abdominal pain
  • Blurred vision
  • Diarrhea
  • Imbalance
  • Weakness in arms and hand area [27]

A number of quantitative surveys for C. botulinum spores in the environment have suggested a prevalence of specific toxin types in given geographic areas, which remain unexplained. [ citation needed ]

North America Edit

Type A C. botulinum predominates the soil samples from the western regions, while type B is the major type found in eastern areas. [28] The type-B organisms were of the proteolytic type I. Sediments from the Great Lakes region were surveyed after outbreaks of botulism among commercially reared fish, and only type E spores were detected. [29] [30] [31] In a survey, type-A strains were isolated from soils that were neutral to alkaline (average pH 7.5), while type-B strains were isolated from slightly acidic soils (average pH 6.23). [ citation needed ]

Europe Edit

C. botulinum type E is prevalent in aquatic sediments in Norway and Sweden, [32] Denmark, [33] the Netherlands, the Baltic coast of Poland, and Russia. [28] The type-E C. botulinum was suggested to be a true aquatic organism, which was indicated by the correlation between the level of type-E contamination and flooding of the land with seawater. As the land dried, the level of type E decreased and type B became dominant. [ citation needed ]

In soil and sediment from the United Kingdom, C. botulinum type B predominates. In general, the incidence is usually lower in soil than in sediment. In Italy, a survey conducted in the vicinity of Rome found a low level of contamination all strains were proteolytic C. botulinum types A or B. [34]

Australia Edit

C. botulinum type A was found to be present in soil samples from mountain areas of Victoria. [35] Type-B organisms were detected in marine mud from Tasmania. [36] [ verification needed ] Type-A C. botulinum has been found in Sydney suburbs and types A and B were isolated from urban areas. In a well-defined area of the Darling-Downs region of Queensland, a study showed the prevalence and persistence of C. botulinum type B after many cases of botulism in horses. [ citation needed ]

C. botulinum is used to prepare the medicaments Botox, Dysport, Xeomin, and Neurobloc used to selectively paralyze muscles to temporarily relieve muscle function. It has other "off-label" medical purposes, such as treating severe facial pain, such as that caused by trigeminal neuralgia.

Botulinum toxin produced by C. botulinum is often believed to be a potential bioweapon as it is so potent that it takes about 75 nanograms to kill a person (LD50 of 1 ng/kg, [37] assuming an average person weighs

75 kg) 1 kilogram of it would be enough to kill the entire human population. For comparative purposes, a quarter of a typical grain of sand's weight (350 ng) of botulinum toxin would constitute a lethal dose for humans.

A "mouse protection" or "mouse bioassay" test determines the type of C. botulinum toxin present using monoclonal antibodies. An enzyme-linked immunosorbent assay (ELISA) with digoxigenin-labeled antibodies can also be used to detect the toxin, [38] and quantitative PCR can detect the toxin genes in the organism. [13]

C. botulinum is a soil bacterium. The spores can survive in most environments and are very hard to kill. They can survive the temperature of boiling water at sea level, thus many foods are canned with a pressurized boil that achieves even higher temperatures, sufficient to kill the spores. [ citation needed ] This bacteria is widely distributed in nature, and can be assumed to be present on all food surfaces. Its optimum growth temperature is within the mesophilic range. In spore form, it is a heat resistant pathogen that can survive in low acid foods and grow to produce toxin. The toxin attacks the nervous system and will kill an adult at a dose of around 75 ng. [37] This toxin is detoxified by holding food at 100 °C for 10 minutes. [ citation needed ]

Botulism poisoning can occur due to preserved or home-canned, low-acid food that was not processed using correct preservation times and/or pressure. [39] Growth of the bacterium can be prevented by high acidity, high ratio of dissolved sugar, high levels of oxygen, very low levels of moisture, or storage at temperatures below 3 °C (38 °F) for type A. For example, in a low-acid, canned vegetable such as green beans that are not heated enough to kill the spores (i.e., a pressurized environment) may provide an oxygen-free medium for the spores to grow and produce the toxin. However, pickles are sufficiently acidic to prevent growth even if the spores are present, they pose no danger to the consumer. Honey, corn syrup, and other sweeteners may contain spores, but the spores cannot grow in a highly concentrated sugar solution however, when a sweetener is diluted in the low-oxygen, low-acid digestive system of an infant, the spores can grow and produce toxin. As soon as infants begin eating solid food, the digestive juices become too acidic for the bacterium to grow. [ citation needed ]

The control of food-borne botulism caused by C. botulinum is based almost entirely on thermal destruction (heating) of the spores or inhibiting spore germination into bacteria and allowing cells to grow and produce toxins in foods. Conditions conducive of growth are dependent on various environmental factors. Growth of C. botulinum is a risk in low acid foods as defined by having a pH above 4.6 [40] although growth is significantly retarded for pH below 4.9. There have been some cases and specific conditions reported to sustain growth with pH below 4.6. [41] [42]

Physicians may consider the diagnosis of botulism based on a patient's clinical presentation, which classically includes an acute onset of bilateral cranial neuropathies and symmetric descending weakness. [43] [44] Other key features of botulism include an absence of fever, symmetric neurologic deficits, normal or slow heart rate and normal blood pressure, and no sensory deficits except for blurred vision. [45] [46] A careful history and physical examination is paramount in order to diagnose the type of botulism, as well as to rule out other conditions with similar findings, such as Guillain-Barre syndrome, stroke, and myasthenia gravis. Depending on the type of botulism considered, different tests for diagnosis may be indicated.

Foodborne botulism: serum analysis for toxins by bioassay in mice should be done, as the demonstration of the toxins is diagnostic. [47]

Wound botulism: isolation of C. botulinum from the wound site should be attempted, as growth of the bacteria is diagnostic. [48]

Adult enteric and infant botulism: isolation and growth of C. botulinum from stool samples is diagnostic. [49] Infant botulism is a diagnosis which is often missed in the emergency room.

Other tests that may be helpful in ruling out other conditions are:

    (EMG) or antibody studies may help with the exclusion of myasthenia gravis and Lambert-Eaton myasthenic syndrome (LEMS). [50]
  • Collection of cerebrospinal fluid (CSF) protein and blood assist with the exclusion of Guillan-Barre syndrome and stroke. [51]
  • Detailed physical examination of the patient for any rash or tick presence helps with the exclusion of any tick transmitted tick paralysis. [52]

In the case of a diagnosis or suspicion of botulism, patients should be hospitalized immediately, even if the diagnosis and/or tests are pending. If botulism is suspected, patients should be treated immediately with antitoxin therapy in order to reduce mortality. Immediate intubation is also highly recommended, as respiratory failure is the primary cause of death from botulism. [53] [54] [55]

In Canada, there are currently only 3 antitoxin therapies available, which are accessible through Health Canada Special Access Program (SAP). [56] The 3 types of antitoxin therapies are: 1) GlaxoSmithKline trivalent Types ABE, 2) NP-018 (heptavalent) Types A to G, and 3) BabyBIG®, Botulism Immune Globulin Intravenous (Human) (BIG-IV) for pediatric patients under the age of one year. [57]

Outcomes vary between one and three months, but with prompt interventions, mortality from botulism ranges from less than 5 percent to 8 percent. [58]

There used to be a formalin-treated toxoid vaccine against botulism (serotypes A-E), but it was discontinued in 2011 due to declining potency in the toxoid stock. It was originally intended for people at risk of exposure. A few new vaccines are under development. [59]


Listeriosis

Listeria monocytogenes is a nonencapsulated, nonsporulating, gram-positive rod and a foodborne pathogen that causes listeriosis. At-risk groups include pregnant women, neonates, the elderly, and the immunocompromised (recall the Clinical Focus case studies in Microbial Growth and Microbial Mechanisms of Pathogenicity). Listeriosis leads to meningitis in about 20% of cases, particularly neonates and patients over the age of 60. The CDC identifies listeriosis as the third leading cause of death due to foodborne illness, with overall mortality rates reaching 16%. 12 In pregnant women, listeriosis can cause also cause spontaneous abortion in pregnant women because of the pathogen&rsquos unique ability to cross the placenta.

L. monocytogenes is generally introduced into food items by contamination with soil or animal manure used as fertilizer. Foods commonly associated with listeriosis include fresh fruits and vegetables, frozen vegetables, processed meats, soft cheeses, and raw milk. 13 Unlike most other foodborne pathogens, Listeria is able to grow at temperatures between 0 °C and 50 °C, and can therefore continue to grow, even in refrigerated foods.

Ingestion of contaminated food leads initially to infection of the gastrointestinal tract. However, L. monocytogenes produces several unique virulence factors that allow it to cross the intestinal barrier and spread to other body systems. Surface proteins called internalins (InlA and InlB) help L. monocytogenes invade nonphagocytic cells and tissues, penetrating the intestinal wall and becoming disseminating through the circulatory and lymphatic systems. Internalins also enable L. monocytogenes to breach other important barriers, including the blood-brain barrier and the placenta. Within tissues, L. monocytogenes uses other proteins called listeriolysin O and ActA to facilitate intercellular movement, allowing the infection to spread from cell to cell (Figure (PageIndex<6>)).

L. monocytogenes is usually identified by cultivation of samples from a normally sterile site (e.g., blood or CSF). Recovery of viable organisms can be enhanced using cold enrichment by incubating samples in a broth at 4 °C for a week or more. Distinguishing types and subtypes of L. monocytogenes&mdashan important step for diagnosis and epidemiology&mdashis typically done using pulsed-field gel electrophoresis. Identification can also be achieved using chemiluminescence DNA probe assays and MALDI-TOF.

Treatment for listeriosis involves antibiotic therapy, most commonly with ampicillin and gentamicin. There is no vaccine available.

Figure (PageIndex<6>): (a) An electron micrograph of Listeria monocytogenes infecting a host cell. (b) Listeria is able to use host cell components to cause infection. For example, phagocytosis allows it to enter host cells, and the host&rsquos cytoskeleton provides the materials to help the pathogen move to other cells. (credit a: modification of work by the Centers for Disease Control and Prevention credit b: modification of work by Keith Ireton)

How does Listeria enter the nervous system?

Hansen&rsquos Disease (Leprosy)

Hansen&rsquos disease (also known as leprosy) is caused by a long, thin, filamentous rod-shaped bacterium Mycobacterium leprae, an obligate intracellular pathogen. M. leprae is classified as gram-positive bacteria, but it is best visualized microscopically with an acid-fast stain and is generally referred to as an acid-fast bacterium. Hansen&rsquos disease affects the PNS, leading to permanent damage and loss of appendages or other body parts.

Hansen&rsquos disease is communicable but not highly contagious approximately 95% of the human population cannot be easily infected because they have a natural immunity to M. leprae. Person-to-person transmission occurs by inhalation into nasal mucosa or prolonged and repeated contact with infected skin. Armadillos, one of only five mammals susceptible to Hansen&rsquos disease, have also been implicated in transmission of some cases. 14

In the human body, M. leprae grows best at the cooler temperatures found in peripheral tissues like the nose, toes, fingers, and ears. Some of the virulence factors that contribute to M. leprae&rsquos pathogenicity are located on the capsule and cell wall of the bacterium. These virulence factors enable it to bind to and invade Schwann cells, resulting in progressive demyelination that gradually destroys neurons of the PNS. The loss of neuronal function leads to hypoesthesia (numbness) in infected lesions. M. leprae is readily phagocytized by macrophages but is able to survive within macrophages in part by neutralizing reactive oxygen species produced in the oxidative burst of the phagolysosome. Like L. monocytogenes, M. leprae also can move directly between macrophages to avoid clearance by immune factors.

The extent of the disease is related to the immune response of the patient. Initial symptoms may not appear for as long as 2 to 5 years after infection. These often begin with small, blanched, numb areas of the skin. In most individuals, these will resolve spontaneously, but some cases may progress to a more serious form of the disease. Tuberculoid (paucibacillary) Hansen&rsquos disease is marked by the presence of relatively few (three or less) flat, blanched skin lesions with small nodules at the edges and few bacteria present in the lesion. Although these lesions can persist for years or decades, the bacteria are held in check by an effective immune response including cell-mediated cytotoxicity. Individuals who are unable to contain the infection may later develop lepromatous (multibacillary) Hansen&rsquos disease. This is a progressive form of the disease characterized by nodules filled with acid-fast bacilli and macrophages. Impaired function of infected Schwann cells leads to peripheral nerve damage, resulting in sensory loss that leads to ulcers, deformities, and fractures. Damage to the ulnar nerve (in the wrist) by M. leprae is one of the most common causes of crippling of the hand. In some cases, chronic tissue damage can ultimately lead to loss of fingers or toes. When mucosal tissues are also involved, disfiguring lesions of the nose and face can also occur (Figure (PageIndex<7>)).

Hansen&rsquos disease is diagnosed on the basis of clinical signs and symptoms of the disease, and confirmed by the presence of acid-fast bacilli on skin smears or in skin biopsy specimens (Figure (PageIndex<7>)). M. leprae does not grow in vitro on any known laboratory media, but it can be identified by culturing in vivo in the footpads of laboratory mice or armadillos. Where needed, PCR and genotyping of M. leprae DNA in infected human tissue may be performed for diagnosis and epidemiology.

Hansen&rsquos disease responds well to treatment and, if diagnosed and treated early, does not cause disability. In the United States, most patients with Hansen&rsquos disease are treated in ambulatory care clinics in major cities by the National Hansen&rsquos Disease program, the only institution in the United States exclusively devoted to Hansen&rsquos disease. Since 1995, WHO has made multidrug therapy for Hansen&rsquos disease available free of charge to all patients worldwide. As a result, global prevalence of Hansen&rsquos disease has declined from about 5.2 million cases in 1985 to roughly 176,000 in 2014. 15 Multidrug therapy consists of dapsone and rifampicin for all patients and a third drug, clofazimin, for patients with multibacillary disease.

Currently, there is no universally accepted vaccine for Hansen&rsquos disease. India and Brazil use a tuberculosis vaccineagainst Hansen&rsquos disease because both diseases are caused by species of Mycobacterium. The effectiveness of this method is questionable, however, since it appears that the vaccine works in some populations but not in others.

Figure (PageIndex<7>): (a) The nose of a patient with Hansen&rsquos disease. Note the lepromatous/multibacillary lesions around the nostril. (b) Hansen&rsquos disease is caused by Mycobacterium leprae, a gram-positive bacillus. (credit a, b: modifications of work by the Centers for Disease Control and Prevention)

  1. What prevents the progression from tuberculoid to lepromatus leprosy?
  2. Why does Hansen&rsquos disease typically affect the nerves of the extremities?

Disfiguring, deadly diseases like leprosy have historically been stigmatized in many cultures. Before leprosy was understood, victims were often isolated in leper colonies, a practice mentioned frequently in ancient texts, including the Bible. But leper colonies are not just an artifact of the ancient world. In Hawaii, a leper colony established in the late nineteenth century persisted until the mid-twentieth century, its residents forced to live in deplorable conditions. 16 Although leprosy is a communicable disease, it is not considered contagious (easily communicable), and it certainly does not pose enough of a threat to justify the permanent isolation of its victims. Today, we reserve the practices of isolation and quarantine to patients with more dangerous diseases, such as Ebola or multiple-drug-resistant bacteria like Mycobacterium tuberculosis and Staphylococcus aureus. The ethical argument for this practice is that isolating infected patients is necessary to prevent the transmission and spread of highly contagious diseases&mdasheven when it goes against the wishes of the patient.

Of course, it is much easier to justify the practice of temporary, clinical quarantining than permanent social segregation, as occurred in leper colonies. In the 1980s, there were calls by some groups to establish camps for people infected with AIDS. Although this idea was never actually implemented, it begs the question&mdashwhere do we draw the line? Are permanent isolation camps or colonies ever medically or socially justifiable? Suppose there were an outbreak of a fatal, contagious disease for which there is no treatment. Would it be justifiable to impose social isolation on those afflicted with the disease? How would we balance the rights of the infected with the risk they pose to others? To what extent should society expect individuals to put their own health at risk for the sake of treating others humanely?

BACTERIAL INFECTIONS OF THE NERVOUS SYSTEM

Despite the formidable defenses protecting the nervous system, a number of bacterial pathogens are known to cause serious infections of the CNS or PNS. Unfortunately, these infections are often serious and life threatening. Figure (PageIndex<8>) summarizes some important infections of the nervous system.

Figure (PageIndex<8>): Bacterial infections of the Nervous system.


Why Scientists Held Back Details On A Unique Botulinum Toxin

Scientists have discovered the first new form of botulinum toxin in over 40 years, but they're taking the unusual step of keeping key details about it secret.

That's because botulinum toxin is one of the most poisonous substances known. It causes botulism, and the newly identified form of it can't be neutralized by any available treatment.

The researchers published two reports describing their work online in The Journal of Infectious Diseases. The information in those reports is deliberately incomplete, to prevent anyone from using it as the recipe for a potent new bioweapon.

"This is not the usual process for publishing manuscripts. We thought in this case an exception was appropriate," says David Hooper, an infectious disease specialist at Massachusetts General Hospital who serves as one of the editors of the journal.

Normally, the journal would require that the scientists disclose the genetic sequences needed to make the toxin. In this case, however, the researchers didn't want to do that because of the security risk.

The journal's editors ultimately agreed that they could go ahead and publish but withhold the information until new treatments were developed. "There was enough scientific importance that we did not want to delay the publication," says Hooper.

Their decision comes as biologists have been grappling with how to handle potentially dangerous information.

Last year, for example, scientists and security experts had a huge argument over whether to publish the details of mutant forms of bird flu that could potentially cause a pandemic in humans.

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Biology has long had a tradition of openness, to allow people to confirm research findings and build upon others' discoveries. But some worry that new technologies have made it easier for basic science to be exploited by people with evil intentions.

And any expert in botulinum toxin knows that its history as a possible bioweapon goes back decades. The Japanese cult Aum Shinrikyo even tried to release it in downtown Tokyo in the 1990s, but these attacks failed.

One scholarly article on the toxin noted that a single gram could potentially kill more than a million people, if it was evenly dispersed through the air and inhaled — although that would be difficult to do.

Botulinum toxin is normally made by bacteria, and it can cause a serious and life-threatening paralytic illness. In the U.S., botulism most commonly occurs in young infants, whose still-developing guts don't have the normal microbes that can inhibit the growth of the bacteria.

The new form of the toxin was discovered by Jason Barash and Stephen Arnon at the California Department of Public Health. They use fecal samples from babies to diagnose botulism and characterize the type of toxin that's producing the disease.

But in the newly reported case, they found a completely unexpected toxin--one that cannot be neutralized by any of the currently available anti-botulinum antiserums.

Barash and Arnon couldn't immediately be reached for comment.

"This toxin has unusual risks and consequences for human health," says David Relman, a microbiologist at Stanford University who was asked by the journal editors to weigh in on the decision to publish the incomplete manuscript. He says if this new type were deliberately misused, we would have no defense.

Relman agreed with the decision to withhold information. "I want to applaud the authors for acting in a way that I think was responsible and prudent," he tells Shots.

An editorial accompanying the report notes that the scientists consulted with numerous officials from government agencies such as the National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention.

"It would seem that this process, or this consultation, was entirely an internal, within-the-government kind of consultation," says Relman.

He serves on a government advisory board called the National Science Advisory Board for Biosecurity, which is supposed to provide guidance on how to handle biological information that could be misused.

But that committee, which played an important role in the recent debate whether to publish controversial research on bird flu, apparently wasn't consulted this time around. "None of us had heard of this work until I was sent it," says Relman.

Updated Oct. 11 at 11:56 a.m.

Asked if people who needed to know the information to develop counter-measures were going to be able to access it, Mass General's Hooper says, "That was our understanding, yes."

But some say that not sharing scientific work in the usual way, because of fears it could fall into the wrong hands, carries its own risks.

Ronald Atlas, a biologist and bioweapons expert at the University of Louisville in Kentucky, says he agrees with the decision in this case. "But I have real concerns about how often we would do this and what it does to the overall implication of advancement in the life sciences," he tells NPR.

He says that advancement depends on biologists being able to replicate each other's work and use that research to take the next step forward — something that's not possible if scientists and journals withhold critical details.

He notes that if this sets a precedent and biologists start withholding information that they deem too risky, that could slow down the community's ability to do things like search for new treatments. "That's the last thing you want when you're facing a public health threat," he notes.


Botulism

In a normal year, on a spring night in a Midwestern field, Joy O'Keefe would raise a banner of fine mesh stretched between wooden poles 30 feet in the air. Fluttering in the twilight like a lunch lady's hairnet gone to war, the mesh would be a snare for O'Keefe's quarry. 

"We like to say we only catch the stupid bats," she told me — the ones that fly headlong into this obvious trap and don't immediately bite their way out afterward. These captured bats teach scientists about the health and well-being of North American bats more broadly. Catching them, measuring them, gluing tiny radio transmitters to their freshly shaven backs — all this is crucial to protecting animals whose numbers are in steep decline, and whose continued existence is vital to human agriculture. 

Why are people hesitant to trust a COVID-19 vaccine?

But the fields were empty in March 2020, and the bats — the brilliant and the dimwitted alike — sailed peacefully through the evening skies. Instead, it was the humans who were trapped — on a massive conference call. COVID-19 had come to America, and scientists already suspected the virus that caused it, SARS-CoV-2, had originated in bats before making a leap to humans. Nobody knew what that might mean for North American bats, though, and so more than 100 epidemiologists, bat researchers, wildlife managers — anyone who might be able to add clarity to a deeply uncertain situation — dialed in to a call to discuss what to do. The stakes were high, time was short and the scientists knew this: The bats would need our help.

"In North America we pose a far greater risk to our bats than they do to us," said O'Keefe, a bat ecologist and professor of environmental science at the University of Illinois at Urbana-Champaign.

ILLUSTRATION BY EMILY SCHERER / GETTY IMAGES

COVID-19 is a zoonotic disease, an illness that jumped from animal hosts to humans. But disease transfer isn't just a one-way street. It takes only a bit of evolutionary bad luck to turn a bat's head cold into a human's killer. But it takes only a little more for the same virus to jump from humans to other animals. Zoonosis begets reverse zoonosis, which can, in turn, come back around to zoonosis again. A virus we give to a bat could, someday, come back around to reinfect us. Animals' health is ours, ours is theirs, theirs is ours. 

For North American bats, contracting this new virus carried the risk of absolute annihilation. Unlike Old World bats, they aren't natural reservoirs for the branch of the coronavirus family that includes SARS-CoV-2 (the official name of the novel coronavirus), so they have no preexisting immunity to it. And spring was a crucial time. COVID-19 reached the U.S. just as bats were waking from winter hibernation and humans were gearing up for bat research season. The people on that March conference call knew that, within weeks, human researchers would begin catching bats — weighing them, measuring them, literally breathing directly into their tiny faces. We barely knew where COVID-19 had come from, and already we had to think about what it might spread to next.

The bats weren't — and still aren't — the only animals of concern. Even now, a year later, researchers are still working to figure out which animals, in which places, are most at risk. It's a question that has consequences for both animals and people. Every new species that becomes a host for COVID-19 is also a population where the virus can change, mutate, and boomerang back to us. Bats are a bellwether, an example of how our relationships with animals can threaten both our health and theirs. 

Andreas Arnold / picture alliance via Getty Images

There's an intimacy to studying bats. But there's also an industrial detachment. The individual creatures pulled from Joy O'Keefe's nets must go through a series of medical tests and sampling. Blood is drawn, hairs are plucked. Genitals are inspected and bats are sorted into spreadsheet cells for males and females. To figure out which females have recently given birth, the scientists blow lightly on the bats' soft, furry chests, a trick that makes their nipples pop out and milk begin to trickle.

But to comply with animal welfare regulations, all this work must be packed into less than 30 minutes. For the sake of speed and efficiency, the bats become widgets in a small mammal assembly line, one human after another holding them, prodding them, breathing above and on them. 

In spring 2020, nobody knew whether North American bats could contract SARS-CoV-2 from humans who were studying them this way. But after the bat signal went up in March, the U.S. Fish and Wildlife Service decided not to take a chance and put a pause on the fieldwork it funded. "We weren't fully sure what the risks were, but we knew what the consequences could be," said Jeremy Coleman, a wildlife biologist at the USFWS who coordinates the agency's response to white-nose syndrome, a deadly fungus that has killed at least 7 million bats in North America since 2006. 

Coleman knew those risks because of his job. Researchers had figured out a little more than a decade ago that scientists themselves were spreading white-nose syndrome from bat colony to bat colony. Full of good intentions but lacking gloves, researchers had become partly responsible for the epidemic. Obviously a horrific loss for the bats themselves, it has also affected humans. That's because bats are an important part of our food supply, eating insects that would otherwise attack crops and pollinating some of our favorite fruit trees.

White-nose syndrome has killed at least 7 million bats in North America since 2006. Humans have helped spread it, worsening the crisis.

Carolyn Cole / Los Angeles Times via Getty Images

That realization changed how research like O'Keefe's is done. After that discovery, she began to wear gloves, changed them between handling each bat and boiled her teams' gear and clothes in a daily dance of decontamination. Reverse zoonosis put the fear of God into the bat research community. 

But, more broadly, reverse zoonosis is still a risk that isn't taken as seriously as it should be, scientists told me. It's probably more common for viruses to spread from humans to animals than we even know, said Kevin Olival, vice president for research at the nonprofit EcoHealth Alliance. And a virus that does this is a virus you can't eradicate. It becomes endemic, waiting patiently, changing in ways that can make it able to infect us again.

Take influenza, a virus as familiar to us as a nosy neighbor, and with the potential to be every bit as obnoxious. When this virus mutates in ways that make it, for a season, a more serious threat, the very names we call it highlight the role animals played in that transformation — swine flu, bird flu. But while it's true that animals were the hosts while various strains of flu swapped genetic information and mutated, the resulting new strains emerged from animals only because humans had passed precursor strains to those creatures to begin with. 

An industrial pig farm, for example, provides ample opportunity for transmission between humans and animals. The strain of influenza that launched the 2009 swine flu pandemic came from farms in Mexico, said Martha Nelson, a staff scientist with the U.S. National Institutes of Health's Multinational Influenza Seasonal Mortality Study. At the time, it wasn't found in domestic pig populations anywhere else in the world, but today you can find the descendent strains of that pandemic in pigs everywhere on earth that pigs are farmed. That's not because the pigs had gone globe-trotting. "Those human viruses have gone back into the pigs and reassorted with endemic swine viruses to create these new [strains], and one of the problems is, that really increases the genetic diversity of influenza in pigs. And some of [those new strains] have proven capable of infecting humans," Nelson said. Since 2011, these new strains have infected more than 400 people, mostly kids who raise pigs for county fairs in the United States. Zoonotic disease is not a straight line it's a flat circle.

Even camels need a nose swab sometimes. In this instance, a camel in Kenya is tested for MERS.

TONY KARUMBA / AFP via Getty Images

But while experts are fairly certain that SARS-CoV-2 came from Asian bats, that knowledge doesn't necessarily tell them which animals humans are likely to spread the virus to. Figuring that out has involved a lot of trial and error. 

Camels and alpacas, for example, are known carriers of MERS, COVID-19's more deadly cousin, but they don't seem to be susceptible to SARS-CoV-2 at all. Bats are thought to carry thousands of coronaviruses, but some bats seem to be susceptible to SARS-CoV-2 while others (like the big brown bat, common to North America) aren't.

How COVID-19 vaccines work

Meanwhile, cell tests on pigs made it seem, at first, as though they could very likely contract the virus. Biologically, SARS-CoV-2 is able to infect vertebrate animals that carry a receptor on the surface of their cells called ACE2. This receptor is basically a lock, and the virus is the key that fits. In a test tube, ACE2 opened pig cells to SARS-CoV-2 like a welcome friend. But it turns out that a pig is more than the sum of its bacon bits.

"The pigs, they do have a good receptor, but the expression of this is different in humans," said Jürgen Richt, director of the Center of Excellence for Emerging and Zoonotic Animal Diseases at Kansas State University. The ACE2 receptor was expressed in the kidney and testicle cells used in the lab. "But not so much in the respiratory tracts," he said. "That's why the cell lines are receptive, but the pigs aren't." 

Some higher-risk species have emerged from the research, though. 

Many animals are at risk of contracting SARS-CoV-2

Animal species for which information on natural or experimental SARS-CoV-2 infection is available, by evidence of transmission

Farmed animals Infection Documented Transmission
Species Susceptibility Occurred in nature? within species? to humans?
American mink High
Ferrets High
Raccoon dogs High
Rabbits High
Pigs, cattle Extremely low
Poultry None
Companion animals Infection Documented Transmission
Species Susceptibility Occurred in nature? within species? to humans?
Domestic cats High
Hamsters High
Dogs Low
Wildlife Infection Documented Transmission
Species Susceptibility Occurred in nature? within species? to humans?
Large cats High
Fruit bats High
Gorillas High
White-tailed deer High
Marmosets High
Macaques High

Source: World Organisation for Animal health

Minks — animals that have already demonstrated in the real world that they can contract SARS-CoV-2 from humans and then spread it back to us — and their relatives, such as ferrets, are vulnerable. Rabbits and domestic cats are both highly susceptible. So are deer and gorillas. In general, the animals that have turned out to be the biggest risks for reverse zoonosis of COVID-19 are more like bats than like pigs. They're not creatures of mass agribusiness. Nor are they animals that are safely off somewhere living free from moments of intense human contact. Instead, they're somewhere in between. And that … well, it's not great news.

Nobody loves vampire bats, but we can learn a lot from them. Like the name implies, these are the only bat species that actually drink blood. Worse, they can spread rabies to the valuable cattle they feed on. While other bats are benefiting from elaborate conservation efforts, multiple governments are actively trying to kill as many vampire bats as possible, said Gerald Carter, a professor of evolution, ecology and organismal biology at Ohio State University whose research focuses on vampire bats.

But culling vampire bats doesn't actually reduce the number of rabid cows. In fact, Carter said, the places that kill more vampire bats end up with higher rates of rabies in livestock. That's because some bats that were already resistant to rabies and weren't spreading it are inevitably eliminated, leaving an ecological niche wide open for other, rabies-carrying bats to fill. 

"One problem we've faced perennially with controlling wildlife diseases is that we've learned we aren't particularly good at it," the USFWS's Coleman told me. And that's why the animals that seem most susceptible to COVID-19 make researchers nervous — they present challenges that, ironically, wouldn't exist if the virus were targeting domestic species that are constantly in close contact with us. 

A respiratory virus on a farm is a bad thing, Richt said, but once you know it's there, it's easy to contain. There's a market for vaccines for pigs, and you can line the pigs right up and give the vaccines out. If that fails, worse comes to worst, you can kill all the animals in a given barn, or a farm. Nobody wants to, but it's an option. Wild animals are another thing entirely. When a virus like SARS-CoV-2 gets into wildlife, what are you going to do? Who is going to pay to vaccinate the wild bats? Logistically, how do you do it?

And the animals that seem to be the most susceptible to contracting COVID-19 aren't just wild. They're a little halvsies, with populations both in and out of human contact. Gorillas that live in the forest but depend on ecotourism for survival. Deer and mink that are both farmed and hunted wild. The tens of millions of feral cats that live together under America's sheds and broken-down Camaros, hesitantly poking their heads out for the kindness of strange humans who will feed and pet them. Even the North American bats, really and truly wild, aren't free from significant human interaction thanks to those biannual research seasons. 

Carolyn Cole / Los Angeles Times via Getty Images

Another problem is we just flat out don't know where all the wild animals are. These are creatures that live and behave and interact in ways we often have no knowledge of. The northern long-eared bat was an extremely common species in North America prior to the apocalypse of white-nose syndrome. People ran into this bat everywhere. We knew a lot about this bat. But we never did figure out where all of them spent the winter, O'Keefe, the bat ecologist, told me.

Wild or semi-wild populations of animals give a virus plenty of new hosts — and new contacts to infect. Circulating in a population of wild animals, the virus will mutate. Some mutations will thrive and others won't the normal and natural process of evolution will happen. Then some of those mutations will make for a virus that can infect whole other species of animals that weren't susceptible before. Viruses don't just stay where you last set them down. 

We can already see this happening. SARS-CoV-2 couldn't infect mice when it was originally identified back in early 2020. But SARS-CoV-2 as it currently exists can. Somewhere along the line, the virus changed in such a way as to make mice susceptible. This is the kind of story that gives North American bat researchers pause, even though there's not yet a lot of evidence that the bats on this continent can catch COVID-19. Over the course of the winter, the USFWS and the U.S. Geological Survey — both of which are responsible for large portions of America's bat science — conducted a more rigorous evaluation of the possibility that human researchers could pass COVID-19 to their bat subjects. The study concluded that if no precautions were taken, the chances of a team of five scientists infecting at least one bat in the course of their work was 1 in 1,000.

Based on that, in-person bat research will resume this spring. Scientists will go back to those twilight fields, and bats — at least, the dimmer ones — will return to their caves with new tales of alien abduction and bizarre medical procedures. 

But risk remains. When the press release announcing this study came out, it read "Low Risk of Researchers Passing Coronavirus to North American Bats." That did not sit well with Coleman. "I have to admit, I'm not real excited about the title that went out with that press release," he told me. "I think this is something that is still of concern." That's because the 1-in-1,000 risk is a snapshot. It captures a moment in time when, as far as we know, no North American bats are particularly susceptible, and no mutations have made any bat more susceptible than it used to be. It doesn't account for change. It doesn't even account for the way different diseases can multiply the risks of one another. White-nose syndrome, for example, is known to reduce the immune response of bats and make them more susceptible to diseases they otherwise might be safe from. Nobody knows yet what effect that could have on the bats' susceptibility to COVID-19, O'Keefe told me. 

But none of this is the bat's fault. It didn't choose to fly into our nets — it's just not really great at avoiding them. The problem is not that animals are dangerous carriers of disease that need to be controlled, experts said. The problem is that humans can't seem to stop getting all up in animals' business in a wide variety of ways, any of which can spread disease — from us to them, or them to us. 

In February, the Centers for Disease Control and Prevention published its guidelines for handling wild animals. These are presented in the form of a pyramid. At the top, the best thing you can do to prevent the spread of SARS-CoV-2: Just don't handle the animals at all. At the bottom, if you can do nothing else, make sure you wear some protective equipment, such as masks.

In the wake of that document, the bat research community has begun to sound a little like a bunch of newly vaccinated humans trying to decide if and when they can have brunch with an unvaccinated friend. The risk is low. But is it really necessary? If we wear masks, is it fine? The answers depend on whether you think wearing a mask is great protection or just the bare minimum you need to do if there's no other way to avoid contact. "I guess I don't really feel like it's solved," O'Keefe said. "The knowledge we've gained has told us it's possible for us to be transmitting to wild animals we haven't even contemplated and probably should be giving it more attention. The precautions we're taking, we should have probably been doing that all along." 

These are hard choices. They force scientists to face the equally firm reality that observing a thing also involves changing it. The act of catching a bat isn't a neutral choice, with no consequence other than the collection of data. Keeping an animal in a zoo, or a wildlife preserve, or under your dad's old car is not neutral either. We keep thinking of our lives as separate from those of wild animals, even when we are actively touching them. We like to pretend that "wild" and "domestic" are hard and fast lines and that there are places animals can live where they aren't affected by us. 

When these delusions catch up with us, we cull the animals. But, said Angela Bosco-Lauth, a professor of veterinary medicine specializing in infectious disease at Colorado State, the truth about zoonosis is that these viruses expose the stark reality of which species you really have to worry about: It's us. "They aren't our problem," she said. "We're theirs."



Comments:

  1. Faular

    It is happiness!

  2. Kagashura

    He refrains from commenting.



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