Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
2. Overview
• Organism
• History
• Epidemiology
• Transmission
• Disease in Humans
• Disease in Animals
• Prevention and Control
Center for Food Security and Public Health, Iowa State University, 2011
4. Salmonellosis
• Gram negative,
facultative rod
• Two species
– S. bongori
– S. enterica
• Six subspecies
• More than 2500 known serovars
– Many zoonotic (non-typhoidal)
Center for Food Security and Public Health, Iowa State University, 2011
6. History
• First isolated in 1884
– S. choleraesuis in pig intestine
• Prevalence in the U.S.
– 1980: 30,000
– 1986: 42,028
– 1998-2002: 128, 370
• Estimated 1.4 million cases/year
– Only 40,000 culture-confirmed
Center for Food Security and Public Health, Iowa State University, 2011
8. Geographic Distribution
• Worldwide
– Related to animal husbandry
– Wild reservoirs
• Serovar distribution varies
– Some geographically limited
• Eradication programs in some
countries
– Sweden
Center for Food Security and Public Health, Iowa State University, 2011
9. U.S. Serotypes, 2009
• Enteritidis
• Typhimurium
• Newport
• Javiana
• Heidelberg
• Montevideo
• 14,[5],12.i:-
• Muenchen
Center for Food Security and Public Health, Iowa State University, 2011
FoodNet
10. Morbidity/Mortality: Animals
• Asymptomatic infections
are common
– 1-3% carriers
– Higher in reptiles,
birds
• Clinical disease
– Young, pregnant/lactating, stress
- Mortality can reach 100%
Center for Food Security and Public Health, Iowa State University, 2011
13. Human Transmission
• Fecal-oral: direct or indirect
• Commonly contaminated items
– Meat, eggs, water
• Fecal material from:
– *Reptiles
– *Chicks
– *Ducklings
– Livestock, dogs, cats, adult poultry
Center for Food Security and Public Health, Iowa State University, 2011
14. Animal Transmission
• Fecal-oral
– Carried asymptomatically
• Fomites, mechanical vectors
• Vertical
– Birds
• In utero
• Contaminated
food and water
Center for Food Security and Public Health, Iowa State University, 2011
16. Disease in Humans
• Incubation period:
– Gastroenteritis: 12 hrs to 3 days
– Enteric fever: 10 to 14 days
• Asymptomatic to severe
• All serovars can
produce all forms
– Reptile-associated is
most severe
Center for Food Security and Public Health, Iowa State University, 2011
17. Clinical Sign: Gastroenteritis
• Nausea, vomiting, cramping
abdominal pain and diarrhea
(may be bloody)
• Headache, fever, chills, myalgia
• Severe dehydration: infants, elderly
• Symptoms resolve in 1 to 7 days
• Sequela: Reiter’s syndrome
Center for Food Security and Public Health, Iowa State University, 2011
18. Clinical Signs: Enteric Fever
• Systemic salmonellosis
• Caused by S. typhi or other species
• Clinical signs
– Non-specific
– Gastrointestinal disease
– Fever, anorexia, headache, lethargy,
myalgias, constipation
• Can be fatal: meningitis, septicemia
Center for Food Security and Public Health, Iowa State University, 2011
19. Diagnosis
• Isolate organism from feces or blood
• Grows on wide
variety of media
– Enrichment
• Biochemical tests
– Antigens
– Phage typing
• PCR
Center for Food Security and Public Health, Iowa State University, 2011
20. Treatment in Humans
• Antibiotics
– Ampicillin, amoxicillin, gentamicin, TMS,
fluoroquinolones
• Treatment indications
– Septicemia, enteric fever
– Elderly, infants, immunosuppressed
• Healthy persons recover 2 to 7 days
without antibiotics
Center for Food Security and Public Health, Iowa State University, 2011
22. Disease in Animals
• Found in all species
– Mammals
– Bird
– Reptiles
– Amphibians
– Fish
– Invertebrates
• Some serovars have
narrow host range
Center for Food Security and Public Health, Iowa State University, 2011
23. Disease in Animals
• Incubation period: highly variable
• Infections become symptomatic
under stressful conditions
– Transport
– Crowding
– Weaning
– Parturition
– Exposure to cold
– Concurrent diseases
Center for Food Security and Public Health, Iowa State University, 2011
24. Clinical Disease: Reptiles
• Clinical disease uncommon
• Syndromes reported
– Subcutaneous
abscesses
– Septicemia
– Osteomyelitis
– Osteoarthritis
Center for Food Security and Public Health, Iowa State University, 2011
25. Acute Enteritis:
Ruminants, Pigs, Horses
• Diarrhea (watery to pasty)
• Dehydration
• Depression
• Abdominal pain
• Anorexia
• Fever
• Decreased milk production
• Death from dehydration, toxemia
Center for Food Security and Public Health, Iowa State University, 2011
26. Enteritis:
Ruminants, Pigs, Horses
• Subacute
– Adults
– Diarrhea
– Weight loss
• Chronic
– Adults, older calves,
growing pigs
– Emaciation, fever,
inappetence, scant feces
Center for Food Security and Public Health, Iowa State University, 2011
27. Septicemia:
Ruminants, Horses, Pigs
• Young animals
– Very young calves
– Lambs, foals
– Pigs up to 6 months
• Clinical signs
– Depression, fever
– CNS signs or pneumonia (calves, pigs)
– Dark discoloration of skin (pigs)
• Death 1 to 2 days
Center for Food Security and Public Health, Iowa State University, 2011
28. Other Signs:
Ruminants, Horses, Pigs
• Abortion
– Associated serovars
• Dublin (cattle)
• Abortusovis (sheep)
• Abortusequi (horses)
– May be first clinical sign
in cows with subacute
enteritis
• Joint infections/gangrene
Center for Food Security and Public Health, Iowa State University, 2011
29. Clinical Signs:
Dogs and Cats
• Acute diarrhea
– Recover 3 to 4 weeks
• Septicemia
• Cats
– Chronic febrile illness
• Abortion
• Birth of weak offspring
Center for Food Security and Public Health, Iowa State University, 2011
30. Clinical Signs: Birds
• Very young birds
• Anorexia
• Lethargy
• Diarrhea
• Increased thirst
• CNS signs
Center for Food Security and Public Health, Iowa State University, 2011
31. Post Mortem Lesions
• Not pathognomonic
• Intestinal lesions
most common
– Lower ileum
– Large intestine
Center for Food Security and Public Health, Iowa State University, 2011
32. Diagnosis
• Isolate organism from feces or blood
– Selective and non-selective media
– Enrichment
– Biochemical tests
• Serology
– Herds or flocks
• PCR
• Healthy carriers
Center for Food Security and Public Health, Iowa State University, 2011
33. Treatment
• Antibiotics
– Septicemia
– Not recommended for enteric disease
• May affect intestinal flora and increase
emergence of resistant strains
• Fluid replacement
• NSAIDs
– Endotoxemia
Center for Food Security and Public Health, Iowa State University, 2011
35. Prevention in Humans
• Food-borne diseases
– Avoid raw or undercooked eggs, poultry,
meat; unpasteurized milk/dairy
– Wash foods before eating
– Avoid cross-contamination of food
• Keep uncooked and cooked foods
• Wash hands and kitchen tools
– Do not feed infants or change diapers
while handling food
Center for Food Security and Public Health, Iowa State University, 2011
36. Prevention in Humans
• Animal contact
– Wash hands after contact
– If immunocompromised, avoid contact
with reptiles, young chicks, ducklings
– Reptiles
• Children under 10 years of age
• Wash hands, cages, and surfaces
• Change clothes
• Supervision
• Do not allow reptiles to roam freely
Center for Food Security and Public Health, Iowa State University, 2011
37. Prevention in Animals
• Herds and flocks
– Buy from Salmonella-free sources
– Isolate new animals
– All in/all out
• Outbreak
– Identify carriers
• Isolate, treat, or cull
– Retest treated animals
– Clean and disinfect
Center for Food Security and Public Health, Iowa State University, 2011
38. Prevention in Animals
• Preventing clinical disease
– Good hygiene
– Minimize stressful events
– Colostrum
– Vaccination
• Also reduces colonization
and shedding
• All reptiles are a source
– Do not treat to eliminate
Center for Food Security and Public Health, Iowa State University, 2011
39. Additional Resources
• World Organization for Animal Health
(OIE)
– www.oie.int
• U.S. Department of Agriculture (USDA)
– www.aphis.usda.gov
• Centers for Disease Control and
Prevention (CDC)
– http://www.cdc.gov/salmonella/
• Center for Food Security and Public Health
– www.cfsph.iastate.edu
Center for Food Security and Public Health, Iowa State University, 2011
40. Acknowledgments
Development of this presentation
was funded by grants from
the Centers for Disease Control and Prevention,
the Iowa Homeland Security and Emergency
Management Division, and the Iowa Department
of Agriculture and Land Stewardship
to the Center for Food Security and Public
Health at Iowa State University.
Author: Sarah Wissmann
Reviewer: Kerry Leedom Larson, DVM, MPH, PhD
Center for Food Security and Public Health, Iowa State University, 2011
Editor's Notes
In today’s presentation, we will cover information regarding the organism that causes non-typhoidal salmonellosis and its epidemiology. We will also talk about the history of the disease, how it is transmitted, species that it affects and clinical and necropsy signs observed. Finally, we will address prevention and control measures for non-typhoidal salmonellosis.
[Photo: Cow. USDA ARS, Peggy Greb]
Salmonella spp. are members of the family Enterobacteriaceae. They are Gram negative, facultatively anaerobic rods. The genus Salmonella contains two species, S. enterica, the type species, and S. bongori. S. enterica. contains six subspecies: S. enterica subsp. enterica, S. enterica subsp. salamae, S. enterica subsp. arizonae, S. enterica subsp. diarizonae, S. enterica subsp. houtenae and S. enterica subsp. indica. Within each subspecies are serovars; over 2500 serovars are presently known. Most of the isolates that cause disease in humans and other mammals belong to S. enterica subsp. enterica. A few serovars, Salmonella ser. Typhi, Salmonella ser. Paratyphi and Salmonella ser. Hirschfeldii are human pathogens that are transmitted from human to human. The remaining Salmonella serovars, sometimes referred to as non-typhoidal Salmonella, are zoonotic or potentially zoonotic.
[Photo: Salmonella spp. CDC Public Health Image Library]
Salmonella was first discovered in 1884 by Dr. DE Salmon; he isolated the bacterium (S. choleraesuis) from the intestine of a pig. By 1980, more than 30,000 people were reported to be infected with Salmonella in the United States. This number increased to 42,028 by 1986. From 1998-2002, the CDC reported 128,370 cases. An estimated 1.4 million cases occur annually in the U.S., although only about 40,000 are culture-confirmed and reported to CDC.
Salmonellosis can be found worldwide but seems to be most common where intensive animal husbandry is practiced. Reservoirs also remain in wild animals. Some Salmonella are geographically limited. Salmonella eradication programs have nearly eradicated the disease in domestic animals and humans in some countries (e.g., Sweden).
The Foodborne Diseases Active Surveillance Network (FoodNet) is the principal foodborne disease component of CDC's Emerging Infections Program (EIP). The project consists of active surveillance for foodborne diseases and related epidemiologic studies designed to help public health officials better understand the epidemiology of foodborne diseases in the United States. States in yellow (figure, above) participate in FoodNet. In 2009, the most common Salmonella serotypes isolated from FoodNet were: Enteritidis, Typhimurium, Newport, Javiana, Heidelberg, Montevideo,14,[5],12.i:-, and Muenchen.
Image: States participating in FoodNet. CDC.
In animals, asymptomatic Salmonella infections are common. Overall, approximately 1-3% of domestic animals are thought to carry Salmonella spp. but the prevalence can be much higher in some species. Among mammals, clinical disease is most common in very young, pregnant or lactating animals, and usually occurs after a stressful event. Outbreaks with a high morbidity rate and sometimes a high mortality rate are typical in young ruminants, pigs, and poultry. In outbreaks of septicemia, morbidity and mortality can reach 100%.
[Photo: Sow with litter. USDA ARS]
Estimates of the carrier rate among reptiles vary from 36% to more than 80-90%, and several serovars can be found in a single animal. Some authorities consider most or all reptiles to be Salmonella carriers. High prevalence rates can also be present in some birds and mammals. Salmonella spp. have been isolated from 41% of turkeys tested in California and 50% of chickens examined in Massachusetts. Salmonella spp. have also been isolated from 1-36% of healthy dogs and 1-18% of healthy cats in various studies, as well as 6% of beef cattle in feedlots. From 2-20% of horses are thought to be healthy shedders.
People are often infected when they eat contaminated foods of animal origin such as meat or eggs. They can also be infected by ingesting organisms in animal feces, either directly or in contaminated food or water. Directly transmitted human infections are most often acquired from the feces of reptiles, chicks and ducklings. Livestock, dogs, cats, adult poultry and cage birds can also be involved.
Salmonella spp. are mainly transmitted by the fecal-oral route. They are carried asymptomatically in the intestines or gall bladder of many animals, and are continuously or intermittently shed in the feces. Vertical transmission occurs in birds, with contamination of the vitelline membrane, albumen and the yolk of eggs. Salmonella spp. can also be transmitted in utero in mammals. Animals may also become infected from contaminated feed (including pastures), drinking water, or close contact with infected animal (including humans). Birds and rodents can spread Salmonella to livestock. Carnivores are also infected through meat, eggs, and other animal products that are not thoroughly cooked.
[Photo: Chickens. USDA ARS, Stephen Ausmus]
In humans, salmonellosis varies from a self-limiting gastroenteritis to septicemia. Whether the organism remains in the intestine or disseminates depends on host factors as well as the virulence of the strain. Asymptomatic infections can also be seen. All serovars can produce all forms of salmonellosis, although a given serotype is often associated with a specific syndrome (e.g. Salmonella choleraesuis tends to cause septicemia). Salmonellosis acquired from reptiles is often severe, and may be fatal due to septicemia or meningitis. Most cases of reptile-associated salmonellosis are seen in children under 10 and people who are immunocompromised.
[Photo: Boy holding turtle. CDC, James Ganthany]
Gastroenteritis is characterized by nausea, vomiting, cramping abdominal pain and diarrhea, which may be bloody. Headache, fever, chills and myalgia may also be seen. Severe dehydration can occur in infants and the elderly. In many cases, the symptoms resolve spontaneously in 1 to 7 days. Deaths are rare except in very young, very old, debilitated or immunocompromised persons. Reiter's syndrome may be a sequela in some cases of gastroenteritis. This syndrome is characterized by mild to severe arthritis, nonbacterial urethritis or cervicitis, conjunctivitis and small, painless, superficial mucocutaneous ulcers. Reiter’s syndrome occurs in approximately 2% of cases of salmonellosis.
Enteric fevers are a severe form of systemic salmonellosis. Although most cases are caused by S. typhi, a human pathogen, other species can also cause this syndrome. Gastrointestinal disease may be the first sign, but it usually resolves before the systemic signs appear. The symptoms of enteric fever are non-specific and may include fever, anorexia, headache, lethargy, myalgias and constipation. This disease can be fatal, due to meningitis or septicemia, if not treated quickly.
Salmonellosis can be confirmed by isolating the organisms from feces or, in cases of disseminated disease, from the blood. Salmonella will grow on a wide variety of selective and non-selective media. Enrichment broths can increase the probability of isolating the organism. Salmonella spp. are identified with biochemical tests, and the serovar can be identified using serology for the somatic (O), flagellar (H) and capsular (Vi) antigens. PCR and other genetic techniques may also be available.
[Photo: Salmonella colonies. Dr. Danelle Bickett-Weddle, CFPSH]
Salmonellosis in humans can be treated with a number of antibiotics including ampicillin, amoxicillin, gentamicin, trimethoprim/sulfamethoxazole and fluoroquinolones. Many isolates are resistant to one or more antibiotics, and the choice of drugs should, if possible, be based on susceptibility testing. Antibiotics are used mainly for septicemia, enteric fever or focal extraintestinal infections. Focal infections may require surgery and prolonged courses of antibiotics. In the elderly, infants and immunosuppressed persons, who are prone to septicemia and complications, antibiotics may be given for gastroenteritis. However most healthy people recover spontaneously in 2 to 7 days and may not require antibiotic treatment. Antibiotics do not usually shorten this form of the disease. They also prolong the period of bacterial shedding and increase the development of antibiotic-resistant strains. Symptomatic treatment of dehydration, nausea and vomiting may be required.
Salmonella spp. have been found in all species of mammals, birds, reptiles, and amphibians that have been investigated. Fish and invertebrates can also be infected. Infections are particularly prevalent in poultry, swine, and reptiles. All species seem to be susceptible to salmonellosis under the right conditions but clinical disease is more common in some animals than others. Some serovars have a narrow host range. Clinical cases are common in cattle, pigs, and horses but are relatively uncommon in cats and dogs.
[Photo: Chicks. USDA, ARS, Keith Weller]
The incubation period in animals is highly variable. In many cases, infections become symptomatic only when the animal is stressed. Clinical disease usually appears when animals are stressed by factors such as transportation, crowding, food deprivation, weaning, parturition, exposure to cold, a concurrent viral or parasitic disease, sudden change of feed, or overfeeding following a fast. The clinical signs vary with the infecting dose, health of the host, Salmonella serovar and strain, and other factors.
[Photo: Pigs in transit. USDA ARS, Scott Baur]
Clinical disease seems to be uncommon in reptiles. Syndromes that have been reported include septicemia (characterized by anorexia, listlessness and death), osteomyelitis, osteoarthritis and subcutaneous abscesses. Progressive, fatal bone infections have been seen in snakes. In one group of free-living turtles, the symptoms included emaciation, lesions of the plastron, a discolored carapace and intestinal, respiratory and hepatic lesions. Salmonella spp. have also been implicated in sporadic deaths among tortoises in zoos.
[Photo : Turtle (Graptemys nigrinoda) hatchlings. Wikimedia Commons]
Acute enteritis is the most common form of salmonellosis in adult animals, and in calves over a week old. This form is characterized by profuse diarrhea, dehydration, depression, abdominal pain and anorexia. The feces are watery to pasty, often foul smelling, and may contain mucus, pieces of mucous membrane, casts, or blood. A fever occurs early in the infection, but can disappear by the time diarrhea develops. In dairy cows, milk production drops acutely. Intestinal salmonellosis usually lasts for 2 to 7 days. Death can occur as the result of dehydration and toxemia. Horses, in particular, often have sever enteritis and may die within 24 to 48 hours. Recovery can be slow.
[Photo: Sick dairy cow. CFSPH]
Subacute enteritis may be seen in adult horses, cattle, and sheep. The most obvious symptoms are persistent soft feces, or diarrhea, and weight loss. There may also be mild fever, inappetence, and some dehydration. Chronic enteritis is mainly seen in older calves, adult cattle and growing pigs. The symptoms can include progressive emaciation (see photo of emaciated horse), low-grade intermittent fever and inappetence. The feces are usually scant and may be normal or contain mucus, casts, or blood. Rectal strictures can be sequelae in growing pigs.
[Photo: Emaciated horse. Cornell College of Veterinary Medicine, Dr. John M. King]
Septicemia is the most common syndrome in very young calves, lambs and foals, and in pigs up to 6 months of age. The symptoms include marked depression, high fever and often, death within 1 to 2 days. Diarrhea can occur in some animals. Central nervous system (CNS) signs or pneumonia may be seen in calves and pigs. Pigs may also develop a dark reddish or purple discoloration of the skin, particularly on the ears and ventral abdomen.
Pregnant animals may abort, either with or without other clinical signs. Serovars often associated with abortions include Salmonella Dublin in cattle, Salmonella Abortusovis in sheep and Salmonella ser. Abortusequi in horses. In cows with subacute enteritis, the first symptom may be abortion, followed after several days by diarrhea. Abortions in pregnant ewes may be followed by fetid, dark red vaginal discharge and sometimes death. Another sign seen in calves are joint infections or gangrene at the limb extremities (see photo), tips of the ears and tail.
[Photo: Gangrene limb of calf. Cornell College of Veterinary Medicine, Dr. John M. King]
In dogs and cats, the most common form is acute diarrhea with or without septicemia. Most cats and dogs with acute diarrhea recover within 3 to 4 weeks. Pneumonia, abscesses, meningitis, osteomyelitis, cellulitis or conjunctivitis may also be seen. A chronic febrile illness characterized by anorexia and lethargy, but no diarrhea, has been reported in cats. Pregnant dogs and cats may abort or give birth to weak puppies or kittens.
[Photo: Veterinarian examining cat. Dr. Danelle Bickett-Weddle, CFSPH]
Most clinical cases are seen in very young birds. The symptoms may include anorexia, lethargy, diarrhea, increased thirst and CNS signs.
[Photo: Chicks in a basket. Steve Roney, USDA]
The necropsy lesions are not pathognomonic. They may include necrotizing fibrinous enteritis (top photo), lesions associated with septicemia, or both. Intestinal lesions are most common and severe in the lower ileum and large intestine. In acute enteritis, there is extensive hemorrhagic enteritis, with mucosal erosions and often whole blood in the lumen (bottom photo). Similar lesions may be found in the abomasum. The mesenteric lymph nodes are usually edematous and hemorrhagic, and there may be inflammation in the wall of the gall bladder. Other lesions may include fatty degeneration in the liver, bloodstained fluid in the serous cavities, and petechial hemorrhages in the heart and sometimes other organs. In cattle with chronic salmonellosis, the intestinal wall is thickened and discrete areas of necrosis are usually found in the mucosa of the cecum and colon. An inflamed granular surface may be seen under the necrotic regions.
[Photo source: Cornell College of Veterinary Medicine, Dr. John M. King]
Salmonellosis can be confirmed by isolating the organisms from feces or, in cases of disseminated disease, from the blood. After an abortion, the bacteria may be found in the placenta, vaginal exudate and fetal stomach. Salmonella spp. are identified with biochemical tests, and the serovar can be identified by serology for the somatic (O), flagellar (H) and capsular (Vi) antigens. Serology can be useful for diagnosis in a herd or flock. It is also used to identify carriers in poultry Salmonella eradication programs. Serologic tests include agglutination tests and enzyme-linked immunosorbent assays (ELISAs). Some ELISAs can be used for bulk milk screening or on freeze thawed muscle tissue samples (tissue fluid) from pigs. Most serologic tests detect a limited number of serovars or serogroups. Serology is of limited use in individual animals, as antibodies do not appear until two weeks after infection, and antibodies may also be present in uninfected animals. Polymerase chain reaction (PCR) and other genetic techniques may also be available. Diagnosis of clinical cases and identification of carriers is complicated because Salmonella spp. can be found in healthy carriers.
[Photo: Researcher testing eggs for Salmonella . USDA ARS]
Septicemic salmonellosis can be treated with a number of antibiotics including ampicillin, amoxicillin, gentamicin, trimethoprim/sulfamethoxazole, third generation cephalosporins, chloramphenicol and fluoroquinolones. Many isolates are resistant to one or more antibiotics, and the choice of drugs should, if possible, be based on susceptibility testing. Antibiotics can favor the persistence of Salmonella spp. in the intestines after recovery, affect the intestinal flora, and increase the emergence of antibiotic-resistant strains. For these reasons, antibiotics might not be used for enteric disease. Fluid replacement, correction of electrolyte imbalances and other supportive care is important in cases of enteritis. Nonsteroidal anti-inflammatory drugs may be given to decrease the effects of endotoxemia. Antibodies to Salmonella lipopolysaccharide may also be used in some cases.
To decrease the risk of salmonellosis, both food safety practices and the prevention of transmission from animals are important. To reduce the risk of food-borne disease: 1) Raw or undercooked eggs, poultry and other meats should be avoided. 2) All meat should be cooked until it is no longer pink in the middle. 3) Unpasteurized milk and other unpasteurized dairy products should not be drunk or eaten. 4) Raw vegetables should be thoroughly washed before eating. 5) Cross-contamination of foods should be prevented. 6) Uncooked meats should be kept separate from produce, cooked and read-to-eat foods. The hands and any kitchen tools that contact uncooked foods should be thoroughly washed after handling potentially contaminated foods. The hands should also be washed before handling foods. 7) Infants should not be fed or have their diapers changed while the caregiver is working with raw meats or eggs.
To reduce the risk of acquiring salmonellosis from animals: 1) The hands should always be washed with hot, soapy water, immediately after contact with any animal feces. 2) People who are immunocompromised should avoid contact with reptiles, young chicks and ducklings. 3) They should also be particularly cautious when visiting farms or petting zoos. Other zoonosis prevention recommendations for those who are immunocompromised can be found on the CDC web site. Extra precautions should be taken with reptiles, as many seem to shed Salmonella spp. Children under 10 seem to be particularly susceptible to severe salmonellosis after contact with reptiles. No human vaccines to prevent zoonotic or foodborne salmonellosis exist.
The risk of introducing salmonellosis into a herd/flock can be decreased by buying animals or eggs from Salmonella-free sources, isolating newly acquired animals, and practicing “all in/all out” herd or flock management, where appropriate. Rodent control is also important. Feed and water sources should be Salmonella- free. During a herd outbreak, carrier animals should be identified and either isolated and treated, or culled. Treated animals must be re-tested several times to ensure that they no longer carry Salmonella. Fecal contamination of feed and water supplies should be prevented. Contaminated buildings and equipment should be cleaned and disinfected, and contaminated material should be disposed of.
[Photo: Isolated beef cow. CFPSH]
Clinical salmonellosis can be decreased by good hygiene and minimizing stressful events. Colostrum is important in preventing disease in young animals. Vaccines are available for some serovars such as Salmonella Dublin, Salmonella Typhimurium, Salmonella Abortusequi and Salmonella Choleraesuis in some countries. Vaccines can reduce the level of colonization and shedding of Salmonella spp. into the environment, as well as clinical disease. Competitive exclusion by administration of Salmonella free cultures of fecal organisms may be used in young birds. All reptiles should be considered to be potential sources of Salmonella. The Association of Reptile and Amphibian Veterinarians (ARAV) discourages veterinarians from treating reptiles with antibiotics to eliminate Salmonella, as this has not been effective in the past and may increase the development of antibiotic-resistant strains of bacteria.