Salmonella from the inside out

If your clients are seeing acute diarrhea in fresh cows, that may be your first indication of a Salmonella infection coursing through the herd. Acute Salmonella infections have their own set of clinical that may point to that organism as a culprit. The diarrhea is usually foul-smelling and may or may not contain blood, clots or sheets of fibrin. The cow is febrile, depressed and off feed. Infection in calves can also result in foul-smelling diarrhea. In very young calves, bacteremia may produce a systemic illness and death. Salmonella Dublin, for some reason, often results in bacteremia in calves 4-10 weeks of age. "They often appear to have pneumonia, but S. Dublin grows in pure culture from the lungs," says Bradford P. Smith, DVM, School of Veterinary Medicine, University of California-Davis.

Shedding
Salmonella infections are dose-dependent. If you expose an animal to a small number of Salmonella, it may not become ill. If you give a dose of billions of Salmonella to an animal, it will probably die. The acutely ill cow or calf with Salmonella is likely to shed over a million organisms per ml or gram of feces. During recovery, once feces look normal, they might shed only hundreds or thousands per gram. Smith adds that a cow or calf that is colonized for a time by Salmonella but never gets sick likewise will shed at a low level for a few weeks.

"S. Dublin is maintained in a herd and spread to other herds mainly by carrier cows, which we believe may be carriers for life, similar to human carriers of typhoid," explains Smith. Salmonella Typhimurium appears to rarely cause carriers but tends to cause an epidemic and then disappears after one to two months. "With the group C Salmonella such as Newport, the jury is still out as to how important carrier cows are. Group C Salmonella tend to persist for years in the herd, but how many individual carrier cows exist is not known. For other serogroups like group E, car-rier cows do not seem to be present and probably do not play a major role."

Immune system
Some Salmonella can be virulent pathogens because they effect several systems of the body, most notably the digestive and immune systems. "There are two factors we can influence to prevent or control Salmonella infections," says Smith. "The number ingested and the calf or cow level of resistance. The level of resistance is both in the gastrointestinal tract and in the immune system."

Resistance is a bell-shaped curve in a herd, running from very resistant animals to very innately susceptible animals. Fresh cows have a less-resistant rumen because they are eating less, and so ingested Salmonella tend to multiple better in the rumen. Fresh cows also have hormonal changes and stresses from lactation that decrease immune functions and make them more susceptible than dry cows or cows in later lactation. New susceptible animals and new youngstock are generally naïve to Salmonella and are also at-risk groups.

After exposure to Salmonella that gain access to the systemic side, a cow develops cell-mediated immunity within days and antibody within two to three weeks. As most of the herd becomes exposed, the herd develops resistance. Smith found that about six to eight weeks after the start of an S. Typhimurium outbreak, over 90% of a herd was seropositive and probably resistant to re-infection for some period.

Many serovars can cause acute illness and death. Salmonella organisms penetrate mucous membranes and the tight junctions between cells and hide intracellularly. Pathogenic Salmonella can evade the immune system by preventing the fusion of the phagosome and lysosome inside the macrophage or neutrophils after they are phagocytized. They do this by sensing that they are under attack and secreting a number of novel proteins that prevent the macrophage from performing normally to kill the bacteria. Then the Salmonella multiply in the phagosome until they rupture the macrophage and are released.

 

Brad Smith, DVM, says the number of Salmonella ingested and the cow or calf's resistance level will determine if the animal becomes ill.

Salmonella can cause abortion by either bacteremia and infecting the fetus (resulting in a culture-positive fetus) or by causing increases in prostaglandins that lyse the corpus luteum and result in abortion. The endotoxin (lipopolysaccharide) in the cell wall of Salmonella can start this "inflammatory cascade" that releases these prostaglandins.

The biggest threat to the cow with an acute Salmonella infection is dehydration. Smith says you can't visually see dehydration until it's at about 5%, and dehydration above 10% is life-threatening. Dehydrated animals will not urinate because the body is trying to conserve water to maintain blood pressure.

Any illness during lactation can decrease the total area under the lactation curve and result in lower milk production. Early lactation illness actually has the largest effect on production. "Once a cow goes off feed and has lower milk production, it is very difficult for her to regain the previous production level," says Smith.

 

John Adaska, DVM, PhD, suggests that if practitioners have performed a field necropsy, they should always submit a complete set of tissues, no matter what they suspect.

Calves
Calves can certainly die from Salmonella infections. A calf is most susceptible when it's a newborn because the GI tract is not populated well with com-peting bacteria and it has an immature immune system. Assuming it received adequate colostrum, it again becomes susceptible when the colostral antibody wanes. "The half-life of IGG is about 20 days, so around 40 days the calf's IGG levels are at their lowest and the calf is less resistant again," explains Smith.

"If we add poor colostral transfer and travel stress, diet stress and chilling or heat to the equation, they are very likely to get sick if even relatively small numbers of Salmonella are present," he adds.

Septicemia, diarrhea, pneumonia and polyarthritis can be seen in a calf with a Salmonella infection. "Salmonella can look just like a pneumonia at six weeks because of S. Dublin in the lung," says Smith.

Necropsy findings
When necropsying suspected Salmonella cases, there are certain behaviors of the organism to keep in mind when collecting samples or looking for gross lesions associated with a Salmonella infection. "We routinely find Salmonella in the intestinal tract of animals with enteritis," says John Adaska, DVM, PhD, California Animal Health and Food Safety Laboratory System, University of California-Davis. "As long as the infection has not escaped the intestine, that is the only place we find the bacteria. As the organisms spread, we will occasionally find them in the liver, including gall bladder, but no other organs. We think this represents an early bacteremia/septicemia with the bacteria gaining access to the portal circulation and then reaching the liver and gall bladder. More commonly, in cases of bacteremia/septicemia, we can isolate the bacteria from most places we look for it. Typically, we culture lung and liver, but occasionally we might include spleen and, with lesser frequency, the kidney."

The histology of the intestine (small and colon) with Salmonella shows moderate to severe mucosal necrosis with large numbers of neutrophils and fibrin. "In cases of S. Dublin septicemia, we also can see multifocal necrosis with neutrophils and fibrin in liver, spleen and/or mesenteric lymph node," notes Adaska. "Also with S. Dublin septicemia, we can see interstitial pneumonia with small neutrophilic aggregates with or without fibrin within alveolar septae." Septicemia with other types of Salmonella can cause similar lesions in the organs, but this occurs less commonly and even when present, the lesions are usually less severe.

All Salmonella serovars represent a spectrum of lesions, and any serovar can occur anywhere along that spectrum. However, in general, S. Dublin presents as a calf that is icteric with a big spleen, a swollen liver with rounded margins and often petecchial hemorrhages in the lung representing the interstitial pneumonia.

 

Cows and calves can suffer dehydration from Salmonella-induced diarrhea. PHOTOS: BRAD SMITH, DVM

"Often animals with S. Dublin have watery intestinal content but minimal or no evident luminal fibrin in the intestine," says Adaska.  He adds that S. Typhimurium, again in general (and S. Typhimurium var Copenhagen), is more commonly seen as solely a fibrinosuppurative enteritis with large amounts of fibrin in the intestinal lumen and adhered to the mucosal surfaces of the intestine, which are roughened and often have some hemorrhage.

Smith adds that due to the inflammatory cascade, the Gram-negative Salmonella organisms release a massive amount of endotoxin, and the animal can have an acute death from septic shock and, therefore, have minimal lesions. They can also have a fever and anorexia and then recover. "There is a tremendous variation in response based on genetic variation and endotoxin load," he says.

Sampling for Salmonella
Adaska suggests that if practitioners have gone to the trouble to perform a field necropsy, they should always submit a complete set of tissues, no matter what they suspect. "Nothing is more frustrating for me than, as an example, receiving a single loop of intestine from a field necropsy case in which many other organs are said to have had lesions and then finding that the intestine is perfectly normal," he explains.

A minimum set of tissues that should be sent to the diagnostic lab include fresh and fixed samples of all the following: lung, heart, liver, spleen, kidney, adrenal gland, mesenteric lymph node, rumen, abomasum, small intestine (three to five sections) and spiral colon (two to three sections). The fresh gut should be bagged separate from all other fresh tissues to prevent cross-contamination. Fresh gut loops should be tied off. Fresh samples do not need to be any bigger than a fist, and formalin-fixed samples should be no more than 1-cm thick. Formalin-fixed gut sections should be opened to allow formalin to reach the mucosal surface.

Smith adds that you should have the lab save Salmonella isolates for serotyping and possible vaccine production. "Find out what the serovar/serotype is," he suggests. "Not just what the serogroup is. It's important to know the serovar/serotype of the Salmonella you are dealing with, as outcomes and control may differ."

Antibiotics and Salmonella
Treating Salmonella infections with antibiotics is mostly unrewarding. "Antibiotics work well if we are able to use an antibiotic that gets good intracellular levels and to which the Salmonella is susceptible," says Smith, but, "unfortunately many of these are not legally permitted for use in food animals because they are reserved for serious human infections or because they may cause some problem if residues are consumed by humans." Smith does suggest, however, to have the lab do antimicrobial susceptibility testing on the Salmonella isolate(s).

Many of the most virulent Salmonella are resistant to permitted antibiotics. Enteric bacteria readily share resistance plasmids, so a resistant Salmonella or even E. coli in the gut can transfer resistance to another Salmonella. To make matters worse, many resistance plasmids have cassettes of resistance to multiple antibiotics. Supportive care, including IV sodium fluids to expand blood volume and increase blood pressure and oral fluids to combat dehydration, are the best methods to treat an acutely affected animal. Smith cautions that giving only fresh water without sodium to an animal with severe diarrhea can result in hypoatremia (low blood sodium).

Preventing Salmonella infection comes down to using the same methods that work well for other enteric disease, including excellent hygiene on the farm and preventing cross-contamination. "Make the animal more resistant and decrease the pathogen load," says Smith. "Salmonella is a numbers game."

Effects of a Salmonella infection

Brad Smith, DVM, outlines a severe Salmonella infection in cows.

  • A temperature of 104.2'-106'F.
  • Elevated heart rate and panting.
  • No urine due to dehydration.
  • Watery feces, fibrin, blood clots.
  • Protein is excreted into the feces, causing cows to smell like a meat-eater; smelly, inflammatory diarrhea.
  • Scleral injection from damage to the lining of the blood vessels; scleral vessels are large, engorged and can leak.

Salmonella delivers and releases endotoxins, which also get absorbed by the damaged bowel wall. Endotoxins may cause:

  • Fever.
  • WBC changes -- they stick to vessel walls.
  • Decreased blood pressure.
  • Endothelial damage -- lining of the blood vessels is damaged.
  • Endotoxic effects are worsened by hot weather.

Salmonella Groups

Samonella organisms that are a particular problem for cattle come from several groups under the Salmonella enterica umbrella. Brad Smith, DVM, suggests that in addition to finding out which group is involved in a case, the specific serotype/serovar should be determined.

Group B

The most common Group B serovar is S. Typhimurium. It is often drug resistant and usually epidemic in fresh cows and calves, causing severe diarrhea. During outbreaks, it tends to peak in a few weeks, then subsides in one to two months when herd immunity develops. This is the number one serovar found in cattle, and the number two serovar found in humans. S. Typhimurium DT104 is highly pathogenic and resistant.

Group C

In Group C, S. Newport tends to cause diarrhea and is often multidrug resistant. Group C Salmonella persist on the farm for a long time and are thus difficult to deal with. S. Newport is non-species-specific and affects humans, as well as animals.

Group D

In Group D, S. Dublin is the principal serovar that affects cattle. It is maintained and moved by carrier cows. Calf losses and some abortions may signal infection with S. Dublin. It is a serious but less common human pathogen than group B and C Salmonella.

Group E

There are several serovars of Group E Salmonella that occasionally cause disease in cattle, but they tend to be of lower pathogenicity than group B, C and D Salmonella.

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