Sepsis in Foals: Early Diagnosis Provides Hope

A new study from Australia has found that sepsis, a major cause of death in neonatal foals that isn’t completely understood, has been associated with increased circulating nucleosome levels in foals.

The study was conducted by researchers out of Charles Sturt University in Wagga Wagga, Australia, and recently published in The Veterinary Journal in January 2025. It provides a new piece to understanding sepsis in foals.

“Sepsis can be difficult to diagnose in foals because they can show very vague signs such as sleeping more and nursing less,” said Emily Birckhead, lead author on the study. “Foals can also deteriorate very quickly if they are not identified and treated early.”

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Sepsis itself is a syndrome of life-threatening organ dysfunction, caused by the body’s dysregulated response to proven or suspected infection. According to the Merck Veterinary Manual’s information on sepsis, written by Daniele Bedenice DVM, “the condition implies an extensive, whole body insult after invasion of bacteria into tissue, bloodstream, body fluid or cavity.” Sepsis in foals has been associated with several specific diseases, including neonatal pneumonia, omphalitis, and neonatal uveitis.

There’s currently no completely reliable diagnostic test for sepsis in neonatal foals. Sick foals have to be assessed using a combination of factors, Birckhead said, such as the mare’s history, birth difficulties, colostrum intake, physical examination, blood test, and culture results.

A study from 2021 published by the Veterinary Record noted that “the non-specific clinical signs and subtle nature of this disease may result in delayed diagnosis until severe progression of the disease; thus, early detection of sepsis remains critical for a favourable outcome.”

Advanced sepsis, where the infection has overwhelmed the body’s immune system, can cause septic shock, with significantly increased mortality rates. Foals affected by septic shock are “severely depressed, recumbent, and hypovolemic,” Dr. Bedenice writes. Bacteria can spread through the blood to various organs, and manifest as “respiratory distress, pneumonia, diarrhea, uveitis, meningitis, osteomyelitis, or septic arthritis.”

A 2015 article put the overall survival rate in septic neonatal foals between 26 to 86 per cent. Neonatal sepsis is a leading cause of death for foals in the first week after foaling.

When treated for sepsis, one study found the reported survival rates may be slightly higher at 50 to 81 per cent, depending on the severity and underlying disease. Dr. Bedenice writes that, “early recognition and intensive treatment of neonatal sepsis improves the outcome, although an average of one to four weeks of intensive care should be expected.” Intensive treatment may include antimicrobial drug administration as well as treatment for inflammation, endotoxaemia and coagulopathy.

If the foal survives sepsis, they can live to be a healthy adult. In one study which examined medical records of bacteremic Thoroughbred foals who were hospitalized between 1982 to 2007, they found that foals that survived were as likely to start races as their maternal siblings. However, compared with their siblings, these surviving foals had significantly fewer wins and earned less money.

Nucleosome levels and early sepsis diagnosis

Going into the study, Birckhead’s hypothesis was that plasma nucleosome levels would be higher in septic foals. Increased circulating nucleosome levels have been found in humans and other animals with sepsis, but never foals.

Nucleosomes are released from damaged and dead cells as well as during neutrophil extracellular trap formation (NET), NETs being web-like structures released by white blood cells to capture organisms and prevent infection. “When this mechanism is uncontrolled, such as in sepsis, it can also cause tissue damage,” Birckhead said.

To date, “there have only been small numbers of veterinary NET studies, and the involvement in equine neonatal sepsis has not been proven,” Birckhead said.

The study has become the first to find circulating nucleosomes in foal plasma. It’s identified that “a small number of foals with severe sepsis did have a significant increase of nucleosome levels,” the study notes, “which may have reflected increased NET release or other forms of cell death.”

During the study, Birckhead was surprised to find that “the increases were only in foals with severe sepsis and not in non-severe sepsis foals.” Similarly, she had expected that nucleosome levels would be greater in the non-surviving sepsis foals than they were.

While the study showed an association with increased plasma nucleosome levels in foals with severe sepsis, there was “a large degree of overlap” between the foals with severe sepsis and other groups in the study, including clinically healthy, sick non-septic and non-severe sepsis foals.

“Perhaps these differences could be teased out further if samples from larger numbers of foals are analysed,” Birckhead said.

Whether or not increased plasma nucleosome levels could be used for diagnostic and prognostic purposes of sepsis in neonatal foals is something that could be explored in future research.

However, “it is unlikely that one single marker will be able to diagnose sepsis, as the condition is a complex syndrome that varies across individuals and over time,” Birckhead said.

“It would be useful to further assess nucleosomes and related markers in septic foals,” Birckhead said. “More generally, it would be interesting to understand the processes causing these increased nucleosome levels,” such as NET formation, cell death, or decreased excretion.

Birckhead said that it would also be interesting to investigate if nucleosome levels were increasing for other reasons, such as non-septic illnesses or developmental changes.

For now, the findings of this study provide “a small piece of the puzzle to further understanding sepsis in foals,” Birckhead said. “It is a small clinical study, and further research is needed to determine if increased nucleosome levels could offer diagnostic and prognostic information.”