What Infections Cause High Calprotectin?

Almost any infection that triggers neutrophil activity in the gut can raise fecal calprotectin, but bacterial intestinal infections push it the highest. Salmonella and Campylobacter routinely produce levels in the hundreds of micrograms per gram, while common viral gastroenteritis bugs tend to leave calprotectin far lower. The picture gets more interesting beyond the gut: bloodstream infections, respiratory infections, parasites, and even certain fungal overgrowths all leave a calprotectin footprint, either in stool or in blood. Understanding which infections drive the marker up, and by how much, matters because calprotectin is increasingly used to decide whether someone needs a colonoscopy or just reassurance.

Why Infections Raise Calprotectin in the First Place

Calprotectin is a protein packed inside neutrophils, the white blood cells your immune system sends first to any site of trouble. When those neutrophils swarm into inflamed tissue, they eventually die or actively expel their contents, releasing calprotectin into the surrounding area. In the intestine, this means the protein winds up in stool in proportion to how many neutrophils showed up. Observations from patients with inflammatory bowel disease first made this connection clear: increased neutrophil migration into the gut leads to calprotectin release as a direct consequence of intestinal inflammation.¹ One mechanism involves neutrophil extracellular traps, web-like structures that neutrophils throw out to ensnare bacteria; calprotectin gets exported along with these traps.² The practical takeaway is simple: the more neutrophils an infection recruits into the intestinal wall, the higher the fecal calprotectin reading.

Bacterial Gut Infections Drive the Biggest Spikes

When it comes to fecal calprotectin, bacteria that invade or damage the intestinal lining are the strongest drivers. A study measuring calprotectin in children with infectious diarrhea found that Salmonella infections produced a median level around 765 µg/g, and Campylobacter infections came in around 689 µg/g. Both of those readings would be flagged as very high by any standard lab reference range.³ By contrast, viral gastroenteritis from rotavirus, norovirus, or adenovirus produced median levels below 100 µg/g in the same study, a range many labs would consider borderline or normal.³

This gap makes biological sense. Bacteria like Salmonella and Campylobacter invade the intestinal lining and provoke a strong inflammatory response with heavy neutrophil recruitment. Most common viruses that cause gastroenteritis damage cells in the small bowel without triggering the same neutrophil flood. A multicenter study of adults with acute diarrhea confirmed the clinical usefulness of this difference: fecal calprotectin had roughly 83% sensitivity and 87% specificity for identifying a bacterial cause behind the diarrhea.⁴ That is not perfect, but it is considerably better than fecal occult blood testing and more specific than lactoferrin for the same purpose.

Clostridioides difficile Infection

C. difficile deserves its own mention because it is one of the most common hospital-acquired gut infections, and calprotectin does more here than just confirm something is wrong. Research has shown that calprotectin levels reflect the severity of C. difficile infection, not just its presence. One study comparing patients with confirmed C. difficile to healthy controls found calprotectin distinguished the two groups well, with about 75% sensitivity and 79% specificity. More usefully, it could also separate severe cases from mild ones, with 70% sensitivity and 80% specificity for that distinction.⁵

The hypervirulent ribotype 027 strain, which has caused outbreaks in hospitals worldwide, produces even higher calprotectin readings than other strains. Patients infected with ribotype 027 had significantly elevated levels compared to those with other ribotypes, and their calprotectin also correlated with higher white blood cell counts in the blood.⁶ For clinicians, this means a very high calprotectin in someone with confirmed C. difficile could signal they are dealing with a more aggressive strain or a case heading toward complications.

COVID-19 and Gut Inflammation

SARS-CoV-2 provided a striking example of a primarily respiratory virus pushing calprotectin up. COVID-19 patients had markedly elevated fecal calprotectin, with a median around 124 µg/g compared to 25 µg/g in uninfected controls in one study.⁷ Those shedding virus in their stool had higher levels still. What made this finding puzzling is that the calprotectin elevation did not track with whether someone actually had gut symptoms like diarrhea or nausea. A separate study confirmed the same pattern: both fecal and serum calprotectin were elevated in COVID-19 patients regardless of gastrointestinal complaints.⁷

The explanation likely involves the virus infecting cells in the gut lining directly, since the ACE2 receptor it uses to enter cells is abundant there. This triggers local inflammation even when the person feels nothing wrong in their abdomen. For anyone who had a calprotectin test done during or shortly after a COVID-19 infection, the reading could easily have been elevated without any underlying bowel disease. That kind of false alarm matters if the test was ordered to screen for conditions like Crohn’s disease or ulcerative colitis.

Parasitic Infections

Parasites are an underappreciated cause of elevated calprotectin, particularly in settings where they are common and may coexist with other gastrointestinal conditions. Giardia, one of the most widespread intestinal parasites globally, has been shown to raise fecal calprotectin meaningfully. In one study of children with diarrhea caused by Giardia, the mean calprotectin was around 164 µg/g compared to about 48 µg/g in uninfected children.⁸ Even the genotype of Giardia mattered: assemblage B infections produced calprotectin levels nearly twice as high as assemblage A.

Entamoeba histolytica, the parasite that causes amoebic dysentery, appears to drive calprotectin even more reliably. One study found that over 40% of patients infected with E. histolytica had positive calprotectin readings, compared to about 21% with Giardia and only around 3% with Blastocystis hominis.⁹ This makes sense given that E. histolytica actively invades the intestinal wall, creating the kind of tissue damage that pulls neutrophils in. Intestinal schistosomiasis and heavy Dientamoeba fragilis infections have also been linked to elevated calprotectin through similar neutrophil-driven inflammation.¹⁰

The clinical implication is real. Someone being evaluated for inflammatory bowel disease who happens to carry a parasitic infection could show an elevated calprotectin and be sent for an unnecessary colonoscopy or started on the wrong treatment. Checking for parasites before assuming that a high calprotectin means IBD is a step that gets skipped more often than it should, especially in non-endemic regions where clinicians may not think of it.

Gastrointestinal Tuberculosis

Intestinal TB is uncommon in high-income countries but remains a significant diagnostic challenge in parts of Asia and Africa, partly because it closely mimics Crohn’s disease on imaging and endoscopy. Calprotectin is elevated in active intestinal TB, with one study reporting a median baseline level around 216 µg/g in patients with confirmed intestinal TB.¹¹ What proved more useful than the baseline number was tracking calprotectin over time. Patients with intestinal TB who were started on anti-tuberculosis treatment showed a sharp drop in calprotectin at two months and near-normal levels at six months. Patients with Crohn’s disease who were mistakenly started on the same drugs showed no such decline, with their levels staying above 200 µg/g at both follow-up points.¹¹ Serial calprotectin measurements, in other words, can help untangle one of the trickier diagnostic dilemmas in gastroenterology.

Fungal Involvement in the Gut

Fungal infections of the gut are less commonly discussed than bacterial or viral ones, but growing evidence connects intestinal fungal overgrowth with calprotectin elevation. In patients with active ulcerative colitis who also had detectable Candida in their stool, treatment with the antifungal fluconazole led to a drop in calprotectin in about 84% of treated patients, compared to only about 37% in the placebo group.¹² That is a striking difference, and it suggests that the fungal component was genuinely contributing to the intestinal inflammation driving calprotectin up, not just tagging along for the ride.

More exotic scenarios also exist. Patients with liver echinococcosis, a parasitic disease caused by tapeworms, showed expansion of opportunistic fungal pathogens in their gut along with elevated calprotectin and markers of gut inflammation, even though echinococcosis is traditionally considered an extraintestinal disease.¹³ The overall takeaway is that fungal overgrowth in the intestine is a legitimate contributor to calprotectin elevation, particularly in immunocompromised patients or those already dealing with another inflammatory gut condition.

Bloodstream and Respiratory Infections

Calprotectin is not just a stool marker. Blood (serum or plasma) calprotectin rises during systemic infections as well, because the same neutrophil-driven mechanism operates anywhere in the body where neutrophils are activated. The CASCADE trial, a prospective study of patients with suspected infections, found that those with positive blood cultures had markedly elevated plasma calprotectin regardless of whether the bacteria were gram-positive or gram-negative.¹⁴ In patients with suspected sepsis evaluated in the emergency department, plasma calprotectin was significantly higher in those who ended up needing intensive care compared to those sent to a regular ward.¹⁵

Respiratory infections tell a similar story. In patients hospitalized with severe bacterial pneumonia or COVID-19, circulating calprotectin measured within the first few days was elevated compared to non-infected controls. Higher levels at admission predicted worse outcomes, including longer hospitalization and higher mortality risk by day 29. The calprotectin readings correlated with other markers of neutrophil activation, reinforcing that calprotectin reflects how aggressively the immune system is deploying neutrophils against the infection.¹⁶ This is primarily of interest in hospital settings rather than outpatient testing, but it underscores that calprotectin is fundamentally an inflammation and neutrophil marker, not a gut-specific one.

Small Intestinal Bacterial Overgrowth

Small intestinal bacterial overgrowth, where bacteria colonize the upper gut in excessive numbers, exists in an interesting middle ground. It is not a classic “infection” in the way Salmonella or C. difficile is, but it involves pathologic microbial activity that provokes inflammation. Among a large group of patients with irritable bowel syndrome, those with elevated calprotectin above 100 µg/g were significantly more likely to also have bacterial overgrowth than those with normal calprotectin levels. A calprotectin above 100 µg/g in IBS patients was also a strong predictor of actual mucosal inflammation in the terminal ileum on biopsy.¹⁷ For patients who have been told they “just have IBS” but whose calprotectin keeps coming back high, bacterial overgrowth is one infection-adjacent cause worth investigating.

Why Calprotectin Is Tricky in Babies and Young Children

Calprotectin interpretation in children requires extra caution, for two reasons. First, healthy infants naturally have much higher fecal calprotectin than adults, with levels that would be considered pathological in a grown-up being entirely normal in a newborn. The marker does not settle into adult ranges until roughly age four or five in most children. Second, the ability to distinguish bacterial from viral diarrhea using calprotectin changes with age. In children under one year old, there was essentially no difference in calprotectin between bacterial and viral causes of diarrhea in one study, with both groups averaging around 390-400 mg/kg.¹⁸ In older children, the distinction was much clearer: bacterial infections produced calprotectin levels several times higher than viral ones in children aged one to seven.

Research from India suggested age-specific cutoff values for predicting bacterial diarrhea in children, with different thresholds for those under one year versus those between one and four years.¹⁹ The bottom line for parents and pediatricians: a single calprotectin number in a young child does not carry the same diagnostic weight it does in an adult, and age-specific reference ranges need to be applied.

Medications and Other Non-Infectious Confounders

If you are trying to figure out whether an infection is responsible for a high calprotectin reading, you also need to account for what else might be pushing the number up. Two of the most common medications on the planet can do it. Nonsteroidal anti-inflammatory drugs like ibuprofen and proton pump inhibitors like omeprazole have both been associated with elevated fecal calprotectin in patients who have no organic bowel disease at all.²⁰ NSAIDs are well known to cause low-grade intestinal inflammation and micro-erosions, which recruits enough neutrophils to show up on a calprotectin test. PPIs alter the gut microbiome and may cause a similar low-grade inflammatory response. In a person taking both, a mildly elevated calprotectin might have nothing to do with an infection or with IBD.

Beyond medications, the practical matter of how the stool sample is collected and processed can shift results. Different extraction methods for calprotectin testing can produce significantly different concentrations from the same sample, with one study finding a mean difference of over 30% between two common extraction approaches.²¹ Stool consistency also played a role, though the differences between methods evened out in very liquid samples. For anyone comparing calprotectin results over time, making sure the same lab and the same test method are used each time matters more than most people realize.

Calprotectin Beyond the Gut

While fecal calprotectin gets the most attention, the protein shows up wherever neutrophil-driven inflammation occurs. Periodontal disease, the chronic infection and inflammation of the tissues around the teeth caused by bacterial biofilms, is one area where calprotectin has been studied as a biomarker. Levels in saliva and gingival crevicular fluid appear to track with the severity of gum disease and respond to treatment.²² This is unlikely to cause confusion with gut-related calprotectin testing, since the sample types are different, but it reinforces the broader principle: calprotectin is not specific to any one organ. It is a readout of neutrophil activity wherever you choose to measure it. A high number in stool means neutrophils are active in the gut; a high number in blood means they are active somewhere in the body. The clinical question is always what is driving those neutrophils, and infection is only one of the possible answers.

1
PubMed Central. Elevated Fecal Calprotectin Accompanied by Intestinal Neutrophil Infiltration and Goblet Cell Hyperplasia in a Murine Model of Multiple Sclerosis
2
PubMed Central. Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with activated neutrophils extruding neutrophil extracellular traps
3
PubMed. Fecal calprotectin as a correlative marker in clinical severity of infectious diarrhea and usefulness in evaluating bacterial or viral pathogens in children
4
PubMed. Prospective multicenter study evaluating fecal calprotectin in adult acute bacterial diarrhea
5
PubMed Central. Fecal Calprotectin Level Reflects the Severity of Clostridium difficile Infection
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PubMed Central. Correlation between fecal calprotectin levels, disease severity and the hypervirulent ribotype 027 strain in patients with Clostridium difficile infection
7
PubMed Central. High fecal calprotectin levels are associated with SARS-CoV-2 intestinal shedding in COVID-19 patients
8
PubMed Central. Possible Correlation between Giardia duodenalis Genotypes and Fecal Calprotectin in Children with Diarrhea
9
International Journal of Current Microbiology and Applied Sciences. Fecal calprotectin among patients infected with some protozoan infections
10
PubMed Central. Can Giardia Infection Impair the Diagnostic Level of Fecal Calprotectin in Patients with Inflammatory Bowel Disease? A Case Report
11
European Journal of Gastroenterology & Hepatology. Serial measurements of faecal calprotectin may discriminate intestinal tuberculosis and Crohn’s disease in patients started on antitubercular therapy
12
Journal of Clinical Gastroenterology. Oral Fluconazole Therapy in Patients With Active Ulcerative Colitis Who Have Detectable Candida in the Stool
13
PubMed Central. Expansion of Opportunistic Enteric Fungal Pathogens and Occurrence of Gut Inflammation in Human Liver Echinococcosis
14
PubMed Central. Blood calprotectin as a biomarker for infection and sepsis – the prospective CASCADE trial
15
PubMed Central. Plasma calprotectin as an indicator of need of transfer to intensive care in patients with suspected sepsis at the emergency department
16
European Respiratory Journal. Circulating calprotectin elevation as a marker of neutrophil extracellular traps in severe bacterial and viral pneumonia
17
Experimental and Clinical Gastroenterology. Interrelation between Fecal Calprotectin Level, Small Intestinal Bacterial Overgrowth and Histological Mucosal Inflammation in the Terminal Ileum in IBS Patients
18
Innovative Journal of Pediatrics. Fecal Calprotectin as a Biomarker Distinguishing Infectious Cause in Acute Intestinal Infections, Comparing Different Age Groups of Children
19
PubMed. Faecal calprotectin as an inflammatory biomarker to distinguish between bacterial and viral causes of childhood diarrhoea in Indian settings
20
PubMed. Prescription of NSAIDs and proton pump inhibitors are associated with increased faecal calprotectin levels in patients with functional bowel disorder
21
PubMed Central. Faecal calprotectin determination: impact of preanalytical sample treatment and stool consistency on within- and between-method variability
22
PubMed Central. Role of Calprotectin as a Biomarker in Periodontal Disease