Scientific letter
Diagnostic utility of fecal calprotectin in chronic diarrhea of bacterial etiology in pediatric patients
Utilidad diagnóstica de la calprotectina fecal en la diarrea crónica de etiología bacteriana en pacientes pediátricos
Esperanza Lepe-Balsalobrea,
, Ricardo Rubio-Sáncheza, Cristina Úbedab, José M. Úbeda Ontiverosc
Corresponding author
a Department of Clinical Biochemistry, Valme University Hospital, Seville, Spain
b Department of Nutrition and Food Science, Toxicology and Legal Medicine, Faculty of Pharmacy, University of Seville, Seville, Spain
c Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville, Spain
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Úbeda Ontiveros" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Esperanza" "apellidos" => "Lepe-Balsalobre" "email" => array:1 [ 0 => "esplepbal@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Ricardo" "apellidos" => "Rubio-Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Cristina" "apellidos" => "Úbeda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "José M." "apellidos" => "Úbeda Ontiveros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Clinical Biochemistry, Valme University Hospital, Seville, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Nutrition and Food Science, Toxicology and Legal Medicine, Faculty of Pharmacy, University of Seville, Seville, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Utilidad diagnóstica de la calprotectina fecal en la diarrea crónica de etiología bacteriana en pacientes pediátricos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 735 "Ancho" => 2175 "Tamanyo" => 84173 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Fecal calprotectin in symptomatic patients without an infection, in patients with bacterial infection and in patients with parasitic infection. (b) ROC curve to differentiate patients with and without bacterial infection.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic diarrhea is defined as a diarrheal process that lasts more than 14 days and that may be associated, although not exclusively, with an infectious cause (persistent diarrhea). It is a relatively common problem in pediatric age, originating approximately 2–5% of pediatric consultations, and it is generally of functional origin.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In this context, it is important to assess the inflammatory status and the quantification of fecal calprotectin is a useful, simple, and non-invasive test that can rule out intestinal inflammation in children with gastrointestinal symptoms. However, diagnostic accuracy of fecal calprotectin has not yet been adequately evaluated in pediatric persistent diarrhea.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the diagnostic utility of fecal calprotectin in chronic diarrhea of bacterial etiology in pediatric patients. Seven hundred and seventy-seven patients (52.3% males, 47.7% females) with a diarrheal process lasting more than 14 days and aged between 1 and 14 years (median: 6 years) were included. This study met ethical recommendations of the Declaration of Helsinki<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> and it was approved by the Sevilla Sur Research Ethics Committee (No.1569-M1-17).</p><p id="par0020" class="elsevierStylePara elsevierViewall">Calprotectin was quantified by fluorescence enzyme immunoassay in a Phadia®100 analyzer (Thermo Fisher Scientific, Germany). A laboratory study of infectious etiology was carried out by molecular techniques (LightMix® Modular-Gastro-Bacteria-Parasite-Virus Multiplex Testing. Roche, USA). Data were processed using R-software (R-Core Team, 2014) and MedCalc 13.0 software (Ostend, Belgium).</p><p id="par0025" class="elsevierStylePara elsevierViewall">The results showed that in 11.3% of patients an infectious cause was detected and in 12.2% an inflammatory process was detected, although, in many cases, these processes were not isolated findings, but they were interrelated. Non-infectious causes were detected in 693 patients with a median calprotectin of 12<span class="elsevierStyleHsp" style=""></span>μg/g (median absolute deviation (MAD): 2; confidence interval (CI) 95%: 10–14.2) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a). Regarding cases in which an infectious origin of diarrhea was found, bacteria of clinical interest were detected in 31 patients (4%) with a median calprotectin of 123<span class="elsevierStyleHsp" style=""></span>μg/g (MAD: 44; CI95%: 95–218) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>): the most prevalent bacteria were <span class="elsevierStyleItalic">Campylobacter</span> spp. with 20 cases (64.5%), followed by <span class="elsevierStyleItalic">Salmonella</span> spp. with 11 cases (35.5%). The presence of parasites was detected in 55 patients (7.1%) with a median calprotectin of 10<span class="elsevierStyleHsp" style=""></span>μg/g (MAD: 0; CI95%: 10–19) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a); in 22 cases (40%) the parasites had a proven clinical value (<span class="elsevierStyleItalic">Giardia</span> spp., <span class="elsevierStyleItalic">Cryptosporidium</span> spp.) while in 33 cases (60%) the parasites were of uncertain clinical significance (<span class="elsevierStyleItalic">Blastocystis</span> spp., <span class="elsevierStyleItalic">Dientamoeba</span> spp.) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a). Viral etiology was not very prevalent, being detected in 2 patients (0.3%), and both corresponding to an infection by adenovirus. Furthermore, in 4 patients, there was a concomitant bacterial and parasitic infection: 2 cases of <span class="elsevierStyleItalic">Giardia</span> spp. and 1 case of <span class="elsevierStyleItalic">Blastocystis</span> spp. associated with diarrhea caused by <span class="elsevierStyleItalic">Salmonella</span> spp., and 1 case of <span class="elsevierStyleItalic">Blastocystis</span> spp. associated with diarrhea caused by <span class="elsevierStyleItalic">Campylobacter</span> spp.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Calprotectin results greater than 50<span class="elsevierStyleHsp" style=""></span>μg/g have been observed in some patients with a parasitic infection and in some patients without an infection. These patients presented a concomitant bacterial infection, inflammatory bowel disease, hematochezia, processes associated with immunoglobulin A deficiency, or autoimmune disease. Specifically, in the hematochezia cases studied, the median calprotectin was 118.5<span class="elsevierStyleHsp" style=""></span>μg/g; other recent studies show that calprotectin represents approximately 30% of neutrophil cytosol and, therefore, calprotectin levels increase as the extent of inflammation and bleeding increases.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">According to the results, the optimal cut-off point to differentiate bacterial diarrhea in the pediatric community was calculated in the ROC (receiver operating characteristic) curve. A calprotectin value of 74<span class="elsevierStyleHsp" style=""></span>μg/g (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b) presented an adequate discriminatory value with a sensitivity of 96.77%, specificity of 97.45%, positive predictive value of 80.6% and negative predictive value of 99.6%.</p><p id="par0040" class="elsevierStylePara elsevierViewall">These results agree with other studies which indicate that fecal calprotectin may be a useful biomarker in children with infectious diarrhea, since calprotectin values increase in an acute bacterial infection and they are related to the severity of symptoms. In the case of chronic diarrhea, different studies have reported its utility in the evaluation and discrimination of infectious diarrhea of bacterial etiology in children.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> Usefulness of calprotectin in parasitic diarrhea in children has not been studied much, but the results of the only available study agree with the findings of our study: in absence of other associated underlying causes, the values of calprotectin in a parasitic infection are very low, except in an <span class="elsevierStyleItalic">Entamoeba histolytica</span> infection.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion, our findings suggest the use of calprotectin as a biomarker of chronic diarrhea of bacterial etiology in pediatric patients. However, the discriminatory value of calprotectin can be affected in other situations such as hematochezia, inflammatory bowel disease, celiac disease, or the inclusion of children under 1 year of age. Therefore, their values should be interpreted in conjunction with clinical symptoms and other laboratory tests.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 735 "Ancho" => 2175 "Tamanyo" => 84173 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Fecal calprotectin in symptomatic patients without an infection, in patients with bacterial infection and in patients with parasitic infection. 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| 2023 July | 95 | 57 | 152 |
| 2023 June | 76 | 4 | 80 |
| 2023 May | 95 | 4 | 99 |
| 2023 April | 44 | 3 | 47 |
| 2023 March | 58 | 4 | 62 |
| 2023 February | 49 | 2 | 51 |
| 2023 January | 24 | 11 | 35 |
| 2022 December | 51 | 12 | 63 |
| 2022 November | 46 | 20 | 66 |
| 2022 October | 45 | 26 | 71 |
| 2022 September | 40 | 23 | 63 |
| 2022 August | 26 | 24 | 50 |
| 2022 July | 24 | 17 | 41 |
| 2022 June | 44 | 9 | 53 |
| 2022 May | 47 | 17 | 64 |
| 2022 April | 34 | 28 | 62 |
| 2022 March | 26 | 11 | 37 |
| 2022 February | 16 | 5 | 21 |
| 2022 January | 22 | 7 | 29 |
| 2021 December | 42 | 11 | 53 |
| 2021 November | 2 | 4 | 6 |
| 2021 October | 14 | 6 | 20 |
| 2021 September | 7 | 0 | 7 |
| 2021 August | 3 | 2 | 5 |
| 2021 July | 4 | 2 | 6 |
| 2021 June | 75 | 27 | 102 |
| 2020 November | 0 | 1 | 1 |
| 2020 October | 0 | 6 | 6 |
Show all
