IL6&8 in Malnourished Children With Acute Diarrhea

NCT ID: NCT05183789

Last Updated: 2022-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-01-01

Study Completion Date

2023-01-31

Brief Summary

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Cytokines, such as IL-6 and IL-8 can be used as markers of acute infections, including acute gastroenteritis. However, there have been no previous studies on the levels of IL-6 and IL-8 in malnourished children with acute diarrhea. This study aims to evaluate serum levels of interleukins 6 and 8 in malnourished children with acute diarrhea.

Detailed Description

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Acute gastroenteritis remains a common health problem among children worldwide with significant morbidity, mortality, and economic burden. Diarrheal diseases account for more than half-million deaths of children under 5 years old every year, most of which take place in low- and middle-income countries (LMICs). Moreover, diarrheal diseases are a leading cause of emergency visits and hospitalization. According to the WHO, acute diarrhea is classified into acute watery diarrhea, acute bloody diarrhea (dysentery), persistent diarrhea, and diarrhea with severe malnutrition. Acute watery diarrhea is the most common category in both high and LMICs. Viral infections (e.g., rotavirus, norovirus, adenovirus) are the leading causes of acute watery diarrhea in children (up to 90% of cases), while bacteria (e.g., shigella, salmonella, Campylobacter, enterotoxigenic E. coli) and parasites (e.g., Cryptosporidium, Giardia, and E. histolytica) account for the remainder of cases.

Cytokines can be used as markers of acute infections, including acute gastroenteritis. Interleukin-6 (IL-6) is produced by lymphoid and non-lymphoid cells and plays important role in regulation of immunity, acute-phase response, and hematopoiesis; IL-6 has a well-known role in the defense mechanism in acute gastroenteritis. Interleukin-8 (IL-8) functions in chemotaxis of inflammatory cells, such as neutrophils and lymphocytes, to the site of inflammation, Both IL-6 and IL-8 are critical for immunity against mucosal infections; they are released from the epithelial cells of the gastrointestinal tract to mount its inflammatory responses to infectious agents at local and systemic levels.

Some studies investigated the role of IL-6 and IL-8 as biomarkers for acute diarrhea in children. Results showed significantly increased serum levels of IL-6 and IL-8 in children with acute GE compared with healthy controls. Moreover, IL-6 is significantly elevated in bacterial gastroenteritis in comparison to viral gastroenteritis. However, none of these studies included children with severe acute malnutrition.

Severe acute malnutrition (SAM) is a severe form of malnutrition resulting from inadequate or poor quality dietary intake. This is a serious public health problem, particularly in developing countries. SAM can be classified into marasmus, characterized by overt loss of subcutaneous fat and muscle mass, and Kwashiorkor, characterized by bilateral pitting edema of lower limbs.

Malnutrition is one of the most common causes of impaired immune function in children. Malnutrition leads to defects of phagocytosis, chemotactic function of neutrophils and monocytes, complement system and opsonization, and the function of antigen presenting cells.

As part of its negative impact on immune system, SAM may impair acute phase inflammatory response, including cytokines. In vitro studies showed that peripheral blood mononuclear cells from malnourished children have reduced ability to produce cytokines, such as IL-1, IL-6, IL-8, and tumor necrosis factor alpha. Some studies showed that children with SAM have significantly lower levels of IL-6 and IL-8 compared with healthy controls \[8\]. In contrast, other studies showed similar or higher levels of pro-inflammatory cytokines in malnourished children compared with healthy controls.

To the best of our knowledge, there have been no previous studies on the levels of IL-6 and IL-8 in children with SAM and acute diarrhea.

The aim of this study is to evaluate serum levels of interleukins 6 and 8 in malnourished children with acute diarrhea.

Conditions

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Acute Diarrhea Severe Acute Malnutrition Acute Gastroenteritis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Cases

Malnourished children with acute diarrhea

Evaluation of serum levels of IL-6 and IL-8

Intervention Type DIAGNOSTIC_TEST

Evaluation of serum levels of IL-6 and IL-8 by Luminex Assay (multiplexed ELISA kits).

Control

Non-malnourished children with acute diarrhea

Evaluation of serum levels of IL-6 and IL-8

Intervention Type DIAGNOSTIC_TEST

Evaluation of serum levels of IL-6 and IL-8 by Luminex Assay (multiplexed ELISA kits).

Interventions

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Evaluation of serum levels of IL-6 and IL-8

Evaluation of serum levels of IL-6 and IL-8 by Luminex Assay (multiplexed ELISA kits).

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Age: 6 months to 5 years.
* Severe acute malnutrition. Infants and children who are 6-59 months of age and have a mid-upper arm circumference \< 115 mm or a weight for height/length \<-3 Z-score of the WHO growth standards or have bilateral edema.
* Acute diarrhea: Defined according to WHO criteria as the "passage of loose or watery stools at least three times in a 24 h period", lasts less than 14 days, with or without fever or vomiting, but considering the importance of change in stool consistency rather than frequency, and the usefulness of parental insight in deciding whether children have diarrhea or not.


* Healthy children aged 6 months to 5 years.
* Acute diarrhea

Exclusion Criteria

* History of antibiotic therapy in the last 72 hours.
* Acute diarrhea in association with systemic infections
* Malignancy
* Chronic diarrhea
* Autoimmune and autoinflammatory diseases.
* Chronic renal/liver failure
* Diabetes mellitus

Group 2: Control (Non-malnourished children with acute diarrhea)


* Malnutrition or obesity
* History of antibiotic therapy in the last 72 hours.
* Acute diarrhea in association with systemic infections
* Malignancy
* Chronic diarrhea
* Autoimmune and autoinflammatory diseases.
* Chronic renal/liver failure
* Diabetes mellitus
Minimum Eligible Age

6 Months

Maximum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sohag University

OTHER

Sponsor Role lead

Responsible Party

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Motaz Mohamed Hassan

Pediatric Resident

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Abdelrahim A Sadek, MD, PhD

Role: STUDY_CHAIR

Faculty of Medicine, Sohag University

Locations

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Sohag University Hospital

Sohag, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Motaz Hassan, MBBCH

Role: CONTACT

00201023286623

Facility Contacts

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Mostafa Abo-Sidera, MD, PhD

Role: primary

00201002028668

References

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Zaki MES, Alsayed MAL, Shrief R. Study of the diagnostic value of interleukin-6 and interleukin-8 in children with acute gastroenteritis. Germs. 2020 Mar 2;10(1):27-33. doi: 10.18683/germs.2020.1182. eCollection 2020 Mar.

Reference Type BACKGROUND
PMID: 32274357 (View on PubMed)

Rankin JA. Biological mediators of acute inflammation. AACN Clin Issues. 2004 Jan-Mar;15(1):3-17. doi: 10.1097/00044067-200401000-00002.

Reference Type BACKGROUND
PMID: 14767362 (View on PubMed)

Svanborg C, Godaly G, Hedlund M. Cytokine responses during mucosal infections: role in disease pathogenesis and host defence. Curr Opin Microbiol. 1999 Feb;2(1):99-105. doi: 10.1016/s1369-5274(99)80017-4.

Reference Type BACKGROUND
PMID: 10047563 (View on PubMed)

Chen SM, Lin CP, Tsai JD, Chao YH, Sheu JN. The significance of serum and fecal levels of interleukin-6 and interleukin-8 in hospitalized children with acute rotavirus and norovirus gastroenteritis. Pediatr Neonatol. 2014 Apr;55(2):120-6. doi: 10.1016/j.pedneo.2013.05.008. Epub 2013 Jul 27.

Reference Type BACKGROUND
PMID: 23899552 (View on PubMed)

Ibrahim MK, Zambruni M, Melby CL, Melby PC. Impact of Childhood Malnutrition on Host Defense and Infection. Clin Microbiol Rev. 2017 Oct;30(4):919-971. doi: 10.1128/CMR.00119-16.

Reference Type BACKGROUND
PMID: 28768707 (View on PubMed)

Marginean CO, Man L, Pitea AM, Man A, Marginean CL, Cotoi OS. The assessment between IL-6 and IL-8 and anthropometric status in malnourished children. Rom J Morphol Embryol. 2013;54(4):935-8.

Reference Type BACKGROUND
PMID: 24398988 (View on PubMed)

Dulger H, Arik M, Sekeroglu MR, Tarakcioglu M, Noyan T, Cesur Y, Balahoroglu R. Pro-inflammatory cytokines in Turkish children with protein-energy malnutrition. Mediators Inflamm. 2002 Dec;11(6):363-5. doi: 10.1080/0962935021000051566.

Reference Type BACKGROUND
PMID: 12581501 (View on PubMed)

Malave I, Vethencourt MA, Pirela M, Cordero R. Serum levels of thyroxine-binding prealbumin, C-reactive protein and interleukin-6 in protein-energy undernourished children and normal controls without or with associated clinical infections. J Trop Pediatr. 1998 Oct;44(5):256-62. doi: 10.1093/tropej/44.5.256.

Reference Type BACKGROUND
PMID: 9819485 (View on PubMed)

Other Identifiers

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IL6&8

Identifier Type: -

Identifier Source: org_study_id

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