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ACEP Now: Vol 34 – No 05 – May 2015

Image Credit: © SHUTTERSTOCK.COM

As educators, we love—and are always humbled by—those moments when we get to say, “I don’t know.” For some of these questions, you may already know the answers.

For others, you may never have thought to ask the question. For all, questions, comments, concerns, and critiques are encouraged. Welcome to the Kids Korner.

Spring often means baseball, warmth…diarrhea, and fever. Let’s take a look at some fun topics on these last two.

Question. Are infants’ intestines commonly colonized with Clostridium difficile bacteria, and if so, how should this impact testing decisions?

An early article by Cooperstock et al prospectively evaluated 107 healthy asymptomatic infants up to a year of age from well-baby clinics.¹ The infants’ ages ranged from 1 to 52 weeks and included a wide range of socioeconomic groups. Evaluating stool samples by ELISA for C. difficile antigens, the authors found that 40 percent (43/107) of infants were asymptomatically colonized with C. difficile. Additionally, there were no significant differences in colonization when these infants were stratified by age (in weeks) or sex. Other older studies have also demonstrated a high incidence of asymptomatic colonization by C. difficile in infants.^2–4 The overall incidence of asymptomatic colonization in infants is reported to be as high as 60 percent to 70 percent.5 Interestingly, in the study by Cooperstock et al, the overall incidence of colonization of breastfed infants versus formula-fed infants was 23 percent versus 62 percent (P<0.001), respectively.¹ This association has been identified in other studies as well.^4,5

Recent studies continue to demonstrate asymptomatic colonization in infants and very young children. A recent 2012 cross-sectional study of two day cares by Rousseau et al demonstrated an asymptomatic C. difficile carriage incidence of 45 percent (38/85 total children).6 Every carrier, except one, was <24 months of age. None of the patients had diarrhea at the time of sampling. The incidence of asymptomatic carriage was approximately 6 percent (1/17) in children 24–36 months old, which is similar to reported adult asymptomatic carrier values of C. difficile.⁶

The overall incidence of asymptomatic colonization in infants is reported to be as high as 60 percent to 70 percent.

A separate cross-sectional study in 1982 by Stark et al demonstrated an asymptomatic carrier incidence of 3 percent (1/37) in children ≥2 years.² In that same study, the asymptomatic adult carrier incidence was 3.6 percent. A different study in 1989 by Tullus et al prospectively followed 343 asymptomatic healthy clinic infants from birth to 18 months, finding that carriage at 18 months of age (3 percent) was similar to adult incidences.⁴

Summary: Infants are common asymptomatic carriers of C. difficile. This incidence of asymptomatic carriage is reported to be as high as 60 percent to 70 percent of infants. These asymptomatic carrier rates probably fall to adult comparable levels between 18 and 24 months of age, but the data are very limited. Consider this before ordering a C. difficile test on a 12-month-old infant in the future.

Q: What is the sensitivity of a Monospot test in children?

The data are very limited on this topic. Approximately 90 percent of adults develop heterophile antibodies, identified by the Monospot test, following an acute Epstein-Barr virus (EBV) infection. Interestingly, though, only about 50 percent of children develop heterophile antibodies following an acute EBV infection.⁷

Only about 50 percent of children develop heterophile antibodies following an acute EBV infection.

A study by Sumaya and Ench looked specifically at the rate of positive heterophile antibody responses in children with confirmed cases of EBV.⁸ The authors evaluated heterophile antibody responses at different ages, stratifying the patients into the following age groups: <2 years, 2–3 years, and ≥4 years. In these age groups, positive heterophile antibody responses were demonstrated in 5.3 percent (1/19), 52 percent (13/25), and 83.6 percent (46/55) of children, respectively. In this single study, the production of heterophile antibodies was near reported adult levels at ≥4 years of age. Overall, children have a relatively poor heterophile antibody response to EBV compared to adults.

A study by Linderholm et al evaluated the sensitivity of a Monospot test in both children and adults.⁹ The authors arbitrarily broke down the groups into ≤12 years and ≥13 years of age. The sensitivity of the Monospot to detect infectious mononucleosis in the 0–12 age group was 38 percent (3/8) compared to 86 percent in the ≥13 years group. It was a very small sample size, and there were only eight patients included in the sensitivity analysis. Overall, there was a poor sensitivity of the Monospot to detect EBV in children 0–12 years of age.

Summary: Ultimately, the Monospot test shows poor sensitivity in children. The limited data that we have suggest that children don’t make near-adult levels of heterophile antibodies until they are at least 4 years of age, resulting in poor Monospot sensitivity. In regard specifically to the Monospot test, the literature suggests that it is not a good test until they are ≥13 years old. For cases where it is important to diagnose mononucleosis and the patient is ≤12 years old, you may want to get the EBV antibody titers additionally or instead.

Dr. Jones is assistant professor of pediatric emergency medicine at the University of Kentucky in Lexington.

Dr. Cantor is professor of emergency medicine and pediatrics, director of the pediatric emergency department, and medical director of the Central New York Poison Control Center at Upstate Medical University in Syracuse, New York.

References

1. Cooperstock M, Riegle L, Woodruff CW, et al. Influence of age, sex, and diet on asymptomatic colonization of infants with Clostridium difficile. J Clin Microbial. 1983;17(5):830-833.
2. Stark PL, Lee A, Parsonage BD. Colonization of the large bowel by Clostridium difficile in healthy infants: quantitative study. Infect Immune. 1982;35(3):895-899.
3. Bolton RP, Tait SK, Dear PR, et al. Asymptomatic neonatal colonization by Clostridium difficile. Arch Dis Child. 1984;59(5):466-472.
4. Tullus K, Aronsson B, Marcus S, et al. Intestinal colonization with Clostridium difficile in infants up to 18 months of age. Eur J Clin Microbiol Infect Dis. 1989;8(5):390-393.
5. Jangi S, Lamont JT. Asymptomatic colonization by Clostridium difficile: implications for disease in later life. J Pediatr Gastroenterol Nutr. 2010;51(1):2-7.
6. Rousseau C, Poilane I, De Pontual L, et al. Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. Clin Infect Dis. 2012;55(9):1209-1215.
7. Papesch M, Watkins R. Epstein-Barr virus infectious mononucleosis. Clin Otolaryngol Allied Sci. 2001;26(1):3-8.
8. Sumaya CV, Ench Y. Epstein-Barr virus infectious mononucleosis in children: heterophile antibody and viral-specific responses. Pediatrics. 1985;75(6):1011-1019.
9. Linderholm M, Boman J, Juto P, et al. Comparative evaluation of nine kits for rapid diagnosis of infectious mononucleosis and Epstein-Barr virus-specific serology. J Clin Microbiol. 1994;32(1):259-261.