In a recent study published on the medRxiv* preprint server, researchers in the United States performed the clinical evaluation of pediatric monkeypox (mpox) samples.
In the 1970s and 1980s, the median age of mpox infection reported in the United States was between four and five years old. However, the median age has increased in recent decades. In the 1980s, pediatric mpox was associated with a mortality rate of up to 10%. Clinical microbiology tests face significant hurdles in diagnosing infectious diseases in a low-risk group. The most concerning challenge is the possibility of reporting false positive test results due to poor positive predictive value in low prevalence settings.
Study: Clinical testing of pediatric Mpox samples: unique features and challenges in a low-prevalence population. Image credit: Dotted Yeti / Shutterstock
About the study
In the current study, researchers retrospectively evaluated the results for pediatric mpox testing.
The team performed mpox virus deoxyribonucleic acid (DNA) detection. Specimens were identified as being obtained from genital regions when specific terms were involved. The samples were classified as “detected” if the cycle threshold (Ct) was less than 34, “not detected” if Ct was more than 50, or “inconclusive” if Ct was between 34 and 50. were classified as: detected if Ct was less than 50 for both replicates, not detected if both replicates had Ct greater than 50, and inconclusive if one replica had Ct less than 50 while the other had Ct greater than 50.
Patient cases were categorized as ‘positive’, ‘false positive’ and ‘inconclusive’. A person with at least one identified specimen was categorized as a positive case. A subject was defined as an inconclusive case if they had at least one inconclusive sample and no samples detected. False positives were classified when the ordering supplier presented a clinical history inconsistent with mpox while no repeat sample testing was detected.
During the study, 13.4% of all mpox tests were performed on pediatric samples. The ratio of children to adults in the cohort was similar at 13.6%. The pediatric cohort consisted of 56.8% males, 42.7% females and 0.5% subjects of unknown gender, while the adult cohort consisted of 66.8% males, 31.0% females and 2.2% subjects of unknown gender. unknown gender. The distribution of gender varied significantly between the two age cohorts. In the pediatric group, 9.0% of samples were obtained from genital sources and 19.6% of adult samples were obtained from genital areas.
Comparison of the adult and pediatric cohorts revealed positive rates of 22.3% and 1.3%, respectively. In addition, the positivity rate reported by the female and male pediatric groups was 1.1% and 1.4%, respectively. In the adult group, the female positivity rate was 3.2% and the male positivity rate was 31.1%. The median Ct value of mpox-positive pediatric samples was 25.2 and that of mpox-positive adult samples was 22.2. However, this difference did not show statistical significance.
Demographic and clinical data for Mpox samples from pediatric and adult individuals. (A) Percentage of total sample volume. (B) Percentage of female, male and unknown sex. (C) Percentage of specimens obtained from genital or non-genital sources. (D) Positivity rate of pediatric and adult specimens stratified by sex. (E) Comparison of Ct values between pediatric and adult specimens positive for mpox
The pediatric cohort reported a median age of 6 ± 5.4 years. The most commonly tested patients were one-year-olds (10.1%), followed by two-year-olds (9.2%), three-year-olds (8.2%) and 17-year-olds (7.3%). Notably, only 3.5% of the patients tested were 11 years old. The age distribution of mpox infections showed bimodal peaks, with the highest percentage of positive cases in 17-year-olds (36.8%), followed by patients less than one year old (26.8%). One positive case was detected in cohorts of children aged one, two, six, eight, nine, 14 and 16 years. The rate of mpox positivity among children under one year was 7.8%, one year was 0.9%, two years was 0.7%, six years was 1.1%, eight years was 1.4%, nine years was 1.9%, 14 years was 1.6%, 16 years was 1.3%, and 17 years was 6.4%. Interestingly, women were diagnosed with mpox at a mean age of 4.5 years, while men showed a mean age of 11.6 years.
Nearly 73% of the 26 subjects for whom MPXV was amplified at least once from a sample were confirmed to be mpox positive, 19% were inconclusive, and 8% were false positive for mpox. The sensitivity and specificity of the test were 100% and 99.9, respectively. In addition, the team noted that two instances of the study represented false positive results. In both cases, the late Ct values of 35.2 and 39.1 did not return after re-extraction and amplification.
The study findings showed that a minority of pediatric subjects were tested for mpox. The overall positivity rate is significantly lower in pediatric subjects than in adult males. Most pediatric samples were from non-genital regions and were obtained from women. The age groups with the highest mpox risk appear to be those less than one year old and 17 years old. Significant numbers of early mpox detections are characterized by inconclusive and false positive results. The researchers advise that careful clinical correlation and repeat testing of patient samples should be considered, especially within the pediatric age groups.
medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.