A Protocol for Low-Input RNA-Sequencing of Patients with Febrile Neutropenia Captures Relevant Immunological Information.

Improved methods are needed for diagnosing infectious diseases in children with cancer. Most children have fever for other reasons than bacterial infection and are exposed to unnecessary antibiotics and hospital admission. Recent research has shown that host whole blood RNA transcriptomic signatures can distinguish bacterial infection from other causes of fever. Implementation of this method in clinics could change the diagnostic approach for children with cancer and suspected infection. However, extracting sufficient mRNA to perform transcriptome profiling by standard methods is challenging due to the patient's low white blood cell (WBC) counts. In this prospective cohort study, we succeeded in sequencing 95% of samples from children with leukaemia and suspected infection by using a low-input protocol. This could be a solution to the issue of obtaining sufficient RNA for sequencing from patients with low white blood cell counts. Further studies are required to determine whether the captured immune gene signatures are clinically valid and thus useful to clinicians as a diagnostic tool for patients with cancer and suspected infection.

Appendicitis Caused by Primary Varicella Zoster Virus Infection in a Child with DiGeorge Syndrome.

INTRODUCTION: Chickenpox is caused by varicella zoster virus (VZV). Although predominantly a mild disease, it can cause considerable morbidity and in rare occasions even mortality in healthy children as well as increased morbidity and mortality in immunocompromised patients. The aetiology of appendicitis is largely unknown but is thought to be multifactorial. Appendicitis is a suspected, but not well documented, complication from varicella zoster virus infection. CASE PRESENTATION: A five-year-old girl diagnosed with DiGeorge syndrome and a prolonged primary VZV infection was admitted due to abdominal pain, increasing diarrhoea, vomiting, and poor general condition. She developed perforated appendicitis and an intraperitoneal abscess. VZV DNA was detected by PCR in two samples from the appendix and pus from the abdomen, respectively. The child was treated with acyclovir and antibiotics and the abscess was drained twice. She was discharged two weeks after referral with no sequela. CONCLUSION: Abdominal pain in children with viral infections can be a challenge, and appendicitis has to be considered as a complication to acute viral diseases, especially if the child is immunocompromised.

Varicella Vaccination of Children With Leukemia Without Interruption of Maintenance Therapy: A Danish Experience.

BACKGROUND: Varicella-zoster virus (VZV) can be fatal or cause severe complications in children with acute lymphoblastic leukemia (ALL). This analysis set out to investigate the morbidity and mortality of VZV vaccination without interruption of maintenance therapy in children with ALL. METHODS: Files of 73 seronegative children with ALL were examined for data regarding VZV vaccination and infection, and long-term seroconversion was measured. Criteria before VZV vaccination were (1) seronegative, (2) in complete remission, (3) age ≥ 1.0 year, (4) lymphocyte count ≥ 0.6 × 10/L at time of vaccination and (5) receiving maintenance therapy. RESULTS: Forty-five children were vaccinated. No child died or experienced serious adverse events due to VZV vaccination. Nine children developed late chickenpox despite vaccination. Long-term protection was found in 86% of children not receiving acyclovir and 78% of the entire population. Long-term seroconversion was found in 52% of the children. There were no severe cases of varicella infection. Acyclovir prophylaxis postvaccination was associated with an increased risk of late chickenpox [hazard ratio = 5.40 (1.43, 20.41), P = 0.01]. In contrast, a vaccine-induced rash reduced the risk of late chickenpox [hazard ratio = 0.08 (0.01, 0.66), P = 0.02]. No child had interruption of maintenance therapy at the time of vaccination, but 33% experienced discontinuation of therapy due to vaccine-induced rash. Dexamethasone was associated with an increased risk of vaccine-induced rash [hazard ratio = 2.9 (1.21, 6.90), P = 0.02]. CONCLUSIONS: This analysis indicates that VZV vaccination is feasible and justified in seronegative children with ALL, in countries where VZV vaccination is not part of the national vaccination program.