A 3-year-old boy from southwestern Georgia, receiving high-risk chemotherapy for B-cell acute lymphoblastic leukemia, was admitted in late July 2025 with febrile neutropenia and profound cytopenias. At presentation his leukocyte count was 110/µL, absolute neutrophil count 20/µL, and platelets 19,000/µL. Two pink papulonodules with central eschar were present on the left upper extremity; parents reported those lesions had drained clear fluid and had been present for about one month, which they had attributed to insect bites. Small pink macules appeared on hospital days 2–3 and progressed over the following days to numerous macules with some vesicles spreading to the face, trunk, and all extremities. Fever persisted despite empiric cefepime and later expanded antimicrobial coverage.
Plasma microbial cell-free DNA sequencing (Karius) performed on a blood sample submitted on hospital day 7 returned positive for Rickettsia parkeri; the source reported a high molecules value. The Centers for Disease Control and Prevention conducted confirmatory testing: DNA extracted from residual plasma was positive by real-time PCR targeting a 96-bp segment of the ompB gene specific to R. parkeri. Formalin-fixed, paraffin-embedded skin biopsy sections stained by immunoalkaline phosphatase demonstrated abundant rickettsial antigen within vessel lumina and endothelium and extending into adjacent dermis. The paper reported concordant molecular and histopathologic evidence indicating disseminated rickettsial infection.
Initial management followed institutional febrile neutropenia algorithms with cefepime after blood cultures. Because the child remained febrile and then clinically declined, care teams broadened empiric therapy to include agents covering gram-positive bacteria, fungal pathogens, and antiviral therapy; micafungin and acyclovir were among the added agents. On hospital day 7 antimicrobials were expanded further to meropenem, vancomycin, amphotericin B, isavuconazole, and doxycycline. The cell-free DNA result identifying R. parkeri returned the day after the patient’s death; the authors reported that outsourcing such testing can delay pathogen-directed therapy. Despite escalation, the patient developed hypotension, respiratory failure, a prolonged cardiac arrest during attempted intubation, and died on hospital day 8.
The investigators noted that Amblyomma maculatum (Gulf Coast tick), the recognized vector for R. parkeri, has a range that includes southwestern Georgia and that adult ticks are most active in July and August near the Gulf Coast. The family reported frequent outdoor play in grass around their suburban home but did not recall seeing a tick on the child. The case occurred in the seasonal window consistent with Gulf Coast tick activity.
The report connected the patient’s profound lymphopenia—exacerbated by underlying leukemia and recent chemotherapy agents including cyclophosphamide, cytarabine, and 6-thioguanine—with increased disease severity. The authors cited prior in vitro and animal data that identify roles for CD4 and CD8 T cells, particularly CD8 responses, in clearing rickettsial infections. They also referenced a mouse model in which high inoculum correlated with lethality, suggesting that either impaired host immunity or a high pathogen burden could explain the atypical severity and fatal outcome observed.
The investigators reported that unbiased plasma microbial cell-free DNA sequencing can detect fastidious pathogens like rickettsiae and has been increasingly used for such diagnoses. They emphasized, however, that the test in this case was performed by an external laboratory and that turnaround time contributed to delayed pathogen identification. The authors presented this diagnostic modality as an important adjunct in complex immunocompromised patients but warned that outsourcing may limit its timeliness when rapid, targeted therapy is required.
This report is a single fatal case; the authors noted that R. parkeri infections have generally been reported as mild to moderate and infrequently pediatric. They acknowledged several factors that limited rapid recognition: the commonality of febrile neutropenia during the chemotherapy phase, the routine use of cefepime for empiric coverage of gram-negative organisms, the atypical and extensive rash in this patient, and lack of an observed tick bite. The source did not report specific inoculation dose, and whether the fatal outcome reflected immune compromise, an unusually high pathogen burden, or both cannot be definitively determined from this case. The delayed return of outsourced cell-free DNA results also limited the opportunity for earlier, targeted antimicrobial therapy. Future investigations—beyond the scope of this report—should define how often R. parkeri causes severe disease in immunocompromised hosts, determine optimal rapid diagnostic pathways in febrile neutropenia when vectorborne exposures are possible, and clarify the relative contributions of pathogen load versus host immune status to outcome.