Rickettsia parkeri Infection Turns Fatal in a Child With Leukemia
A fatal case of Rickettsia parkeri rickettsiosis in a 3-year-old boy receiving chemotherapy for high-risk B-cell acute lymphoblastic leukemia in Georgia shows how quickly a tickborne illness can be hidden inside the far more familiar syndrome of febrile neutropenia. The child arrived in late July 2025 with profound neutropenia, thrombocytopenia, fever, and skin lesions that were initially easy to misread as nonspecific insect bites. By the time the diagnosis was confirmed with plasma microbial cell-free DNA sequencing and CDC testing, the illness had already progressed to shock, respiratory failure, cardiac arrest, and death.
One lesion on the left arm had been present for about a month. In a child with cancer, that history invites a wide differential, but it also creates room for a rickettsial eschar to be missed long before the bloodstream becomes involved.
Febrile Neutropenia Masked a Tickborne Infection
At admission, the boy’s leukocyte count was 110/µL, the absolute neutrophil count was 20/µL, and platelets were 19,000/µL. He was in the second month of delayed intensification chemotherapy and had received cyclophosphamide, cytarabine, and 6-thioguanine 2 weeks earlier. His physical examination was otherwise unremarkable except for 2 pink papulonodules with central eschars on the left upper extremity. Empiric cefepime followed blood culture collection, a standard first response to febrile neutropenia because gram-negative bacterial sepsis remains the immediate danger in that setting.
The eruption then evolved. On hospital days 2 and 3, small pink macules appeared on the upper back and arms, then spread over the next 3 days into numerous pink macules with vesicles involving the face, trunk, and all extremities. The distribution was broader than the classic scattered rash usually described with R. parkeri infection. Fever persisted despite cefepime, blood cultures remained negative, and pancytopenia continued with unmeasurable lymphocyte count. Micafungin and acyclovir were added while clinicians pursued disseminated fungal and viral disease. PCR testing for herpes simplex virus and varicella zoster virus from an unroofed vesicle was negative.
The clinical picture kept widening while the cause remained narrow and elusive.
Imaging added evidence of systemic illness rather than a clear pathogen. Computed tomography of the lungs showed minimal ground-glass opacities, and abdominal ultrasound revealed hepatomegaly, trace ascites, and thickened, inflamed small bowel loops consistent with neutropenic enteritis. By hospital day 7, the child had hypotension and respiratory failure, prompting intensive care transfer and bilevel positive airway pressure. Antimicrobials were broadened to meropenem, vancomycin, amphotericin B, isavuconazole, and doxycycline, but he continued to deteriorate. Intubation was complicated by a 20-minute cardiac arrest. After return of spontaneous circulation, he developed fixed and dilated pupils, and life-sustaining treatment was withdrawn. He died on hospital day 8.
Molecular Testing Confirmed the Diagnosis Too Late for Treatment
The next day, plasma microbial cell-free DNA sequencing returned positive for R. parkeri at 8,374 molecules/100 nL. Confirmatory testing at CDC strengthened the diagnosis: DNA extracted from residual plasma was positive by real-time PCR targeting a 96-bp segment of the ompB gene specific for R. parkeri. Skin biopsy sections were even more striking. Immunoalkaline phosphatase staining for spotted fever group Rickettsia showed abundant rickettsiae and rickettsial antigens in vessel lumina, with invasion through the endothelium into adjacent dermal tissue.
Endothelial infection is the biologic signature of spotted fever rickettsioses. Once the organism targets vascular endothelium, capillary injury, leakage, tissue edema, and hemorrhage can accelerate rapidly. In an immunocompetent host, early doxycycline usually halts that process before multiorgan injury becomes established. In this child, profound lymphopenia and chemotherapy-related immune suppression likely removed key cellular defenses at the exact moment they were needed most.
Why the Illness Escalated So Quickly
R. parkeri rickettsiosis is usually described as a mild to moderately severe spotted fever illness marked by fever, myalgias, headache, rash, and often an eschar at the tick attachment site. Since 2020, nearly 5,000 spotted fever group rickettsiosis cases have been reported in the United States, and most do not require hospitalization. A systematic review of 77 R. parkeri cases found hospitalization in only 9% overall and 16% of confirmed cases, with children accounting for only 7% and 3%, respectively. Against that background, a fatal pediatric case in an immunocompromised host is a sharp outlier.
Adult and pediatric patterns also complicated recognition. R. parkeri infection is more commonly diagnosed in adults older than 40 years, so a 3-year-old was already outside the typical demographic frame. The child’s leukemia treatment created an even stronger diagnostic pull toward bacterial, fungal, and viral causes of febrile neutropenia. A large study of more than 600 children with acute lymphoblastic leukemia found that 72.9% of those receiving high-risk delayed intensification were hospitalized at least once, making admission during this treatment phase unremarkable on its face. In that environment, a tickborne rickettsiosis can be easy to overlook, especially when no tick is seen.
Geography and season fit the diagnosis. R. parkeri is transmitted by the Gulf Coast tick, Amblyomma maculatum, whose range includes southwestern Georgia. Adult ticks are most active in July and August near the Gulf Coast, matching the timing of this illness. The family reported presumed insect bites, but no tick or insect was ever visualized.
A Warning for Clinicians Caring for Immunocompromised Children
This case shows that tickborne disease belongs in the differential diagnosis of febrile neutropenia when eschars or vesicular rashes are present, especially in regions where Gulf Coast ticks circulate. The skin lesions were the most important early clue, yet they were easy to discount because the child had severe cytopenias and a plausible alternative explanation for fever. When delayed recognition meets endothelial-invasive infection, the window for doxycycline can close quickly.
Advanced diagnostics can change that timeline, but not always fast enough. Unbiased cell-free DNA sequencing expands detection of fastidious pathogens and has already been used to identify rickettsial species, yet outsourcing can still delay actionable results. In this child, the assay identified the pathogen only after death. The case leaves a concrete clinical challenge: recognizing when a presumed neutropenic infection is not behaving like ordinary febrile neutropenia and when a tickborne rickettsiosis deserves immediate empiric treatment, even before the laboratory closes the loop.