Influenza A (H5N1) is a highly pathogenic zoonotic virus with a human fatality rate of approximately 60%. Pediatric cases and associated neurological manifestations remain poorly documented in Latin America. This report describes the first confirmed Ecuadorian pediatric case of H5N1-associated encephalitis and multisystem organ failure in a previously healthy 9-year-old female following direct contact with infected poultry. The clinical course was characterized by an atypical initial presentation of bilateral periorbital edema and headache, progressing to acute encephalitis, cerebral ischemia, flaccid tetraplegia, central diabetes insipidus, and refractory septic shock. Diagnostic confirmation was achieved via nasopharyngeal RT-PCR, with additional RT-PCR and sequencing performed on cerebrospinal fluid, which identified conserved influenza A M1/M2 gene fragments, while laboratory markers—including marked elevations in IL-6, ferritin, and CRP—indicated a severe hyperinflammatory state. Management involved an intensive multidisciplinary approach utilizing oseltamivir, intravenous immunoglobulin, modulated-dose corticosteroids, desmopressin, and mechanical ventilation. Despite a severe clinical course, the patient achieved a favorable recovery, with a Glasgow Coma Scale score of 15/15 at discharge and only partial residual paresis and left hypoacusia as sequelae. This landmark case provides rare evidence of H5N1 neuroinvasion in a pediatric patient and demonstrates that timely detection combined with aggressive immunotherapy and antiviral treatment can improve survival. Furthermore, it underscores the critical necessity for strengthened regional molecular surveillance and clinical training to recognize atypical presentations of emerging zoonoses in Latin America, especially in cases involving contact with sick poultry.

Hemophagocytic lymphohistiocytosis (HLH) remains one of the greatest diagnostic challenges in pediatric critical care because of its high mortality and the complexity of its clinical presentations. We report the case of an 18-month-old boy who presented with persistent fever, a respiratory tract infection, pancytopenia, hepatosplenomegaly, and progressive neurological deterioration, fulfilling the diagnostic criteria of the HLH-2004 protocol [2]. His clinical course was complicated by concurrent viral infections (adenovirus and parainfluenza virus type III) and antibody-mediated neurological autoimmunity (anti-NMDA receptor encephalitis), an association rarely reported in the current literature [4,5]. A broad differential diagnosis was evaluated with immunologic, genetic, and neuroimaging studies. The combination of autoimmunity, recurrent infections, and positive family history suggested secondary HLH on the background of an underlying primary immunodeficiency [9]. The patient's outcome and the death of a sibling with a similar clinical picture indicate that this episode was not merely secondary HLH, but the first manifestation of a severe primary immune dysregulation, possibly related to mutations in genes such as CTLA4, LRBA, or STAT3—genes recognized within the spectrum of autoimmune lymphoproliferative immunodeficiency disorders (ALPID) [9,10]. This case illustrates the most aggressive facet of pediatric HLH and underscores the need to suspect hidden primary immunodeficiencies in patients with recurrent infections and early autoimmunity. Early recognition of this phenotype can make the difference between a fatal outcome and the possibility of offering targeted immunomodulatory or potentially curative therapies [12,13]. In critical pediatrics, HLH should no longer be considered a final diagnosis but rather a warning sign of an underlying genetic immune dysregulation.