Pathology of Chikungunya Virus Infection: Emergence and Clinical Insights

CHIK in Pediatrics

Pediatric hospitalized-based studies from La Réunion or India during the recent epidemics showed that the classic triad (fever, arthralgia and rash) of CHIK fever is found in more than 50% of patients.^[46–48] CHIKV fever is usually benign in children. Death is rare, and in La Réunion, only three deaths were reported (one neonatal infection, one case of acute disseminated encephalomyelitis and one case of acute hemorrhagic shock syndrome).^[37,49] However, atypical manifestations, sometimes with subsequent sequelae, have been described, especially in small infants. Neurologic manifestations ranging from simple and complex febrile seizures to meningeal syndrome, acute encephalopathy, diplopia, aphasia, acute disseminated encephalomyelitis and encephalitis have been reported, with often unremarkable cerebrospinal fluid findings.^[47–50] Risk factors for residual neurologic deficit (20% of the patients) included young age (neonatal infection), severe initial clinical presentation (encephalitis) and pathological MRI findings.^[49] Severe skin blistering in infants younger than 6 months of age affecting more than 10% of the total body surface area has been described, with intraepidermal vesiculobullous lesions sometimes having a higher mean viral load than in concurrent serum.^[48,49] All infants required hospitalization in the intensive care unit, with repeated dressings under general anesthesia. Other complications related to pediatric CHIKV infection included dehydration with dyselectrolytemia and acute renal failure, poor tolerance due to high-grade fever, bacterial secondary infection, hypoglycemia and cardiac manifestations.^[47,48,50] Conversely, persistent arthralgia and exacerbation of underlying medical conditions seem to be very rare in children, and no fulminant hepatitis has been described.

Symptomatic treatment in pediatrics can be problematic during CHIKV fever. Hyperalgesia, with refusal to feed and the need for intravenous level III analgesics in small infants, was not an uncommon cause of hospitalization.^[47] Salicylates and other NSAIDs should be avoided as they may precipitate bleeding manifestations.

Recently, the development of polyvalent immunoglobulins purified from human plasma samples of convalescent CHIK patients exhibited in vitro and in vivo neutralizing activities.^[51] CHIKV immunoglobulin administration abolished viral detection in serum and dissemination to the brain in a mouse model. Viremic mothers in labor and neonates born to viremic mothers, patients with severe neurological presentation of the disease, small infants with rapidly extensive skin blistering or adults with severe underlying comorbidities could benefit from this passive immunization technique.