Clinical manifestations, treatment, and outcome of cytomegalovirus infections in infants, children, and adolescents

	Congenital infection	Early postnatal infection	Infection in immunocompetent children and adolescents	Infection in immunocompromised children and adolescents
Clinical manifestations	At birth, 90% of cases are asymptomatic. Clinical and laboratory findings include: Petechiae Jaundice at birth Hepatosplenomegaly Petechial rash Small size for gestational age Thrombocytopenia Microcephaly Intracranial calcifications Polymicrogyria Ventriculomegaly Sensorineural hearing loss Chorioretinitis Seizures	Term infants – Most infants are asymptomatic. Clinical and laboratory findings are usually transient and include: Fever Hepatosplenomegaly Mild pneumonitis Abnormal blood counts Abnormal liver function tests Premature and VLBW infants – Infection can be severe and life-threatening. Clinical and laboratory manifestations include: Sepsis-like syndrome Hepatosplenomegaly Pneumonitis Hepatitis NEC Abnormal blood counts	Most children are asymptomatic. Clinical and laboratory findings include: Fever Fatigue Pharyngitis Mononucleosis-like syndrome Adenopathy Hepatitis Headache Abdominal pain Diarrhea Arthralgias Rash Lymphocytosis or lymphopenia Thrombocytopenia Abnormal liver function tests Negative monospot test	Infection can be severe and life-threatening. Clinical and laboratory findings include: Fever Malaise Leukopenia Hepatitis Pneumonitis Colitis Graft loss (in patients with organ transplant) Myocarditis Retinitis Encephalitis/encephalopathy (especially in patients with HIV)
Treatment	Asymptomatic infants do not require antiviral treatment. Ganciclovir or valganciclovir for symptomatic infections*.	Most term infants and asymptomatic preterm infants do not require antiviral treatment. Ganciclovir or valganciclovir for severe symptomatic infections in premature infants*.	Antiviral treatment is generally not indicated. Supportive care with hydration and fever control.	Ganciclovir or valganciclovir^¶.
Outcome	Overall mortality rate is 4 to 8%. Mortality rate with severe fulminant disease is as high as 30%. Long-term sequelae include hearing loss, cerebral palsy, intellectual disability, vision impairment, and seizures.	Term infants – No permanent sequelae. Premature and VLBW infants – Mortality rate with symptomatic infection is 5 to 10%. There does not appear to be increased risk of hearing loss, cerebral palsy, or other neurodevelopmental disability; however, long-term outcomes are not clearly understood.	No permanent sequelae.	High risk of morbidity and mortality, which depends in part on the underlying condition.

VLBW: very low birth weight; NEC: necrotizing enterocolitis; CMV: cytomegalovirus; AIDS: acquired immunodeficiency syndrome.
* For treatment of congenital and severe early postnatal CMV infections, the dose of ganciclovir is 6 mg/kg/dose administered intravenously every 12 hours. The dose of valganciclovir is 16 mg/kg/dose of commercially available suspension administered orally every 12 hours. Doses of both medications must be adjusted in renal insufficiency. These dosing regimens have not been studied in infants <32 weeks gestation. Refer to UpToDate topics on congenital CMV infection for details regarding monitoring and duration of therapy.
¶ For treatment of CMV infections in immunocompromised children, the induction dose of ganciclovir is 5 mg/kg/dose intravenously every 12 hours for 2 to 3 weeks, depending upon the clinical and virologic response. Maintenance dosing is provided for high-risk patients (including bone marrow transplant recipients, patients with AIDS, or those in whom prolonged immunosuppression is anticipated). Maintenance therapy usually consists of a single daily dose of ganciclovir intravenously at 5 mg/kg administered every other day or 5 days a week. Valganciclovir, at 15 mg/kg/dose of commercially available suspension orally every 12 hours, may be used for maintenance therapy in patients who are able to tolerate and absorb oral medication. Doses of both medications must be adjusted in renal insufficiency. Refer to UpToDate topic on acquired CMV infection in infants, children, and adolescents for details on antiviral therapy.

References:

Harrison GJ. Cytomegalovirus. In: Feigin and Cherry's Textbook of Pediatric Infectious Diseases, 7th ed, Cherry JD, Harrison GJ, Kaplan SL, et al (Eds), Elsevier Saunders, Philadelphia 2014. p.1969.
Kimberlin DW, Jester PM, Sánchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 2015; 372:933.
American Academy of Pediatrics. Cytomegalovirus infection. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW (Ed), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.317.

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Clinical manifestations, treatment, and outcome of cytomegalovirus infections in infants, children, and adolescents