Two Cases of Sepsis-Like Illness in Infants Caused by Human Parechovirus Traced Back to Elder Siblings with Mild Gastroenteritis and Respiratory Symptoms

Abstract

c Sepsis and sepsis-like illness in neonates and infants are serious emergencies. Recently, human parechovirus type 3 (HPeV-3) has been identified as a further etiologic agent of these conditions. We report two unlinked cases of infant HPeV-3 sepsis-like illness whose sources could be traced back to elder siblings with mild gastroenteritis and respiratory symptoms. CASE REPORTSP atient 1, a 7-day-old full-term male newborn with a birth weight of 3,750 g was admitted in August 2010 to the intensive care unit of a pediatric tertiary-care center because of his severely reduced general condition and pale skin color. A physical examination revealed tachyarrhythmia, mild hypertonia, a prolonged capillary filling time, a slightly elevated temperature (38°C), and an erythematous macular rash. A chest X-ray, a cranial ultrasound, and an electroencephalogram demonstrated no abnormalities. An abdominal ultrasound examination detected a slight increase of the amount of free fluid and a remarkably echogenic pancreas. Serum analysis showed a slightly raised C-reactive protein (CRP) level (28.3 mg/liter; normal, Յ3 mg/liter) and an elevated interleukin-6 concentration (191 pg/ml; peak, 272 pg/ml on day 2; normal, Յ15 pg/ml), and a moderately reduced platelet count (165 ϫ 10 9 /liter; nadir, 107 ϫ 10 9 /liter on day 6; normal, 230 ϫ 10 9 to 520 ϫ 10 9 /liter) ( Fig. 1). Empirical antibiotic therapy with tobramycin and piperacillin-tazobactam was initiated. Antiviral therapy with acyclovir was initiated in parallel but withdrawn after a negative result of a herpes simplex virus (HSV) PCR assay of cerebrospinal fluid was obtained.Bacterial cultures of blood and swabs from the ear canal, nose, throat, and rectum yielded no pathological findings. PCR or reverse transcription (RT)-PCR assays of cerebrospinal fluid, serum, EDTA blood, nasopharyngeal aspirate, urine, and feces were negative for HSV, cytomegalovirus (CMV), measles virus, and enterovirus. All specimens except urine tested positive for human parechovirus (HPeV) by RT-PCR, as illustrated in the top panel of Fig. 1 (for the method used, see reference 1). Because virus was detected in cerebrospinal fluid, cranial magnetic resonance imaging was done but no structural abnormalities or signs of meningoencephalitis were seen. Exanthema and enanthema disappeared after 4 days. Of note, HPeV viremia remained detectable up to days 6 and 8 of hospitalization. The patient was discharged after 10 days in good clinical condition. The full genome of the virus was sequenced (7,278 nucleotides), indicating the presence of HPeV type 3 (HPeV-3) with a recombination pattern involving nonstructural protein genes typical of HPeV-6 (breakpoint around nucleotide position 5150, according to the position numbering of HPeV-3 reference strain A308/99, GenBank accession no. AB084913; please note that HPeV types are defined upon their structural [capsid] gene portions; sequencing was performed using BigDye Terminator Cycle Sequencing chemistry [Applied Biosystems, Darmstadt, Germany], and the sequence...

Asymptomatic children might transmit human parechovirus type 3 to neonates and young infants

“…Although HPeV3 transmission in symptomatic household members has been reported, [7,17,18] and about half the present patients had a sick contact with family members, the sources of HPeV3 infection in the remaining patients are unknown. Because neonates and young infants remain at home, we speculate that exposure to the virus happens there.…”

Genome analysis revealed novel genotypes and recombination of the human parechoviruses prevalent in children in Eastern China

“…Among the four strains related with this recombination event, FM178558 belongs to HPeV-1 which was isolated from human feces from Netherland [25]. AB252582 was isolated from cerebrospinal fluid from a patient in Japan [13], while JX682576 was isolated from feces of a newborn with gastroenteritis in Germany [26]. To confirm the recombination event, the relevant strains were analyzed by neighbor joining trees using MEGA5.0.…”

Changes in Human Parechovirus Profiles in Hospitalized Children with Acute Gastroenteritis after a Three-Year Interval in Lanzhou, China

“…In addition, HPeV3 is the most common genotype identified in cerebrospinal fluid and displays a peculiarly biennial cycle [6], [8]–[15]. Various clinical manifestations from asymptomatic infection to moderate gastroenteritis or respiratory infection, serious sepsis-like illness [7], [16]–[20], encephalitis [21]–[25], encephalomyelitis [26], transient paralysis [5] or sudden infant death syndrome [27] have been reported in HPeV-infected subjects. However, some investigators believe that HPeV may be incidental and not play a significant role in disease outcome [3], [28]–[31].…”