Pathology of Chikungunya Virus Infection: Emergence and Clinical Insights

CHIK & Pregnancy

Mother-to-child transmission of CHIKV was first reported during the 2005–2006 outbreak on La Réunion Island,^[36,37] with similar cases published afterwards in India and Sri Lanka.^[38,39] This novel mode of transmission occurs during the peripartum maternal infection when there is insufficient time for the maternal production of protective antibodies. In a population-based series of 47 cases of perinatal mother-to-child CHIKV infection in La Réunion, maternal infection occurred from 4 days prepartum to 2 days after delivery, and neonates developed illness from days 2–10 (mean 4 days) after birth. Clinical signs included hyperalgia (100%), fever (77%), erythrodermia with secondary peripheral skin peeling (79%), refusal to feed requiring tube feeding (87%), edema of extremities (55%) and diarrhea (32%).^[40] All neonates except for one were hospitalized and 16 (34%) presented with severe complications including encephalopathy with seizures in nine cases, hemorrhagic manifestations (n = 9) with concomitant thrombocytopenia and hemostatic disturbances, and hemodynamic disorders (n =10) such as hypotension, left ventricular dysfunction, pericarditis and hyperechoic coronary arteries. Mechanical ventilation was needed in 25% of patients due to apneic spells, status epilepticus or hemodynamic instability. One neonate died on day 6 because of necrotizing enterocolitis. Interestingly, pathological brain MRI was noted in 17 out of 30 patients with scattered white matter lesions, parenchymal hemorrhages and early cytotoxic edema on diffusion-weighted sequences, and CHIKV RNA was detected in spinal fluid, even in apparently uncomplicated cases. Preliminary data concerning long-term follow-up of the infected neonates confirm poor outcome, with a mean developmental quotient of 86 (51% of the cases <85) compared with 100 in the control group (p < 0.001).^[41]

Conversely, maternal infection occurring a long time from delivery is rarely harmful. In a prospective study comparing birth outcomes between 655 women not infected during pregnancy with 658 who were infected during pregnancy, only the number of hospital admissions differed between infected and uninfected women (40 vs 29%).^[42] There was no propensity to prematurity, growth restriction, fetal deaths, stillbirths, congenital anomalies or other complications of pregnancy such as vaginal bleeding or third-stage hemorrhage. Newborns seem to be healthy at birth with no detectable IgM antibody and maternally transferred IgG antibodies cleared progressively, indicating absence of in utero infection.^[19] Antepartum fetal contamination seems to be very unusual, with only three cases described in La Réunion during a term of 12–15 weeks.^[43]

Mother-to-child infection around delivery is probably due to intrapartum contamination of the fetal blood by free virus particles from highly viremic mothers through placental breaches initiated by induction of labor. However, cesarean section does not seem to be protective and is not recommended.^[19] A mouse model study^[44] and the rarity of placental histologic lesions in human studies^[42] confirm the non-permissiveness of the placental barrier during antepartum exposure.

The risk for CHIKV transmission through breastfeeding during maternal illness or its protective role in women previously infected by CHIKV remains unknown. CHIKV RNA was not detected in 20 maternal milk samples, including eight that were collected during viremia in La Réunion. However, as a precaution, breastfeeding was not recommended during the acute febrile phase of the disease.^[45] In a study of 39 women who were infected in the peripartum period, there was no statistical difference in the rate of breastfeeding between infected (n = 16) and noninfected neonates (n = 23) [Ramful D, Unpublished Data].