Vaginal seeding has been proposed to restore the microbiome of babies born via caesarean section, but the associated risk of infection is unknown. We present the first case of disseminated candidiasis after vaginal seeding in an infant with chronic granulomatous disease and the challenges faced in controlling the early-onset infection.
A 15-day-old Chinese-Caucasian male presented with fever, hepatitis, and generalized maculopapular rash that was refractory to antibiotics. His older brother was recently transplanted for chronic granulomatous disease (CGD), and his mother carried the CYBB c.674+1G>A mutation. Routine Bacille Calmette-Guérin (BCG) vaccination was omitted in view of family history, but vaginal seeding was performed due to caesarean delivery. Blood cultures grew Candida species (Meyerozyma guilliermondii), and the infection was controlled with intravenous amphotericin-B; however, fever was recurrent on oral voriconazole until subcutaneous interferon-gamma was added. He developed symptomatic hypercalcemia and nephrocalcinosis presumably from excessive macrophage conversion of vitamin D to the active form within granulomas, requiring special low-calcium formula milk for control. He also developed massive hepatosplenomegaly, transaminitis, and portal hypertension. At 7 months old, he received a TCRαβ/CD45RA-depleted haploidentical stem cell transplantation from his father with myeloablative conditioning (alemtuzumab, fludarabine, thiotepa, and treosulfan). Post-transplant, he required CD3+ donor lymphocyte infusions for silent graft rejection and low CD3 chimerism, with eventual full chimerism and resolution of infection, hepatosplenomegaly, and portal hypertension.
This early presentation with disseminated candidiasis highlights the pitfalls of vaginal seeding in neonates with underlying immunodeficiency. Vaginal seeding should be avoided if there is a family history of immunodeficiency or other risk factors. Hypercalcemia is common in granulomatous inflammation, though not previously reported in CGD; it can also be exacerbated by initiation of interferon-gamma. Early diagnosis of CGD and stem cell transplant can potentially reverse complications from disseminated fungal infection, including portal hypertension.
Family history of immunodeficiency or early deaths from infection should be listed as a contraindication to vaginal seeding, and this history should be actively sought and documented during consent taking. Although interferon-gamma is typically used prophylactically in CGD, there may be an adjunct role for control of active fungal infections in CGD patients, which warrants further investigation.
