Candida infections in immunocompromised children

Abstract

Objective: Deep Candida infection (DCI) is a serious complication with high mortality in immunocompromised patients. The following studies (I, II, III, IV and V) were designed to investigate the relationship between infantile diarrhoea and faecal occurrence of Candida spp., the efficacy of anti-Candida antibody and antigen tests for early diagnosis of DCI, and the risk factors for DCI and its occurrence and clinical characteristics in immunocompromised children.

Methods: Malnourished infants with diarrhoea (n=119) and non-diarrhoeal controls (n=46) from Pakistan, were investigated by microscopy and fungal stool culture (1). IgG, IgM and IGA antibody response to Candida was determined in 277 healthy children (11), to obtain reference values for DCI diagnosis in paediatric series: liver transplant (LTX) recipients (n=19; 111), allogeneic bone marrow transplant (BMT) recipients (n=58; IV), children treated for leukaemia (n=14; V). Significant risk factors for DCI were determined in BMT recipients.

Results and discussion: I) In <8-months-old infants, especially if malnourished, Candida may be suspected to the cause of diarrhoea if faecal smear microscopy shows the presence of pseudohyphal yeasts. II) In healthy children, no anti-Candida IgG antibodies were detected; IgM antibody response was almost undetectable in those under 2 years of age, and had not reached adult levels even in the older children; IgA antibody titres were low in the <2year-old age group, but were higher than normal adult levels in the 13-15-year-old age-group. In children with verified candidal infections, however, anti-Candida IgG antibodies were detected and both IgM and IgA antibody titres were higher than the respective normal age-related levels. Thus, the data for healthy children may serve as reference values in diagnosing Candida infections in paediatric cases. III) The findings suggested paediatric LTX recipients to be at high risk of developing DCI early after transplantation, particularly those with high pre-transplant anti-Candida IgM or IgA antibody titres. Serology may be useful before LTX in identifying those at risk of DCI, and in its early diagnosis after LTX. IV) In BMT recipients, the incidence of fatal DCI before engraftment was 8.7%. Risk factors for DCI or suspected DCI were: a high pre-transplant titre of anti-Candida IgA or IgM antibodies, BMT from a donor other than an HLA-identical sibling, or an HSV- positive donor.

The findings suggested that paediatric BMT recipients at risk may benefit from systemic antifungal prophylaxis, and that serology may be useful before BMT in identifying those at risk of DCI, and in its early diagnosis after BMT. V) The findings suggested leukaemic children to be at risk of DCI shortly after leukaemia diagnosis or shortly after relapse. In leukaemic children with DCI, Candida serology was positive in 75% (6/8). On being cured of their DCI, their IgG antibodies disappeared and their IgM and IgA antibody levels fell to the respective age-related normal ranges. Thus, monitoring antibody titres may be useful in assessing the efficacy of systemic antifungal treatment.