## 3 Results
### Outcome
#### 3.3.5 Oral candidiasis and Candida spp  
Cardiage  
Reports on _Candida_ spp. carriage, species typing and associations with oral candidiasis in children with DS were extremely heterogeneous and, therefore, must be considered individually.  
In 1996, [PERSON] et al. [11] reported oral carriage of Candida species in a case-control study enrolling 50 DS subjects aged 0.6-20.5 years and 50 age- and sex-matched healthy controls: in DS subjects, _C. albicans_ colonization was significantly higher (69% vs. 35% of controls, \(p\) value < 0.001) and significantly higher at tongue and palate as well as oral signs of erythemat caudidiasis (40% vs. 1.8% in healthy controls), while white pseudomembranous lesions did not statistically differ between groups. As for other Candida species, _C. parapsilosis_, _C. guillermondii_, and _C. tropicalis_ were rarely found in both groups (0-1.8%) and did not differ significantly.  
In 2002, [PERSON] et al. [13] evaluated the relationships between angular cheilitis, lip fissures, and _C. albicans_ in a series of 50 DS subjects aged between 0-60 years and stratified by age. _C. albicans_ was isolated in 11 of 13 subjects (84.6%) aged 0-10 years and in 7 of 12 (58%) aged 11-20 years. The presence of _C. albicans_ was very frequently associated with lip lesions (in 80% of DS subjects aged 0-10 years and in 100% of those aged 11-20 years).  
Four years later, [PERSON] et al. [15] conducted a case-control study on morphotyping and enzymotyping of _C. albicans_ in 35 children aged 0-10 years (25 with DS and 10 controls); results showed significantly higher levels of two fungal enzymes in DS compared to the control group, proteinase (96% in DS children vs. 40%) and phospholipase (88% vs. 80%).  
In 2012, [PERSON] et al. [19] published a case-control study to correlate relative frequencies of _Streptococcus mutans_, _Lactobacillus_, and _Candida_ spp. in salivary samples from DS children and their healthy siblings closest in age. Although the work has focused on the synergistic effect of _Candida_ spp. with Streptococcus on the onset of caries, the work reported that the frequency of the _Candida_ spp. carriage was higher in the control group than in the DS group, without reaching statistical significance, but according to the low caries rates reported in the DS subjects.  
[PERSON] et al. [14] reported that _C. albicans_ had been cultured twice frequently in those DS patients with lip lesions compared to those without lip lesions.  
Recently, [PERSON] et al. [16] identified _Candida_ spp. in a case-control study on 80 DS (7.7 mean age) and 80 non-syndromic volunteers (12.8 mean age), finding a statistically significant higher percentage of _Candida_ carriers among the case group than in the control group (57.5 vs. 12%). Of these, _C. albicans_ was the most prevalent species in both groups (93% of the DS subjects and 60% of the controls); _C. glabrata_ was found alone in 7% of DS children and associated with _C. albicans_ in 35% of them, while it was reported as the first and only species in 20% of controls. _C. tropicalis_ and _C. krusei_ were both found in 1% of controls as the only isolated species, while in DS subjects they were found as second species in association with _C. albicans_ in 15% (_C. albicans_ + _C. tropicalis_) and 4% (_C. albicans_ + _C. krusei_), respectively, but never alone. In the DS group, 49% referred to previous oral candidiasis on questionnaires and 21% of them presented active candidiasis at the oral examination; the relative percentages in the control groups were 63% (history of oral candidiasis) and 0% (active oral candidiasis at examination), respectively.