| Objective: In order to enhance awareness of invasive fungal infection (IFI) in children and to provide clinical basis for early diagnosis and treatment of the disease by investigating the clinical characteristics.Methods: The characteristics of epidemiology,predisposing factors, clinical manifestations, laboratory and imaging findings, treatment and prognosis were evaluated retrospectively in 79 hospitalized cases of IFI in Children's Hospital of Chongqing Medical University.Results: (1) IFI occurred sporadically in four seasons. The ratio of city versus village was 1:2.3. The ratio of boys versus girls was 2:1. IFI occurred in children of all ages. CNS fungal infection often happened in preschool (37.5%) and school-age (50.0%). Pulmonary fungal infections often happened in young children (30.0%), preschool (20.0%) and school-age (30.0%), intestinal fungal infection often happened in infants (69.7%) and young children (18.2%). (2) Intestinal (46.8%) was the organ mostly involved followed by lung (36.7%), brain (25.3%), liver and spleen (5.1%), blood (5.1%), lymph nodes (5.1% ), heart (1.3%), bone marrow (1.3%), skin (1.3%), nail (1.3%). (3) The mainly clinical manifestations of fungal pneumonia were fever (96.6%), cough and expectoration (76.3%), polypnea (37.9%), the wet and dry sound of lung (51.7%). Images of chest CT were variety: patchy and nodular change (58.3%), pneumonia-type (41.7%). The characteristic signs of pulmonary fungal infection such as"empty sign","air crescent sign"or/and"halo sign"were just appeared in 12.5% patients with fungal pneumonia. The mainly clinical manifestations of CNS fungal infection were fever (100%), headache (70.0%), vomiting (65.0%) and convulsion (30.0%), meningeal irritation (60.0%), eye and hearing damage and paralysis of limbs also can be seen. Head CT or MRI performance mainly showed hydrocephalus (71.4%), brain and meninges infectious diseases (35.7%), and cerebral atrophy (14.3%). All of the CSF examinations were abnormal. Leukocyte count was increased in 73.7% of patients which were from 10×10~6/L to 306×10~6/L and 26.3% of leukocyte count were normal. Monocyte ratio was above 0.5 in 71.4%. The protein in 68.4% of patients had a lever less than 1g/L. Glucose was decreased in 52.6%, and chloride was decreased in 89.5%. The clinical manifestations of fungal enteritis were diarrhea. The stools were yellow dilute water samples or thin paste-like in which bubble, mucus, bean dregs or occasionally bloodshot can be seen. The diarrhea was 2 to 10 times a day. WBC≥5 /HP were rare in stool routine. The staging of hemogram after removal of the patients of neutropenia and intestinal fungal infections showed that 31.0% of the patients had WBC 4×10~9 /L～10×10~9/L and 38.0% of the patients had and WBC 10×10~9/ L～20×10~9/L. There was 37.9% of the patients had a percentage of neutrophils 50.0%～70.0% and 37.9% of the patients >70.0%. (4) There were 47 fungal strains by culture in which 63.8% was Candida (in which 66.7% was C.albicans) followed by Cryptococcus neoformans (21.4%) and Aspergillus spp. (8.5%). All of the fungal strains cultured from cerebrospinal fluid were Cryptococcus neoformans and fungal strains cultured from stool were Candida. All of C.albicans strains came from sputum and stool. All of Cryptococcus neoformans strains came from cerebrospinal fluid and blood. The susceptibility rate of Candida to fluconazole, itraconazole, amphotericin B and 5-fluorocytosine were 30.8%,9.1%,84.6% and 84.6% respectively. The susceptibility rate of fungal strains in this study to amphotericin B was 85.7%. (5) The predisposing factors included application of antibiotics≥5 days (58.2%), cancer chemotherapy (21.5%, including 11.7% neutropenia≥7 days and 3.8% non-neutropenia), malnutrition (11.4%), tuberculosis (6.3%), purely neutropenia (3.8%), neonatal (2.5%) and adrenocorticotropic hormone (1.3%). Fungal pneumonia is commonly founded in cancer patients followed antibiotics treatments and neutropenia after chemotherapy. The patients with intestinal fungal infections particularly have the history of using antibiotics because of suffering from pneumonia. (6) There were 32 cases (40.5%) cured, 35 cases (44.3%) improved and 12 cases (15.2%) deteriorated. Therefore the efficiency happened in 84.8% of patients. The cure rate and the efficiency of amphotericin B or L-AMB was 30.1% and 87.8%. The cure rate and the efficiency of voriconazole was 10.0% and 40.0%. The efficiency of itraconazole was 33.3%. The efficiency of fluconazole was 66.7%. By Kruskal-wallis testing, diagnosis time (p = 0.0018) and anti-fungal treatment time(p = 0.0003) had influence on the prognosis.Conclusions:(1) IFI seems mostly happens in male and in rural areas than cities, which is sporadic case. (2) IFI in children often occurs in the digestive tract, respiratory tract and CNS. The age distribution between different parts of fungal infections was different: lung and CNS fungal infections often happend in young child, preschool and school-age and the intestinal fungal infections often happen in infant and young children. (3)Candida, Cryptococcus neoformans and Aspergillosis spp. are the major pathogen of IFI in children. C.albicans is still the most common species. Pathogens in different infection sites are different. The main pathogen of multi-system fungal infections is Cryptococcus neoformans and Candida. The main pathogen of CNS fungal infections is Cryptococcus neoformans. The main pathogens of fungal pneumonia are Candida albicans and Aspergillosis spp.. The main pathogen of fungal enteritis is Candida albicans. This study showed that Candida were in the high rate of resistance to fluconazole and itraconazole, but had no significant resistance to amphotericin B. Experience therapy against IFI in children can be administrated based on the clinical features and local epidemiology. (4)Application of antibiotics≥5 days, neutropenia≥7 days after using chemotherapeutic drugs or/and malnutrition are predisposing factors of IFI in children. Predisposing factors are found in most of pulmonary and intestinal fungal infections. Therefore these patients should be on monitoring of fungi in order to reduce the incidence of fungal infections or diagnosis IFI early. (5)The clinical performance of IFI is non-specific. When the pulmonary or multi-system damage are ineffective with antibiotic treatment , the possibility of fungal infection should be considered. IFI (particularly CNS fungal infection) need to be differentiated from tuberculosis and to be on guard combining co-infection of fungal and M tuberculosis. Fungal antigen detection and gene detection by molecular biologic technique should be carried out to improve the diagnosis of IFI. (5) Amphotericin B can be used as the standard treatment of IFI, of which efficacy is superior to fluconazole, itraconazole, voriconazole. Early and long course of antifungal treatment can improve the prognosis of IFI.
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