Deep Candida infection in children with leukaemia: clinical presentations, diagnosis and outcome.

OBJECTIVES: To analyse the clinical features associated with deep Candida infection (DCI) and the outcome in children with leukaemia, and to evaluate various diagnostic methods. MATERIALS AND METHODS: Serum samples were analysed to determine Candida IgA, IgM and IgG antibodies and defect free C. albicans glucoprotein antigen and C. enolase antigen in eight children who had nine episodes of DCI and six with suspected DCI. RESULTS: DCI occurred shortly after the leukaemia diagnosis (median 40 days) or after the leukaemia relapse (median 30 days). Children with DCI had fever (100%), skin lesions/exanthema (45%), oral thrush (45%), oesophagitis (22%) and laryngo-tracheitis (22%). Candida endocarditis, arthritis and hepatic candidosis were diagnosed in one patient each. Two children with disseminated candidosis died in leukaemia relapse. In patients with C. albicans infections serology had a sensitivity of 83%. However, in patients with C. parapsilosis infection antibody detection was negative. As the patients were cured of their Candida infection, the IgG antibodies disappeared and the IgM and IgA antibodies fell within the normal range for age. CONCLUSION: DCI in children occurs shortly after the leukaemia diagnosis or shortly after relapse of leukaemia. The clinical features are many. Candida serology may help to diagnose or confirm DCI. The dynamics of antibody titres may help to establish the efficacy of antifungal treatment.

Deep Candida infection in children receiving allogeneic bone marrow transplants: incidence, risk factors and diagnosis.

Fifty-eight children, who received 60 allogeneic bone marrow transplants (BMT), were studied with regard to incidence, risk factors and diagnosis of deep Candida infection (DCI). Serum samples were analysed for the presence of Candida IgA, IgM and IgG antibodies and free C. albicans glucoprotein antigen (Ag). Five children (8.7%) had a confirmed DCI and died before engraftment of the new bone marrow. When four patients with suspected deep Candida infection (SDCI) were included, the incidence was 15.6%. Four of the five children (80%) with DCI had pathological Candida IgM antibody (Ab) titers and/or free C. albicans glucoprotein Ag, 2-50 days before DCI was verified by culture, direct microscopy and/or autopsy. Risk factors, using Fisher's exact test for DCI, included not receiving bone marrow from an HLA-identical sibling donor, having a seropositive Herpes simplex virus (HSV) donor and pathological IgA and/or IgM Ab titers against Candida before BMT. In conclusion, a child with the above-mentioned risk factors, runs a risk of acquiring fatal DCI before engraftment. The institution of systemic antifungal prophylactic treatment may prevent death from DCI. After BMT, serological examinations may be of value in the early detection of DCI.

Malnutrition and pharmacokinetics of penicillin in Ethiopian children.

Penicillin was given to 104 children with different nutritional status, normal, underweight, marasmus and kwashiorkor. Penicillin was given either intravenously, intramuscularly or orally and the plasma concentration was followed at regular times after administration. There was a significantly decreased plasma clearance of penicillin in all malnourished groups compared to the normal weight-for-age group. The half-lives of penicillin were, however, not significantly different between the nutritional groups. This was explained by the fact that also the volume of distribution was decreased in the malnourished group with a net result that the half-life was unchanged. The bioavailability was decreased if penicillin was given to non-fasting individuals. The greatest difference between fasting and non-fasting was seen in the severely malnourished children with marasmus and kwashiorkor. Therefore, it is advised that, if penicillin is given orally to very sick and undernourished children, the dose should be increased and preferably be given in the fasting state.

Deep Candida infection in child liver transplant recipients: serological diagnosis and incidence.

Nineteen children who received 22 orthotopic liver grafts on 20 occasions were studied with regard to Candida infection. Serum samples were analysed to determine Candida, IgA, IgM and IgG antibodies and detect free C. albicans glucoprotein antigen. Five children (25%) had a confirmed deep C. albicans infection (DCI) during the first 2 weeks after transplantation. In all children with DCI, serology was positive, a median of 6 days (range 2-9 days) before Candida infection was verified by fungal culture, direct microscopy and/or autopsy. The positive predictive values for Candida IgG, IgM and IgA antibodies in children with DCI were 100%, 78% and 100%, respectively, and for free C. albicans antigen, 45%. Pathological titres of IgM and IgA antibodies against Candida before liver transplantation were present in three of four children who later developed a DCI and in no child without infection. In conclusion, regular screening by Candida serology is recommended both before and after liver transplantation.

Antibody response to Candida and its use in clinical practice.

Reference values for specific IgM, IgA and IgG antibodies against three defined Candida antigens were determined in 280 healthy Swedish children aged 1 month to 15 years. The antibody response in 10 children with Candida infections was also determined. Precipitating IgG antibodies to a mannan-free Candida protein antigen were detected only in children with Candida infection. The haemagglutinating IgM antibody response in healthy children to a polysaccharide Candida antigen was weak. Adult levels of < or = 320 (95% confidence interval, CI) were not reached even in the oldest children (< or = 160). All children with Candida infections had elevated IgM titres. Adult levels of IgA antibodies to Candida mannan were reached at 10-12 years of age; at 13-15 years the titres were higher (< or = 1600) than in healthy adults (< or = 1000, 95% CI). All children with an acute Candida infection had elevated IgA titres. Our study shows that antibody testing may be used to diagnose systemic Candida infection in children and to follow the progression and resolution of systemic Candida infection with the rise and fall of antibody titres.

Serum IgA immune response to individual rotavirus polypeptides in young children with rotavirus infection.

A human IgA-radioimmunoprecipitation assay (IgA-RIPA) utilizing the galactose-binding lectin jacalin from the jack-fruit Artrocarpus integrifolia was developed. Among the human immunoglobulins, jacalin binds specifically to immunoglobulin A. The IgA-RIPA was used to characterize the serum IgA response to individual rotavirus polypeptides in nine paired sera from children (8-34 months of age) with an acute rotavirus infection. In acute sera the IgA response was mainly directed against the inner capsid proteins VP2 and VP6, with VP2 surprisingly being the most immunogenic protein while in the convalescent sera, the IgA response was directed not only against structural but also against non-structural proteins.

Serum anti-gliadin antibody profile in childhood protracted diarrhoea due to coeliac disease and other causes in a developing country.

Serum anti-gliadin antibody (AGA) titres were estimated by diffusion in a gel enzyme-linked immunosorbent assay in children with coeliac disease (n = 11), protracted diarrhoea of non-coeliac causes (n = 110), acute gastroenteritis (n = 20), protein energy malnutrition (n = 20), and asymptomatic, well-nourished children (n = 66). The mean IgG and IgA AGA titres were significantly higher (p less than 0.001) in children with coeliac disease than in any other groups. There was no significant difference (p greater than 0.01) in AGA titres in relation to age, nutritional status, or severity of villous injury. In patients with coeliac disease AGA titres showed a good correlation with disease activity. The specificity and sensitivity of the assay are discussed.

Intestinal permeability assessed with polyethylene glycols in children with diarrhea due to rotavirus and common bacterial pathogens in a developing community.

Intestinal permeability was assessed with different-sized polyethylene glycols (PEG 400 and PEG 1,000) in small children with acute diarrhea. All children with acute diarrhea absorbed and excreted less PEG of all molecular sizes into the urine when compared with healthy control children (p less than 0.001). Children with acute rotavirus infection excreted significantly less PEG of all sizes than children with Shigella, Salmonella, and enteropathogenic Escherichia coli (EPEC) infection (p less than 0.001-0.01), suggesting a more severe mucosal lesion caused by rotavirus. In patients with severe malnutrition there was also a significant decrease in absorption of PEGs observed. In addition, malnourished patients with rotavirus diarrhea showed a pronounced decrease of PEGs in comparison with well-nourished patients. The ratio between the recovery of a large PEG molecule, 1,074 Da, and a small molecule, 370 Da, was utilized to assess the absorption of large molecules in relation to that of smaller ones. On applying this ratio, it was noted that the intestine in children with Shigella and EPEC infection was relatively more permeable to larger molecules than in healthy controls, while in rotavirus and Salmonella infection it was less permeable to larger molecules. In this study significant differences in the permeability characteristics were observed, suggesting etiology-specific effects on the mucosal barrier.

Detection of human rotaviruses which do not react with subgroup I- and II-specific monoclonal antibodies.

Of 126 rotavirus-positive specimens, 7 could not be subgrouped (I or II). These strains showed a distinct reaction with a monoclonal antibody recognizing a common region on VP6, but they did not react with VP6 subgroup-specific monoclonal antibodies although they contained as much viral antigen as the subgrouped strains.

Role of enteric adenoviruses and rotaviruses in mild and severe acute enteritis.

The role of enteric-type adenoviruses and rotaviruses in mild and severe acute gastroenteritis was investigated among children younger than 5 years of age seeking treatment at an urban hospital (UH) and at a rural health center (RHC) in India. There were 330 children at the UH and 340 at the RHC; 319 and 315 age matched nondiarrheal children served as controls for the respective groups. Rotavirus was detected in 15.2% of 330 cases and 1.9% of 319 controls at the UH (P less than 0.001) and in 16.5% of 340 cases and 2.9% of 315 controls at the RHC (P less than 0.001). RV excretion was 3- to 5-fold more common in severe compared with mild diarrhea at the UH and at the RHC (P less than 0.001). The detection rate for enteric-type adenoviruses was similar in patients and controls, respectively, at the UH (0.9%; 2.5%) and RHC (3.8%; 2.5%). At the RHC adenovirus types other than 40 and 41 were excreted by 8.8% of the patients and by only 1.0% of the controls (P less than 0.001). It is possible that the diarrheagenic role of adenoviruses may not be restricted to types 40 and 41.

Neonatal rotavirus infection and its relation to cord blood antibodies.

Among 274 neonates born at the maternity services of an urban hospital in India, 36.1% of the infants shed rotavirus in feces (as detected by ELISA) by 72 h of life. The excretion rate increased to 70.3% among the 120 infants who stayed for 5 days or more at the hospital. Diarrhoeal symptoms of mild and self-limited nature were observed only in 19.2% of the rotavirus excretors, the remaining being asymptomatic. Among the 98 infants who received supplement feeds, 49% acquired rotavirus infection as against 24.7% of the 150 exclusively breast fed infants (p less than 0.001). Viral RNA in the feces of all rota positive infants showed the same electropherotype, indicating infection from a common source. The mean percentage rotavirus inhibitory activity of cord sera in the infected and non-infected infants was 50.2 +/- 21.7 and 56.6 +/- 19.2 respectively (p greater than 0.05), suggesting that cord blood antibodies do not offer significant protection against neonatal rotavirus infection.