Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the impact of MBL on susceptibility and severity of infection in preterm neonates during their first month of life. One hundred fifty eight preterm neonates were genotyped for MBL mutations by heteroduplex analyses. Consecutive serum MBL levels were measured by ELISA and clinical and laboratory data, including blood cultures, were collected for each baby. A third of the premature neonates had genetically determined MBL deficiency. In addition, MBL levels were also low in the first week of life and lower in neonates with a wild type genotype who were less than 28 wk gestation or a birth weight of less than 1000 g, thereby increasing the number of neonates with a low MBL level at birth. MBL deficiency was associated with an increased risk of sepsis (p Ͻ 0.01). This study indicates that MBL levels are low in neonates at birth and renders premature neonates to an increased risk of infection. (Pediatr Res 63: 680-685, 2008)

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Infection with HIV represents a significant global health problem, with high infection rates and high mortality worldwide. Treatment with antiretroviral therapy is inaccessible to many patients and efficacy is limited by development of resistance and side effects.

Highly active antiretroviral therapy (HAART) slows the progression of human immunodeficiency virus (HIV) disease and lowers mortality and morbidity in children. Coincident with these advances, an increasing number of side effects are being reported. We describe an adolescent boy with perinatally acquired HIV infection who developed significant bilateral breast enlargement as a result of HAART. He required bilateral mastectomies. Pediatricians need to be aware of less common side effects of HAART.

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Background Mannose-binding lectin (MBL; encoded by MBL-2) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs, leading to complement activation and cell lysis. Mutations in the MBL-2 promoter and of the MBL-2 gene exon 1 result in reduced protein levels and increased susceptibility to infection. We have investigated the effect of MBL-2 polymorphisms on susceptibility and progression of HIV-1 infection in children. Patients and methods One-hundred and twenty-eight children, aged 2–16 years were recruited. MBL-2 genotypes were determined by PCR and heteroduplex analyses. Serum MBL levels were measured by ELISA. Comparison of genotypes (A=wild type, 0=variant alleles) and protein levels between groups was performed using χ2, Mann–Whitney U or Kruskal–Wallis tests. Results Children were classified according to the Centers for Disease Control and Prevention clinical classification: A, B or C (mildly symptomatic [ n=39], moderately symptomatic [ n=58] or severely symptomatic AIDS [ n=31]) or immune category 1 ( n=77), 2 ( n=46) or 3 ( n=5). Analysis of MBL-2 genotypes with respect to clinical classification yielded minimal differences. However, patients in immunological categories 2 and 3 (<25% CD4+ T cells) were more likely to have MBL-2 variant alleles ( P=0.01). We further explored MBL status with respect to disease progression. Only 1/10 long-term non-progressors (LTNPs) had an MBL-2 mutation (A/D) with a corresponding protein level of 611 ng/ml. Conclusions MBL deficiency was more frequent in patients with severe disease as assessed by CD4+ T-cell status. MBL-2 variants may be less frequent in children classified as LTNPs. MBL analysis could be useful in identifying children with slow disease progression and, consequently, may not require immediate antiretroviral treatement.

Objectives: Antiretroviral therapy (ART) has been associated with lipodystrophy in children. We evaluated changes in various anthropometric measurements for the assessment of lipodystrophy and assessed whether there was an association with use of protease inhibitors (PI), non-PI containing ART and/or stavudine (d4T). Methods: Eighty-five HIV-infected children attending the HIV clinic at Great Ormond Street Hospital (GOSH) were included. The average follow-up was 8.4 months (range 3 -12 months). Body fat redistribution was assessed by anthropometric measurements including skinfold thickness and circumferences of upper and lower limbs. Measurements were converted to age-and sex-adjusted z-scores through development stages including puberty. Results: Sixty children had taken ART; 37 received PI-containing; 38 received d4T; 25 had never been treated. In the studied population, clinically important changes with decreases in biceps (BSF), subscapular skinfolds and total body fat (4SFT) over period of 12 months were observed. Some increase was noticed in triceps skinfolds (TSF). Limbs circumferences remained at the same level. Further we looked at 4 months basis changes in anthropometric measurements stratified by baseline ART. Generally z-scores of anthropometric measurements were lower in therapy naive children when compared to ART groups. PI-based ART regimens resulted in significant increases in BSF with a trend towards increases in TSF, suprailiac and 4SFT. Mid-arm and thigh circumferences were higher in PI compared to naive group. Similarly, significant changes in BSF z-scores were associated with d4T use. Increases were seen in TSF and mid-arm circumference and decreases were observed in subscapular skinfolds and calf circumference z-scores. Conclusions: Body fat redistribution in HIV-infected children with sub-clinical lipodystrophy could be detected by anthropometric measurements, particularly when PI or d4T is included in ART. Over time, changes with increase in arm and trunk fat, and no change or decrease in leg fat were more pronounced among ART-receiving children.

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