Rita Y.T. Sung

Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus

BACKGROUND Human infection with an avian influenza A virus (subtype H5N1) was reported recently in Hong Kong. We describe the clinical presentation of the first 12 patients and options for rapid viral diagnosis. METHODS Case notes of 12 patients with virus-culture-confirmed influenza A H5N1 infection were analysed. The clinical presentation and risk factors associated with severe disease were defined and the results of methods for rapid virus diagnosis were compared. FINDINGS Patients ranged from 1 to 60 years of age. Clinical presentation was that of an influenza-like illness with evidence of pneumonia in seven patients. All seven patients older than 13 years had severe disease (four deaths), whereas children 5 years or younger had mild symptoms with the exception of one who died with Reyes syndrome associated with intake of aspirin. Gastrointestinal manifestations, raised liver enzymes, renal failure unrelated to rhabdomyolysis, and pancytopenia were unusually prominent. Factors associated with severe disease included older age, delay in hospitalisation, lower-respiratory-tract involvement, and a low total peripheral white blood cell count or lymphopenia at admission. An H5-specific reverse-transcription PCR assay (RT-PCR) was useful for rapid detection of virus directly in respiratory specimens. A commercially available enzyme immunoassay was more sensitive than direct immunofluorescence for rapid viral diagnosis. Direct immunofluorescence with an H5-specific monoclonal antibody pool was useful for rapid exclusion of H5-subtype infection. INTERPRETATION Avian Influenza A H5N1 virus causes human influenza-like illness with a high rate of complications in adults admitted to hospital. Rapid H5-subtype-specific laboratory diagnosis can be made by RT-PCR applied directly to clinical specimens.

Effects of Diet and Exercise on Obesity-Related Vascular Dysfunction in Children

Background—The prevalence of obesity in both adults and children is increasing rapidly. Obesity in children is independently associated with arterial endothelial dysfunction and wall thickening, key early events in atherogenesis that precede plaque formation. Methods and Results—To evaluate the reversibility of obesity-related arterial dysfunction and carotid intima-media thickening by dietary and/or exercise intervention programs, 82 overweight children (body mass index, 25±3), 9 to 12 years of age, were randomly assigned to dietary modification only or diet plus a supervised structured exercise program for 6 weeks and subsequently for 1 year. The prospectively defined primary end points were ultrasound-derived arterial endothelial function (endothelium-dependent dilation) of the brachial artery and intima-media thickness of common carotid artery. At 6 weeks, both interventions were associated with decreased waist-hip ratio (P <0.02) and cholesterol level (P <0.05) as well as improved arterial endothelial function. Diet and exercise together were associated with a significantly greater improvement in endothelial function than diet alone (P =0.01). At 1 year, there was significantly less thickening of the carotid wall (P <0.001) as well as persistent improvements in body fat content and lipid profiles in the group continuing an exercise program. Vascular function was significantly better in those children continuing exercise (n=22) compared with children who withdrew from the exercise program (n=19) (P <0.05). Conclusions—Obesity-related vascular dysfunction in otherwise healthy young children is partially reversible with diet alone or particularly diet combined with exercise training at 6 weeks, with sustained improvements at 1 year in those persisting with diet plus regular exercise.

Pathology of fatal human infection associated with avian influenza A H5N1 virus

Eighteen cases of human influenza A H5N1 infection were identified in Hong Kong from May to December 1997. Two of the six fatal cases had undergone a full post‐mortem which showed reactive hemophagocytic syndrome as the most prominent feature. Other findings included organizing diffuse alveolar damage with interstitial fibrosis, extensive hepatic central lobular necrosis, acute renal tubular necrosis and lymphoid depletion. Elevation of soluble interleukin‐2 receptor, interleukin‐6 and interferon‐γ was demonstrated in both patients, whereas secondary bacterial pneumonia was not observed. Virus detection using isolation, reverse transcription‐polymerase chain reaction and immunostaining were all negative. It is postulated that in fatal human infections with this avian subtype, initial virus replication in the respiratory tract triggers hypercytokinemia complicated by the reactive hemophagocytic syndrome. These findings suggest that the pathogenesis of influenza A H5N1 infection might be different from that of the usual human subtypes H1‐H3. J. Med. Virol. 63:242–246, 2001.

Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening.

OBJECTIVE: We sought to study arterial endothelial function and carotid intima-media thickness (IMT), both early markers of atherosclerosis, in overweight compared to normal children.DESIGN: Case–control comparison.SUBJECTS: A total of 36 asymptomatic overweight children (body mass index (BMI)>23; mean 25±3) aged 9–12 y and 36 age- and gender-matched nonobese healthy children (BMI<21) from a school community.MEASUREMENTS: The key parameters were: BMI, arterial endothelial function (ultrasound-derived endothelium-dependent dilation) and carotid artery IMT. The secondary parameters measured included body fat content, waist–hip ratio (WHR), blood pressures, blood lipids, insulin and glucose.RESULTS: The two groups were well matched for blood pressures, cholesterol and glucose levels, but BMI (P<0.0001), body fat (P=0.001), WHR (P<0.05), fasting blood insulin (P=0.001) and triglyceride levels (P<0.05) were higher in obese children. Overweight was associated with impaired arterial endothelial function (6.6±2.3 vs 9.7±3.0%, P<0.0001) and increased carotid IMT (0.49±0.04 mm vs 0.45±0.04 mm, P=0.006). The degree of endothelial dysfunction correlated with BMI (P<0.003) on multivariate analysis.CONCLUSION: Obesity, even of mild-to-moderate degree, is independently associated with abnormal arterial function and structure in otherwise healthy young children.

Waist circumference and waist-to-height ratio of Hong Kong Chinese children

BackgroundCentral body fat is a better predictor than overall body fat for cardiovascular (CV) risk factors in both adults and children. Waist circumference (WC) has been used as a proxy measure of central body fat. Children at high CV risk may be identified by WC measurements. Waist-to-height ratio (WHTR) has been proposed as an alternative, conveniently age-independent measure of CV risk although WHTR percentiles have not been reported. We aim to provide age- and sex-specific reference values for WC and WHTR in Hong Kong Chinese children.MethodsCross sectional study in a large representative sample of 14,842 children aged 6 to 18 years in 2005/6. Sex-specific descriptive statistics for whole-year age groups and smoothed percentile curves of WC and WHTR were derived and presented.ResultsWC increased with age, although less after age 14 years in girls. WHTR decreased with age (particularly up to age 14). WHTR correlated less closely than WC with BMI (r = 0.65, 0.59 cf. 0.93, 0.91, for boys and girls respectively).ConclusionReference values and percentile curves for WC and WHRT of Chinese children and adolescents are provided. Both WC and WHTR are age dependent. Since the use of WHRT does not obviate the need for age-related reference standards, simple WC measurement is a more convenient method for central fat estimation than WHRT.

Measurement of body fat using leg to leg bioimpedance

AIMS (1) To validate a leg to leg bioimpedance analysis (BIA) device in the measurement of body composition in children by assessment of its agreement with dual energyx ray absorptiometry (DXA) and its repeatability. (2) To establish a reference range of percentage body fat in Hong Kong Chinese children. METHODS Sequential BIA and DXA methods were used to determine body composition in 49 children aged 7–18 years; agreement between the two methods was calculated. Repeatability for the BIA method was established from duplicate measurements. Body composition was then determined by BIA in 1139 girls and 1243 boys aged 7–16 years, who were randomly sampled in eight local primary and secondary schools to establish reference ranges. RESULTS The 95% limits of agreement between BIA and DXA methods were considered acceptable (−3.3 kg to −0.5 kg fat mass and −3.9 to 0.6% body fat). The percentage body fat increased with increasing age. Compared to the 1993 Hong Kong growth survey, these children had higher body mass index. Mean (SD) percentage body fat at 7 years of age was 17.2% (4.4%) and 14.0% (3.4%) respectively for boys and girls, which increased to 19.3% (4.8%) and 27.8% (6.3%) at age 16. CONCLUSION Leg to leg BIA is a valid alternative method to DXA for the measurement of body fat. Provisional reference ranges for percentage body fat for Hong Kong Chinese children aged 7–16 years are provided.

Effects of dietary intervention and strength training on blood lipid level in obese children

Aims: To evaluate effects of a low energy diet, with or without strength training, on blood lipid profile in obese children. Methods: Eighty two obese children were enrolled into a six week dietary programme, and were randomly allocated to a training group or a non-training group. The training group underwent regular exercise sessions with emphasis on strength training. Results: Height increased significantly, with a non-significant reduction in body mass index. Fat free mass increased significantly in the training group. Serum total cholesterol was significantly reduced in both groups. The LDL:HDL ratio significantly decreased in the training group. Conclusion: Results support the potentially beneficial effects of both diet and physical training. Further and longer term evaluation of such programmes is required.

BMI and Waist Circumference in Predicting Cardiovascular Risk Factor Clustering in Chinese Adolescents

Objective: To derive the optimal BMI and waist circumference (WC) cut‐off values to predict clustering of cardiovascular risk factors in Hong Kong Chinese adolescents.

Epidemiology and aetiology of acute bronchiolitis in Hong Kong infants

The epidemiological, clinical and virological features of 1220 children with acute bronchiolitis admitted to the Prince of Wales Hospital, Hong Kong, from 1985 to 1988 are reported. They accounted for 6.6% of total paediatric admissions and provided a case incidence of bronchiolitis requiring admission to hospital of approximately 21 per 1000 children 0-24 months of age. The clinical course and outcome was in general benign. The average hospital stay was 5 days and there were no deaths. Ten per cent of patients were repeatedly admitted to hospital with recurrent wheezing after discharge. Two infants developed bronchiolitis obliterans. Respiratory syncytial virus (RSV) was shown by direct immunofluorescence, virus culture and serology to be the commonest cause of acute bronchiolitis in Hong Kong. Other aetiological agents included parainfluenza and influenza viruses, adenoviruses, and Mycoplasma pneumoniae. In contrast to western countries, a seasonal variation of bronchiolitis was found with a peak incidence in the summer months. The significance of these observations is discussed.

Effects of strength training on body composition and bone mineral content in children who are obese.

The purpose of this study was to test the hypothesis that strength training benefits diet-controlled obese children with respect to lean mass and bone mineral acquisition. Eighty-two Hong Kong school children (aged 10.4 ± 1.0 years, 70 in Tanner stage 1, 12 in stage 2) who were obese/overweight were randomly assigned to receive either a balanced low-energy (900–1200 cal) diet plus strength training (n = 41) (training group) or the diet alone (n = 41) (control group). The training group attended a 75-minute strength exercise program 3 times/week for 6 weeks (phase 1), after which they were offered and 22 children opted to continue a once-weekly program for a further 28 weeks (phase 2). All children were evaluated at baseline, after 6 weeks, and at the end of the 36-week study (including an intervening 2-week introduction to phase 2). Body composition and bone mineral content were measured by dual-energy X-ray absorptiometry, and diet was assessed by food-frequency questionnaire. The results showed that the exercise programs were well accepted, with good attendance at the exercise classes. After 6 weeks, the children in the training group showed significantly larger increases in lean body mass (1 0.8 kg [2.4%] vs. 10.3 kg [1.0%], p < 0.05) and total bone mineral content (146.9 g [3.9%] vs. 133.6 g [2.9%], p < 0.05) than those in the control group. At the end of the study, these trends were maintained in the continued-training subgroup, though no longer reaching statistical significance. We conclude that in diet-controlled prepubertal obese/over-weight children, participation in an exercise program with emphasis on strength training resulted in improved lean mass and bone mineral accrual.