Stanley Read

Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza

Background: Limited data are available on disease characteristics and outcomes of children with 2009 pandemic influenza A(H1N1) virus infection (pandemic H1N1 influenza) who have required hospital admission. Methods: We reviewed the charts of 58 children with pandemic H1N1 influenza admitted to a large pediatric hospital in Ontario, Canada, between May 8 and July 22, 2009. We compared risk factors, severity indicators and outcomes of these children with those of 200 children admitted with seasonal influenza A during the previous 5 years (2004/05 to 2008/09). Results: Children with pandemic H1N1 influenza were significantly older than those with seasonal influenza (median age 6.4 years v. 3.3 years). Forty-six (79%) of the children with pandemic H1N1 influenza had underlying medical conditions; of the other 12 who were previously healthy, 42% were under 2 years of age. Children admitted with pandemic H1N1 influenza were significantly more likely to have asthma than those with seasonal influenza (22% v. 6%). Two children had poorly controlled asthma, and 6 used inhaled medications only intermittently. The median length of stay in hospital was 4 days in both groups of children. Similar proportions of children required admission to the intensive care unit (21% of those with pandemic H1N1 influenza and 14% of those with seasonal influenza) and mechanical ventilation (12% and 10% respectively). None of the children admitted with pandemic H1N1 influenza died, as compared with 1 (0.4%) of those admitted with seasonal influenza. Interpretation: Pandemic H1N1 influenza did not appear to cause more severe disease than seasonal influenza A. Asthma appears to be a significant risk factor for severe disease, with no clear relation to severity of asthma. This finding should influence strategies for vaccination and pre-emptive antiviral therapy.

Colchicine: a state-of-the-art review.

Colchicine is an ancient drug that is attracting renewed interest because of its actions at a subcellular level. Specifically, it interferes with microtubule growth and therefore affects mitosis and other microtubule‐dependent functions. Various mechanisms have been proposed to account for the action of colchicine in acute gouty arthritis, its interaction with cellular membrane and cyclic 3′,5′‐adenosine monophosphate, and its action in amyloidosis. Pharmacokinetic studies have been relatively limited and their results somewhat contradictory, with mean terminal elimination half‐lives of 19 minutes to 9 hours being reported. Some of these differences may be attributed to assay difficulties. Colchicine can cause gastrointestinal side effects and should be used with care to protect patients from toxic doses. Colchicine‐induced myopathy and neuropathy may be more frequent than previously recognized, and therefore patients receiving long‐term therapy should be monitored carefully. Bone marrow depression has been reported, primarily in cases of acute colchicine intoxication, and intravenous administration of the drug has been associated with severe pancytopenia and death. Colchicine intoxication causes multiple organ failure. Because of its cytogenic effects and reported association with Downs syndrome, the agent should not be used by pregnant women.

Toronto street youth and HIV/AIDS: prevalence, demographics, and risks

PURPOSE The purposes of this study were: (a) to identify human immunodeficiency virus (HIV) prevalence in Toronto street youth through paired blood and saliva specimens; (b) to identify the HIV risk and prevention behaviors of street involved youth; and (c) to identify demographic or other factors that may contribute to the risk of street youth becoming infected with HIV/acquired immunodeficiency syndrome (AIDS) in the future. METHODS This was a cross-sectional convenience study of street-involved youth aged 14-25 years. The youth participated in interviews to identify HIV-related knowledge and personal risk and preventive behaviors. Following interviews, they were asked to provide a saliva sample, blood spot, or both. They could refuse one or both samples without jeopardizing their involvement or receiving an honorarium. Two males were the only participants who declined to provide a sample. RESULTS Fifteen of 695 (2.2%) youth tested positive for HIV infection. All were male, ranging in age from 18 to 25 years. Same and opposite sex, intravenous (IV) drug use, prostitution, and incarceration were risk factors associated with positive HIV test results. The rate of HIV infection was seven times greater for the group 20 years of age and older (20-25) compared to the younger group aged 14-9 years. The proportion testing positive for HIV from small cities, towns, and rural communities in Ontario was 40%; yet, they represented 21% of the study population. Most (57%) youth had been on their own for no more than 3 years and had moved frequently. Nearly two thirds (60%) had stayed in hostels or homeless shelters in the previous 6 months. CONCLUSION Street youth in Canada are at high risk of HIV infection with their risk increasing with age. Unprotected (same and opposite) sex, IV drug use, prostitution and incarceration were linked to their HIV infections. The high level of mobility identified by street youth challenges governments, communities, and public health officials to develop appropriate prevention strategies and to carefully monitor the spread of HIV infection in this vulnerable population.

A national review of vertical HIV transmission

Objectives:Prevention of vertical HIV transmission has evolved significantly in Canada over the last two decades. The aim of this analysis is to describe the surveillance programme used, rate of vertical HIV transmission and changing epidemiology of HIV-affected pregnancies in Canada. Design:National perinatal HIV surveillance programme. Methods:From 1990, annual retrospective data was collected on demographic and clinical characteristics of HIV-infected mothers and their infants referred to 22 participating sites across Canada either before/during pregnancy or within 3 months after delivery. Factors impacting HIV transmission and demographic features were explored. Results:Two thousand, six hundred and ninety-two mother–infant pairs were identified. The overall rate of vertical HIV transmission was 5.2%, declining to 2.9% since 1997. The rate of transmission for mothers who received HAART was 1%, and 0.4% if more than 4 weeks of HAART was given. Forty percent of women delivered by caesarean section, with no difference in transmission rate compared with vaginal delivery for women treated with HAART (1.4 vs. 0.6%, P = 0.129) but significant risk reduction for those who did not receive HAART (3.8 vs. 10.3%, P = 0.016). Black women were the largest group; proportions of black and aboriginal women increased significantly over time (P < 0.001 for both). Heterosexual contact was the most common risk category for maternal infection (65%), followed by injection drug use (IDU) (25%). Conclusion:Vertical HIV transmission in Canada has decreased dramatically for women treated with HAART therapy. All pregnant women should be evaluated for HIV infection and programmes expanded to reach vulnerable populations including aboriginal, immigrant and IDU women.

Cognitive development in school-age children with vertically transmitted HIV infection.

We examined a broad range of neuropsychological functioning in school-age children with vertically transmitted HIV infection and a control group made up of siblings of children with HIV infection. Fourteen children with HIV (2 asymptomatic, 8 mildly symptomatic, and 4 with AIDS) and 11 control children were administered a battery of neuropsychological tests assessing intelligence, receptive language, expressive language, visual and verbal memory, visual-motor speed and coordination, visual-motor and visual-spatial processing, fine motor skill, and academic achievement. Results revealed that school-age children with vertically transmitted HIV infection show many areas of cognitive function within the normal range. Despite normal cognitive development, subtle motor impairments were documented in children with vertically transmitted HIV infection. Our results are the first report of fine motor and motor strength deficits in school-age children with vertically transmitted HIV. Lastly, computed tomography (CT) results suggest that children with HIV who have documented structural anomalies in the brain may be at risk for deficits in visual-motor and visual-spatial processing. This finding should be explored with larger samples and other measures to determine its generalizability.

Foscarnet therapy of cytomegalovirus retinitis in AIDS

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in AIDS. Twenty patients were treated with a 21-day course of foscarnet therapy by continuous infusion. Response to therapy was good in eight (47%) of 17 evaluable patients; partial arrest of progression was observed in eight (47%); and no response was obtained in one (6%). Foscarnet therapy did not lead to suppression of urinary excretion of CMV in four of 12 patients who nonetheless had improvement in retinal lesions. Toxic effects, especially reversible renal failure, were common, with blood creatinine increase in 50% and dialysis in two patients. Renal toxicity occurred primarily during the third week of therapy. Anemia (hemoglobin <80 g/L) occurred in 10 patients after a mean of 14.5 + 5.1 days of therapy and required transfusion. Review of this study and of data from a previous case series, however, was inconclusive regarding the additional benefit of a third week of therapy. Maintenance therapy was given to seven patients. Four had recurrence of CMV retinitis at a mean interval of 62 + 52 days. Only one patient has maintained prolonged remission on maintenance (>24 weeks). Toxicity on the maintenance protocol included anemia (two of seven patients) and increased creatinine blood levels (one of seven patients). Zidovudine therapy in six patients did not contribute to increased toxicity of induction or maintenance therapy. Drug levels during continuous infusion were stable for individual patients but showed wide inter-patient variability. Peak levels of post-maintenance infusion varied both within and between patients.

Cognitive and motor development in children with vertically transmitted HIV infection

This study was designed to examine mental and motor development in infants with vertically transmitted human immunodeficiency virus (HIV) infection. Early neurodevelopment was examined in 25 young children with HIV infection acquired through vertical transmission. Compared with 25 children born to HIV-positive mothers but not infected with the virus, and after controlling for developmental risk factors, the HIV-infected group showed impairments in mental and motor development. Mental and motor development were assessed using the Bayley Scales of Infant Development. On the mental scale (MDI), the HIV-infected infants obtained significantly lower scores than the uninfected infants. On the performace scale (PDI), the HIV-infected infants obtained significantly lower standard scores than the uninfected infants. CT scan results were available for 20 of the HIV-infected children. CT abnormalities were associated with developmental delays, particularly for motor development. The results point to the importance of early abnormalities in myelination and of subcortical lesions of cognitive and motor development.

Serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor-treated and naive HIV-infected children.

Objective: To determine the extent and degree of abnormalities of serum lipids, glucose homeostasis and abdominal adipose tissue distribution in protease inhibitor (PI)‐treated and PI‐naive HIV‐infected children. Design: A cross‐sectional study involving HIV‐infected children, 3–18 years of age, in a paediatric tertiary care centre. Main outcome measures: Total, HDL and LDL‐cholesterol, triglycerides, glucose, insulin, proinsulin and C‐peptide were determined in the fasting state. Insulin resistance was assessed using the homeostatic model assessment–insulin resistance (HOMA–IR). Abdominal adipose tissue distribution was determined by single‐slice computed tomography at the umbilical level. Results: Thirty PI‐treated and 20 PI‐naive children were evaluated (76% prepubertal). PI‐treated children had significantly higher total cholesterol (P = 0.0021), LDL‐cholesterol (P = 0.019) and triglycerides (P = 0.0018). Serum glucose, insulin, proinsulin and C‐peptide, the insulin: glucose ratio, HOMA–IR and abdominal adipose tissue distribution were similar in the two groups. Clinical and immunological HIV categories, viral load, CD4 cell count and stavudine therapy were not significantly associated with serum lipids, insulin resistance or abdominal adipose tissue distribution. The predictor variable most strongly associated with fasting serum insulin and HOMA–IR was the Tanner stage. Age was the most significant predictor variable of the visceral: subcutaneous adipose tissue ratio. Conclusion: In this cohort of predominantly prepubertal HIV‐infected children, PI therapy was associated with an atherogenic dyslipidemia but not with insulin resistance or abnormal abdominal adipose tissue distribution. The results suggest that children, particularly prepubertal children, are less susceptible than adults to PI‐induced changes in glucose homeostasis and abdominal adipose tissue distribution.

Cytomegalovirus retinitis in immunosuppressed children.

PURPOSE To describe the ocular and systemic features of children with cytomegalovirus retinitis and their disease outcomes. METHODS Review of all cases of cytomegalovirus retinitis diagnosed or treated at a tertiary care pediatric hospital during a 10-year period. RESULTS Nine immunocompromised children younger than 16 years were diagnosed as having cytomegalovirus retinitis. The underlying causes of immunocompromise were severe combined immunodeficiency syndrome (n = 2), severe combined immunodeficiency syndrome after bone marrow transplantation (n = 1), acquired immunodeficiency syndrome (AIDS) (n = 2), AIDS and previous bone marrow transplantation for leukemia (n = 1), immunosuppressive therapy after renal transplantation (n = 1), chemotherapy for leukemia (n = 1), and congenital cytomegalovirus infection (n = 1). Five children (56%) had symptomatic extraocular cytomegalovirus infection. Only two children reported visual symptoms with cytomegalovirus retinitis at initial examination. Cytomegalovirus retinitis was bilateral in eight children (89%) and involved the posterior pole in at least one eye of all nine children. Four children (44%) died within 10 months of being diagnosed with cytomegalovirus retinitis. The remaining five children were alive, with follow-up ranging from 14 to 70 months. Successful bone marrow transplantation in one child and discontinuation of immunosuppressive medications in two children improved systemic immune function and permitted discontinuation of anticytomegaloviral therapy. CONCLUSION Pediatric cytomegalovirus retinitis is often asymptomatic and bilateral and involves the posterior pole at initial examination. Recovery of systemic immune function may occur in some children. Evaluation of children at risk and prompt treatment of cytomegalo. virus retinitis are important to prevent long-term visual morbidity.

Vitamin D Supplementation and CD4 Count in Children Infected with Human Immunodeficiency Virus

OBJECTIVE To evaluate, in a randomized fashion, the impact of vitamin D supplementation on CD4 count and measures of vitamin D homeostasis in children infected with human immunodeficiency virus (HIV). STUDY DESIGN Children infected with HIV (n = 54) were randomized to receive no supplementation (group 1), vitamin D 5600 IU/week (group 2), or vitamin D 11 200 IU/week (group 3) for 6 months. Viral load, CD4 percent, CD4 count, 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D, and other measures of vitamin D metabolism were measured at baseline and 6 months later. RESULTS A total of 53 participants completed the study. The mean age, CD4 percent, CD4 count, and log(10) viral load at baseline were 10.3 ± 3.9 years, 33% ± 10%, 927 ± 468 cells/μL, and 1.63 (95% CI, 0.76-2.50), respectively. The mean baseline 25(OH)D level was 53.1 ± 24.8 nmol/L; 85% of participants were vitamin D insufficient or deficient (<75 nmol/L). Serum levels of 25(OH)D increased significantly in participants who received supplementation with vitamin D (P = .0002 and P < .001 for participants receiving 800 IU/day and 1600 IU/day, respectively), but not in participants who did not receive supplementation (P = .27). Participants treated with 1600 IU/day of vitamin D achieved a higher mean increase in 25(OH)D than participants treated with 800 IU/day (P = .02). However, only 67% of the group supplemented with higher dose achieved vitamin D sufficiency. Vitamin D supplementation did not lead to an increase in CD4 percent or CD4 count. CONCLUSION In children infected with HIV with relatively preserved immune function, vitamin D supplementation in doses as high as 1600 IU/day does not impact CD4 count. Vitamin D insufficiency is common in this population, and achieving vitamin D serum levels of >75 nmol/L may require a daily intake ≥1600 IU.