Impact of zinc supplementation in children with acute diarrhoea in Turkey

Objective

Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhoea. Our aim was to evaluate the effect of daily zinc supplementation for 14 days on diarrhoea duration, severity, and morbidity in children.

Methods

In a randomised, open label non‐placebo controlled trial, we assessed the efficacy of providing zinc sulfate to 6–60 month old children with acute diarrhoea for 2 weeks followed by 3 months of morbidity surveillance. Children were randomly assigned to zinc (n = 150) and control (n = 130) groups and received 15–30 mg elemental zinc daily.

Results

Supplemented children had significantly improved plasma zinc levels by day 14 of therapy. Zinc deficiency was observed in 2.6% of the treatment and 3.3% of the control group. The mean duration of diarrhoea after starting supplementation was 3.02±2 days in the zinc group and 3.67±3.2 days in the control group. There was no significant difference in diarrhoea duration by treatment group (p>0.05). The number of stools after starting supplementation was 5.8±3.7 and 5.1±3.9 on day 1, 2.9±1.6 and 3.0±2.2 on day 2, and 1.8±1.1 and 1.6±0.9 on day 3 in the zinc and control groups, respectively. There was no significant difference in diarrhoea severity by treatment group (p>0.05). No significant effect was found on the incidence and prevalence of diarrhoea in the zinc compared with the control group.

Conclusion

Our data indicate that supplementing children with acute diarrhoea in Turkey with 3 RDA of elemental zinc for 14 days improved neither diarrhoea duration nor severity despite significant increments in plasma zinc.     

Comparison of alteplase and heparin in maintaining the patency of paediatric central venous haemodialysis lines: a randomised controlled trial

Objectives

To determine whether the tissue plasminogen activator, alteplase, is more effective than heparin in preventing blood clots developing in children''s haemodialysis central lines between dialysis sessions.

Design

A prospective double‐blind, within‐patient multiperiod cross‐over controlled trial of instilling a “lock” of either heparin 5000 U/ml or alteplase 1 mg/ml into the central lines of two children haemodialysed twice weekly, and seven dialysed thrice weekly, over 10 weeks.

Setting

A UK paediatric nephrology unit.

Main outcome measures

Weight of blood clot aspirated from the line at the start of the next dialysis session.

Results

The odds of a clot forming was 2.4 times greater with heparin than alteplase (95% CI 1.4 to 4.0; p = 0.001), and when present they were 1.9 times heavier (31 vs 15 mg; 95% CI 1.5 to 2.4; p<0.0005). There was no effect of inter‐dialytic interval. One child required an alteplase infusion to clear a blocked line following a heparin lock. We subsequently changed our routine locks from heparin to alteplase. Comparing the year before and after that change, the incidence of blocked lines requiring an alteplase or urokinase infusion fell from 2.7 to 1.2 per child (p<0.03), and the need for surgical replacements from 0.7 to nil (p<0.02).

Conclusion

Alteplase is significantly more effective than heparin in preventing clot formation in central haemodialysis lines. This reduces morbidity and improves preservation of central venous access. It is more expensive, though relatively economic if packaged into syringes and stored frozen until needed, but reduces the costs of unblocking or replacing clotted lines.     

Does splenectomy in cystic fibrosis related liver disease improve lung function and nutritional status? A case series

Aims

To review the effect of total splenectomy on lung function and nutrition in children with cystic fibrosis related liver disease (CFLD) and associated portal hypertension. The stated indications for surgery and the short and long term risks of the procedure were also documented.

Method

Over a 25 year period from January 1980 to June 2005, approximately 650 patients with cystic fibrosis (CF) were treated at the Royal Children''s Hospital, Melbourne, Australia. Nine patients with CFLD who underwent a splenectomy during that time were identified and their medical records were reviewed.

Results

FEV₁% predicted dropped by −16±11% in the two years pre‐splenectomy. This contrasts with the increase in FEV₁% predicted of 2±16% in the two years post‐splenectomy (p = 0.05). The cumulative gain in WAZ score (ΔWAZ pre) over the two years prior to splenectomy of 0.045±0.69 was not significantly different from the cumulative gain in WAZ score (ΔWAZ post) for the two years after splenectomy of 0.15±0.36 (p = 0.65). The average age at splenectomy was 14.8 years (SD = 3 years). The average weight of an excised spleen was 983 g (SD = 414 g). There were no deaths associated with splenectomy. The median length of follow up post‐splenectomy was 6.0 years (range 0.7–15.8). There were no episodes of bacterial peritonitis or overwhelming sepsis.

Conclusions

Splenectomy may have a beneficial effect on lung function although this may not manifest itself until the second year post‐splenectomy. Splenectomy in patients with CFLD appears to be a safe procedure.     

Relationship between five common viruses and febrile seizure in children

Objectives

To examine the role of viruses in febrile seizures (FS) by comparing the relative risk (RR) of developing FS with common viral infections and subsequent risk of recurrence.

Methods

We matched the medical records of all children admitted with FS over 5 years and the contemporary records for all admissions for febrile illnesses associated with influenza, adenovirus, parainfluenza, respiratory syncytial virus (RSV) and rotavirus to calculate the RR of FS following these viral infections. For patients admitted for a first FS, we carried multivariate analysis for type of viral infection, age of onset, family history, complex FS features and maximum temperature during the episode, to identify the risk factors for recurrence.

Results

There were 923 admissions for FS, of which 565 were for first seizures. The five most common viruses in FS were influenza (163/923, 17.6%), adenovirus (63/923, 6.8%), parainfluenza (55/923, 6%), RSV (25/923, 2.7%) and rotavirus (12/923, 1.3%). Incidences of FS in febrile illnesses due to these viruses were 20.8% (163/785) for influenza, 20.6% (55/267) for parainfluenza, 18.4% (63/343) for adenovirus, 5.3% (25/468) for RSV and 4.3% (12/280) for rotavirus. Complex FS occurred in 20.6% (n = 191) and the risk of developing complex FS was similar for the five viruses. Overall recurrence rate was 20.5% and was not predicted by type of viral infection.

Conclusion

The risk of developing FS is similar with influenza, adenovirus or parainfluenza and is higher than with RSV or rotavirus. Type of viral infection is not important in predicting complex features or future recurrences.     

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is associated with a prolonged gestational age

Background

The timing of parturition in most mammals is thought to be linked to a late gestational rise in corticosteroid production by the fetal adrenal gland. We hypothesised that gestational age would be prolonged in our patients with impaired cortisol production secondary to congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency.

Methods

We compared the gestational age of patients affected by salt‐wasting CAH due to 21‐hydroxylase deficiency (born 1978–2004; n = 31) with that of children with congenital hypothyroidism (born 1981–2003; n = 30) and a control group of short normal children (born 1980–2002; n = 120). Each group was compared with national (England 2002–3) and regional (2003–4) data on gestational age from hospital episode statistics. Post‐term delivery was defined as birth beyond 41 completed weeks.

Results

National statistics reveal a frequency of 4.4% for singleton deliveries beyond 41 weeks. In our region the frequency was 4.6%. In the group of children with CAH, the frequency of post‐term delivery was 19.3% (p<0.001). In patients with congenital hypothyroidism, the frequency was 13.3% (p = 0.02). The proportion of short children who did not have a recognised endocrinopathy born post term was comparable to national and regional data at 6.7%.

Conclusions

A prolonged gestation is more likely in pregnancies where the fetus has the salt‐wasting form of CAH. This may be due to impaired cortisol production, although other changes in steroidogenesis may also be contributory.     

Polyethylene glycol 3350 plus electrolytes for chronic constipation in children: a double blind, placebo controlled, crossover study

Objectives

To assess the efficacy and safety of polyethylene glycol 3350 plus electrolytes (PEG+E) for the treatment of chronic constipation in children.

Design

Randomised, double blind, placebo controlled crossover trial, with two 2‐week treatment periods separated by a 2‐week placebo washout.

Setting

Six UK paediatric departments.

Participants

51 children (29 girls, 22 boys) aged 24 months to 11 years with chronic constipation (lasting ⩾3 months), defined as ⩽2 complete bowel movements per week and one of the following: pain on defaecation on 25% of days; ⩾25% of bowel movements with straining; ⩾25% of bowel movements with hard/lumpy stools. 47 children completed the double blind treatment.

Main outcome measures

Number of complete defaecations per week (primary efficacy variable), total number of complete and incomplete defaecations per week, pain on defaecation, straining on defaecation, faecal incontinence, stool consistency, global assessment of treatment, adverse events and physical examination.

Results

The mean number of complete defaecations per week was significantly higher for children on PEG+E than on placebo (3.12 (SD 2.05) v 1.45 (SD 1.20), respectively; p<0.001). Further significant differences in favour of PEG+E were observed for total number of defaecations per week (p = 0.003), pain on defaecation (p = 0.041), straining on defaecation (p<0.001), stool consistency (p<0.001) and percentage of hard stools (p = 0.001). Treatment related adverse events (all mild or moderate) occurred in similar numbers of children on PEG+E (41%) and placebo during treatment (45%).

Conclusions

PEG+E is significantly more effective than placebo, and appears to be safe and well tolerated in the treatment of chronic constipation in children.Constipation affects 5–10% of school aged children in the UK¹ and accounts for 3% of general paediatric consultations and 25% of consultations with paediatric gastroenterologists.² Chronic constipation can follow an inadequately managed acute problem.³Measures to induce defaecation in chronically constipated children include regular use of laxatives, increased consumption of fruit and green fibre, ensuring that the child drinks adequate fluids, and encouraging the child to sit on the toilet three or four times a day after meals. Despite common practice, the evidence for the use of laxatives in children is poor; for example, in a recent Cochrane review,⁴ no randomised controlled trials of the use of stimulant laxatives were found in the literature.Movicol (Norgine, Uxbridge, UK) is formulated as a powder containing the osmotic agent polyethylene glycol (PEG) 3350 and electrolytes. When the powder is dissolved in the correct volume of water, the resulting solution is iso‐osmolar with respect to colonic extracellular fluid and therefore does not draw fluid into the colon from the body. This distinct mode of action is in contrast to that of hypertonic inorganic laxatives (eg, magnesium hydroxide or sodium sulphate) and organic laxatives (eg, lactulose), and means that PEG resists the normal drying action of the bowel to remove water from the faecal mass. As a result, the faeces are hydrated and bulked, stimulating peristalsis.The combination of PEG 3350 with electrolytes (PEG+E) has been shown to be effective for treating chronic constipation and faecal impaction in adults⁵ and faecal impaction in children.⁶ The present trial was conducted to assess the efficacy and safety of PEG+E in children with chronic constipation who were being managed in a specialist paediatric outpatient setting.     

Is omitting post urinary‐tract‐infection renal ultrasound safe after normal antenatal ultrasound? An observational study

Background

Guidelines recommend obtaining a renal ultrasonogram (RUS) for young children after a first urinary tract infection (UTI).

Objective

The aim of the current study was to assess the concordance of prenatal and post‐UTI RUS findings in children with a first simple UTI.

Methods

This was a prospective study and included all children aged 5 years or younger who were hospitalised with a first simple UTI (determined as clinical response and normalisation of temperature within 48 h on initiation of antibacterial therapy with no complications). Data were collected from each child regarding the results of prenatal and post‐UTI RUS.

Results

Overall, 250 children were included in the study and the results of late‐pregnancy and post‐UTI RUS were available for 84% (n = 209). Complete concordance between the two RUS was demonstrated in 96% (n = 201). The predictive value of normal antenatal to normal post‐UTI RUS was 96% (95% CI: 93% to 99%). These results include four children with mild transient pelvic dilatation. In eight children in whom renal anomalies were demonstrated only in post‐UTI RUS, the influence of these anomalies on the children''s management was negligible.

Conclusions

Prenatal‐RUS have been performed in most children <5 years old hospitalised with a first simple UTI. Concordance with post‐infection tests is very high. Findings which appear only in post‐infectious RUS usually have negligible effects on children''s management. Thus, in such children with normal antenatal RUS omitting post‐UTI RUS could be considered.     

A prospective study of the immediate and delayed adverse events following intravenous immunoglobulin infusions

Aim

To document the incidence of immediate and delayed adverse events (AE) following intravenous immunoglobulin (IVIG) infusion in children.

Methods

Immediate and delayed adverse events were prospectively recorded for 345 infusions in 58 children receiving IVIG for immunodeficiency (n = 33) or immunomodulation (n = 25). For each infusion adverse events were documented during the infusion and by follow up interview 4–7 days later.

Results

Immediate adverse events occurred in 10.3% and delayed adverse events in 41.4% of children treated during the study period. Three and a half per cent of the infusions were associated with immediate AE and 20.9% with delayed adverse events. Headache was the most common delayed AE, occurring in 24.1% of patients and 12.8% of infusions.

Conclusions

Delayed adverse events to IVIG infusions are common in children. They occur more frequently than immediate adverse events and are the cause of significant morbidity. Recognition of the high frequency of delayed adverse events is important in the care of children receiving IVIG therapy.     

Prednisolone versus dexamethasone in croup: a randomised equivalence trial

Background

Croup remains a common respiratory problem presenting to emergency departments. A single oral treatment of oral dexamethasone results in improved outcome. Prednisolone has similar pharmacokinetic properties and has a significant advantage in that it is commercially available in liquid preparations.

Objective

To ascertain whether a single oral dose of prednisolone was equivalent to a single oral dose of dexamethasone (matched for potency) in children with mild to moderate croup.

Design

A double blind, randomised, controlled equivalence trial

Setting

Tertiary paediatric emergency department.

Patients

133 children aged 3 to 142 months presenting with mild to moderate croup.

Interventions

Children received either a single oral dose of dexamethasone 0.15 mg/kg or single oral dose of prednisolone 1 mg/kg.

Outcome

The main outcome measure was unscheduled re‐presentation to medical care as determined by telephone follow up at 7 to 10 days. Croup score, adrenaline (epinephrine) use, time spent in the emergency department, and duration of croup and viral symptoms were secondary outcome measures.

Results

Children treated with prednisolone were more likely to re‐present: 19 of 65 children (29%) reattended medical care compared with 5 of 68 (7%) from the dexamethasone group. The confidence intervals around this 22% difference in outcome were 8% to 35%, outside the 0% to 7.5% range of equivalence. There were no significant differences in other outcome measures.

Conclusion

A single oral dose of prednisolone is less effective than a single oral dose of dexamethasone in reducing unscheduled re‐presentation to medical care in children with mild to moderate croup.     

Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study

Aims

To determine whether the risk of hyponatraemia in children with gastroenteritis receiving intravenous (IV) fluids is decreased by the use of 0.9% saline.

Methods

A prospective randomised study was carried out in a tertiary paediatric hospital. A total of 102 children with gastroenteritis were randomised to receive either 0.9% saline + 2.5% dextrose (NS) or 0.45% saline + 2.5% dextrose (N/2) at a rate determined by their treating physician according to hospital guidelines and clinical judgement. Plasma electrolytes, osmolality, and plasma glucose were measured before (T₀) and 4 hours after (T₄) starting IV fluids, and subsequently if clinically indicated. Electrolytes and osmolality were measured in urine samples. Results were analysed according to whether children were hyponatraemic (plasma sodium <135 mmol/l) or normonatraemic at T₀.

Results

At T₀, mean (SD) plasma sodium was 135 (3.3) mmol/l (range 124–142), with 37/102 (36%) hyponatraemic. At T₄, mean plasma sodium in children receiving N/2 remained unchanged in those initially hyponatraemic (n = 16), but fell 2.3 (2.2) mmol/l in the normonatraemic group. In contrast, among children receiving NS, mean plasma sodium was 2.4 (2.0) mmol/l higher in those hyponatraemic at baseline (n = 21) and unchanged in the initially normonatraemic children. In 16 children who were still receiving IV fluids at 24 hours, 3/8 receiving N/2 were hyponatraemic compared with 0/8 receiving NS. No child became hypernatraemic.

Conclusions

In gastroenteritis treated with intravenous fluids, normal saline is preferable to hypotonic saline because it protects against hyponatraemia without causing hypernatraemia.     

An 8 year study of risk factors for SIDS: bed-sharing versus non-bed-sharing

Background

It is unclear if it is safe for babies to bed share with adults. In Ireland 49% of sudden infant death syndrome (SIDS) cases occur when the infant is bed‐sharing with an adult.

Objective

To evaluate the effect of bed‐sharing during the last sleep period on risk factors for SIDS in Irish infants.

Design

An 8 year (1994–2001) population based case control study of 287 SIDS cases and 831 controls matched for date, place of birth, and sleep period. Odds ratios and 95% confidence intervals were calculated by conditional logistic regression.

Results

The risk associated with bed‐sharing was three times greater for infants with low birth weight for gestation (UOR 16.28 v 4.90) and increased fourfold if the combined tog value of clothing and bedding was ⩾10 (UOR 9.68 v 2.34). The unadjusted odds ratio for bed‐sharing was 13.87 (95% CI 9.58 to 20.09) for infants whose mothers smoked and 2.09 (95% CI 0.98 to 4.39) for non‐smokers. Age of death for bed‐sharing and sofa‐sharing infants (12.8 and 8.3 weeks, respectively) was less than for infants not sharing a sleep surface (21.0 weeks, p<0.001) and fewer bed‐sharing cases were found prone (5% v 32%; p = 0.001).

Conclusion

Risk factors for SIDS vary according to the infant''s sleeping environment. The increased risk associated with maternal smoking, high tog value of clothing and bedding, and low z scores of weight for gestation at birth is augmented further by bed‐sharing. These factors should be taken into account when considering sleeping arrangements for young infants.     

Micronutrients (including zinc) reduce diarrhoea in children: the Pakistan Sprinkles Diarrhoea Study

Aims

To examine the effect of the daily use of micronutrients (including zinc) or the same micronutrients plus heat inactivated lactic acid bacteria (LAB), on diarrhoea in children compared to placebo.

Methods

A triple blind randomised clinical trial in an urban slum of Karachi, Pakistan. Micronutrients (including zinc), micronutrients (including zinc and LAB), or placebo, were provided daily for two months to 75 young children (aged 6–12 months) identified at high risk for diarrhoea related mortality on the basis of history of at least one episode of diarrhoea in the preceding two weeks. The longitudinal prevalence of diarrhoea was defined as the percentage of days a child had diarrhoea out of the days the child was observed.

Results

Mean longitudinal prevalence of diarrhoea in the micronutrient–zinc group was 15% (SD = 10%) child‐days compared to 26% (SD = 20%) child‐days in the placebo group and 26% (SD = 19%) child‐days in the micronutrient–zinc–LAB group. The difference between the micronutrient–zinc–LAB and placebo groups was not significant.

Conclusion

The daily provision of micronutrients (including zinc) reduces the longitudinal prevalence of diarrhoea and thus may also reduce diarrhoea related mortality in young children; heat inactivated LAB has negative effects in these children.     

Birth prevalence of cryptorchidism and hypospadias in northern England, 1993-2000

Aim

There is much debate as to whether the prevalence rates of cryptorchidism and hypospadias are increasing. To address this issue we investigated the birth prevalence of cryptorchidism and hypospadias in the northern region of England during the period 1993–2000.

Methods

Cases of cryptorchidism and hypospadias were identified from northern region hospital episodes statistics (HES). Trends in birth prevalence, based on the number of male live births, were assessed using linear regression.

Results

Prevalence was 7.6 per 1000 male live births for cryptorchidism and 3.1 per 1000 male live births for hypospadias. The orchidopexy rates for 0–4 year olds and 5–14 year olds were 1.8 and 0.8 per 1000 male population, respectively. The rates for hypospadias repair for 0–4 year olds and 5–14 year olds were 0.6 and 0.1 per 1000 male population, respectively. There was a statistically significant decreasing temporal trend for the corrective procedure in cryptorchidism of 0.1 per 1000 male population aged under 5 years per annum (95% confidence interval: −0.01 to −0.05, p<0.001), but no temporal change for the corrective procedure in hypospadias (p = 0.60).

Conclusion

HES data were of high quality for the study period. There was no significant change in the prevalence of surgically corrected hypospadias. However, there was an apparent decline in the prevalence of surgically corrected cryptorchidism that may reflect a decrease in the prevalence of the condition or may be due to a decrease in the rate of surgical intervention.     

Effect of parental smoking on cotinine levels in newborns

Background

Smoking is a major risk factor for cot death. Many infants smoke passively as a result of parental smoking. This paper reports on infants exposed to a smoking environment and how they accumulate metabolites of cigarette smoke, such as cotinine, which may be physiologically harmful.

Aim

To assess cotinine levels in infants of smoking parents.

Method

Cotinine excretion in urine was assessed in 104 infants, of whom 71 had smoking parents and 33 had non‐smoking parents. All cotinine levels were measured at approximately 12 weeks of age. The subjects were selected from a database of infants in developmental physiological studies which assessed the impact of various factors on early postnatal development.

Results

On average babies with at least one parent who was a current cigarette smoker excreted 5.58 (95% CI 3.4 to 9.5) times as much cotinine in the urine as did the babies of non‐smoking parents. Maternal smoking was the largest contributing factor. Co‐sleeping (p = 0.037) and the minimum room temperature (p = 0.028) were significant contributory factors.

Conclusion

Infants from smoking households accumulate cotinine, a metabolite of nicotine, which may have a detrimental effect on the cardiorespiratory system.     

Association between allergic rhinitis, bottle feeding, non-nutritive sucking habits, and malocclusion in the primary dentition

Aim

To determine the association between allergic rhinitis, bottle feeding, non‐nutritive sucking habits, and malocclusion in the primary dentition.

Methods

Data were collected on 1160 children aged 4–5 years, who had been longitudinally followed since the age of 4 months, when they were admitted to nurseries in a suburban area of Tampico–Madero, Mexico. Periodically, physical examinations were conducted and a questionnaire was given to their parents or tutors.

Results

Malocclusion was detected in 640 of the children (51.03% had anterior open bite and 7.5% had posterior cross‐bite). Allergic rhinitis alone (adjusted odds ratio = 2.87; 95% CI 1.57 to 5.25) or together with non‐nutritive sucking habits (adjusted odds ratio = 3.31; 95% CI 1.55 to 7.09) had an effect on anterior open bite. Bottle feeding alone (adjusted odds ratio = 1.95; 95% CI 1.07 to 3.54) or together with allergic rhinitis (adjusted odds ratio = 3.96; 95% CI 1.80 to 8.74) had an effect on posterior cross‐bite. Posterior cross‐bite was more frequent in children with allergic rhinitis and non‐nutritive sucking habits (10.4%).

Conclusions

Allergic rhinitis alone or together with non‐nutritive sucking habits is related to anterior open bite. Non‐nutritive sucking habits together with allergic rhinitis seem to be the most important factor for development of posterior open bite in children under the age of 5 years.     

Adrenocortical suppression increases the risk of relapse in nephrotic syndrome

Objective

Children with nephrotic syndrome (NS) are usually treated with long‐term low dose alternate day prednisolone with or without glucocorticoid sparing therapy, such as levamisole or ciclosporin, to maintain remission. The degree of hypothalamic‐pituitary‐adrenal axis (HPA) suppression with such therapeutic strategies has not been studied systematically. HPA suppression could cause a relapse or adrenal crisis.

Study design

To study the risks of HPA suppression, a modified low dose synacthen test (0.5 μg) was administered to 32 patients (22 male,10 female) with a mean age of 9.7 years (range 3.8–17.6 years) with NS receiving long‐term alternate day prednisolone for over 12 months. Twelve patients received alternate day prednisolone, 11 alternate prednisolone+levamisole and nine alternate prednisolone+ciclosporin. All patients were followed up for 3 years and the relapse rate noted.

Results

20/32 (62.5%) patients had a peak serum cortisol concentration of <500 nmol/l, which suggested suboptimal cortisol secretion and possible HPA suppression. 10/12 children in the prednisolone group and 8/11 in the levamisole group had a suboptimal cortisol response compared with 2/9 in the ciclosporin group. During follow‐up, the 20 children who had a suboptimal cortisol response had significantly more relapses (95 relapses) compared to the 12 children with a normal cortisol response who had 24 relapses (p = 0.01).

Conclusions

Children with NS receiving long‐term alternate day prednisolone therapy are at risk of developing HPA suppression and should be evaluated using the modified synacthen test. Children with evidence of HPA suppression are at a greater risk of relapse.     

Impact of HIV-1 status on the radiological presentation and clinical outcome of children with WHO defined community-acquired severe pneumonia

Aims

We compared the radiological features and outcome of WHO defined severe pneumonia among HIV infected and exposed uninfected children randomised to receive penicillin or oral amoxicillin in Durban, South Africa.

Methods

Of 425 children aged between 3 and 59 months with WHO defined severe pneumonia, 366 had anonymous HIV testing performed. Outcome was assessed by failure to improve at 48 h after enrolment or deterioration within 14 days. Chest radiographs were evaluated according to WHO defined radiological criteria for pneumonia and internationally standardised radiological criteria. Findings were stratified for HIV status.

Results

82 (22.4%) children were HIV infected, 40 (10.9%) were HIV exposed and 244 (66.7%) were HIV uninfected. The day 14 outcome in children <12 months of age was significantly worse in HIV‐1 infected than HIV uninfected children (OR 2.8 (95% CI 1.35 to 3.5), p = 0.002), while HIV‐1 infected and uninfected children aged ⩾12 months had equivalent outcomes. Parental penicillin and oral amoxicillin had equivalent response rates in all HIV groups. According to the WHO radiological classification, children who failed WHO standard antimicrobial treatment had significantly higher “other consolidates/infiltrates” than “endpoints for consolidation” in the HIV infected group (OR 5.45 (95% CI 1.58 to 21.38), p<0.002), while the reverse was true for HIV exposed uninfected children (OR 4.13 (95% CI 0.88 to 20.57), p<0.036).

Conclusions

The WHO standard treatment guideline for severe pneumonia is inadequate for HIV‐1 infected infants. The increased prevalence of “other consolidates/infiltrates” among HIV‐1 infected children who failed standard treatment supports the addition of co‐trimoxazole to WHO standard treatment.The global incidence of acute lower respiratory infections (ALRI) is 154 million new episodes per annum with 7–13% of patients requiring hospitalisation.¹ ALRI causes 1.9 million deaths among children annually, accounting for over a fifth of all deaths in Africa.² The World Health Organization (WHO) response to this burden of disease has been the introduction of standard case management guidelines. The benefit of this intervention in HIV non‐endemic areas was recently shown in a meta‐analysis where pneumonia related mortality among neonates, infants and children between 0 and 4 years of age was reduced by 27%, 27% and 20%, respectively.³ The HIV‐1 epidemic has altered the prevalence, presentation and outcome of ALRI.The role of chest radiographs in the management of children with ALRI has had mixed reviews. Some studies suggest that radiographs help confirm the diagnosis of pneumonia in only 36% of episodes, help change the diagnosis in approximately 20% of cases and result in a change in treatment plan in 34%.^4,5 The chest radiographic features of HIV associated pneumonia in childhood have scarcely been reported. Sivit et al described the radiological features of Pneumocystis jiroveci (carinii) pneumonia in infancy (PCP) and found that a ground glass interstitial appearance with pulmonary air cysts and thoracic air leak syndromes were common.⁶ The WHO has defined radiological criteria to assist in the determination of bacterial pneumonia in their vaccine trials on streptococcal pneumonia.⁷ While several studies have described the aetiology of HIV related pneumonia in children, none have evaluated the differences in radiology and response rates to standard WHO therapy.We therefore performed a prospective nested substudy of a larger international pneumonia study⁸ to define the radiological features on admission and clinical response at day 14 of HIV‐1 infected and exposed children with WHO defined severe pneumonia treated with either oral amoxicillin or injectable penicillin.     

Decline in pneumococcal meningitis after the introduction of the heptavalent-pneumococcal conjugate vaccine in northern France

Background

The impact of the heptavalent‐pneumococcal conjugate vaccine on the incidence of pneumococcal meningitis in Europe has not yet been assessed.

Objective

To determine whether heptavalent‐pneumococcal conjugate vaccine implementation in northern France has resulted in a decrease in the incidence of pneumococcal meningitis in children.

Design

Multicentre retrospective cohort study from 2000 through 2005.

Settings

All paediatric departments of the 18 hospitals in northern France.

Patients

Patients <18 years of age, admitted for laboratory‐confirmed pneumococcal meningitis during the study period, were included.

Interventions

Data were collected from medical files and the microbiological laboratories of each hospital and compared with the regional hospital discharge codes, using a capture–recapture method.

Main outcome measures

The study assessed and compared global and age‐related incidence rates of pneumococcal meningitis in 2001 (pre‐vaccine era) and 2005.

Results

77 cases were found through the capture–recapture method. The incidence rate of pneumococcal meningitis varied from 1.65/100 000 children <18 years in 2001 to 0.80/100 000 children in 2005 (53% reduction, 95% CI 31 to 74; p = 0.08). This has so far been significant only for children <2 years of age (8.9/100 000 in 2001 to 1.8/100 000 in 2005; 82% reduction, 95% CI 52 to 95; p = 0.03).

Conclusion

A decline in pneumococcal meningitis has been observed in infants since heptavalent‐pneumococcal conjugate vaccination began in our area.In the United States, Streptococcus pneumoniae has been considered to be the principal pathogen for bacterial meningitis (47%) since Haemophilus influenzae type b vaccination became widespread during the 1990s and before the implementation of vaccination with the heptavalent‐pneumococcal conjugate vaccine (PCV7, Prevenar).¹ In Western Europe, the mean incidence rate of pneumococcal meningitis has averaged 8.7 cases/100 000 in children <2 years old with incidence rates varying from 3.8 to 14.6/100 000 between countries.² Between 2001 and 2004, the French Bacterial Meningitis Surveillance Network reported that S pneumoniae caused 42% of all cases of bacterial meningitis in children, 70% of these occurring in children <2 years old.³ The case‐fatality rate for this disease is estimated at 8–12% in children and has not dramatically changed for 20 years despite progress in diagnosis and treatment.^1,4 Sequelae occur in 20–35% of cases and include deafness, motor deficits, learning disorders linked with concentration disorders, and memory problems.^5,6PCV7, first approved in the US in 1999, targets the seven serotypes involved most frequently in the invasive pneumococcal diseases of young children.^7,8 Serotypes 6B, 9V, 14, 18C and 23F, all present in this vaccine, account for most cases of pneumococcal meningitis today.⁹ PCV7 received marketing authorisation in Europe in February 2001, was available in France in April 2001 and was recommended in March 2002 for children with a disease at high risk of invasive pneumococcal infections (immunosuppression, sickle cell disease, etc),¹⁰ and children aged 2–24 months with risk factors for pneumococcal infection (ie, children cared for more than 4 h/week with more than two other children, children with breast‐feeding duration <2 months, children with at least two siblings), criteria which covered between 79 and 89% of children <2 years of age.¹¹ The vaccination schedule uses a four‐dose regimen, at 2, 3 and 4 months of age and a booster dose during the second year of life. The impact of the PCV7 on the incidence of meningitis and other invasive pneumococcal diseases has been clearly demonstrated in North America and Australia,^{12,13,14,15,16} whose vaccination schedules are different from those in France.The aim of this study was to determine whether PCV7 implementation in a large area of northern France affected the incidence of pneumococcal meningitis in children.     

Vaccine-related pain: randomised controlled trial of two injection techniques

Objective

To compare acute pain response during immunisation in infants using a slow standard of care injection technique versus a rapid pragmatic technique.

Design

Randomised controlled trial.

Setting

Single‐centre, urban paediatric primary care practice.

Subjects

Healthy infants 4–6 months of age receiving their routine DPTaP‐Hib immunisation.

Interventions

Standard of care group: slow aspiration prior to injection, slow injection and slow withdrawal. Pragmatic group: no aspiration, rapid injection and rapid withdrawal.

Main outcome measures

Immediate infant pain measured by the Modified Behavior Pain Scale (MBPS), crying and parent/paediatrician visual analogue scale (VAS).

Results

113 infants participated; there were no observed differences in age, birth order or prior analgesic use. Mean MBPS scores (95% confidence interval (CI)) were higher (p<0.001) for the standard group compared to the pragmatic group, 5.6 (5 to 6.3) vs 3.3 (2.6 to 3.9). The standard group was more likely to cry, 47/57 (82%) vs 24/56 (43%), to cry longer, median (interquartile range (IQR)) 14.7 s (8.7–35.6) vs 0 s (0–11.30), and to take longer to have the vaccine injected, median (IQR) 8.8 s (7.9–10.3) vs 0.9 s (0.8–1.1), p<0.001 for all comparisons. The median (IQR) VAS scores by parents and paediatricians were higher for the standard group: VAS parent, 3.5 (1.6–5.5) vs 1.9 (0.1–3.1) and VAS paediatrician, 2.8 (2.0–5.1) vs 1.4 (0.2–2.4). There were no adverse events.

Conclusion

Immunisation using a pragmatic rapid injection technique is less painful than a slow standard of care technique and should be recommended for routine intramuscular immunisations.