The added benefit of zinc supplementation after zinc treatment of acute childhood diarrhoea: a randomized,double‐blind field trial

Objectives To determine whether continuing with zinc supplementation after zinc treatment (ZT) of an acute diarrhoea episode will result in additional clinical benefits beyond ZT alone. Methods Children 6–23 months of age, living in an urban slum in Dhaka, Bangladesh with acute childhood diarrhoea (ACD), were enrolled in a randomized, double‐blind field trial. All children received 10 days of ZT (20 mg/day) and were then randomized to zinc (10 mg/day) or placebo supplementation for 3 months. Weekly follow‐up of all children occurred over a period of 9 months. Results A total of 353 subjects were enrolled, with 93% of the zinc supplemented and 96% of the placebo children followed for 9 months. The incidence density of ACD among those receiving zinc supplementation compared to those receiving placebo was reduced by 28% (2.64 vs.3.66 episodes/p‐y follow‐up) over the 3 months while on supplementation and by 21% (2.05 vs.2.59 episodes/p‐y follow‐up) over the 9 months of follow‐up. There was no observed effect on the incidence of acute respiratory infections (ARIs) or on growth. Conclusions Zinc supplementation after treatment provides additional preventive ACD benefits to children in early childhood. Larger, effectiveness trials of this strategy are warranted.     

Incidence of pneumonia,bacteremia, and invasive pneumococcal disease in Pakistani children

Objective To determine the incidence of pneumonia, bacteremia, and invasive pneumococcal disease (IPD) in Pakistani children <5 years old. Methods Household surveillance from 1st February 2007 to 12th May 2008 was conducted in two low‐income, coastal communities of Karachi. Community health workers referred each sick child <5 years old to the local clinic. Blood culture was obtained whenever possible from children meeting inclusion criteria. Results Overall, 5570 children contributed 3949 observation years. There were 1039 clinical cases of pneumonia, of which 54 were severe pneumonia and four cases of very severe disease according to WHO criteria. The overall pneumonia incidence was 0.26 (95% CI: 0.25–0.28) episodes per child‐year. A pathogen was isolated from the blood of 29 (2.8%) pneumonia cases. Bacteremia incidence was 912 (95% CI: 648–1248) episodes per 100 000 child‐years with a case fatality rate of 8%. The detected IPD incidence was 25 (95% CI: 1–125) episodes per 100 000 child‐years. The under‐five mortality rate was 55 per 1000 live births, with pneumonia causing 12 (22%) deaths among children <5 years old. Conclusion Clinical pneumonia is common in Pakistani children, with one in four deaths attributable to the disease. Bacteremia occurs at a high rate but surveillance for pneumococcus underestimates the burden of IPD.     

Vitamin D levels in IBD: a randomised trial of weight-based versus fixed dose vitamin D supplementation

Abstract

Objectives: Body weight is one of the factors affecting blood levels of 25-hydroxyvitamin D (25OHD). The aim of this study was to establish whether a vitamin D (vitD) weight-based dosing is more appropriate to a fixed daily dose in patients with inflammatory bowel disease (IBD).

Materials/methods: This was an open label randomised trial. Patients with IBD were assigned to receive oral cholecalciferol at a dose of 28?IU/kg (IU/kg) or 2000?IU per day (IU/day) for 12?weeks during winter months. 25OHD plasma levels and other biochemical parameters were measured at baseline and after supplementation period. The primary outcome measure was 25OHD level after a follow-up period.

Results: A total of 173 patients were analysed. The mean BMI was 25.5?±?5.1 and initial mean 25OHD level was 62.7?±?25.5?nmol/l. A similar increase (9.7?±?26.9 vs 9.8?±?26.7?nmol/l) in 25OHD levels occurred both in IU/kg and IU/day group. The proportion of subjects with normal and sub-normal levels following the substitution was comparable irrespective of body weight. The change in 25OHD level correlated positively only with the dose of vitD (p?<?.001) and negatively with the baseline 25OHD level (p?<?.001). A sustained 25OHD level of 75?nmol/l corresponds with a calculated daily vitD dose of 2034?IU.

Conclusions: Weight-based dosing of vitamin D is not superior to a fixed dose in order to maintain stable 25OHD levels in IBD patients. Cholecalciferol dose of 2,000?IU/day is safe and sufficient during winter period.     

Supplementation of 1,25 dihydroxy vitamin D3 in patients with treatment naive early rheumatoid arthritis: a randomised controlled trial

Aim: 1,25 dihydroxy vitamin D3 has immunomodulatory functions in rheumatoid arthritis (RA) and is an anti‐osteoporotic agent. No studies exist to assess its pain‐relieving action in RA. Methods: An open‐labeled randomized trial comparing triple disease‐modifying anti‐rheumatic drug (DMARD) therapy and 500 IU 1,25 dihydroxy vitamin D3 + calcium combination versus triple DMARD and calcium alone was conducted. The primary outcome was the time to pain relief by patients’ visual analogue scale (VAS). Changes in VAS after first achievement of pain relief and after 3 months were noted. 25 hydroxy‐vitamin D levels were correlated with disease activity scor (DAS‐28), adjusting for sun exposure. Comparisons between the groups were done by Mann–Whitney test and independent samples test. Results: Patients on the vitamin D group (n = 59) had higher pain relief than the control group (n = 62) (50%vs. 30%, P = 0.006). There was no significant difference in the time taken for initial pain relief between the two groups. Occurrence of hypovitaminosis D in RA patients (68.1%) is comparable to published normal Indian prevalence. There was no correlation between 25 hydroxy vitamin D levels and disease activity. Conclusions: Supplementation of 500 IU of 1,25 dihydroxy vitamin D3 daily to previously DMARD‐naïve patients with early RA along with triple DMARD therapy results in a significantly higher pain relief at the end of 3 months. The number needed to treat for this additional pain relief was 5. The prevalence of vitamin D deficiency in the study population was 68.1%.     

Mortality of HIV‐infected and uninfected children in a longitudinal cohort in rural south‐west Uganda during 8 years of follow‐up

Objectives To determine the impact of HIV on child mortality and explore potential risk factors for mortality among HIV‐infected and HIV‐exposed uninfected children in a longitudinal cohort in rural Uganda. Methods From July 2002 to March 2010, HIV‐infected and HIV‐exposed uninfected children aged 6 weeks–13 years were enrolled in an open population‐based clinical cohort. Antiretroviral therapy (ART) was introduced in 2005. Clinical and laboratory data were collected every 3 months. Person‐years at risk were calculated from time of enrolment until earliest date of ART initiation, death or last visit. Cox regression was used to estimate hazard ratios (HR) for mortality. Results Eighty‐nine (30.2%) HIV‐infected and 206 (69.8%) HIV‐exposed but uninfected children were enrolled. Twenty‐one children died. The mortality rate was six times higher in ART‐naive HIV‐infected children than in HIV‐exposed but uninfected children (HR = 6.4, 95% CI = 2.4–16.6). Among HIV‐infected children, mortality was highest in those aged <2 years. Decreasing weight‐for‐age Z (WAZ) score was the strongest risk factor for mortality among HIV‐infected children (HR for unit decrease in WAZ = 2.6, 95% CI = 1.6–4.1). Thirty‐five children (aged 7 months–15.6 years; median, 5.4 years) started ART. Conclusions Mortality among HIV‐infected children was highest among those aged <2 years. Intensified efforts to prevent mother‐to‐child transmission of HIV and ensure early HIV diagnosis and treatment are required to decrease child mortality caused by HIV in rural Africa.     

Long‐term effects of malaria prevention with insecticide‐treated mosquito nets on morbidity and mortality in African children: randomised controlled trial

Objective The objective is to investigate the effect of malaria control with insecticide‐treated mosquito nets (ITNs) regarding possible higher mortality in children protected during early infancy, due to interference with immunity development, and to assess long‐term effects on malaria prevalence and morbidity. Methods Between 2000 and 2002, a birth cohort was enrolled in 41 villages of a malaria holoendemic area in north‐western Burkina Faso. All neonates (n = 3387) were individually randomised to ITN protection from birth (group A) vs. ITN protection from age 6 months (group B). Primary outcome was all‐cause mortality. In 2009, a survey took place in six sentinel villages, and in 2010, a census was conducted in all study villages. Results After a median follow‐up time of 8.3 years, 443/3387 (13.1%) children had migrated out of the area and 484/2944 (16.4%) had died, mostly at home. Long‐term compliance with ITN protection was good. There were no differences in mortality between study groups (248 deaths in group A, 236 deaths in group B; rate ratio 1.05, 95% CI: 0.889–1.237, P = 0.574). The survey conducted briefly after the rainy season in 2009 showed that more than 80% of study children carried asexual malaria parasites and up to 20% had clinical malaria. Conclusion Insecticide‐treated mosquito net protection in early infancy is not a risk factor for mortality. Individual ITN protection does not sufficiently reduce malaria prevalence in high‐transmission areas. Achieving universal ITN coverage remains a major challenge for malaria prevention in Africa.     

Growth response to antiretroviral treatment in HIV‐infected children: a cohort study from Lilongwe,Malawi

Objective Malnutrition is common in HIV‐infected children in Africa and an indication for antiretroviral treatment (ART). We examined anthropometric status and response to ART in children treated at a large public‐sector clinic in Malawi. Methods All children aged <15 years who started ART between January 2001 and December 2006 were included and followed until March 2008. Weight and height were measured at regular intervals from 1 year before to 2 years after the start of ART. Sex‐ and age‐standardized z‐scores were calculated for weight‐for‐age (WAZ) and height‐for‐age (HAZ). Predictors of growth were identified in multivariable mixed‐effect models. Results A total of 497 children started ART and were followed for 972 person‐years. Median age (interquartile range; IQR) was 8 years (4–11 years). Most children were underweight (52% of children), stunted (69%), in advanced clinical stages (94% in WHO stages 3 or 4) and had severe immunodeficiency (77%). After starting ART, median (IQR) WAZ and HAZ increased from ?2.1 (?2.7 to ?1.3) and ?2.6 (?3.6 to ?1.8) to ?1.4 (?2.1 to ?0.8) and ?1.8 (?2.4 to ?1.1) at 24 months, respectively (P < 0.001). In multivariable models, baseline WAZ and HAZ scores were the most important determinants of growth trajectories on ART. Conclusions Despite a sustained growth response to ART among children remaining on therapy, normal values were not reached. Interventions leading to earlier HIV diagnosis and initiation of treatment could improve growth response.