Safety and efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Zambian children

<p>Abstract</p> <p>Background</p> <p>Malaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL) that has proved to be highly efficacious against multidrug resistant <it>Plasmodium falciparum</it>.</p> <p>Objective</p> <p>The study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP) had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated <it>P. falciparum </it>malaria in Ndola, Zambia.</p> <p>Methods</p> <p>Between 2005 and 2006, 304 children (6-59 months old) with uncomplicated <it>P. falciparum </it>were enrolled, randomized to AL (101) or DHA/PQP (203) and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF), late clinical failure (LCF, late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR). Recurrent infections were genotyped to distinguish between recrudescence and new infection.</p> <p>Results</p> <p>No ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p < 0.001). Most failure were new infections and PCR-corrected ACPR was similar in the two study arms (OR: 0.69; 95%CI: 0.22-2.26; p = 0.33). Similar results were observed for day 42, i.e. higher PCR-uncorrected ACPR for DHA/PQP, mainly due to the difference observed up to day 28, while the PCR-corrected ACPR was similar: DHA/PQP: 93% (179/192), AL: 93% (84/90), (OR: 0.92; 95%CI: 0.30-2.64; p = 0.85). Except for cough, more frequent in the DHA/PQP arm (p = 0.04), there were no differences between treatment arms in the occurrence of adverse events. Two serious adverse events were probably associated to AL treatment.</p> <p>Conclusion</p> <p>DHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia.</p> <p>Trial Registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN16263443">ISRCTN16263443</a>, at <url>http://www.controlled-trials.com/isrctn</url></p

Complementary feeding: a Global Network cluster randomized controlled trial

Background: Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated. Methods/Design: A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women\u27s and Children\u27s Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry, dietary variety and diversity scores, biomarkers of iron, zinc and Vitamin B(12) status (18 months), neurocognitive development (12 and 18 months), and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial. Discussion: Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale for global efforts to enhance local supplies of meat as a complementary food for young children

Obesity indicators and cardiometabolic status in 4-y-old children1–3

Background: In adults and adolescents, obesity is positively associated with cardiovascular disease risk factors; however, evidence in preschool children is scarce. Objective: The objective was to assess the relations between obesity indicators and cardiometabolic risk factors in 324 Chilean children 4 y of age. Design: We collected anthropometric measurements and calculated general indicators of obesity [weight, body mass index (BMI), sum of 4 skinfold thicknesses, percentage fat, and body fat index] and central obesity (waist circumference, waist-to-hip ratio, waist-toheight ratio, and truncal fatness based on skinfold thickness). We measured blood sample concentrations of C-reactive protein, interleukin- 6, homeostasis model assessment of insulin resistance, triglycerides, and total, LDL, and HDL cholesterol. We used correlation and multiple linear regression analyses. Results: The prevalence of obesity (BMI-for-age z score .2, World Health Organization 2006), central obesity ( 90th percentile, third National Health and Nutrition Examination Survey), and lipid disorders was high (13%, 11%, and 20%, respectively), and 70% of the children had at least one cardiometabolic risk factor. Most correlations between obesity and central obesity indicators were moderate to strong (0.40 , r , 0.96). Obesity was positively but weakly associated with C-reactive protein in both sexes and with homeostasis model assessment of insulin resistance only in girls (all r , 0.3, P , 0.05). Obesity indicators were unrelated to interleukin-6 and lipid concentrations (P . 0.05). Overall, obesity indicators explained, at most, 8% of the variability in cardiometabolic risk factors. Conclusions: Obesity and central obesity were common, and most of the children had at least one cardiometabolic risk factor, particularly lipid disorders. Obesity and central obesity indicators were highly intercorrelated and, overall, were weakly related to cardiometabolic status. At this age, body mass index and waist circumference were poor predictors of cardiometabolic status.Supported by the Ellison Medical Foundation/International Nutrition Foundation and the Chilean National Science and Technology Fund (Fondecyt) project no. 1060785

Unhealthy Snack Food and Beverage Consumption Is Associated with Lower Dietary Adequacy and Length-for-Age z-Scores among 12-23-Month-Olds in Kathmandu Valley, Nepal.

BACKGROUND: Consumption of unhealthy snack foods and beverages (USFBs) in low- and middle-income countries (LMICs) is rising, with global awareness increasing about risks of overnutrition. However, little is known about the relation between USFB consumption and young children's diet/nutritional outcomes in contexts where nutrient density of complementary foods is often low. OBJECTIVES: This study assessed the association of high USFB consumption, compared with low consumption, with nutrient intakes, dietary adequacy, iron status, and growth in young children in Kathmandu Valley, Nepal. METHODS: A cross-sectional survey was conducted in a representative sample of 745 primary caregivers of children aged 12-23 mo. Food consumption was measured through quantitative 24-h recalls, and child anthropometric measurements and capillary blood samples were collected. Using adjusted linear/logistic regression models, nutrient intakes, dietary adequacy, length-for-age and weight-for-length z-scores (LAZ and WLZ, respectively), and iron status were compared between lowest and highest tertiles of consumption based on the contribution of USFBs to total energy intakes (TEIs). Mediation of the relation between USFB consumption and LAZ via lowered dietary adequacy was explored using structural equations modeling. RESULTS: On average, USFBs contributed 46.9% of TEI among the highest tertile of consumers, compared with 5.2% of TEI among the lowest. Compared with low-USFB consumers, high-USFB consumers had lower nutrient intakes and a greater proportion were at risk of inadequate intakes for 8 nutrients. Mean LAZ was nearly 0.3 SD lower among high-USFB consumers than low consumers (P = 0.003), with this relationship partially mediated through dietary adequacy. No associations were found with stunting prevalence or iron status. Prevalence of overweight/obesity was low. CONCLUSIONS: In this LMIC context, high USFB consumption among young children was associated with inadequate micronutrient intakes, which can contribute to poor growth outcomes. Addressing increased availability of USFBs in LMIC food systems should be a priority for policies and programs aiming to safeguard child nutrition

Obesity and the food system transformation in Latin America

The Latin America and the Caribbean (LAC) region faces a major diet-related health problem accompanied by enormous economic and social costs. The shifts in diet are profound: major shifts in intake of less-healthful low-nutrient-density foods and sugary beverages, changes in away-from-home eating and snacking and rapid shifts towards very high levels of overweight and obesity among all ages along with, in some countries, high burdens of stunting. Diet changes have occurred in parallel to, and in two-way causality with, changes in the broad food system – the set of supply chains from farms, through midstream segments of processing, wholesale and logistics, to downstream segments of retail and food service (restaurants and fast food chains). An essential contribution of this piece is to marry and integrate the nutrition transition literature with the literature on the economics of food system transformation. These two literatures and debates have been to date largely ‘two ships passing in the night’. This review documents in-depth the recent history of rapid growth and transformation of that broad food system in LAC, with the rapid rise of supermarkets, large processors, fast food chains and food logistics firms. The transformation is the story of a ‘double-edged sword’, showing its links to various negative diet side trends, e.g. the rise of consumption of fast food and highly processed food, as well as in parallel, to various positive trends, e.g. the reduction of the cost of food, de-seasonalization, increase of convenience of food preparation reducing women's time associated with that and increase of availability of some nutritious foods like meat and dairy. We view the transformation of the food system, as well as certain aspects of diet change linked to long-run changes in employment and demographics (e.g. the quest for convenience), as broad parameters that will endure for the next decades without truly major regulatory and fiscal changes. We then focus in on what are the steps that are being and can be taken to curb the negative effects on diet of these changes. We show that countries in LAC are already among the global leaders in initiating demand-related solutions via taxation and marketing controls. But we also show that this is only a small step forward. To shift LAC's food supply towards prices that incentivize consumption of healthier diets and demand away from the less healthy component is not simple and will not happen immediately. We must be cognizant that ultimately, food industry firms must be incentivized to market the components of healthy diets. This will primarily need to be via selective taxes and subsidies, marketing controls, as well as food quality regulations, consumer education and, in the medium term, consumers' desires to combine healthier foods with their ongoing quest for convenience in the face of busy lives. In the end, the food industry in LAC will orient itself towards profitable solutions, ie those demanded by the broad mass of consumers

Child-centered food systems: reorienting food systems towards healthy diets for children

Current food systems are failing to guide children towards healthy diets. This paper presents a tool to identify the actions needed to reorient food systems to become more child-centred from a nutrition perspective. To connect the dots between children's lives, their food environments and food supply systems, the tool takes a child-centred, food systems approach. Comprising six methodological steps, the tool starts by measuring and understanding children's realities and then working back up into the system to identify how food environments and supply systems could make relevant foods more or less available, affordable, appealing and aspirational in the contexts of children's lives. The paper spells out the mix of methods needed to make this assessment, gives examples of the data and studies already available and type of insights they provide, and discusses the methodological challenges and gaps. It presents a worked example that shows how following these steps in sequence enables the identification of a package of actions that can act coherently to reorient food systems in the way most likely to have impact on child malnutrition