The time of day and the interval since previous meal are associated with plasma zinc concentrations and affect estimated risk of zinc deficiency in young children in Peru and Ecuador.

BACKGROUND/OBJECTIVES: Plasma zinc concentration is the preferred biomarker of zinc status, but the time of day and time since previous meals can modify the results. Measuring fasting plasma zinc concentration is not feasible among young children, so adjustments need to be developed for interpreting results. Our objective is to develop correction factors to adjust for the effects of time of day and interval since the previous meal when measuring plasma zinc concentrations of young children. SUBJECTS/METHODS: We measured plasma zinc concentrations among young Peruvian (n =297) and Ecuadorian (n=466) children, and constructed regression models adjusting for time of day, interval since previous meal and infections. RESULTS: Plasma zinc concentrations were positively related to the number of hours since the previous meal in the Peru trial (r =0.22, P<0.0001) and negatively related to the time of day of blood sampling in both Peru (r = -0.24, P<0.0001) and Ecuador (r = -0.18, P<0.001). In multivariate models, plasma zinc concentrations were ~2 µg per 100 ml less for each hour later in the morning when blood samples were collected, in both populations, and concentrations were ~1.0 µg per 100 ml greater for every hour since previous meal consumption in Peru. The percentage of children with low plasma zinc concentrations varied according to both these factors. CONCLUSIONS: The time of day and the interval since the preceding meal should be recorded when measuring plasma zinc concentration and incorporated into the statistical analysis and interpretation when assessing population zinc status.

Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria.

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment.

The beneficial effects of weekly low-dose vitamin A supplementation on acute lower respiratory infections and diarrhea in Ecuadorian children.

BACKGROUND: Previous studies of large-dose vitamin A supplementation on respiratory morbidity have produced conflicting results in a variety of populations. The influence of malnutrition has not been examined in the majority of these trials. We hypothesized that weekly low-dose vitamin A supplementation would prevent respiratory and diarrheal disease morbidity and that malnutrition might influence the efficacy of vitamin A supplementation. METHODS: In a randomized, double-blind, placebo-controlled field trial of 400 children, 6 to 36 months of age in a high Andean urban slum, half of the children received 10 000 IU of vitamin A weekly and half received placebo for 40 weeks. Children were visited weekly at home by physicians and assessed for acute diarrheal disease and acute respiratory infections. RESULTS: Acute diarrheal disease and acute respiratory infection did not differ globally or by severity between supplement-treated and placebo groups. However, the incidence of acute lower respiratory infection (ALRI) was significantly lower in underweight (weight-for-age z score [WAZ] <-2 SD) supplement-treated children than in underweight children on placebo (8.5 vs 22.3 per 10(3) child-weeks; rate ratio: 0.38 [95% CI: 0.17-0.85]). ALRI incidence was significantly higher in normal-weight (WAZ >-2 SD) supplement-treated children than in normal-weight children on placebo (9.8 vs 4.4 per 10(3) child-weeks; rate ratio: 2.21 [95% CI: 1.24-3.93]). By logistic regression analysis the risk of ALRI was lower in underweight supplement-treated children than in underweight children on placebo (point estimate 0.148 [95% CI: 0.034-0.634]). In contrast, risk of ALRI was higher in normal-weight supplement-treated children (WAZ >-1 SD to mean) than in normal-weight children on placebo in the same WAZ stratum (point estimate: 2.51 [95% CI: 1.24-5.05]). The risk of severe diarrhea was lower in supplement-treated children 18 to 23 months of age than in children on placebo in this age group (point estimate: 0.26 [95% CI: 0.06-1.00]). CONCLUSIONS: Weekly low-dose (10 000 IU) vitamin A supplementation in a region of subclinical deficiency protected underweight children from ALRI and paradoxically increased ALRI in normal children with body weight over -1 SD. Protection from severe diarrhea was consistent with previous trials. Additional research is warranted to delineate potential beneficial and detrimental interactions between nutritional status and vitamin A supplementation regarding ALRI.

Effects of short-term zinc supplementation on cellular immunity, respiratory symptoms, and growth of malnourished Equadorian children.

OBJECTIVE: To assess the effect of zinc supplementation on respiratory tract disease, immunity and growth in malnourished children. DESIGN: A randomized double-blind placebo-controlled trial. SETTING: A day-care center in Quito, Ecuador. SUBJECTS: Fifty children (12-59 months old) recruited by height-for-age and weight-for-age deficit. INTERVENTIONS: Twenty-five children (supplemented, S group) received 10 mg/day of zinc as zinc sulfate, and 25 (nonsupplemented, NS group) received a placebo during 60 days. All were also observed during a 60-day postsupplementation period. Two children of the S group dropped out. Daily the clinical presence of cough, respiratory tract secretions, and fever, was recorded. On days 0,60 and 120, the cutaneous delayed-type hypersensitivity (DTH) to multiple antigens, and anthropometric parameters were assessed. On days 0 and 60 serum zinc levels were also measured. RESULTS: On day 60, DTH was significantly larger (20.8 +/- 7.1 vs 16.1 +/- 9.7 mm), and serum zinc levels were significantly higher (118.6 +/- 47.1 vs 83.1 +/- 24.5 micrograms/dl) in the S group than in the NS group (P <0.05 for each). The incidence of fever [relative risk (RR): 0.30, c.i. = 0.08- 0.95, P =0.02], cough (RR): 0.52, c.i. = 0.32-0.84, P = 0.004) and upper respiratory tract secretions (RR):0.72, c.i. = 0.59-0.88, P = 0.001) was lower in the S group than in the NS group at day 60. At the end of the postsupplementation observation period (day 120), the incidence of fever and upper respiratory tract secretions was the same in both the S and NS groups. The incidence of cough was higher at day 120 in the S group than in the NS group (RR): 2.28, c.i. = 1.37-3.83, P = 0.001). CONCLUSIONS: This study supports a role for zinc in immunity, and immunity to respiratory infections, while pointing out the need for larger studies.

Risk of diarrheal disease in Ecuadorian day-care centers.

To determine the risk for diarrheal disease (DD) in day-care centers (DCC) for children residing in a poor urban slum area of Quito, Ecuador, compared with that for children from the same environment but cared for in their own residential home (RH), a prospective age-, sex- and locale-controlled study of DD was conducted, including 115 children in DCC and 115 in RH, ages 12 to 42 months. The overall incidence of DD was 46/1000 child weeks. Diarrhea was more common in DCC than in RH (relative risk (RR), 1.75; 95% confidence interval (CI), 1.38 to 2.22; P < 0.001). Poor hygienic practices were more prevalent in DCC than in RH. The use of reused water for child handwashing before eating and for washing raw vegetables was associated with a higher risk of DD in DCC than in RH (RR = 4.08, CI 2.93 to 5.67, P < 0.001; RR = 3.90, CI 2.79 to 5.44, P < 0.001, respectively). These two practices were risk factors in the DCC (RR = 2.74, CI 2.08 to 3.68, P < 0.001; RR = 2.05, CI 1.55 to 2.71, P < 0.001, respectively) when compared with their absence in the same DCC. Shigella (RR = 3.58, CI 1.19 to 10.78, P < 0.02), Aeromonas (RR = 10.47, CI 1.35 to 81.05, P < 0.01), rotavirus (RR = 2.86, CI 1.87 to 4.39, P < 0.001) and Giardia (RR = 1.59, CI 1.00 to 2.59, P < 0.05) were more common in DCC than in RH. More than two-fifths of the Shigella and Aeromonas isolates were resistant to trimethoprim-sulfamethoxazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety, immunogenicity and protective effect of the SPf66 malaria synthetic vaccine against Plasmodium falciparum infection in a randomized double-blind placebo-controlled field trial in an endemic area of Ecuador.

A total of 537 subjects were randomized to receive either SPf66 malaria vaccine against Plasmodium falciparum or placebo in three doses (days 0, 30 and 180). Subjects completing the course of vaccination (230 in the vaccine and 238 in the placebo group) were followed up for a further 12 months. Case detection surveillance was implemented by parasitological cross-sectional surveys every 2 months and by monthly household visits to each participant. Symptomatic subjects were also diagnosed in a local health centre. Minor local side-effects were observed mainly after the second dose in about 19% of the vaccinated subjects and in 3.7% of the placebo group. Thirty days after the third dose the prevalence of anti-SPf66 antibodies was 57% in the vaccine and 8.8% in the placebo groups. The prevaccination prevalence of antibodies measured by indirect immunofluorescence assay increased with age and seemed to be inversely related to anti-SPf66 antibody production. Immune response to SPf66 was independent of age. Vaccine efficacy was calculated based on person-time of exposure. The protective effect considering any malaria episode was 66.8% (95% confidence interval = -2.7-89.3%) and considering only one episode per individual was 60.2% (95% confidence interval = -26-87.5%).