Immune Response to SARS-CoV-2 Infection in Obesity and T2D: Literature Review.

In December 2019, a novel coronavirus known as SARS-CoV-2 was first detected in Wuhan, China, causing outbreaks of the coronavirus disease COVID-19 that has now spread globally. For this reason, The World Health Organization (WHO) declared COVID-19 a public health emergency in March 2020. People living with pre-existing conditions such as obesity, cardiovascular diseases, type 2 diabetes (T2D), and chronic kidney and lung diseases, are prone to develop severe forms of disease with fatal outcomes. Metabolic diseases such as obesity and T2D alter the balance of innate and adaptive responses. Both diseases share common features characterized by augmented adiposity associated with a chronic systemic low-grade inflammation, senescence, immunoglobulin glycation, and abnormalities in the number and function of adaptive immune cells. In obese and T2D patients infected by SARS-CoV-2, where immune cells are already hampered, this response appears to be stronger. In this review, we describe the abnormalities of the immune system, and summarize clinical findings of COVID-19 patients with pre-existing conditions such as obesity and T2D as this group is at greater risk of suffering severe and fatal clinical outcomes.

Effects of Data Aggregation on Time Series Analysis of Seasonal Infections.

Time series analysis in epidemiological studies is typically conducted on aggregated counts, although data tend to be collected at finer temporal resolutions. The decision to aggregate data is rarely discussed in epidemiological literature although it has been shown to impact model results. We present a critical thinking process for making decisions about data aggregation in time series analysis of seasonal infections. We systematically build a harmonic regression model to characterize peak timing and amplitude of three respiratory and enteric infections that have different seasonal patterns and incidence. We show that irregularities introduced when aggregating data must be controlled during modeling to prevent erroneous results. Aggregation irregularities had a minimal impact on the estimates of trend, amplitude, and peak timing for daily and weekly data regardless of the disease. However, estimates of peak timing of the more common infections changed by as much as 2.5 months when controlling for monthly data irregularities. Building a systematic model that controls for data irregularities is essential to accurately characterize temporal patterns of infections. With the urgent need to characterize temporal patterns of novel infections, such as COVID-19, this tutorial is timely and highly valuable for experts in many disciplines.

Household Costs Associated with Hospitalization of Children with Severe Pneumonia in Quito, Ecuador.

Pneumonia remains a leading cause of morbidity and mortality in young children. The total cost of pneumonia-related hospitalization, including household-level cost, is poorly understood. To better understand this burden in an urban setting in South America, we incorporated a cost study into a trial assessing zinc supplements in treatment of severe pneumonia among children aged 2-59 months at a public hospital in Quito, Ecuador, which provides such treatment at no charge. Data were collected from children's caregivers at hospitalization and discharge on out-of-pocket payments for medical and nonmedical items, and on employment and lost work time. Analyses encompassed three categories: direct medical costs, direct nonmedical costs, and indirect costs, which covered foregone wages (from caregivers' self-reported lost earnings) and opportunity cost of caregivers' lost time (based on the unskilled labor wage in Ecuador). Caregivers of 153 children completed all questionnaires. Overall, 57% of children were aged less than 12 months, and 46% were female. Just over 50% of mothers and fathers had completed middle school. Most reported direct costs, which averaged $33. Most also reported indirect costs, the mean of which was $74. Fifty-seven reported lost earnings (mean = $79); 29 reported lost time (estimated mean cost = $37). Stratified analyses revealed similar costs for children < 12 months and ≥ 12 months, with variations for specific items. Costs for hospital-based treatment of severe pneumonia in young children represent a major burden for households in low- to middle-income settings, even when such treatment is intended to be provided at no cost.

Air pollution control and the occurrence of acute respiratory illness in school children of Quito, Ecuador.

Because of air quality management and control, traffic-related air pollution has declined in Quito, Ecuador. We evaluated the effect of a city-wide 5-year air pollution control program on the occurrence of acute respiratory illness (ARI). We compared two studies conducted at the same location in Quito: in 2000, 2 years before the policy to control vehicle emission was introduced, and in 2007. Each study involved ~ 730 children aged 6-12 years, observed for 15 weeks. We examined associations between carboxyhemoglobin (COHb) serum concentration-an exposure proxy for carbon monoxide (CO)-ambient CO, and ARI in both cohorts. In 2007, we found a 48% reduction in the ARI incidence (RR 0.52; 95% CI 0.45-0.62, p < 0.0001), and 92% decrease in the percentage of children with COHb > 2.5% as compared to the 2000 study. We found no association between COHb concentrations above the safe level of 2.5% and the ARI incidence (p = 0.736). The decline in air pollution due to vehicle emissions control was associated with a lower incidence of respiratory illness in school children.

Vitamin D status is associated with underweight and stunting in children aged 6-36 months residing in the Ecuadorian Andes.

OBJECTIVE: There is limited knowledge on vitamin D status of children residing in the Andes and its association with undernutrition. We evaluated the vitamin D status of children residing in a low socio-economic status (SES) setting in the Ecuadorian Andes and assessed the association between vitamin D status, stunting and underweight. We hypothesized that children who were underweight would have lower serum 25-hydroxyvitamin D (25(OH)D) levels and lower 25(OH)D levels would be associated with a higher risk of stunting. DESIGN: We conducted a cross-sectional secondary analysis of a randomized controlled trial, the Vitamin A, Zinc and Pneumonia study. Children had serum 25(OH)D concentrations measured. A sensitivity analysis was undertaken to determine a vitamin D cut-off specific for our endpoints. Associations between serum 25(OH)D and underweight (defined as weight-for-age Z-score≤-1) and stunting (defined as height-for-age Z-score≤-2) were assessed using multivariate logistic regression. SETTING: Children residing in five low-SES peri-urban neighbourhoods near Quito, Ecuador. SUBJECTS: Children (n 516) aged 6-36 months. RESULTS: Mean serum 25(OH)D concentration was 58·0 (sd 17·7) nmol/l. Sensitivity analysis revealed an undernutrition-specific 25(OH)D cut-off of <42·5 nmol/l; 18·6 % of children had serum 25(OH)D<42·5 nmol/l. Children who were underweight were more likely to have serum 25(OH)D<42·5 nmol/l (adjusted OR (aOR)=2·0; 95 % CI 1·2, 3·3). Children with low serum 25(OH)D levels were more likely to be stunted (aOR=2·8; 95 % CI 1·6, 4·7). CONCLUSIONS: Low serum 25(OH)D levels were more common in underweight and stunted Ecuadorian children.

Etiology of severe pneumonia in Ecuadorian children.

BACKGROUND: In Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador. METHODS: This observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2-59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction. Risk factors for specific respiratory pathogens were also evaluated. RESULTS: Among 406 children tested, 159 (39.2%) had respiratory syncytial virus (RSV), 71 (17.5%) had human metapneumovirus (hMPV), and 62 (15.3%) had adenovirus. Streptococcus pneumoniae was identified in 37 (9.2%) samples and Mycoplasma pneumoniae in three (0.74%) samples. The yearly circulation pattern of RSV (P = 0.0003) overlapped with S. pneumoniae, (P = 0.03) with most cases occurring in the rainy season. In multivariable analysis, risk factors for RSV included younger age (adjusted odds ratio [aOR] = 1.9, P = 0.01) and being underweight (aOR = 1.8, P = 0.04). Maternal education (aOR = 0.82, P = 0.003), pulse oximetry (aOR = 0.93, P = 0.005), and rales (aOR = 0.25, P = 0.007) were associated with influenza A. Younger age (aOR = 3.5, P = 0.007) and elevated baseline respiratory rate were associated with HPIV-3 infection (aOR = 0.94, P = 0.03). CONCLUSION: These results indicate the importance of RSV and influenza, and potentially modifiable risk factors including undernutrition and future use of a RSV vaccine, when an effective vaccine becomes available. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00513929.

Study on inflammation-related genes and microRNAs, with special emphasis on the vascular repair factor HGF and miR-574-3p, in monocytes and serum of patients with T2D.

BACKGROUND: Recently, we reported signs of inflammation (raised IL-8, reduced miR-146a) and signs of vascular repair (raised HGF) in the serum of Ecuadorian patients with type 2 diabetes (T2D). In contrast, we found that the circulating monocytes lacked up-regulation of classical inflammatory genes (IL-1B, IL-6, and TNF) and there was even significant down-regulation of PTGS2. Notably, genes and a microRNA involved in adhesion, cell differentiation and morphology (CD9, DHRS3, PTPN7 and miR-34c-5p) were up-regulated in the T2D monocytes, suggesting a role of the anti-inflammatory cells in adhesion, vascular repair and invasion. AIM: To determine the gene expression of the vascular repair factor HGF in the circulating monocytes of patients with T2D and to investigate the relationship between HGF and the expression of the other previously tested monocyte genes and the contribution to the raised serum level of HGF. In addition, we tested the level of 6 microRNAs, which were previously found abnormal in the circulating monocytes, in the serum of the patients. METHODS: A gene and microRNA expression study in monocytes and serum of 64 Ecuadorian patients with T2D (37-85 years) and 44 non-diabetic controls (32-87 years). RESULTS: The gene expression of HGF was significantly raised in the monocytes of the patients with T2D and associated with the expression of genes involved in adhesion, cell differentiation and morphology. HGF gene expression did not correlate with the serum level of HGF. The monocyte expression of pro-inflammatory cytokine genes was also not associated with the serum levels of these cytokines. The level of miR-574-3p was significantly decreased in the serum of the patients with T2D, and correlated in expression with the decreased well-established inflammation-regulating miR-146a. The level of the microRNAs in serum did not correlate with their expression level in monocytes. CONCLUSION: In circulating monocytes of Ecuadorian T2D patients, the microRNA and gene expression of important inflammatory/chemotactic/motility/vascular repair factors differs from the expression in serum. While monocytes show a gene expression profile compatible with an anti-inflammatory state, serum shows a molecular profile compatible with an inflammatory state. Both compartments show molecular signs of vascular repair support, i.e. up-regulated HGF levels.

Type 2 Diabetes Monocyte MicroRNA and mRNA Expression: Dyslipidemia Associates with Increased Differentiation-Related Genes but Not Inflammatory Activation.

OBJECTIVE: To study the expression pattern of microRNAs and mRNAs related to inflammation in T2D monocytes. DESIGN: A microRNA finding study on monocytes of T2D patients and controls using array profiling was followed by a quantitative Real Time PCR (qPCR) study on monocytes of an Ecuadorian validation cohort testing the top over/under-expressed microRNAs. In addition, monocytes of the validation cohort were tested for 24 inflammation-related mRNAs and 2 microRNAs previously found deregulated in (auto)-inflammatory monocytes. RESULTS: In the finding study, 142 significantly differentially expressed microRNAs were identified, 15 having the strongest power to discriminate T2D patients from controls (sensitivity 66%, specificity 90%). However, differences in expression of these microRNAs between patients and controls were small. On the basis of >1.4 or <0.6-fold change expression 5 microRNAs were selected for further validation. One microRNA (miR-34c-5p) was validated as significantly over-expressed in T2D monocytes. In addition, we found over expression of 3 mRNAs (CD9, DHRS3 and PTPN7) in the validation cohort. These mRNAs are important for cell morphology, adhesion, shape change, and cell differentiation. Classical inflammatory genes (e.g. TNFAIP3) were only over-expressed in monocytes of patients with normal serum lipids. Remarkably, in dyslipidemia, there was a reduction in the expression of inflammatory genes (e.g. ATF3, DUSP2 and PTGS2). CONCLUSIONS: The expression profile of microRNAs/mRNAs in monocytes of T2D patients indicates an altered adhesion, differentiation, and shape change potential. Monocyte inflammatory activation was only found in patients with normal serum lipids. Abnormal lipid values coincided with a reduced monocyte inflammatory state.

Decreased serum level of miR-146a as sign of chronic inflammation in type 2 diabetic patients.

BACKGROUND: There is increasing evidence that chronic inflammation is an important determinant in insulin resistance and in the pathogenesis of type 2 diabetes (T2D). MicroRNAs constitute a newly discovered system of cell regulation and in particular two microRNAs (miR-146a and miR-155) have been described as regulators and biomarkers of inflammation. AIM: To determine a putative association between the levels of miR-146a and miR-155 in serum of T2D patients, clinical parameters and serological indicators of inflammation. METHODS: We performed quantitative Real Time PCR (qPCR) of microRNAs from serum (56 Ecuadorian T2D ambulatory patients and 40 non-diabetic controls). In addition, we evaluated T2D-related serum cytokines.chemokines and growth factors using a commercially available multi-analyte cytometric bead array system. We correlated outcomes to clinical parameters, including BMI, HbA1c and lipid state. RESULTS: The Ecuadorian non-diabetic controls appeared as overweight (BMI>25: patients 85%, controls 82.5%) and as dyslipidemic (hypercholesterolemia: patients 60.7%, controls 67.5%) as the patients. The serum levels of miR-146a were significantly reduced in T2D patients as compared to these non-diabetic, but obese/dyslipidemic control group (mean patients 0.61, mean controls set at 1; p = 0.042), those of miR-155 were normal.The serum levels of both microRNAs correlated to each other (r = 0.478; p<0.001) and to leptin levels. The microRNAs did not correlate to BMI, glycemia and dyslipidemia.From the tested cytokines, chemokines and growth factors, we found IL-8 and HGF significantly raised in T2D patients versus non-diabetic controls (p = 0.011 and 0.023 respectively). CONCLUSIONS: This study shows decreased serum anti-inflammatory miR-146a, increased pro-inflammatory IL-8 and increased HGF (a vascular/insular repair factor) as discriminating markers of failure of glucose control occurring on the background of obesity and dyslipidemia.

Zinc as an adjunct to the treatment of severe pneumonia in Ecuadorian children: a randomized controlled trial.

BACKGROUND: Studies of zinc as an adjunct to treatment of severe pneumonia in children have shown mixed results, possibly because of poor information on zinc status and respiratory pathogens. OBJECTIVE: We evaluated the effect of zinc given with standard antimicrobial treatment on the duration of respiratory signs in children with severe pneumonia. Zinc status and pathogens were assessed. DESIGN: Children aged 2-59 mo with severe pneumonia who were admitted to the main children's hospital in Quito, Ecuador, were given standard antibiotics and randomly allocated to receive zinc supplements twice daily or a placebo. Measurements included anthropometric variables, breastfeeding, hemoglobin, plasma zinc, and common bacteria/viral respiratory pathogens. The primary outcome was time to resolution of respiratory signs. The secondary outcome was treatment failure. RESULTS: We enrolled 225 children in each group. There was no difference between groups in time to resolution of respiratory signs or treatment failure; pathogens were not associated with outcomes. Tachypnea and hypoxemia resolved faster in older children (P = 0.0001) than in younger ones. Higher basal zinc concentration (P = 0.011) and better height-for-age z score (HAZ) (P = 0.044) were associated with faster resolution of chest indrawing. Better weight-for-height z score (WHZ) (P = 0.031) and HAZ (P = 0.048) were associated with faster resolution of tachypnea. Increased C-reactive protein was associated with a longer duration of tachypnea (P = 0.044). CONCLUSIONS: Zinc did not affect time to pneumonia resolution or treatment failure, nor did type of respiratory pathogens affect outcomes. Higher basal zinc and better HAZ and WHZ were associated with reduced time to resolution of respiratory signs. These results suggest the need for prevention of chronic zinc deficiency and improvement of general nutritional status among Ecuadorian children.

Air pollution and anemia as risk factors for pneumonia in Ecuadorian children: a retrospective cohort analysis.

BACKGROUND: Ambient air pollution and malnutrition, particularly anemia, are risk factors for pneumonia, a leading cause of death in children under five. We simultaneously assessed these risk factors in Quito, Ecuador. METHODS: In 2005, we studied two socioeconomically similar neighborhoods in Quito: Lucha de los Pobres (LP) and Jaime Roldos (JR). LP had relatively high levels of air pollution (annual median PM2.5 = 20.4 µg/m3; NO2 = 29.5 µg/m3) compared to JR (annual median PM2.5 = 15.3 µg/m3; NO2 = 16.6 µg/m3). We enrolled 408 children from LP (more polluted) and 413 children from JR (less polluted). All subjects were aged 18-42 months. We obtained medical histories of prior physician visits and hospitalizations during the previous year, anthropometric nutrition data, hemoglobin levels, and hemoglobin oxygen saturation via oximetry. RESULTS: In anemic children, higher pollution exposure was significantly associated with pneumonia hospitalization (OR = 6.82, 95%CI = 1.45-32.00; P = 0.015). In non-anemic children, no difference in hospitalizations by pollution exposure status was detected (OR = 1.04, NS). Children exposed to higher levels of air pollution had more pneumonia hospitalizations (OR = 3.68, 1.09-12.44; P = 0.036), total respiratory illness (OR = 2.93, 95% CI 1.92-4.47; P < 0.001), stunting (OR = 1.88, 1.36-2.60; P < 0.001) and anemia (OR = 1.45, 1.09-1.93; P = 0.013) compared to children exposed to lower levels of air pollution. Also, children exposed to higher levels of air pollution had significantly lower oxygen saturation (92.2% ± 2.6% vs. 95.8% ± 2.2%; P < 0.0001), consistent with air pollution related dyshemoglobinemia. CONCLUSIONS: Ambient air pollution is associated with rates of hospitalization for pneumonia and with physician's consultations for acute respiratory infections. Anemia may interact with air pollution to increase pneumonia hospitalizations. If confirmed in larger studies, improving nutrition-related anemia, as well as decreasing the levels of air pollution in Quito, may reduce pneumonia incidence.

Metabolic syndrome in the elderly living in marginal peri-urban communities in Quito, Ecuador.

OBJECTIVE: The proportion of the Latin American population aged >60 years is expected to double during the next few decades. Metabolic syndrome (MetS) is associated with high morbidity and mortality worldwide. However, little is known about MetS in Latin America in general, and in Ecuador in particular. The present study aimed to examine the prevalence of MetS and its association with blood micronutrient, homocysteine (Hcy) and C-reactive protein (CRP) concentrations in the elderly living in a low-income urban area. DESIGN: We performed a cross-sectional study. MetS, using the International Diabetes Federation definition, dietary intake and plasma micronutrient, CRP and Hcy concentrations were assessed. SUBJECTS: A total of 352 elderly (≥65 years) Ecuadorians. SETTING: Quito, Ecuador. RESULTS: MetS was prevalent (40%)--considerably more so among women (81%) than men (19%; χ² = 32·6, P < 0·0001). Further, 53 % of those without MetS exhibited two or more of its components. Micronutrient deficiencies were prevalent, including those of vitamin C, zinc, vitamin B12 and folate. Vitamin C and E concentrations were inversely (OR = 0·78, 95% CI 0·71, 0·86; OR = 0·16, 95% CI 0·03, 0·81, respectively) and CRP (OR = 1·79, 95 % CI 1·04, 3·06) was positively associated with MetS. CONCLUSIONS: The coexistence of MetS with micronutrient deficiencies suggests that elderly Ecuadorians suffer from the double burden of diseases that are increasingly being observed in less developed countries. More research is needed to determine the causal factors, but results presented suggest that these older adults would benefit from interventions to reduce the risk factors for MetS, in particular higher consumption of micronutrient-rich foods.

The effect of Helicobacter pylori infection on growth velocity in young children from poor urban communities in Ecuador.

OBJECTIVE: To characterize the potential effects of Helicobacter infections on growth velocity in low socioeconomic status young children in a developing country. METHODS: Children were recruited in poor suburbs of Quito, Ecuador. Normally nourished, mildly and substantially malnourished children (defined using weight-for-age Z-scores at recruitment) formed equal strata. Six height and weight measurements were collected during one year. Enrollment and exit serum samples were analyzed for anti-Helicobacter IgG and exit non-diarrheal feces tested for Helicobacter antigen. RESULTS: Among 124 participants (enrollment age 19 ± 9 months), 76 (61%) excreted fecal antigen at exit (were infected). Of these, 44 were seropositive at least once (chronic infections) and 32 tested seronegative both times (new or acute phase infections). The adjusted linear growth velocity during follow-up in children with new infections was reduced by 9.7 (3.8, 15.6) mm/year compared to uninfected controls and 6.4 (0.0, 12.9) mm/year compared to children with chronic infections. The effects of Helicobacter infections on ponderal growth were not significant. CONCLUSION: These results suggest that linear growth velocity is reduced in young children during the initial phase of Helicobacter infection.

Spatial and temporal variations and mobile source emissions of polycyclic aromatic hydrocarbons in Quito, Ecuador.

Motor vehicles are a major source of air pollution in Quito, Ecuador; however, little work has been done to characterize spatial and temporal variations in traffic-related pollutants, or to measure pollutants in vehicle emissions. We measured PAH continuously for one year at two residential sites in Quito, and PAH and traffic patterns for one week near a busy roadway. Morning rush-hour traffic and temperature inversions caused daily PAH maxima between 06:00 and 08:00. SO2, NOx, CO, and PM(2.5) behaved similarly. At the residential sites PAH levels during inversions were 2-3-fold higher than during the afternoon, and 10-16-fold higher than 02:00-03:00 when levels were lowest. In contrast, at the near-roadway site, PAH concentrations were 3-6-fold higher than at the residential sites, and the effects of inversions were less pronounced. Cars and buses accounted for >95% of PAH at the near-roadway site. Near-roadway PAH concentrations were comparable to other polluted cities.

Setting priorities for zinc-related health research to reduce children's disease burden worldwide: an application of the Child Health and Nutrition Research Initiative's research priority-setting method.

OBJECTIVE: To make the best use of limited resources for supporting health-related research to reduce child mortality, it is necessary to apply a suitable method to rank competing research options. The Child Health and Nutrition Research Initiative (CHNRI) developed a new methodology for setting health research priorities. To broaden experience with this priority-setting technique, we applied the method to rank possible research priorities concerning the control of Zn deficiency. Although Zn deficiency is not generally recognized as a direct cause of child mortality, recent research indicates that it predisposes children to an increased incidence and severity of several of the major direct causes of morbidity and mortality. DESIGN: Leading experts in the field of Zn research in child health were identified and invited to participate in a technical working group (TWG) to establish research priorities. The individuals were chosen to represent a wide range of expertise in Zn nutrition. The seven TWG members submitted a total of ninety research options, which were then consolidated into a final list of thirty-one research options categorized by the type of resulting intervention. RESULTS: The identified priorities were dominated by research investment options targeting Zn supplementation, and were followed by research on Zn fortification, general aspects of Zn nutrition, dietary modification and other new interventions. CONCLUSIONS: In general, research options that aim to improve the efficiency of an already existing intervention strategy received higher priority scores. Challenges identified during the implementation of the methodology and suggestions to modify the priority-setting procedures are discussed.

Micronutrient deficiencies are associated with impaired immune response and higher burden of respiratory infections in elderly Ecuadorians.

The proportion of the Latin American population above age 65 y is expected to rise substantially. To better define the prevalence of infectious diseases and micronutrient deficiencies, assess immunological status, and evaluate associations between nutritional status and infection, we performed a cross-sectional study of elderly Ecuadorians in a low-income peri-urban community in Quito, Ecuador. Culturally adapted questionnaires, delayed type hypersensitivity (DTH) skin response, micronutrient, and immunological assays were performed in randomly selected Ecuadorians aged > or = 65 y. Multiple linear and logistic regression models were developed to assess relationships between micronutrient concentrations and history of infection, DTH, and immune function. Participants (n = 352; mean age +/- SD, 74.4 +/- 6.4 y) recalled recent episodes of colds/influenza-like syndromes (62.8%), cough (61.0%), urinary tract infection (37.9%), diarrhea (32.2%), fever (24.1%), and pneumonia (3.5%). A prospective substudy of respiratory infections (RI) in 203 elderly revealed similar findings. Colds and pneumonia occurred in 42.8 and 7.9% of participants, respectively, during 737 person-weeks of observation (3.6 +/- 1.1 wk per person). Anemia and micronutrient deficiencies, especially for vitamins C, D, B-6, and B-12 and folic acid and zinc, were common. Plasma vitamin C was associated with interferon-gamma (IFNgamma) (P < 0.01) and zinc with IFNgamma and interleukin-2 (each P < 0.0001). RI history was associated with any micronutrient deficiency (P < 0.001). The burden of infectious diseases, micronutrient deficiencies, and anemia was substantial in this elderly Ecuadorian population. Deficiencies of essential vitamins and minerals place these elderly adults at risk for infections through their negative impact on immune function.

Dose-response trial of prophylactic zinc supplements, with or without copper, in young Ecuadorian children at risk of zinc deficiency.

BACKGROUND: Multiple studies have shown the benefits of zinc supplementation among young children in high-risk populations. However, the optimal dose and safe upper level of zinc have not been determined. OBJECTIVES: The objectives of this study were to measure the effects of different doses of supplemental zinc on the plasma zinc concentration, morbidity, and growth of young children; to detect any adverse effects of 10 mg supplemental Zn on markers of copper or iron status; and to determine whether any adverse effects are alleviated by providing copper with zinc. DESIGN: This randomized, double-masked, community-based intervention trial was conducted in 631 Ecuadorian children who were 12-30 mo old at baseline and who had initial length-for-age z scores <-1.3. Children received 1 of 5 daily supplements for 6 mo: 3, 7, or 10 mg Zn as zinc sulfate, 10 mg Zn + 0.5 mg Cu as copper sulfate, or placebo. RESULTS: The change in plasma zinc concentration from baseline was positively related to the zinc dose (P < 0.001). Zinc supplementation, including doses as low as 3 mg/d, reduced the incidence of diarrhea by 21-42% (P < 0.01). There were no other significant group-wise differences. CONCLUSIONS: Zinc supplementation with a dose as low as 3 mg/d increased plasma zinc concentrations and reduced diarrhea incidence in the study population. There were no observed adverse effects of 10 mg Zn/d on indicators of copper or iron status. The current tolerable upper level of zinc recommended by the Institute of Medicine should be reassessed for young children.

Growth and micronutrient status in children receiving a fortified complementary food.

Linear growth retardation and anemia are the most prevalent nutritional problems in the world; effective interventions are urgently needed. We evaluated Ecuador's National Food Nutrition Program (PANN 2000) that included a micronutrient-fortified complementary food (FCF), Mi Papilla, in poor periurban and rural communities of Ecuador. The program is preventive and targeted to all infants and young children living in poor communities and receiving government health services. We compared dietary intake, micronutrient status, and growth over 11 mo in a cohort of children from the catchment areas of the PANN 2000 with same-age control children in nearby communities eligible to enter the program 1 y later. PANN 2000 children enrolled in the program when they were age 9-14 mo and were age 20-25 mo at the final survey. They consumed significantly more energy, protein, fat, iron, zinc, vitamin A, and calcium than control children because of their FCF consumption. Anemia, 76% in both groups at baseline, fell to 27% in PANN 2000 children but only to 44% in control children (P < 0.001). The odds of being anemic were 58% lower for PANN 2000 children (P = 0.003). The effects on linear growth and weight were limited to children who were older when the program began (12-14 mo) and were significant for weight (interaction with age, 0.38 kg; P = 0.029) and positive but not significant for length (0.66 cm; P = 0.08). An FCF, including ferrous sulfate, delivered through public health services, is highly effective in improving weight and hemoglobin and reducing anemia.

Chloramphenicol versus ampicillin plus gentamicin for community acquired very severe pneumonia among children aged 2-59 months in low resource settings: multicentre randomised controlled trial (SPEAR study).

OBJECTIVE: To evaluate whether five days' treatment with injectable ampicillin plus gentamicin compared with chloramphenicol reduces treatment failure in children aged 2-59 months with community acquired very severe pneumonia in low resource settings. DESIGN: Open label randomised controlled trial. SETTING: Inpatient wards within tertiary care hospitals in Bangladesh, Ecuador, India, Mexico, Pakistan, Yemen, and Zambia. PARTICIPANTS: Children aged 2-59 months with WHO defined very severe pneumonia. INTERVENTION: Chloramphenicol versus a combination of ampicillin plus gentamicin. MAIN OUTCOME MEASURES: Primary outcome measure was treatment failure at five days. Secondary outcomes were treatment failure defined similarly among all participants evaluated at 48 hours and at 10 and 21 days. RESULTS: More children failed treatment with chloramphenicol at day 5 (16% v 11%; relative risk 1.43, 95% confidence interval 1.03 to 1.97) and also by days 10 and 21. Overall, 112 bacterial isolates were obtained from blood and lung aspirates in 110 children (11.5%), with the most common organisms being Staphylococcus aureus (n=47) and Streptococcus pneumoniae (n=22). In subgroup analysis, bacteraemia with any organism increased the risk of treatment failure at 21 days in the chloramphenicol group (2.09, 1.41 to 3.10) but not in the ampicillin plus gentamicin group (1.12, 0.59 to 2.13). Similarly, isolation of S pneumoniae increased the risk of treatment failure at day 21 (4.06, 2.73 to 6.03) and death (5.80, 2.62 to 12.85) in the chloramphenicol group but not in the ampicillin plus gentamicin group. No difference was found in treatment failure for children with S aureus bacteraemia in the two groups, but the power to detect a difference in this subgroup analysis was low. Independent predictors of treatment failure by multivariate analysis were hypoxaemia (oxygen saturation <90%), receiving chloramphenicol, being female, and poor immunisation status. CONCLUSION: Injectable ampicillin plus gentamicin is superior to injectable chloramphenicol for the treatment of community acquired very severe pneumonia in children aged 2-59 months in low resource settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN39543942.

Emergency room visits for respiratory conditions in children increased after Guagua Pichincha volcanic eruptions in April 2000 in Quito, Ecuador observational study: time series analysis.

BACKGROUND: This study documented elevated rates of emergency room (ER) visits for acute upper and lower respiratory infections and asthma-related conditions in the children of Quito, Ecuador associated with the eruption of Guagua Pichincha in April of 2000. METHODS: We abstracted 5169 (43% females) ER records with primary respiratory conditions treated from January 1-December 27, 2000 and examined the change in pediatric ER visits for respiratory conditions before, during, and after exposure events of April, 2000. We applied a Poisson regression model adapted to time series of cases for three non-overlapping disease categories: acute upper respiratory infection (AURI), acute lower respiratory infection (ALRI), and asthma-related conditions in boys and girls for three age groups: 0-4, 5-9, and 10-15 years. RESULTS: At the main pediatric medical facility, the Baca Ortiz Pediatric Hospital, the rate of emergency room (ER) visits due to respiratory conditions substantially increased in the three weeks after eruption (RR = 2.22, 95%CI = [1.95, 2.52] and RR = 1.72 95%CI = [1.49, 1.97] for lower and upper respiratory tract infections respectively. The largest impact of eruptions on respiratory distress was observed in children younger than 5 years (RR = 2.21, 95%CI = [1.79, 2.73] and RR = 2.16 95%CI = [1.67, 2.76] in boys and girls respectively). The rate of asthma and asthma-related diagnosis doubled during the period of volcano fumarolic activity (RR = 1.97, 95%CI = [1.19, 3.24]). Overall, 28 days of volcanic activity and ash releases resulted in 345 (95%CI = [241, 460]) additional ER visits due to respiratory conditions. CONCLUSION: The study has demonstrated strong relationship between ash exposure and respiratory effects in children.