Incidencia de desnutrición crónica y factores asociados en una cohorte de niños menores de 5 años / Incidence of chronic malnutrition and associated factors in a cohort of children under 5 years of age: A multicenter observational study

Introducción: La desnutrición crónica es un problema de difícil erradicación con grandes repercusiones en la población infantil. En el Ecuador 1 de cada 5 niños menor de cinco años, presenta desnutrición crónica. El objetivo del presente estudio fue determinar incidencia y factores asociados al desarrollo de desnutrición crónica en una cohorte de niños menores de 5 años durante un periodo de seguimiento de un año, en la provincia de Chimborazo, 2018-2019. Métodos: Se realizó un estudio de cohorte prospectivo, con seguimiento de 2018-2019. La población estuvo conformada por 1228 niños, de los cuales se tomó una muestra de 138 niños. Se tuvieron en cuenta variables como la edad, sexo, ubicación geográfica, nivel socioeconómico, acceso a servicios de salud, servicios básicos y tierras, prácticas de alimentación, antropometría, desnutrición crónica, talla de la madre, infecciones, y parasitosis. Se calculó el Riesgo Relativo (RR) y sus respectivos intervalos de confianza al 95% usando modelos lineales generalizados (familia binomial). Resultados: La incidencia de desnutrición crónica fue de 20,3%. Los factores asociados fueron: dificultad para acceder a los servicios de salud [RR: 4.87; IC 95%: 1.89-12.55]; y LME < 6 meses [RR: 3.44, IC 95%: 2.14-5.55]. Conclusiones: La incidencia de desnutrición crónica en menores de cinco años en la provincia Chimborazo es elevada; por lo que se precisa de intervenciones que garanticen el acceso a los servicios de salud y educación nutricional para eliminar este problema de salud.

Introduction: Chronic malnutrition is a problem that is difficult to eradicate with significant repercussions on the child population. In Ecuador, 1 in 5 children under five have chronic malnutrition. This trial aimed to determine the incidence and factors associated with the development of chronic malnutrition in a cohort of children under five years of age during a one-year follow-up period in the province of Chimborazo, 2018-2019. Methods: A prospective cohort study was conducted with a 2018-2019 follow-up. The population consisted of 1,228 children, from which a sample of 138 children was taken. Variables such as age, gender, geographic location, socioeconomic level, access to health services, essential services and land, feeding practices, anthropometry, chronic malnutrition, mother's height, infections, and parasitosis were taken into account. The Relative Risk (RR) and their respective 95% confidence intervals were calculated using generalized linear models (binomial family). Results: The incidence of chronic malnutrition was 20.3%. The associated factors were: difficulty in accessing health services [RR: 4.87; 95% CI: 1.89-12.55]; and EBF <6 months [RR: 3.44, 95% CI: 2.14-5.55]. Conclusions: The incidence of chronic malnutrition in children under five years of age in the Chimborazo province is high; therefore, interventions are needed to guarantee access to health services and nutritional education to eliminate this health problem.

A Single Dose of Oral BCG Moreau Fails to Boost Systemic IFN-γ Responses to Tuberculin in Children in the Rural Tropics: Evidence for a Barrier to Mucosal Immunization.

Immune responses to oral vaccines are impaired in populations living in conditions of poverty in developing countries, and there is evidence that concurrent geohelminth infections may contribute to this effect. We vaccinated 48 children living in rural communities in Ecuador with a single oral dose of 100 mg of BCG Moreau RDJ and measured the frequencies of tuberculin-stimulated peripheral blood mononuclear cells expressing IFN-γ before and after vaccination. Vaccinated children had active ascariasis (n = 20) or had been infected but received short- (n = 13) or long-term (n = 15) repeated treatments with albendazole prior to vaccination to treat ascariasis. All children had a BCG scar from neonatal vaccination. There was no evidence of a boosting of postvaccination IFN-γ responses in any of the 3 study groups. Our data provide support for the presence of a barrier to oral vaccination among children from the rural tropics that appeared to be independent of concurrent ascariasis.

Risk factors for atopic and non-atopic asthma in a rural area of Ecuador.

BACKGROUND Asthma has emerged as an important public health problem of urban populations in Latin America. Epidemiological data suggest that a minority of asthma cases in Latin America may be associated with allergic sensitisation and that other mechanisms causing asthma have been overlooked. The aim of the present study was to investigate risk factors for atopic and non-atopic asthma in school-age children. METHODS A cross-sectional study was conducted among 3960 children aged 6-16 years living in Afro-Ecuadorian rural communities in Esmeraldas province in Ecuador. Allergic diseases and risk factors were assessed by questionnaire and allergic sensitisation by allergen skin prick reactivity. RESULTS A total of 390 (10.5%) children had wheeze within the previous 12 months, of whom 14.4% had at least one positive skin test. The population-attributable fraction for recent wheeze associated with atopy was 2.4%. Heavy Trichuris trichiura infections were strongly inversely associated with atopic wheeze. Non-atopic wheeze was positively associated with maternal allergic symptoms and sedentarism (watching television (>3 h/day)) but inversely associated with age and birth order. CONCLUSIONS The present study showed a predominance of non-atopic compared with atopic wheeze among schoolchildren living in a poor rural region of tropical Latin America. Distinct risk factors were associated with the two wheeze phenotypes and may indicate different causal mechanisms. Future preventive strategies in such populations may need to be targeted at the causes of non-atopic wheeze.

Estimating adjusted prevalence ratio in clustered cross-sectional epidemiological data.

BACKGROUND: Many epidemiologic studies report the odds ratio as a measure of association for cross-sectional studies with common outcomes. In such cases, the prevalence ratios may not be inferred from the estimated odds ratios. This paper overviews the most commonly used procedures to obtain adjusted prevalence ratios and extends the discussion to the analysis of clustered cross-sectional studies. METHODS: Prevalence ratios(PR) were estimated using logistic models with random effects. Their 95% confidence intervals were obtained using delta method and clustered bootstrap. The performance of these approaches was evaluated through simulation studies. Using data from two studies with health-related outcomes in children, we discuss the interpretation of the measures of association and their implications. RESULTS: The results from data analysis highlighted major differences between estimated OR and PR. Results from simulation studies indicate an improved performance of delta method compared to bootstrap when there are small number of clusters. CONCLUSION: We recommend the use of logistic model with random effects for analysis of clustered data. The choice of method to estimate confidence intervals for PR (delta or bootstrap method) should be based on study design.

Impact of long-term treatment with ivermectin on the prevalence and intensity of soil-transmitted helminth infections.

BACKGROUND: Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children. METHODS AND FINDINGS: A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6-16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0-5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR = 0.06, 95% CI 0.03-0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11-0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments. CONCLUSION: Annual and twice-annual treatments with ivermectin over a period of up to 17 years may have had a significant impact on T. trichiura infection. The present data indicate that the long-term control of onchocerciasis with ivermectin may provide additional health benefits by reducing infections with trichuriasis. The addition of a second anthelmintic drug such as albendazole may be useful for a long-term effect on A. lumbricoides infection.

Repeated treatments with albendazole enhance Th2 responses to Ascaris Lumbricoides, but not to aeroallergens, in children from rural communities in the Tropics.

Geohelminth infections are associated with modulation of immunity to parasite antigens and aeroallergens. To investigate the possibility that this modulation is affected by anthelmintic treatment, we compared cytokine responses in children who were treated with repeated doses of albendazole over 1 year versus those in children who had were not treated. Whole-blood samples were cultured with Ascaris antigen and house dust mite and cockroach allergens, and levels of interleukin (IL)-5, IL-13, interferon-gamma, and IL-10 were measured. Anthelmintic treatment was associated with enhanced production of Th2 cytokines in response to parasite antigen but did not affect responses to aeroallergens. The data indicate that long-term treatment may be associated with increased Th2 antiparasite immunity.

Environmental determinants of total IgE among school children living in the rural Tropics: importance of geohelminth infections and effect of anthelmintic treatment.

BACKGROUND: The environmental factors that determine the elevated levels of polyclonal IgE observed in populations living in the Tropics are poorly understood but may include geohelminth infections. We investigated the association between geohelminth infections and total IgE levels in school children in rural tropical Ecuador, and assessed the effect on IgE of repeated anthelmintic treatments over a period of 12 months. The study was nested within a cluster-randomized study that randomized 68 schools to receive either 400 mg of albendazole every 2 months over a year or no treatment. We studied random samples of children completing follow-up and representing four groups stratified by the presence of geohelminth infection at baseline and treatment allocation. We measured levels of total IgE and anti-A. lumbricoides IgG (used as a measure of past and current geohelminth infectious exposure) in blood samples collected at the start of the study and after 12 months. RESULTS: We observed elevated levels of total IgE (compared to standard reference values) at the start of the study in this population of school children (geometric mean, 1,004 IU/mL, range 12 to 22,608 IU/mL)) and baseline IgE levels were strongly associated with parameters of geohelminth infection but not with age, nutritional and socioeconomic status. After 12 months, levels of IgE fell significantly in the treatment (by 35.1%) and no treatment (by 10.4%) groups, respectively, but the fall was significantly greater in the treatment group. Falls in IgE were independently associated with albendazole treatment, having a baseline geohelminth infection and with high baseline levels of anti-A. lumbricoides IgG. Increases in IgE at 12 months were associated with the presence of geohelminth infections and increasing levels of anti-A. lumbricoides IgG at 12 months independent of treatment allocation. CONCLUSION: The data provide evidence that geohelminth infections are an important determinant of total IgE in school children in the rural Tropics and that periodic anthelmintic treatments over 12 months are associated with reductions in IgE. The failure of anthelmintic treatment to reduce IgE levels to that considered normal in industrialized countries may be attributed to continued exposure of children to geohelminths or to the effects of infections in early life in programming a long-lasting Th2-biassed immunity.

Ascaris lumbricoides-induced interleukin-10 is not associated with atopy in schoolchildren in a rural area of the tropics.

BACKGROUND: In areas where intestinal helminth infections are endemic, infections by these parasites may protect against skin test-measured reactivity to allergens, and it has been suggested that interleukin (IL)-10 may mediate this effect. This study investigated whether IL-10 and populations of IL-10+ T cells may modulate atopy in children living in an area where intestinal helminth infections are endemic. METHODS: Ecuadorian schoolchildren from rural communities were assessed for skin test-measured reactivity to Periplaneta americana allergen and Dermatophagoides pteronyssinus allergen. Blood samples were collected from 39 skin test-positive and 41 skin test-negative children, and peripheral-blood leukocytes were cultured in the presence of Ascaris lumbricoides antigen, to measure IL-10 protein and the frequency of T cell populations expressing intracellular IL-10. We also investigated whether these immunological factors affected the association between allergen-specific IgE and skin test-measured reactivity to aeroallergens. RESULTS: There was no evidence of association between the level of A. lumbricoides-induced IL-10 protein or IL-10+ T cells and skin test-measured reactivity to allergens. The association between allergen-specific IgE and skin test-measured reactivity was not affected by the level of IL-10 protein or the frequency of IL-10+ T cells. CONCLUSIONS: The results of this study do not support the notion that IL-10 plays a role in modulating atopy in children living in a tropical area where intestinal helminth infections are endemic.

Effect of albendazole treatments on the prevalence of atopy in children living in communities endemic for geohelminth parasites: a cluster-randomised trial.

BACKGROUND: Epidemiological studies have shown inverse associations between geohelminth (intestinal helminth) infection and atopy, leading to the suggestion that geohelminths might protect against allergy. Periodic deworming of school children with anthelmintics is a widely implemented intervention and has raised concerns that such programmes could increase allergy. We investigated the effect of repeated anthelmintic treatments with albendazole over 12 months on the prevalence of atopy and clinical indices of allergy. METHODS: We did a cluster-randomised controlled trial in schoolchildren from 68 rural schools. Children were randomly assigned by school to either albendazole (34 schools, 1164 children) every 2 months for 12 months, or to no intervention (34 schools, 1209 children). The intervention schools received a total of seven albendazole treatments. The primary outcome was atopy at 12 months (allergen skin-test reactivity), and analysis was by intention-to-treat for whole-school analyses and per protocol for children. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN61195515. FINDINGS: Data for analysis were available for all schools and from 67.4% (784 of 1164) and 70.1% (848 of 1209) of children in albendazole and no-treatment groups, respectively. Albendazole treatment caused large reductions in geohelminth prevalence over the study period (adjusted odds ratio 0.13, 95% CI 0.09-0.19, p<0.001), but there was no evidence that treatment was associated with an increase in atopy prevalence (0.97, 0.68-1.39, p=0.862), or clinical allergy (wheeze, 1.07, 0.54-2.11, p=0.848) in the albendazole compared with the no-treatment group. INTERPRETATION: We saw no increase in the prevalence of atopy or clinical allergy associated with albendazole treatment. Deworming programmes for schoolchildren are unlikely to be accompanied by an increase in allergy.

Geohelminth infections: impact on allergic diseases.

Geohelminth infections are highly prevalent infections with a worldwide distribution. Epidemiological studies have shown an inverse relationship between geohelminth infection and allergy leading to the suggestion that geohelminths protect against allergy. A causal association is supported by the findings of intervention studies in humans and experimental animal models. Geohelminths cause chronic infections during which an intimate host-parasite interaction develops permitting the parasite to survive but protecting the host from damaging inflammation. Geohelminth parasites modulate allergic inflammation directed against parasite antigens and the same mechanisms may affect responses to inhalant aeroallergens. The mechanisms proposed to explain the allergy-modulatory effect of geohelminths include the induction of regulatory T cells and the creation of an immunosuppressive environment in relevant tissues. New treatments being considered for the treatment of asthma include live infections with hookworms. Insights provided by how geohelminths modulate inflammatory responses may allow the development of new treatments that mimic these effects.