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    ARTCULOS ORIGINALES

    Epidemiological analysis of eosinophilia and elevationof immunoglobulin E as a predictable and relative risk

    of enteroparasitosisDra. Cyntia Cristina Vieira Silva,IDr. C. Renato Ribeiro Nogueira Ferraz,IEnf.Joo Victor Fornari,IDr. C. Anderson

    Sena BarnabeI

    ABSTRACT

    Introduction: among the intestinal parasites, the helminthiasis occupies a prominent position in Brazil, since it worsensmalnutrition and the gives rise to neurovegetative disorders. Helminths like Ascaris lumbricoides, Enterobius vermicularis,hookworm, Trichuris trichiura and Strongyloides stercoralis stand out due to several factors that modulate the immune responseof individuals. Among the protozoa are Giardia lamblia, Entamoeba histolytica /E. dispar. Parasitic helminth antigens areimportant to stimulate the production of cytokines such as interleukin-4 and interleukin-5, which act through the induction ofIgE synthesis and activation of eosinophils. Eosinophilia is usually detectable in pre-patent period of parasitism, initially linked

    to B lymphocytes, under the command of Th-2 lymphokines (IL-4 and IL-5), producing IgE in response to initial exposure toan antigen or allergen. Serum IgE high levels occur in tissue migration of larvae or harboring of parasites in tissues. Objective:to determine the presence of eosinophils and IgE elevation in children with intestinal parasites. Methods: high levels of IgE andeosinophils were observed in groups infected and not infected (allergic) to calculate the relative risk of intestinal parasitespresumptive differentiated between protozoa and helminths and check what values of these indicators are observed in theepidemiological profile of the surveyed population. Results: the values obtained by calculating the relative risk for eosinophilia,compared with helminths and allergies was 11.71, but when examined by giardiasis compared with other diseases, the relative riskwas 0.75. Since the comparison of helminths and giradiase, the relative risk was 27.33. Since IgE and its parameters wereappropriate commit Helminth relative risk 0.39; Giardiasis had relative risk 8, 18 and Helminths compared with giardiasis had0.03. Conclusion: in this study it was possible to observe that helminthiasis is connected with cases of eosinophilia withalteration of IgE, which in turn contributes to the presence of IgE eosionofilia and has an effector response against helminthsthat provides the expulsion of its larvae.

    Key words: epidemiology, eosinophilia, intestinal parasites.

    REV CUBANA MED TROP 2012;64(1):22-6

    I Universidade Nove de Julho, So Paulo, Brasil.

    INTRODUCTION

    Enteroparasitoses are a serious problem inpublic health, especially in the third world coun-tries,1 and they provoke frequent malnutritionand diarrhea, as well as physical and mentalproblems in children.2 Among the parasitic patho-gens more frequently found in human beings,there are the helminths Ascaris lumbricoides,Enterobius vermiculares, Ancylostoma duo-

    denale, Strongiloides stercoralis and Trichuristrichura,3 as well as the intestinal protozoa, such

    as Giardia lamblia.3 Transmitting these parasitesto another host depend on complex epidemiologicalcycles, on a great variety of beings and on the lackof basic sanitation, making it difficult to control suchdiseases. These factors demand social actions, aswell as public health policies.4 The epidemiological,biological and immunological study of parasitediseases is necessary, in order to contribute moreapplication in early diagnosis and prevention of thesediseases. The immunological response caused bya parasite infection is complex and multiple, due to

    the great metabolic diversity of these beings. Thus,

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    there are consequences of Th1 or Th2 responses,

    depending on the kind of parasite on the host. Inaccordance with Machado et al5 giardiasis is akind of parasite infection that causes intenseeosinophilia, as well as the helminths mentionedabove.6 However, Melo-Reis et al7 do not agreewith this idea and state that the relation betweeneosinophilia (common in T2 responses) andprotozoa is little described on the scientific literature;also, they say it is important to emphasize that notall intestinal parasites especially those that areon the intestinal light are able to induce toeosinophilia, what would not make this biologicalparameter a good indicator of protozoa parasitosis.On the other hand, in helminthiasis, the parasiteantigens stimulate an intense Th2 response, withproduction of inter-leukin-4 and interleukin-5, whatinduce to the synthesis of Immunoglobulin E (IgE)and eosinophils activation.8 Eosinophilia is generallydetectable in the prepatent period of parasitism,that is, its detection occurs before helminths turninto adults and the occurrence of parasite biologicalforms that can be detectable.9 The function ofeosinophils is to destroy some helminths throughcellular cytotoxicity that depends on the antibody.10

    One of the mechanisms within this process is thereaction started by IgE. Initially, B lymphocytes,directed by Th-2 lymphokine (IL-4 e IL-5), produ-ce IgE in response to the initial exposure to anantigen or allergen.11 In parasite infections, highIgE serum levels appear on the tissue migration oflarvae or parasite housing in tissues.12

    Eosinophilia and elevation of IgE, however, arenot initial indicators of parasitosis, because it occursin other pathological conditions(ex:allergies). Thereis no data on literature about serum values of theindicators mentioned, regarding the epidemiologicalprofile of people in our society who suffer fromparasitosis, but the occurrence and indication ofeosinophilia and IgE high levels in people with suchpathologies is wide. Thus, we propose a quantitativeanalysis on a sample of individuals believed to haveenteroparasitosis, of the relative risk (RR) in thiscondition, as well as of the presence of eosinophiliaand elevation of IgE. The aim of this study was tocompare eosinophils mean values and elevation ofIgE in children with and without parasitosis,obtaining reference values of these biological

    indicators as a clue of the latency period of

    enteroparasitosis. Also, intend evaluating thequantitative differences between these immuno-logical indicators regarding helminthiasis, protozoadiseases and other pathologies, analyzing the RRvalues to the parasitic conditions and eosinophilia,as well as elevation of IgE.

    METHOD

    This study approaches qualitatively and

    quantitatively, carried out between June 2009 andJune 2010. The sample in this research constitutedby 83 exams believed to have enteroparasitosis,performed at the Alpha Clin lab, in So Paulo,Brazil. The variables observed were concentrationof eosinophils and of IgE, as well as diagnosissuspect of enteroparasitosis. The data wereevaluated through application of descriptivestatistics of central tendency, using standarddeviation as a measure of dispersion. Besides thedescription of the values of these indicators, it was

    performed a test of statistical hypothesis, in whichH0 was taken as a null hypothesis (there is nodifference in the values of eosinophils and IgE incases of parasitosis and other pathologies), and H1was taken as an alternative hypothesis (there aredifferences between the values observed on theconcentration of eosinophils and IgE and thecondition of being a carrier of intestinal hel-minthiasis). The values of eosinophilia and IgE wereindividually submitted to a test Kruskall-Wallisbetween the groups with and without parasitic

    infections. All the statistical tests were carried outconsidering a significance level of p< 0.05, anda confidence level of 95 % was esta-blished asappropriate. In the analyses, we used EPI-INFO2000 (Centers for Disease Control and Prevention,a software of data tabulation in epidemiology.Available in: http://www.cdc.gov/epiinfo.). Thepositive exams were diagnosed by sedimentationcoproscopy techniques ofHofman, Pons andJanner,13 and by the Faustmethod.14 Eosinophilsconcentration was analyzed by an automatedelectrical impedance technique, spectrophotometryand optical dispersion (STKS device), and itsreference value in percentage ranged from 1.0 to

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    parasitosis carriers and non-carriers, Kruskall-

    Wallis test showed, at the established levels,significantly greater relations between the conditionof a carrier and the elevated levels of eosinophilsand IgE, with the same parameters, in non-carriersof parasitosis.

    A few works demonstrated that Giardialamblia is able to induce an immunological responsewith elevation of eosinophils.7,10,11 From the datapresented in this work, we observed that patientswith giardiasis may present normal values ofeosinophils, which confirmedMelo-Reis,7Fonte-

    neleet al10 andRosrioet al,11 but contradictedMachado et al.6

    Analyzing RR, we noticed relevance ineosinophilia as a remarkable factor of association(between the events pathology and elevationof indicators): in helminthiasis and giardiasis, of27.33 times; in helminthiasis and other pathologies,RR is 11.71 times; and in giardiasis and in otherpathologies, RR is only 0.75, which is higher than1.0 and, thus, constitute a risk factor, in accordancewith Pereira.17 The elevation of IgE did not show

    relevance between helminthiasis and giardiasis(0.03), between helminths and other pathologies(0.39), but presented risk between giardiasis andother pathologies (8.18). In its turn, IgE proved tobe a be tt er indicator to giardi as is than tohelminthiasis, partly confirmingMachadoet al.6

    Regarding the hypotheses, we deny H0 andnoticed a more remarkable difference in the RRof these indicators between parasitosis than in otherdiseases; however, we accept H1, in which thereare statistical differences of RR between helmin-thiasis carriers and the elevation in the mentionedindicators.

    Patients with parasitosis vary in their clinicalcondition, as asymptomatic and symptomatic,altering the polymorphic form of these diseases.They present diarrhea, weight loss, among othermanifestation, or they do not present any importantsymptomatology for a long time.18Thus, eosinophiliais a highly important hematological parameter,and it should be considered when approachingand assessing a patient who presents it, for itsuggests intestinal parasitosis, specifically pre-

    patent helminthiasis. Also, the association of thisindicator with the condition of the carrier shouldbe observed.

    In this study, it was possible to observe that

    helminthiases are associated with cases ofeosinophilia. The values observed can indicatehelminth infections (RR) and they are very differentfrom other pathological conditions. This study ishighly important for public health, forenteroparasitoses are among its main problems.Their diagnosis depends on a laboratorial structureand experienced professionals with biologicalinformation regarding the immunological system.However, we accept that the number of individualsin this study is not sufficient to a good analysis,

    although it is a good tool for new researches onImmunology, parasite biology and public health.

    Anlisis epidemiolgico de eosinofilia y la elevacinde inmunoglobulina E como riesgo relativo y predeciblede enteroparasitosis

    RESUMEN

    Introduccin: entre los parsitos intestinales, la hel-mintiasis ocupa un lugar destacado en Brasil, porquecausa malnutricin y la instalacin de cuadros detrastornos neurovegetativos. Helmintos como Ascarislumbricoides,Enterobius vermicularis, anquilostoma,Trichuris trichiura y Strongyloides stercoralis sedestacan debido a varios factores que modulan larespuesta inmune de los individuos. Entre los pro-tozoos, los ms destacados son Giardia lamblia yEntamoeba histolytica/E. dispar. Los antgenos dehelmintos parsitos son importantes para estimular la

    produccin de citocinas como la interleucina-4 einterleucina-5, que actan a travs de la induccin de lasntesis de IgE y la activacin de los eosinfilos. Laeosinofilia es detectable por lo general en el perodo

    pre-patente de parasitismo, inicialmente vinculada a los

    linfocitos B, bajo el mando de Th-2 linfocinas (IL-4 e IL-5),la produccin de IgE en respuesta a la exposicin iniciala un antgeno o alergeno. Los niveles sricos de IgE se

    producen en la migracin de las larvas de los tejidos o laacogida de los parsitos en estos. Objetivo: determinarla presencia de eosinfilos y la elevacin de IgE ennios con parsitos intestinales y cuantificar el riesgorelativo de estos parmetros biolgicos. Methods: seobservaron altos niveles de IgE y de eosinfilos engrupos infectados y no infectados (alergias) a fin decalcular el riesgo relativo (RR) de parsitos intestinales

    presuntamente di fe renc iados entre protozoos yhelmintos, as como chequear qu valores de estosindicadores se observan en el perfil epidemiolgico dela poblacin estudiada. Resultados: los valoresobtenidos mediante el clculo del riesgo relativo para la

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    eosinofilia, en comparacin con helmintos y otras

    enfermedades fue 11,71, pero cuando se examina por lagiardiasis en comparacin con alergias result de 0,75.En la comparacin de los helmintos y la giardiasis, elriesgo relativo fue de 27,33. Dado que la IgE y sus

    parmetros eran adecuados, entonces helmintos RR 0,39;giardiasis RR 8,18; y helmintos en comparacin congiardiasis 0,03. Conclusin: con este estudio se pudoobservar que las helmintiasis estn relacionadas concasos de eosinofilia con alteracin de la IgE; este ltimo,que a su vez contribuye a la presencia de IgE eosionofiliay a tener una respuesta efectora frente a helmintos quecausan la expulsin de sus larvas.

    Palabras clave: epidemiologa, eosinofilia, parsitosintestinales.

    REFERENCES

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    2. Ferreira CB, Maral Junior O. Enteroparasitoses em escolaresdo Distrito de Martinsia, Uberlndia, MG: um estudo piloto.Rev Soc Bras Med Trop. 1997;30(5):373-77.

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    Recibido: 2 de marzo de 2011. Aprobado: 10 de septiembrede 2011.Anderson Sena Barnabe. Universidade Nove de Julho, So Paulo,Brasil. Email: [email protected]