soil - transmitted helminths ( sth ) or geohelminths infect more than 2 billion people worldwide , especially in developing countries located in tropical and subtropical regions .
the most prevalent species are ascaris lumbricoides ( roundworm ) , trichuris trichiura ( whipworm ) , and hookworms ( necator americanus and ancylostoma duodenale ) .
children and women of childbearing age are among the high - risk groups for these parasitic diseases .
the morbidity caused by sth infections is highly associated with the size of the worm population residing in the intestines ( also known as worm burden ) .
infections of heavy intensity are more likely to cause impaired physical growth and cognitive development as well as micronutrient deficiencies , including iron - deficiency anaemia [ 1 , 2 ] .
further , due to their chronic and insidious nature , even light intensity infections may compromise health outcomes . to reduce the morbidity caused by these parasitoses , the world health organization ( who ) recommends cyclical ( annual or biannual ) benzimidazole - based mass drug administration to groups at high - risk of infection , especially pre- and schoolchildren .
the basic premise of this strategy is that even though this intervention may not decrease transmission and prevalence , it will in time reduce hosts ' worm burden with the ensuing reduction in health impact .
in addition to health impact , sth infections affect the human host in more subtle manner : as extracellular metazoan parasites , helminths trigger type-2 immune response mediated by t - helper type 2 ( th2 ) cells .
this response is typically characterized by expansion of mast cells , eosinophils , basophils , group 2 innate lymphoid cells ( ilc-2 ) , and alternatively activated macrophages ( aams ) , as well as increased production of th2 cytokines ( e.g. , il-4 , il-5 , il-9 , and il-13 ) and ige [ 35 ] . on the other hand ,
intracellular pathogens such as viruses , bacteria , protozoa , and fungi elicit a type-1 response , characterized by increased numbers of phagocytic neutrophils and macrophages , as well as cytotoxic cd8 t cells and th1 cells .
antigen - presenting dendritic cells ( dcs ) secrete interleukin- ( il- ) 12 promoting differentiation of naive cd4 cells , first into null t - helper ( th0 ) and then into th1 . via production of interferon - gamma ( ifn- ) and il-2 to a lesser degree , th1 cells direct , maintain , and enhance the antimicrobial effect of type-1 response . both subsets of t - helper cells
naturally , a healthy resolution of infections relies on a dynamic combination of the two [ 5 , 7 ] .
chronic helminth infections such as the ones caused by sth exhibit a modified type-2 response , in which a superimposition of regulatory mechanisms exerted over the basic response pattern takes place .
this regulation is mainly achieved by the expansion and induction of regulatory t cells ( treg )
. increased levels of anti - inflammatory cytokines il-10 and transforming growth factor beta ( tgf- ) are hallmarks of this response [ 4 , 8 , 9 ] .
it has been suggested that , during chronic helminthiases , this anti - inflammatory network may play a key role in the lower prevalence of allergic disease observed in th2-skewed populations [ 7 , 1012 ] .
conversely , helminth - induced il-10-mediated immunosuppression has raised concerns for populations in which sth infections coexist with other morbidities such as hiv / aids , malaria , and tuberculosis , as clearance for the latter depends on an active and timely type-1 response [ 8 , 1316 ] . in this context , successful deworming treatment has been proposed as a practical and inexpensive way to rebalance the immune response [ 17 , 18 ] .
recent studies have observed that after administration of anthelminthic medication , eosinophil counts , il-10 levels [ 1921 ] , and ige concentrations   show a significant decrease from pretreatment values .
moreover , in hiv-1 infected individuals , deworming was shown to promote a significant decrease in plasma hiv rna levels [ 18 , 22 ] and cd8 t cells counts .
also , a randomized control trial in kenya demonstrated a significant increase in cd4 t cell counts after deworming .
other studies , however , found no evidence of this effect [ 18 , 19 ] .
the principal aim of the present study was to characterize the immune profile in schoolchildren infected with geohelminths .
the study was conducted in april 2014 and data were collected from schoolchildren living in linaca , a rural community of the municipality of tatumbla , department of francisco morazn in honduras .
the study was approved by brock university 's bioscience research ethics board ( file number bu 12 - 262 , dated june 27 , 2013 ) as well as by the research ethics board of the master 's program in infectious and zoonotic diseases , school of microbiology , national autonomous university of honduras , unah ( file number cei - meiz 01 - 2013 , dated september 23 , 2013 ) .
the school of linaca participates in the honduras national deworming program , which provides enrolled children with a 400  mg single - dose albendazole annually . at the time of the study ,
children who had not received deworming treatment from other sources in the past 3 months were included in the study .
basic demographic and epidemiological data of participant children were obtained using a structured questionnaire during a 5-minute face - to - face interview conducted in spanish .
body weight and height of participants were measured twice by different researchers and their average was used to calculate the following anthropometric indicators : ( a ) height - for - age z - score ( haz ) , ( b ) weight - for - age z - score ( waz ) , and ( c ) body - mass - index - for - age z - score ( baz ) .
these indicators were used to ascertain children 's nutritional status as per international parameters : stunted growth ( chronic malnutrition ) , thinness , and underweight , respectively . a same - day
samples were kept in portable coolers and examined early afternoon at the laboratory facilities of unah 's school of microbiology .
the presence of intestinal parasites was assessed using both kato - katz and formol - ethyl acetate concentration methods . for the latter ,
microscopic examination of kato - katz smears was done between 30 and 60  min of preparation .
helminth eggs were identified and counted and the number of eggs per gram ( epg ) was calculated .
infection intensities were classified as light , moderate , or heavy , based on the epg calculations , according to who criteria .
diagnostic accuracy was ensured by having 100% of negative and 10% of positive smears read again by a different researcher immediately after the first reading .
formol - ethyl acetate was done one month after sample collection and sediments were observed with dry and immersion oil objective lenses in order to identify helminth and protozoa stages , respectively .
blood samples obtained from the cubital vein were collected in 3  ml tubes of each k2edta and serum separator and clot activator ( bd vacutainer , nj , usa ) .
the latter were centrifuged within 4 hours and serum was stored at 21c until immunological analysis .
hematological automated analyses were performed within 4 hours of sample collection and were done with an abx pentra 120 ( horiba - abx - sas , montpellier , france ) . according to the parameters established in the most recent ( 2011 - 2012 ) demographic and health survey in honduras ( dhs - hn ) , anaemia was defined as hb concentration < 12  g / dl .
eosinophilia was defined according to international standards as eosinophil count  500/l in peripheral blood .
mild , moderate , or severe eosinophilia were defined if cell counts were 5001500/l , > 15005000/l , or > 5000/l , respectively .
cytokine concentrations in serum samples were measured using a magpix magnetic beads platform ( luminex xmap , austin , tx , usa ) .
multiplex panels containing magnetic beads covered with fluorescent dyed conjugated to a monoclonal antibody specific for each target molecule were used to quantify th1/th2 cytokines ( il-2 , il-6 , il-8 , il-12p70 , ifn- , gm - csf , tnf- , il-4 , il-5 , and il-13 ) and the regulatory cytokine il-10 .
serum concentrations of total ige were also quantified using magnetic beads platform but with singleplex kits , bio - plex pro human ige isotyping ( bio - rad laboratories , inc .
hyper - ige was defined as a serum concentration exceeding 100  iu / ml and was classified as mild ( > 100399  iu / ml ) , moderate ( > 399999 
cytokine and ige tests were performed according to the manufacturer 's instructions ( bio - rad laboratories , inc .
descriptive statistics were used to characterize the study population . point prevalence with 95% confidence intervals ( 95% ci ) was calculated for overall sth infections and for each parasite species , as well as for mixed sth infections ( i.e. , infected with two or more species ) .
associations between nutritional indicators and parasite infections were explored using both univariate and multivariable logistic regression models .
unadjusted and adjusted odds ratio ( or and adj . or ) with 95% ci were determined .
due to the non - gaussian distribution of the immunological markers , nonparametric methods were used as follows . geometric means and
kruskal - wallis test was used to assess differences among groups , followed by dunn 's test to investigate individual group differences .
all statistical analyses were conducted using stata 13 ( statacorp lp , tx , usa ) and the level of significance was defined as p < 0.05 .

 table 1 summarizes the characteristics and parasitological findings in the study population . a total of 225 schoolchildren attending grades 1 to 6 ( age 613 ) participated in the study .
most of the children lived in households with piped water ( 88% ) and flushing toilet and/or latrines ( 98% ) but 40% lived in households with earthen floor .
qualitative kato - katz results were 100% correlated with those of formol - ethyl acetate .
no cases of s. stercoralis or hookworm infections were found with either technique but one case of taenia solium was identified by the presence of gravid proglottids in the stool sample . among pathogenic protozoa ,
giardia intestinalis and entamoeba histolytica / dispar were present in 4% and 9% of the samples , respectively .
prevalence for t. trichiura and a. lumbricoides was 22.2% ( 95% ci = 17.228.2 ) and 20.4% ( 95% ci = 15.626.2 ) , respectively .
mixed sth infections represented 43% of all infections observed . while the majority ( 84% ) of trichuriasis cases were light intensity ,
about one - third ( 32.6% ) of ascariasis cases were moderate - to - heavy intensity ( table 1 ) .
only 20% of moderate - to - heavy infections with both a. lumbricoides and t. trichiura occurred as single infections . in the multivariable analysis ,
almost three - quarters ( 71.7% ) of ascariasis cases occurred in boys and they had almost three times the odds of having a. lumbricoides infections compared to girls ( adj . or = 2.82 , 95% ci = 1.345.94 , and p = 0.006 ) .
children living in households with earthen floor had twice the odds of helminthic infections ( adj . or = 2.29 , 95% ci = 1.154.55 , and p = 0.018 ) .
conversely , children with access to piped water in their households showed 64% reduced odds of ascariasis ( adj .
about 12% of the children were overweight , and this condition was significantly higher in boys than girls ( 73% versus 27% , p = 0.036 ) ; only one of these children was stunted .
multivariable logistic models controlling for age and sex were constructed , and adjusted or were calculated . in this population , stunting was significantly associated with the age of participants as well as with trichuriasis . per every year of age , the odds of stunting increased in 34% ( adj . or = 1.34 , 95% ci = 1.031.73 , and p = 0.025 ) .
similarly , children harbouring t. trichiura infections had almost four times the odds of being stunted ( adj . or = 3.93 , 95% ci = 1.0314.93 , and p = 0.045 ) when compared with children without sth infection .
further , children harbouring moderate - to - heavy trichuriasis had an additional 70% increased odds of being stunted ( adj . or = 6.64 , 95% ci = 1.1937.09 , and p = 0.031 ) . figures 1 and 2 depict the variation observed in eosinophils count ( cells/l ) and serum levels of ige by sth infection and infection intensity . the geometric means and 95% ci of these parameters by sth infection
the overall prevalence of eosinophilia was 31.7% ( 95% ci = 25.938.1 ) , and mild eosinophilia accounted for the vast majority ( 91.5% ) of cases .
multivariable logistic models found no association between eosinophilia and sex or age of the studied children .
significantly higher mean counts of eosinophils were found in children infected with t. trichiura alone or in those harbouring mixed infections compared to nonparasitized children .
children harbouring mixed infections had 2.5-fold increased odds of having eosinophilia when compared to nonparasitized children ( adj . or = 2.59 , 95% ci = 1.135.90 , and p = 0.023 ) .
similar increased odds were observed in children with single infection by t. trichiura , although this effect was only marginally significant ( adj . or = 2.48 , 95% ci = 0.986.26 ,
eosinophilia was positively correlated with intensity of infection by both a. lumbricoides and t. trichiura ( rs = 0.26 , p < 0.001 and rs = 0.33 , p < 0.001 , resp . ) .
children with moderate - to - heavy ascariasis had five times the odds of presenting eosinophilia ( adj . or = 5.23 , 95% ci = 1.6916.12 , and p = 0.004 ) compared to their nonparasitized counterparts . likewise , moderate - to - heavy trichuriasis was associated with a 7-fold increased odds of eosinophilia ( adj . or = 7.19 , 95% ci = 1.4136.70 , and p = 0.018 ) .
the overall prevalence of hyper - ige was 90.2% ( 95% ci = 85.593.5 ) .
more than half of these cases ( 51.0% ) were severe , whereas mild and moderate hyper - ige accounted for 24.3% and 24.7% of the cases , respectively .
no significant correlation was found between ige levels and sex or age of participant children .
compared to those without sth infections , children with mixed sth infections had significantly higher mean levels of ige ( table 2 ) .
there was a moderate positive correlation between ige serum levels and eosinophils count ( rs = 0.43 , p < 0.001 ) .
similarly , ige levels were positively correlated with intensity of infection of both a. lumbricoides and t. trichiura .
children with moderate - to - heavy ascariasis or trichuriasis had significantly higher mean values of ige compared to those uninfected or with only light infections ( p < 0.001 ) ( figure 2 ) .
table 2 summarizes the geometric mean values and 95% ci of these cytokines by sth infection . in general ,
cytokine mean concentrations did not differ significantly when comparing the parasitized with the nonparasitized group .
however , children with single infections by a. lumbricoides had significantly higher levels of il-10 and il-13 compared to children without infection , with single t. trichiura infections or with mixed infections ( p = 0.018 and p = 0.004 , resp . ) .
spearman 's rank correlation coefficients showed a significant , although weak , negative correlation between il-10 levels and age ( rs = 0.23 , p < 0.001 ) .
il-10 levels were not significantly correlated with infection intensity , whereas for il-13 a weak but significant positive correlation with a. lumbricoides infection intensity was found ( rs = 0.22 , p = 0.012 ) .
significantly lower values of ifn- were found in children with single infections by t. trichiura ( p = 0.043 ) and these values showed a weak , negative correlation with t. trichiura infection intensity , although this correlation was not statistically significant ( rs = 0.17 , p = 0.069 ) ( figure 3 ) . on the other hand , ifn- values were significantly negatively associated with a. lumbricoides infection intensity ( p = 0.007 ) . children with moderate - to - heavy ascariasis had lower ifn- mean values ( 37.6 [ 15.790.0 ] pg / ml ) compared with those having no or light infections ( 131.5 [ 98.4175.8 ] pg / ml and 214.4 [ 99.0464.4 ] pg / ml , resp . ) ( figure 3 ) .
th2/th1 ratios , as well as il-4/ifn- and il-10/ifn- , were also calculated ; significantly higher il-4/ifn- ratios were obtained in children with moderate - to - heavy infections by a. lumbricoides ( 0.020 [ 0.0100.042 ] ) , compared to those without ( 0.011 [ 0.080.014 ] ) or light infections ( 0.007 [ 0.0020.022 ] ) ( p = 0.046 and p = 0.021 , resp . )
a very similar pattern in il-4/ifn- ratio was found for t. trichiura infection intensity , although differences were only marginally significant ( p = 0.057 and p = 0.059 , resp . ) .
finally , the potential effect of pathogenic protozoa in children 's immune response was assessed but this assessment was done only in children without sth infections .
it was found that ifn- mean values were significantly higher in children harbouring pathogenic protozoa ( i.e. , g. intestinalis and/or e. histolytica / dispar ) compared to those infected with commensals only or to those with no protozoa at all ( 332.9 [ 146.7755.8 ] pg / ml , 93.7 [ 60.9144.2 ] pg / ml , and 145.6 [ 93.8225 ] pg / ml , resp . ) .
il-10/ifn- ratios were significantly lower in children infected with pathogenic protozoa when compared to those uninfected or infected with commensals only ( 0.044 [ 0.0190.105 ] , 0.095 [ 0.0620.144 ] , and 0.124 [ 0.0720.214 ] , resp . ) ( figure 4 ) .
no statistically significant associations could be established between protozoa infection and eosinophil counts , ige levels , or the remaining cytokines studied .
the parasitological findings of this study demonstrate a moderately high ( 30% ) overall sth prevalence and specific prevalence for t. trichiura and a. lumbricoides of about 20% among schoolchildren living in linaca .
school teachers reported that the school is reached by the national deworming program and thus receives a single - dose 400  mg albendazole tablet per child on a yearly basis .
no records are kept at the school in terms of deworming tablets intake and no parasitological baseline data have been obtained during governmental surveys ( data reviewed in ) . to our knowledge , prior to the present study , two parasitological surveys had been undertaken in the study community . in 1985 ,
a study investigating causes of diarrhea in honduras included a small number of preschoolchildren and found prevalence of 48% and 30% for a. lumbricoides and
compared to the sth prevalence found in the present study , it appears that there has been an important decrease in sth prevalence among linaca 's children . due to insufficient data on deworming
, we did not attempt to identify if this strategy has served an important function in decreasing sth prevalence or at least worm burden .
thus , whether or not deworming has contributed to sth prevalence reduction remains an open question .
our findings , however , show that improved household conditions were strong protective factors for ascariasis . in this case , there might be a synergy between the built environment and anthelminthic medication , which may not be sufficient to protect against t. trichiura infection as one dose of alb treatment is largely ineffective to clear this parasite . even though a similar proportion of children were found with either excess weight ( 12% ) or chronic malnutrition ( stunted growth , ~10% ) , the latter
similarly , despite the fact that trichuriasis prevalence was at a moderate level and that the majority of infections were light , a significant association was documented between stunting and both t. trichiura infection and infection intensity .
this finding aligns with observations from other studies conducted in honduras , ethiopia , mexico , and brazil [ 33 , 34 ] .
the concerning association between trichuriasis and chronic malnutrition , along with the fact that t. trichiura has been found consistently as the most prevalent geohelminth in honduras [ 27 , 35 , 36 ] , suggests that ( i ) a reexamination of the current deworming guidelines are necessary ; ( ii ) improvements in sanitary conditions and health education are indispensable components of sth control initiatives ; and ( iii ) it is important to monitor for potential benzimidazole resistance in this parasite .
it has been shown that , in developing countries , eosinophilia is most commonly induced by tissue - invasive parasites , particularly helminths [ 25 , 38 ] .
sth infections have been largely associated with eosinophilia , especially in early stages of infection , when larval migration occurs .
the association between eosinophilia and sth in the present study is consistent with results from previous work conducted in honduras [ 39 , 40 ] and other countries such as brazil [ 41 , 42 ] , philippines , indonesia , and spain .
whereas other causes of eosinophilia can not be ruled out , it is likely that , in this particular group of children , such eosinophilia was reactive ( i.e. , secondary to an external stimulus ) and most likely associated to sth infection .
this inference is supported by data contained in linaca 's health centre morbidity report for 2014 , which shows that < 2% of children 's visits were due to asthma or allergic dermatitis ( linaca health care centre 2014 report , unpublished ) . moreover , a comprehensive socioeconomic and life conditions study conducted in the municipality of tatumbla , where linaca is located , contained no reference to allergic conditions being a health issue among inhabitants .
rather , it revealed that childhood acute respiratory infections accounted for > 50% of visits to the health centre .
the use of eosinophilia as a biomarker for helminthiases remains without consensus . as a predictor of current helminthic infections , some authors consider eosinophilia 's predictive value very limited , while others regard it as a suitable indicator of helminthiases in people from tropical and subtropical areas [ 26 , 42 , 44 , 46 ] .
future studies should investigate eosinophilia at the individual level in order to better understand this dynamic relationship .
our study revealed strikingly high prevalence of hyper - ige among the studied children ; it also highlighted a significant association between sth infections and increased total ige levels .
such findings are consistent with observations in studies conducted in nigeria [ 47 , 48 ] , ecuador , venezuela , spain , and brazil [ 41 , 51 , 52 ] .
helminth - induced ige is mostly characterized by a nonspecific polyclonal stimulation with only a small fraction of parasite - specific ige .
however , it is the parasite - specific ige which plays an important role in helminth clearance as well as in preventing reinfection [ 48 , 50 , 5355 ] . in a study of venezuelan children , hagel and
collaborators demonstrated that total ige levels were inversely correlated with parasite - specific ige levels .
they also showed that reinfection with a. lumbricoides was significantly associated with high pretreatment total ige but low parasite - specific ige levels .
another interesting finding in the present investigation was the significant association observed between high total ige levels and intensity of infection ( i.e. , worm burden ) .
some studies have shown that specific ige levels reflect the parasite infection intensity ; therefore , higher specific antibody levels would be expected in lightly infected individuals when compared with those heavily infected .
total ige levels in the studied children were significantly positively correlated with eosinophils counts ; this finding is not surprising due to the ability of ige to induce a cytotoxic response against helminthic parasites mediated by mast cells and eosinophils .
it has been demonstrated that helminth infections strongly induce an immune response involving elevated th2 cytokines ( i.e. , il-4 , il-5 , il-9 , and il-13 ) , ige , iga , eosinophilia , and mucus secretion [ 5860 ] .
helminth - caused tissue damage triggers the response by releasing danger - associated molecular patterns ( damps ) and cytokine alarmins , particularly il-25 and il-33 .
these alarmins promote the activation of basophils and innate lymphoid cells ( ilc-2 ) to support a type-2 innate immune response needed to signal the type-2 adaptive immunity .
in this context , large quantities of il-5 and il-13 are primarily produced by ilc-2 cells .
il-5 promotes the eosinophils differentiation and activation which promote il-4 production , the main primer of cd4 th2 cells activation and expansion , with further release of il-4 , il-5 , and il-13 by this type of cells [ 3 , 6062 ] . in this environment ,
il-4 and il-13 induce aams , which mainly promote tissue repair and fibrosis by expression of different markers such as arginase-1 , ym1 , ym2 , and relm-. these aams also express regulatory il-10 and tgf- able to downregulate inflammatory response [ 35 , 9 , 6163 ] .
instead , the majority of children showed either low or nondetectable values of this cytokine .
this was an unexpected finding since il-5 is essential for eosinophilic differentiation , proliferation , and activation .
since the participant children have probably experienced repeated sth infections since they were much younger , their immune response may have already changed to a modified type 2 response , where inflammatory th2 shifted to an attenuated phenotype characterized by the shutdown of effector cytokines such as il-5 , retention of il-4 , and reinforcement of anti - inflammatory cytokines such as il-10 and/or tgf- [ 4 , 9 ] . instead ,
as recently determined by fulkerson and colleagues , an alternative il-5-independent pathway for promoting eosinophilia might be in place .
this pathway would contribute to persistent eosinophil differentiation and survival even after a complete il-5 withdrawal . finally , periodic deworming followed by reinfection along several years is likely disturbing the antiparasitic immune responses as described in the literature .
we found that il-13 levels were significantly increased in children infected with a. lumbricoides and that these levels were positively correlated with worm burden .
il-13 is a th2 pleiotropic cytokine with an important function in the intestinal epithelia , controlling the rate of transit of epithelial cells toward the outmost layer and promoting a harsh environment that might help in gut parasite expulsion ( i.e. , increased luminal fluids , mucus , from goblet cells , increased edema , and muscle contractility ) [ 7 , 60 , 61 ] .
gallo and colleagues demonstrated that il-13 may also be produced by th1 and th17 cells , suggesting that this cytokine can have either a pro- or anti - inflammatory effect , depending on the environment .
nevertheless , demonstrating an association between sth and il-13 overproduction has not been achieved by other research groups in india   and brazil . some studies in cameroon [
68 , 69 ] found high levels of il-13 associated with lower intensity of infection , but the present study did not establish such association .
it can be produced by diverse type of cells such as macrophages , dendritic cells ( dc ) , b cells , and various subsets of cd4 and cd8 t cells .
regardless of the type of infection , il-10 limits th1 and th2 effector responses by suppressing function of macrophages and dcs .
the timing , site of its production , and strength may favor ( a ) simultaneous pathogen clearance and suppression of downstream pathologies ; ( b ) potential benefit to both the host and the pathogen ( limiting pathology and allowing persistent infection ) ; ( c ) severe tissue damage ; or ( d ) overwhelming infection [ 70 , 71 ] . in our study , statistically significant higher il-10 values were found in children with ascariasis , although they did not correlate with infection intensity of this parasite .
similar findings have been frequently reported by other researchers [ 66 , 69 , 7274 ] , with some exceptions .
this is congruent with previous studies conducted in a different community in honduras   as well as with other studies in nigeria   and cameroon [ 68 , 76 ] .
although its efficacy is species - dependent , albendazole generally reduces the duration and/or intensity of helminth infections . in our study , ifn- levels
it is well known that ifn- is downregulated by type-2 cytokines making our finding consistent with the literature .
ifn- is the most important type-1 cytokine and is produced by a diverse type of cells from both innate and adaptive immune arms such as natural killer ( nk ) , cd4 th1 , cd8 tc , and eosinophils .
it interacts with macrophages to activate direct antimicrobial and antitumor mechanisms as well as upregulating antigen processing and presentation pathways .
the overall interpretation of the different cytokines , their levels , and relationships with helminthic infections is an interesting challenge . in moderate - to - heavy ascariasis
this response was characterized by upregulation of il-13 and downregulation of ifn- , as well as by significantly higher il-4/ifn- ratio and ige levels .
results from t. trichiura infections were not as well - defined as those from ascariasis . nonetheless and similarly to a. lumbricoides , infections of high intensity were associated with lower values of ifn- and higher il-4/ifn- ratios and ige levels .
these findings confirm that a type-2 response against this parasite was also displayed in our study population .
as mentioned earlier , a type-1 immune response is needed for the control and clearance of intestinal protozoa such as entamoeba histolytica , cryptosporidium spp . , and giardia intestinalis .
although , particularly in the case of g. intestinalis , mixed th1-th2 responses have been reported , human and animal studies have shown that increased levels of ifn- play a crucial role in orchestrating the immune response and appear to be one of the main signatures in individuals with these parasitoses [ 7881 ] .
this description is in agreement with our findings of significantly higher ( up to 3-fold ) levels of ifn- found in children harbouring g. intestinalis and/or e. histolytica / dispar without the immune influence of sth infections ( i.e. , negative for helminthic infections ) .
the significantly lower il10/ifn- ratios observed in this group of children indicate a th1-biased response . additionally , in a 6-year longitudinal study in bolivia , blackwell and colleagues described an antagonist relationship between g. intestinalis and geohelminths where giardiasis was less likely to be present in helminth - infected individuals
likewise , they also found that infection with helminths was less likely for individuals with giardiasis .
our data , though cross - sectional , support these observations : none of the children infected with giardia intestinalis had ascariasis and only 10% of them had concomitant trichuriasis . since clearance and protective immunity against g. intestinalis require also th2 cytokines and antibodies , iga , igg , and ige [ 78 , 79 , 81 ] , a plausible scenario has been suggested : helminth - induced th2 response might provide cross - immunity against this protozoan .
a proper interpretation of our findings must be done considering the limitations of the present study .
firstly , its cross - sectional nature only allows establishing associations but no causality and , therefore , strong inferences can not be made .
secondly , we did not obtain a complete medical history from participating children or an accurate deworming history .
this is important as a variety of unmeasured confounding variables ( e.g. , bacterial and viral infections , autoimmune diseases , asthma , and other allergic diseases , as well as environmental and genetic factors ) may have contributed to skew the th1/th2 balance among research participants .
thirdly , we measured circulating levels of cytokines , which may not be an accurate representation of local immune responses in the gut milieu .
notwithstanding , the study has several strengths : an adequate sample size , determination of both helminthic and protozoal infections , and the use of highly sensitive and accurate methodology for biomarkers analysis .
this is the first study providing a comprehensive immune profile in honduran children infected with geohelminths or pathogenic protozoa .
our study shows that higher intensities of sth infections are associated with a polarized th2 response , characterized by reduced proinflammatory and increased regulatory cytokines , eosinophilia , and hyper - ige .
the interpretation of the host 's immune response against helminth represents challenging undertaking due to the high complexity of multiple host - parasite interactions and potential unmeasured confounders .
pivotal to characterizing and understanding the immune response is obtaining a meticulous clinical history from study participants , their deworming history , and very importantly the existence of multiple infections including pathogenic protozoa .
further , the role of the intestinal microbiota and its interplay with the host and its parasites can no longer be ignored .
 soil - transmitted helminth infections typically induce a type-2 immune response ( th2 ) , but no immunoepidemiological studies have been undertaken in honduras , an endemic country where the main control strategy is children 's annual deworming . 
 we aimed to characterize the immune profile of honduran schoolchildren harbouring these parasitoses . 
 demographic and epidemiological data were obtained through a survey ; nutritional status was assessed through anthropometry ; intestinal parasites were diagnosed by formol - ether and kato - katz ; and blood samples were collected to determine immunological markers including th1/th2 cytokines , ige , and eosinophil levels . 
 a total of 225 children participated in the study , all of whom had received deworming during the national campaign five months prior to the study . 
 trichuriasis and ascariasis prevalence were 22.2% and 20.4% , respectively . 
 stunting was associated with both age and trichuriasis , whereas ascariasis was associated with sex and household conditions . 
 helminth infections were strongly associated with eosinophilia and hyper - ige as well as with a th2-polarized response ( increased levels of il-13 , il-10 , and il4/ifn- ratios and decreased levels of ifn- ) . 
 pathogenic protozoa infections were associated with a th1 response characterized by elevated levels of ifn- and decreased il10/ifn- ratios . even at low prevalence levels , 
 sth infections affect children 's nutrition and play a polarizing role in their immune system . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusion