Clinical Pediatrics: Open Access
Open Access

Parasitic Infection as a Risk Factor for Childhood Asthma in Upper Egypt

Mohamed Alameldin Abdallah^1*, Randa E Abd-Elkader² and Doaa A Yones^{3 *}Correspondence: Mohamed Alameldin Abdallah, Department of Medicine, Assiut University, Children Hospital, Assiut, Egypt, Tel: +966557627259, Email:

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Introduction

Asthma as one of the most common allergic diseases causes major public health problem in many developed and developing countries. Asthma is characterized by chronic inflammation of the airways and it is one of the most common diseases among children worldwide. Asthma affects 300 million people worldwide.

The multidimensional relationship between parasitic infections and asthma. And atopy has been previously reported in many studies. However, the association between parasitic infection and childhood asthma and atopy remains controversial [1].

The immunomodulatory effects of some parasites and their protective effects upon asthma had been addressed in many studies. On the other hand A. Lumbricoides eggs were associated with an increased prevalence of asthma and anti- Ascaris IgE had been reported to be associated with an increased risk of asthma symptoms.

Human toxocariasis is a cosmopolite helminthic zoonosis caused by Toxocara canis and Toxocara cati, which are common roundworms of dogs and cats, respectively. It has been reported that an increased risk of wheeze in some populations may be associated Toxocara infections and that may be caused by the host response to the parasite or by parasite-enhanced Th2 responses to aeroallerges.

Activation of Th2-type immune response which takes place in giardiasis and proved by enhanced IgE production pointed to and confirmed its association with allergy. Also IgE production is larger and more severe in allergy-complicated giardiasis than that of uncomplicated cases.

The aim of this study was to assess the relationship between certain parasitic infection and the development and severity of asthma among children living [2].

Materials and Methods

A cross-sectional descriptive study was performed which included 140 children with persistent bronchial asthma (78 males and 62 females) recruited at Assiut University Children Hospital. Their ages were ranging from 5 to 14 years. As well as 70 apparently healthy children with matched age and sex were participated as controls.

Inclusion criteria

Agreement to participate; recurrent episodes of coughing, wheezing and breathlessness, especially if aggravated or triggered by exposure to inhaled allergens, viral infection or exercise and relieved by the use of bronchodilators, corticosteroids or subcutaneous epinephrine. Children should not take antiparasitic medication in the previous 6 months and provided three samples for parasite tests on alternate days [3].

Exclusion criteria

Not meeting all inclusion criteria, other causes of wheezy chest such as: tuberculosis, foreign body inhalation, bronchiectasis, bronchopneumonia or any other anatomic or congenital malformations

All cases and controls included in the study were subjected to:

• Meticulous history taking including

• Thorough clinical examination

• Laboratory investigations

Pulmonary function tests (PEFR and FEV1), stool examination, absolute eosinophilic count, IgE antibodies to Ascaris lumbricoides by serology, IgG antibodies to Toxocara canis by ELISA, serum IL-5 level and urinary Leukotriene E4 in urine. As regard the severity of asthma, we classified patients into 3 groups according to the Global Initiative for Asthma 2002.

• 20 patients had mild persistent asthma (12 males and 8 females)

• 60 patients had moderate persistent asthma (34 males and 28 females).

• 60 patients had severe persistent asthma (32 males and 26 females).

Stool examination

We collected stool samples from all participants in sterile clean stool plastic disposable cups with lids labeled with the patient’s serial number, name, age, and sex, group of BA and date of collection. Within half an hour all collected samples were examined parasitologically. We used iodine and lactophenol cotton blue for direct wet smear. Then, fomol-ether sedimentation was done to the stool samples and examined [4].

Urinary leukotriene E4

Urinary LTE4 levels were assessed using the commercially available enzyme immunoassay.

Blood samples

We collected blood samples from the participants by venipuncture. Cellular assay (AEC) was performed, and then the serum samples collected were stored at -70ºC until the serological analysis.

Total IgE levels

We used ELISA to measure total IgE levels where levels above 200 IU/mL were considered high. All samples were measured in duplicate.

Human IL-5 level assay

Human enzyme-linked immunosorbent assay kit is used to measure IL-5 levels, according to the manufacturer’s instructions. The lowest level of detection of IL-5 was 2 pg/mL. The intra-assay coefficient of variation was 7.4%, and the interassay coefficient of variation was 10%.

Detection of Ascaris lumbricoides infection in seology

We measured specific IgE levels against Ascaris by the CAP-FEIA fluoro enzyme immunoassay method.

Detection of Toxocara canis Infection in serology

Were prepared excretory or secretory antigens from laboratory cultivated second stage larvae. The antigen was stored at -70ºC until used as a crude antigen. We used ELISA technique to detect IgG against T. canis according to Van Kanpen. ELISA plates were coated by the prepared antigen [5].

Statistical analysis

We used SPSS statistics version 22 to analyze our data. Values were expressed as means and Standard Deviation (SD). Qualitative variables were presented as number (n) and percentage (%). We used Chi-square test to compare qualitative variables between groups. Unpaired t-test and Mann-Whitney “U” tests were used to compare quantitative variables. Anti- Ascaris IgE was classified into quartiles based on the distribution of the study participants.

Results

Regarding pulmonary functions, all groups of patients showed significantly lower PEFR% and FEV1% than controls but only FEV1% was insignificantly lower in mild group than controls. Regarding AEC, all patients showed significantly higher values than controls. IL-5 was significantly higher in different groups of patients than   controls.   Furthermore,   asthmatic   patients whatever collectively or subgroups showed significantly higher urinary LTE4 levels than controls.

Patients with severe and moderate asthma showed significantly lower PEFR% and FEV1% than mild patients and also severe patients showed significantly lower PEFR% and FEV1 % than moderate patients (Table 1) [6].

Table 1: Prevalence of parasitic infection among the examined asthmatic patients and controls.

As regard AEC, serum IL-5 and urinary LTE4, severe and moderate asthmatics showed significantly higher values than mild patients. Also, severe patients showed significantly higher values compared to moderate patients [7].

Among the studied patients Ascaris lumbricoides and Toxocara infections showed similar occurrence where they were detected in sera of 26 (18.6%), whereas Giardia infection was detected in stools of 28 (20%) of patients. Among 26 patients infected with Ascaris 15 patients have severe asthma, 9 patients have moderate asthma and 2 patients have mild asthma while among 26 patients infected with Toxocara 13 patients have severe asthma, 10 patients have moderate asthma and 3 patients have mild asthma. As regard 28 patients infected with Giardia 15 patients have severe asthma, 12 patients have moderate asthma and 1 patient have mild asthma. Among controls only Giardia infection was detected in stools of 4 (2.8%) of controls. Polyparasitism was not detected among patients or controls (Table 2) [8].

Table 2: Pulmonary functions, A.E.C, serum IL-5 and urinary LTE4 in patien ts with +ve and –ve Ascaris lumbricoides infection versus controls.

• PEFR: Peak Expiratory Flow Rate

• A.E.C : Absolute Eosinophilic Count

• HS: Highly significant (P<0.001)

• FEV1: Forced Expiratory Volume in 1 second

• ABG : Arterial Blood Gases

• NS: Non sngificant (P>0.05)

• IL-5: Interleukin-5

• S: Significant (P<0.05)

• MS: Moderately significant (P<0.005)

• LTE4: Leukotriene E

Regarding pulmonary functions, no significant difference was found between patients who were positive and those who were negative regarding Ascaris infection whereas, both groups showed significantly lower values of PEFR% and FEV1 % compared to controls (Table 3) [9].

Table 3: Pulmonary functions, A.E.C, serum IL-5 and urinary LTE4 in patients with +ve and –ve Toxocara canis infection versus controls.

Regarding AEC, patients with positive Ascaris infection showed significantly higher value than those with negative Ascaris infection. Both groups showed significantly higher values of AEC compared to controls. Regarding serum IL-5 and urinary LTE4, patients who were positive for Ascaris infection showed significantly higher values than those with negative Ascaris infection. Furthermore, both groups showed significantly higher values of serum IL-5 and urinary LTE4 compared to controls

Regarding pulmonary function, no significant difference was found between patients with positive and negative Toxocara infection whereas, both groups showed significantly lower values of PEFR% and FEV1 % compared to controls (Table 4) [10].

Table 4: Pulmonary functions, A.E.C, serum IL-5 and urinary LTE4 in patients with +ve and –ve Giardia infection versus controls.

Regarding AEC, patients who were positive for Toxocara infection showed significantly higher value than those with negative Toxocara infection. Both groups showed significantly higher values of AEC compared to controls. Regarding serum IL-5 and urinary LTE4, patients who were positive for Toxocara infection showed significantly higher values than those with negative Toxocara infection. Furthermore, both groups showed significantly higher values of serum IL-5 and urinary LTE4 compared to controls [11].

Regarding pulmonary functions, Giardia positive patients showed significantly lower PEFR % and FEV1% than patients with negative Giardia infection. Furthermore, both groups showed significantly lower PEFR% and FEV1% compared to controls.

Regarding AEC and urinary LTE4, patients with positive Giardia infection showed significantly higher values than patients with negative Giardia infection. Furthermore, both groups showed significantly higher values than controls. Regarding serum IL-5, patients with negative Giardia infection showed significantly higher value than patients with positive Giardia infections. Both groups showed significantly higher value than controls [12].

Discussion

Asthma is a chronic lung disease characterized by reversible airway obstruction, inflammation, and bronchial hyper responsiveness. In this study, the relationship between Ascaris lumbricoides, Toxocara canis, Giardia lamblia infections and development and severity of childhood asthma has been studied as regard the association of parasitic infections and bronchial asthma, ascariasis were detected in the sera of 26 patients (18.6%) and toxocariasis showed similar occurrence, whereas giardiasis was detected in the stools of 28 patients (20%). On the other hand only giardiasis was detected in stools of 4 (2.8%) of controls. It is possible for these parasites to be important risk factors in our communities. Our study revealed that parasitic infections with Ascaris, Toxocara and Giardia were more common among severely asthmatic children than among moderately and mildly asthmatics. This was supported by the finding of significantly higher levels of AEC, urinary LTE4 and IL-5 in Ascaris, Toxocara and Giardia positive asthmatics than negative ones. Also, pulmonary functions were insignificantly lower in the earlier than the latter [13].

These results were in line with previous studies who reported the increased prevalence of parasitic infections and possible influence of parasitic infections on the development and severity of allergic conditions in the tropical environment.

Our results were in agreement with systematic review and met analysis of 30 cross-sectional studies found that A. lumbricoids infection appeared to increase asthma risk.

Previous studies have provided conflicting evidence regarding relationship between parasitic infections and development of asthma. These studies showed that helminth infection can inhibit, cause or is unrelated to asthma. The role of anti-Ascaris IgE in the development of asthma is not clear. One possible explanation for the relationship is that elevated anti-Ascaris IgE levels are associated with larval migration after re-infection, as Ascaris migrates through the lungs during maturation and causes pulmonary infiltrates of Th2 immunity and episodic airway obstruction associated with wheezing. Repeated Ascaris infections and larval migration due to high rate of infection could increase the risk of asthma symptoms. Another explanation is that anti-Ascaris IgE acts as IgE specific to common inhaled aero-antigens directly triggering mast cell activation. This finding was supported by two other studies. The third explanation is that the higher anti-Ascaris IgE levels in the wheezing group simply mean that atopic children produce more anti-Ascaris IgE in response to Ascaris infection. Parallel to this observation, reported that exposure to Toxocara infection was suggested to be a possible risk factor for asthma. One good explanation for that is, Toxocara species can cause allergy (asthma) in man by liberation of larval excretory/secretory antigens. Moreover, Toxocara was found to induce polyclonal activation of IgE producing B-cells as well as peripheral and tissue eosinophilia. These phenomena are commonly occurred with IgE mediated diseases such as allergy [14].

There is hypothesis that many zoonotic helminth infections cannot develop to maturity in the human host and therefore, larvae may migrate for prolonged periods in the tissues. Examples are infections with Toxocara spp, Ascaris suum, and dog hookworms. Such infections cause allergic type syndromes such as cutaneous and visceral larva migrans. Damage of these tissues can be caused by allergic inflammation directed against the migrating larvae associated with failure of immune regulation during such infections probably because host and parasite have not co-evolved [15].

Our results were in line with Di Prisco found that Giardia lamblia parasitized children showed significantly higher levels of both total and specific serum IgE antibodies against allergens compared both with the non-parasitized group and those infected with parasites other than Giardia. The investigators concluded that there was a clear relation between giardiasis and allergy, possibly because infection by this protozoan enhanced sensitization towards food antigens, due to increased antigen penetration through damaged intestinal mucosa.

It has been reported that activation of the immune system takes occurs in giardiasis. It is wider and more severe in allergy- complicated giardiasis than that of uncomplicated cases, most probably due to non-invasive character of G. lamblia. Enhanced IgE production pointed to Th2-type immune response and confirms its association with allergy [16].

Conclusion

Ascaris, Toxocara and Giardia infections are more common among asthmatic children compared to healthy children and they were significantly associated with the disease severity therefore, infection with these parasites may be a risk factor for the development and severity of bronchial asthma among children in Upper Egypt.

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