Association of atopy, asthma, allergic rhinoconjunctivitis, atopic dermatitis and intestinal helminth infections in Cuban children


Corresponding Author Meike Wördemann, Department of Parasitology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium. Tel.: +32 3 247 6353; Fax: +32 3 247 6359; E-mail:


Objective  To examine the relationship of past and current intestinal helminth infections with asthma, allergic rhinoconjunctivitis, atopic dermatitis and atopy.

Methods  Cross-sectional study of 1320 children aged 4–14 years from two Cuban municipalities. Helminth infections were determined by stool examination and parental questionnaire. Asthma, rhinoconjunctivitis and atopic dermatitis were diagnosed by International Study of Asthma and Allergies in Childhood questionnaire, asthma additionally by spirometry, atopy by skin prick testing.

Results  Questionnaire-based frequencies were 21% for asthma, 14% for allergic rhinoconjunctivitis and 8% for atopic dermatitis. According to spirometry, 4% had asthma; 20% had a positive skin prick test. A history of infection for Enterobius vermicularis was associated with increased risk of atopic dermatitis (OR 1.88, = 0.001) and allergic rhinoconjunctivitis (OR 1.34, = 0.046), and hookworm with increased risk of allergic rhinoconjunctivitis (OR 2.77, = 0.021). A positive stool examination for Ascaris lumbricoides infection was negatively associated with atopic dermatitis (OR 0.22, = 0.007). Asthma and atopy were unrelated to helminth infections.

Conclusion  Current A. lumbricoides infection protects against atopic dermatitis in Cuban children, while past infection with E. vermicularis and hookworm are risk factors for allergic rhinoconjunctivitis and/or atopic dermatitis. Apparently, interactions differ depending on the type of helminth and atopic disease and on the time of helminth infestation.


Association entre atopie, asthme, rhinoconjonctivite allergique, dermatite atopique et infections intestinales à helminthes chez des enfants cubains

Objectifs  Examiner l’association entre des infections intestinales courantes et celles du passéà helminthes avec l’asthme, la rhinoconjonctivite allergique, la dermatite atopique et l’atopie.

Méthodes  Etude transversale sur 1320 enfants âgés de 4 à 14 ans dans deux municipalités cubaines. Les infections à helminthes ont été déterminées par l’examen de selles et un questionnaire parental. L’asthme, la rhinoconjonctivite et la dermatite atopique ont été diagnostiqués grâce au questionnaire de l’Etude Internationale de l’Asthme et des Allergies de l’enfance, l’asthme a été diagnostiqué en plus par la spirométrie et l’atopie par le test de piqûre de la peau.

Résultats  les taux obtenus selon le questionnaire étaient de 21% pour l’asthme, 14% pour la rhinoconjonctivite allergique et 8% pour la dermatite atopique. Selon la spirométrie, 4% des enfants avaient de l’asthme, 20%étaient positifs pour le test de piqûre de la peau. Un historique d’infection par E. vermicularisétait associéà un plus grand risque de dermatite atopique (OR = 1,88; P = 0,001) et de rhinoconjonctivite allergique (OR = 1,34; P = 0,046), et l’ankylostome était associéà un plus grand risque de rhinoconjonctivite allergique (OR = 2,77; P = 0,021). Un examen positif des selles pour l’infection àA. lumbricoidesétait négativement associéà la dermatite atopique (OR = 0,22; P = 0,007). L’asthme et l’atopie étaient indépendants des infections à helminthes.

Conclusion  L’infection courante àA. lumbricoides protège contre la dermatite atopique chez les enfants cubains, alors que l’infection par le passéàE. vermicularis et l’ankylostome est un facteur de risque pour la rhinoconjonctivite allergique et/ou la dermatite atopique. Les interactions diffèreraient selon le type d’helminthe et de maladie atopique et selon la période de l’infestation par des helminthes.


Asociación entre atopia, asma y rinoconjuntivitis alérgica, dermatitis atópica y helmintiasis intestinal en niños Cubanos

Objetivos  Examinar la relación existente entre una helmintiasis intestinal pasada o actual, con el asma, la rinoconjuntivitis alérgica, dermatitis atópica y atopia.

Métodos  Estudio croseccional de 1320 niños con edades comprendidas entre los 4 y 14 años, procedentes de dos municipalidades Cubanas. Se determinó la infección con helmintos mediante examen coprológico y un cuestionario a los padres. El asma, la rinoconjuntivitis y la dermatitis atópica se diagnosticaron mediante el cuestionario del Estudio Internacional de Asma y Alergias en Niños, y adicionalmente el asma mediante espirometría, y la atopia en piel mediante pruebas cutáneas (prick test).

Resultados  Las frecuencias, basadas en el cuestionario, fueron de 21% para el asma, 14% rinoconjuntivitis alérgica y 8% dermatitis atópica. Según la espirometría, un 4% tenía asma. Un 20% tuvo una prueba cutánea positiva. Se asoció una historia de infección por E. vermicularis con un mayor riesgo de dermatitis atópica (OR 1.88, P = 0.001) y rinoconjuntivitis alérgica (OR 1.34, P = 0.046), y anquilostoma con un mayor riesgo de rinoconjuntivitis alérgica (OR 2.77, P = 0.021). Un examen coprológico positivo para infección con A. lumbricoides estaba asociado de forma negativa con dermatitis atópica (OR 0.22, P = 0.007). El asma y la atopia no estaban relacionadas con infecciones por helmintos.

Conclusión  Un infección activa con A. lumbricoides protege contra dermatitis atópica en niños cubanos, mientras que infecciones pasadas con E. vermicularis y anquilostoma son factores de riesgo para rinoconjuntivitis alérgica y/o dermatitis atópica. Aparentemente las interacciones difieren dependiendo del tipo de helminto y de enfermedad atópica presente en el momento de infestación con helmintos.


The observation that atopic diseases are very common and helminthic infections relatively uncommon in developed countries and that the inverse is true in many developing countries has led to the speculation that the two phenomena may be inversely associated. The idea is part of a broader hypothesis suggesting that exposure to infections in early childhood reduces the risk of developing allergies, the so-called ‘hygiene hypothesis’. However, the relationship between atopic diseases and helminthic infection remains uncertain and controversial (Nyan et al. 2001; Sharghi et al. 2001; Palmer et al. 2002; Cooper et al. 2004; Van den Biggelaar et al. 2004).

Most studies have been on intestinal helminth infection in relation to asthma and atopy, and little is known on the association with other atopic outcomes such as atopic dermatitis and allergic rhinoconjunctivitis (Huang et al. 2002; Schäfer et al. 2005). Moreover, they focussed on the current exposure to helminth infections, which makes it difficult to identify the temporal sequence between the two phenomena. In this study, we examined the association of past and current intestinal helminth infections with asthma, atopic dermatitis, allergic rhinoconjunctivitis and atopy among schoolchildren in two Cuban municipalities where helminth infections are prevalent and atopic disease levels are reported to be very high (Masoli et al. 2004; Wördemann et al. 2006a). We also investigated the contribution of other common risk factors which have been found to be associated with atopic diseases and/or atopy in literature (Bufford & Gern 2005).


Study group

A cross sectional study was performed between 2003 and 2004 in San Juan y Martínez, a municipality in the West of Cuba and in Fomento, a municipality in the center of the island. In San Juan y Martínez all children (= 398) from five, and in Fomento all children (= 922) from 14 primary schools were included in the study. Using Survey Select, SAS version 8.0 (SAS Institute Inc., Cary, NC, USA), schools were randomly selected after stratification for municipality (San Juan y Martinez or Fomento) and area (urban or rural); all children from each school were included. Both municipalities are rural mountainous areas which have been reported to be endemic for helminthiasis (Escobedo et al. 2007; Wördemann et al. 2006b).

Informed written consent was obtained from the parents of each child. The study was approved by the ethical committees of the Institute of Tropical Medicine in Antwerp, Belgium, the Pedro Kouri Institute of Tropical Medicine (IPK) and the National Institute for Hygiene, Epidemiology and Microbiology (INHEM) in Havana, Cuba.

Study design

All participating children were submitted to spirometry before and after exercise, skin prick testing and stool examination. Furthermore, a parent or guardian of each child was interviewed using an extended version of the standard Spanish version of the ISAAC questionnaire (Asher et al. 1995). ISAAC definitions of atopic diseases were used: current asthma was defined as an affirmative answer to the second ISAAC core asthma question on current wheeze (The ISAAC Steering Committee 1998); allergic rhinoconjunctivitis was diagnosed as defined by Strachan et al. (1997) and atopic dermatitis as defined by Williams et al. (1999) (an affirmative answer to the second and third core question of the ISAAC rhinitis or dermatitis questionnaire, respectively). Additional questions concerned factors that have been described to be associated with allergic sensitisation or atopic diseases in literature (Bufford & Gern 2005): intake of antibiotics during first year of life, pet ownership or contact during first year of life, pet ownership or contact at present, gastroesophageal reflux (either frequent vomiting, or pyrosis, or sourly smelling breath, or regular refused feeding during infancy), smoking in the household, family atopy (atopy of father, mother or sibling), presence of siblings, pre-school daycare attendance and being breastfed during infancy.

Atopy was defined as a positive skin prick test reaction to at least one of the applied allergens. Skin prick testing was performed using extracts of seven allergens that have been used worldwide by ISAAC (Dermatophagoides pteronyssinus, D. farinae, cat dander, mixed tree, mixed grass, Alternaria alternata, and cockroach) produced by ALK, Nieuwegein, The Netherlands. Histamine (10 mg/ml) was used as a positive and allergen diluent as a negative control. The extracts and controls were placed on the volar side of the left forearm using separate ALK lancets. Skin response was measured after 15 min, considering the largest weal dimension (3 mm or larger) in the absence of significant reactivity of the diluent control as a positive reaction.

To demonstrate bronchial hyperresponsiveness (BHR), spirometry was performed before and 5 and 10 min after exercise (6 min free running) according to ATS (American Thoracic Society) guidelines (The American Thoracic Society, Medical Section of the American Lung Association 1987; The American Thoracic Society 2000) in all children (4–14 years old) using a handheld computerized spirometer (Spirobank, MIR, Rome, Italy). If at baseline the FEV1 was lower than 70% of the predicted value as defined by the European Respiratory Society and Knudson et al. (1976), or if the FEV1 had fallen more than 15% either 5 or 10 min after exercise, spirometry was considered abnormal. In such a case the child received a bronchodilator to aid recovery, and spirometry was repeated after 20 min to make sure that for all children the baseline values were obtained again.

One fresh stool sample was collected from each child for one direct smear and two 25 mg Kato Katz examinations (Katz et al. 1972). Current helminth infections were defined by the presence of helminth eggs (Ascaris lumbricoides, Trichuris trichiura, hookworm or Enterobius vermicularis) detected by either of the two methods. Furthermore, a history of helminth infections was taken for each subject. The parents were asked if their child ever had a parasite infection, and if yes, which parasite. If the parents did not know the name of the parasite, its appearance was described to them (e.g. lombrices pequenos or lombricillas for ‘small white worms’, i.e. E. vermicularis, or lombrices blancos grandes for ‘large white worms’, i.e. A. lumbricoides). No pictures were used.

For all statistical computations stata for Windows, version Intercooled stata 9 was used. A P-value of ≤0.05 was considered statistically significant. Statistical analyses were adjusted for the sampling design using the school as primary sampling unit. Municipality (San Juan y Martinez or Fomento) and area (rural/urban) were included as stratification variables. Factors identified as statistically significant in the univariate analyses were entered into a stepwise logistic regression model adjusted for age (linear), sex, municipality, area and household income (≤250 pesos, or >250 pesos).


A total of 1320 children were sampled from 19 schools. The age range of the participating children was 4–14 years (median 8 years); 679 boys (51%) and 641 girls (49%). Response rate to the questionnaires was 100% (1320/1320) and 99–100% for the other tests (1319/1320 for skin prick test, 1308/1320 for spirometry). Of the 1313 children who provided stool samples, 83 (6%) were positive for A. lumbricoides, 126 (10%) for T. trichiura, 121 (9%) for hookworm, and 36 (3%) for E. vermicularis; 295 (22%) children were positive for at least one of these helminths. Geometric mean egg counts for helminth positive children were 947.1 eggs per gram of feces (epg) for A. lumbricoides, 133.6 epg for T. trichiura and 210.5 epg for hookworm; eggs were not counted for E. vermicularis. Of the 1320 children whose parents were interviewed, 349 (26%) had a history for A. lumbricoides, 5 (<1%) for T. trichiura, 39 (3%) for hookworm and 763 (58%) for E. vermicularis. 279 (21%) of the children were reported to have current wheeze, 54 (4%) had an abnormal spirometry, 267 (20%) showed a positive reaction to the skin prick test, 179 (14%) had allergic rhinoconjunctivitis as defined by Strachan and 110 (8%) had atopic dermatitis as defined by Williams.

After adjusting for age, sex, municipality, urban/rural background and income, history of hookworm infection was associated with increased risk of allergic rhinoconjunctivitis, and a history of infection with E. vermicularis with increased risk of atopic dermatitis and allergic rhinoconjunctivitis. A positive stool examination for A. lumbricoides was inversely related to atopic dermatitis. Trichuris trichiura did not have a significant effect on any of the atopic diseases, neither by questionnaire nor by stool examination. Skin prick test reactivity, current wheeze and spirometry were not significantly associated with any of the examined helminths on multiple regression (Tables 1 and 2).

Table 1.   Results of the univariate analysis for associations between atopic diseases and helminth infections as well as other common risk factors. Univariate logistic regression was adjusted for age, sex, municipality, urban/rural background and income; = number of children within subgroup; % = percentage of children within the subgroup who show the outcome
 Allergic rhinoconjunctivitisAtopic dermatitisCurrent wheezeSpirometrySkin prick test
Risk factor
History of parasite infection
Ascaris lumbricoidesYes34923.31.1530.3429.71.2170.38329.51.5740.0196.31.5570.02319.51.2790.100
No96914.5  7.8  18.1  3.2  20.6  
No127916.0  8.4  20.8  4.0  20.6  
Enterobius vermicularisYes76318.01.5030.00210.21.8900.00122.71.3520.0923.80.9750.93820.10.8490.363
No55414.3  5.8  19.0  4.3  20.8  
Current parasite infection
 Any helminth Yes No29518.61.0840.6606.40.7000.25622.71.0120.9323.00.5860.17818.30.8820.426
101716.1  9.0  20.8  4.3  20.9  
A. lumbricoidesYes8323.50.9160.6862.40.2220.00826.50.9480.8462.40.3780.16513.30.8880.729
No123015.9  8.8  20.8  4.1  20.9  
No119216.5  8.3  21.6  4.0  20.6  
E. vermicularisYes3612.50.8800.7605.60.6320.46016.70.9020.7950Too few samples 11.10.4560.149
No127716.4  8.5  21.3  4.0  20.7  
Trichuris trichiuraYes12622.81.3240.2755.60.5880.09429.41.4550.0564.00.8810.76120.61.0860.629
No117515.8  8.8  20.4  4.0  20.6  
Other common risk factors
 Antibiotics first yearYes64322.82.1520.00110.91.8970.00229.12.5200.0004.71.2990.25520.01.0760.468
No67610.3  5.9  13.5  3.3  20.3  
 Current pet ownership Yes104516.00.9600.8887.80.7050.03120.90.9560.8504.00.9820.96920.60.8760.508
No27618.1  10.5  22.1  4.0  19.2  
 Current pet contactYes114015.81.0950.7068.31.0400.88820.40.9470.8184.56.3900.02220.80.7990.514
No18121.9  8.3  26.0  1.1  17.1  
 Previous pet ownershipYes81114.20.7400.1128.10.9380.84320.70.9480.6474.81.9150.05121.31.0200.858
No51020.2  8.6  21.8  2.8  18.6  
 Previous pet contactYes51416.11.1040.7009.01.1970.47922.41.2290.1555.31.8840.12922.01.0540.733
No80716.7  7.9  20.3  3.2  19.2  
 Symptoms of refluxYes71621.02.0730.00110.11.4960.05626.01.9290.0004.91.7770.00920.00.9370.604
No60410.3  6.3  15.4  3.0  20.1  
 Smoking in householdYes64516.40.9870.9287.40.7360.10419.90.8200.2233.30.6650.22320.91.1160.302
No67616.5  9.2  22.3  4.7  19.7  
 Family atopyYes60321.11.9100.00210.51.6020.02329.92.9340.0005.82.7120.00022.41.3260.100
No71312.4  6.5  13.7  2.5  18.5  
 Presence of siblingsYes108617.31.2750.2288.71.4000.23521.61.1720.3554.11.1760.69619.70.9310.742
No21613.7  7.0  19.5  3.2  21.3  
 Daycare attendanceYes23116.81.3180.1098.21.0920.69224.81.4410.0483.00.7010.39519.10.8570.190
No109016.4  8.4  20.4  4.2  20.1  
No5318.4  5.7  28.3  7.6  11.3  
Table 2.   Results of the final multivariate logistic regression models for associations between atopic diseases and helminth infections as well as other common risk factors. Factors identified as statistically significant at the 5% level in univariate analysis were entered into a stepwise forward logistic regression model. Multiple logistic regression was adjusted for age, sex, municipality, urban/rural background and income irrespective of their significance level. Only significant results are shown
Variable/risk factorOR95% CIP-value
Allergic rhinoconjunctivitis
 Hookworm (history)2.811.23–6.420.017
Enterobius vermicularis (history)1.341.00–1.790.048
 Symptoms of reflux1.741.24–2.440.003
 Family atopy1.671.07–2.590.025
 Antibiotics first year1.801.28–2.530.002
Atopic dermatitis
E. vermicularis (history)1.861.34–2.580.001
Ascaris lumbricoides (feces)0.230.08–0.680.011
 Family atopy1.561.09–2.240.017
 Antibiotics first year1.611.10–2.350.017
 Current pet contact0.680.48–0.980.039
Current wheeze
 Family atopy2.602.00–3.38<0.001
 Antibiotics first year2.111.55–2.86<0.001
 Symptoms of reflux1.591.20–2.110.003
Abnormal spirometry before or after exercise
 Current pet contact 6.561.30–33.130.025
Family atopy2.771.94–3.97<0.001


Despite evidence that helminth infections and atopic diseases are inversely associated (Scrivener et al. 2001; Cooper et al. 2004; Van den Biggelaar et al. 2004) the relationship between the two is still not clear (Palmer et al. 2002). Previous studies have provided conflicting evidence showing that helminthiases either cause (Palmer et al. 2002), inhibit (Scrivener et al. 2001; Cooper et al. 2004; Van den Biggelaar et al. 2004) or are unrelated to atopic diseases (Sharghi et al. 2001; Davey et al. 2005; Cooper et al. 2006); or that atopic diseases protect from helminth infections (Nyan et al. 2001). Our study confirms the existence of different associations between helminth infections and atopic diseases, the nature of which appears to depend on the type of helminth infection and atopic disease studied. Also, the time of worm infestation seems to play a role as suggested by the questionnaire based results in comparison with those based on stool examination. Unfortunately, prior data on stool examination were not available, so we had to rely on questionnaires to obtain information on the children’s history of helminth infections, as has been done by others (Palmer et al. 2002; Schäfer et al. 2005). We are, however, aware of the limitations of this approach. The method is rather unspecific and insensitive, with the risk of measuring the effect of conspicuous and heavy worm infections only. The cross-sectional study design and potential information and recall bias in the questionnaire data do not allow making any strong temporal associations. Longitudinal studies are certainly a more valid approach to examine the causal association between helminth infections and atopic diseases. Nevertheless, we think that our data do give an indication of the importance of time of worm infestation in this relationship. In general, the results of cross sectional studies have an important value in the design of new longitudinal studies.

We found a negative association between current A. lumbricoides infection and atopic dermatitis, suggesting that A. lumbricoides might protect against atopic dermatitis. However, the inverse cannot be excluded either, especially since a history of infection with A. lumbricoides did not have any effect on atopic dermatitis. A bi-directional inverse relationship between helminthic infections and atopic dermatitis was reported by Schäfer et al. (2005), who used questionnaire data on the history of atopic dermatitis and worm infestations including extra questions on their time of onset. Taking into account the temporal sequence of the onset of atopic dermatitis and time of infestation, they found prior worm infestations to be negatively associated with atopic dermatitis and prior atopic dermatitis to be negatively associated with worm infestations.

Data on the relationship between intestinal parasites and atopic dermatitis and allergic rhinoconjunctivitis are scarce (Huang et al. 2002; Schäfer et al. 2005). We found a history of infection with E. vermicularis to be associated with an increased risk of allergic rhinoconjunctivitis and atopic dermatitis, the latter in contrast to Schäfer et al., who reported a negative association between prior infestation with E. vermicularis and atopic dermatitis in East German schoolchildren.

We did not find any association between current E. vermicularis infection and atopic dermatitis or allergic rhinitis. Huang et al. (2002) had similar results for atopic dermatitis, but reported a negative association with allergic rhinitis and asthma. But in Huang’s study current infection with E. vermicularis was based on tape test examination. We only used stool examination, which is much less sensitive (Tsibouris et al. 2005) and may thus explain the lack of an effect of current E. vermicularis infection on atopic diseases in our study population.

In our Cuban study population, a history of infection with hookworm was associated with an increased risk for allergic rhinoconjunctivitis. To our knowledge we are the first to find an association between hookworm infections and allergic rhinoconjunctivitis.

Trichuris trichiura was not related to any atopic disease. These results are in line with the results by Dagoye et al. (2003), who found T. trichiura to be unrelated to wheeze in contrast to other helminths. Especially helminths with a systemic phase in their life cycle could influence atopic disease (Scrivener et al. 2001; Dagoye et al. 2003).

Asthma in Cuban children was not related to helminthiasis, whether defined as current wheeze or as abnormal spirometry. The percentage of children with bronchial hyperresponsiveness found with spirometry (4%) and of those with current wheeze reported by parents (21%) differed considerably, as has been described before (Wördemann et al. 2006a). Both methods have limitations and their use for the diagnosis of asthma, separately or together, has been debated (Demissie et al. 1998; Remes et al. 2002; Gruchalla et al. 2003). Also skin prick test reactivity was not affected by helminths, confirming the results of Palmer et al. (2002) and Cooper et al. (2006). Skin prick test reactivity in relation with helminth infections may depend on intensity and chronicity of helminth infections, such that heavy and chronic helminth infections protect from atopy (Lau & Matricardi 2006). Thus the lack of an effect of worm infection on skin prick test reactivity in our study and those of Palmer et al. (2002) and Cooper et al. (2006) might be due to the rather lower intensities and prevalences than those in which skin prick test reactivity was inversely related with helminthiasis (Cooper et al. 2003; Van den Biggelaar et al. 2004).

We also examined the effect of other common risk factors for atopic diseases and/or atopy (Bufford & Gern 2005). Antibiotic intake during the first year of life was significantly associated with an increased risk for current wheeze, atopic dermatitis and allergic rhinoconjunctivitis in our study population. An interference of antibiotic intake with intestinal flora and a subsequent impact on the development of atopy and atopic diseases has been suggested before (Hart et al. 2002). Yet the association between antibiotic intake and atopic diseases could also be inverse, with an increased antibiotic intake due to allergic symptoms wrongly diagnosed as bacterial infections or due to respiratory infections requiring antibiotic treatment in asthmatic children, as suggested by Bufford and Gern (2005). Symptoms of reflux were associated with allergic rhinoconjunctivitis and current wheeze. The latter has been found by Nordenstedt et al. (2006) in Norway as well and seems to be due to heightened bronchial reactivity and microaspirations in patients with reflux.

Current animal contact was negatively associated with atopic dermatitis. In literature animal contact is generally described to have a protective effect against atopic diseases (Bufford & Gern 2005). Other risk factors, such as breastfeeding, sibling size, daycare attendance, smoking in household, pet ownership or contact during first year of life did not have a significant impact on atopic diseases. A recent overview shows that associations between the above mentioned risk factors and atopic diseases often are inconsistent (Bufford & Gern 2005).


Current A. lumbricoides infection protects against atopic dermatitis in Cuban children, while past infection with E. vermicularis and hookworm are risk factors for allergic rhinoconjunctivitis and/or atopic dermatitis. Apparently, interactions differ depending on the type of helminth and atopic disease and on the time of helminth infestation.


We thank all children, parents, teachers, school staff as well as the staff in the policlinics, the health authorities and all field workers who participated in this study.