The immune system has evolved, in large part, through its interaction with microbes and parasites, an interaction that drives specific or specialized immune responses to deal with the widely varying groups of microorganisms. For example, parasite-derived induction of interleukin (IL)-4, IL-5, and IL-13 coordinate the prototypical responses to metazoan helminth pathogens,1 whereas viral- and bacterial-specific induction of Type 1 and Type 2 interferons are required for control of these types of infections.1 Interestingly, these responses (broadly inflammatory in nature) themselves, if uncontrolled, can harm the host by causing allergic diseases (Th2-associated inflammation) or autoimmune/inflammatory disorders (typically Th1- and/or Th17-associated). Typically, on the heels of such inflammation come anti-inflammatory networks that are required to prevent long-standing tissue damage.2
These regulatory (or anti-inflammatory) processes triggered during infection underlies the “Hygiene Hypothesis”3 that states that infections, especially during childhood when immune responses are being “educated” and the T- and B-cell memory pool is being created, protect against inflammation-associated disorders4 because they modulate or limit immune-mediated effector responses. Indeed, the presence of helminth infections has been associated (to a small degree) with modulation of the severity of inflammatory bowel disease,5 diabetes,6 and arthritis7–9 to cite just a few examples.
There is little consensus among the many studies that have examined the interaction between helminth infection and atopy (Table 1). This lack of consensus is most likely related to the differences in outcome measures/definitions used in the many studies that have used a variety of outcomes including: 1) the severity or frequency of asthma, rhinitis, or eczema; 2) the frequency of allergen sensitization by skin prick tests (SPTs); or 3) the levels of allergen-specific IgE (asIgE) levels in the blood. Other causes for the disparate results relate to variation among the species of infecting helminths and differences in the age of the populations being studied. To attempt to reconcile these differences, meta-analyses have been performed; these, too, have not been conclusive. For example, while Ascaris lumbricoides was found to be a risk factor for the development of asthma, hookworm infection was associated with a protective effect.60 Infection with other parasites such as Trichuris trichiura, Enterobius vermicularis, and Strongyloides stercoralis had no effect on the outcome of asthma.60 Conversely, the presence of A. lumbricoides was found to lower the frequency of atopy (measured by SPT) to at least one environmental allergen in most studies61 (Table 1), but not to the perennial allergens, cockroach or house dust mite (HDM).61 Hookworm infection has also been associated with protection from atopy to some allergens, but not to HDM or to cockroach extract.61 Interestingly, the majority of the published studies demonstrate that while helminth infection decreases the frequency of SPT positivity, these infections are associated with increased allergen-specific IgE (asIgE) (Figure 1).
Detailed list of human studies examining the influence of helminth infection on atopy
| First author, year | Country | N | Helminth | Allergen(s) | Clinical evaluation | SPT‡ | asIgE§ | |
|---|---|---|---|---|---|---|---|---|
| Parasites* | Assessed† | Outcome | Effect | Prevalence | ||||
| Authors concluded that helminths offer protection against allergies | ||||||||
| Hagel, 199310 | Venezuela | 89 | Al | Not informed | ND | ↓ | ↓ | |
| van den Biggelaar, 200011 | Gabon | 520 | Sh | HDM | ND | ↓ | ND | |
| Araujo, 200012 | Brazil | 175 | Sm | HDM, mold | ND | ↓ | Trend ↓ | |
| van den Biggelaar, 200113 | Gabon | 520 | Sh | HDM | ND | ↓ | ↑ | |
| Nyan, 200114 | Gambia | 429 | Al | Various | Wheeze | No change | ↓ | ND |
| Scrivener, 200115 | Ethiopia | 604 | Hkw, Al | HDM | Wheeze | ↓ | No change | No change |
| Huang, 200216 | Taiwan | 3,107 | Ev | Not informed | Asthma, rhinitis | ↓ | ND | ND |
| Cooper, 2003a17 | Ecuador | 4,433 | Al, Tt | Various | Wheeze, rhinitis, rash | No change | ↓ | ND |
| Cooper, 2003b18 | Ecuador | 2,865 | Various | Various | ND | ↓ | ||
| Dagoye, 200319 | Ethiopia | 563 | Al | HDM, CR | Wheeze | ↓ | No change | |
| Wahyuni, 200520 | Indonesia | 466 | Bm | HDM | ND | Trend ↓ | ↑ | |
| Flohr, 200621 | Vietnam | 1,601 | Hkw, Al | HDM, CR | ND | ↓ | ND | |
| Rodrigues, 200822 | Brazil | 1,055 | Al, Tt | Various | ND | ↓ | ||
| Endara, 201023 | Ecuador | 3,901 | Al, Tt | Not informed | Eczema | ↓ | ↓ | ND |
| Supali, 201024 | Indonesia | 441 | Bm | CR | ND | ↓ | ||
| Rujeni, 201225 | Zimbabwe | 672 | Sh | HDM | ND | ↓ | ↓ | |
| Kanobana, 201226 | Cuba | 958 | Tc, Al, Hkw | Not informed | Asthma | ↑ (Tc) ↓ (Hkw) | ND | ND |
| Alcantara-Neves, 201227 | Brazil | 1,445 | Various | Various | Asthma/wheeze | No change | ↓ | No change |
| Mendonça, 201228 | Brazil | 1,148 | Tc | HDM, CR | ND | ↓ | ↑ | |
| Manuel, 201229 | Malaysia | 170 | Tc | Not informed | Rhinitis | ↓ | ||
| Oliveira, 201430 | Brazil | 91 | Sm | HDM, CR, mold | ND | ↓ | ND | |
| Authors found mixed or no association or took no conclusions | ||||||||
| Davey, 200531 | Ethiopia | 7,649 | Various | HDM, CR | Wheeze | No change | ↓ | |
| Ponte, 200632 | Brazil | 113 | Al | HDM | Asthma | No change | No change | No change |
| Calvert, 201033 | South Africa | 3,322 | Al | HDM | EIB | ↑ | ↓ | No change |
| Vereecken, 201234 | Cuba | 1,285 | Al, Tc, Hkw | HDM, CR | Asthma | No change | ↓ | ↑ |
| Souza, 201435 | Brazil | 20 | Al | HDM | ND | ND | No change | |
| Alcantara-Neves, 201436 | Brazil | 1,271 | Al, Tt, Tc | Various | ND | ↓ | No change | |
| Hamid, 201537 | Indonesia | 623 | Al, Tc | HDM, CR | Wheeze, eczema | No change | ↓ | ↑ (Tc) |
| Wordemann, 200838 | Cuba | 1,320 | Ev, Hkw, Al | Various | Asthma, rhinitis, AD | ↑ (Ev, Hkw) ↓ (Al) | No change | ND |
| Obeng, 201439 | Ghana | 1,385 | Sh, Al, Tt | Various | Asthma/wheeze | No change | ↓ (Sh) ↑ (Tt) | NE |
| Authors concluded that helminths are a risk factor for allergies | ||||||||
| Kayhan, 197840 | Turkey | 100 | Al | Not informed | Asthma | ↑ | ND | ND |
| Joubert, 198041 | South Africa | 259 | Al | Various | ND | ↑ | ↑ | ↑ |
| Alshishtawy, 199142 | Egypt | 105 | Sm | HDM, pollen | Asthma | ↑ | ND | ↑ |
| Buijs, 199743 | Netherlands | 1,379 | Tc | HDM, cat, dog | Asthma | ↑ | ↑ | |
| Lynch, 199744 | Venezuela | 89 | Al | HDM | Asthma | ↑ | ↑ | ↑ |
| Dold, 199845 | Germany | ∼2,300 | Al | Various | Asthma, rhinitis | ↑ | ↑ | ↑ |
| Palmer, 200246 | China | 2,164 | Al | Various | Asthma | ↑ | ↑ | ND |
| Benicio, 200447 | Brazil | 1,132 | Al, Tt | Not informed | Wheeze | ↑ | ND | ND |
| Daschner, 200548 | Spain | 135 | As | AsE | Chronic urticaria | ↑ | ND | ND |
| Obihara, 200649 | South Africa | 359 | Al(IgE) | HDM | Asthma | ↑ | ↑ | ↑ |
| Bahceciler, 200750 | Istanbul | 1,018 | Ev | Various | Wheeze, rhinitis | ↑ | No change | ND |
| Pereira, 200751 | Brazil | 1,011 | Al | Various | Wheeze/asthma | ↑ | ↓ | |
| Hagel, 200752 | Venezuela | 470 | Al | AlE, HDM | Asthma | ↑ | ↑ (Al-IgE) | ND |
| Hunninghake, 200753 | Costa Rica | 439 | Al | HDM, CR | Asthma | ↑ | ↑ | ↑ |
| Alcantara-Neves, 201054 | Brazil | 682 | (IgE)Tt, Al | Various | Wheeze | ↑ | ND | ↑ |
| Walsh, 201155 | United States | 12,174 | Tc | NE | Asthma | ↑ | ND | ND |
| Choi, 201156 | Korea | 1,116 | Cs | Various | Asthma, rhinitis | No change | ↑ | ↑ |
| Moncayo, 201257 | Ecuador | 376 | Al | AlE, HDM, CR | Wheeze | ↑ | No change | ↑ |
| Buendia, 201558 | Colombia | 313 | Al | HDM | Asthma | ↑ | ↑ | ↑ |
| Webb, 201659 | Uganda | 2,316 | Various | Various | Wheeze | ↑ | ↑ | ↑ |
Al = Ascaris lumbricoides; As = Anisakis simplex; Bm = Brugia malayi; Cs = Clonorchis sinensis; Ev = Enterobius vermicularis; Hkw = hookworm; Sh = Schistosoma haematobium; Sm = Schistosoma mansoni; Tc = Toxocara canis; Tt = Trichuris trichiura.
AlE = Ascaris lumbricoides extract; AsE = Anisakis simplex extract; CR = cockroach; HDM = house dust mite.
SPT = skin prick test.
asIgE = aeroallergen-specific IgE; AD = allergic dermatitis; EIB = exercise-induced bronchorreactivity; ND = not determined.
Aggregated overview of multiple studies on the helminth/allergy interface. The areas shaded black indicate increased prevalence of allergic reactivity in the presence of helminth infection, the areas shaded white indicate decreased prevalence, and those in gray indicate no change in prevalence on clinical outcome (left circle), skin prick test (SPT; middle circle), and aeroallergen-specific IgE (asIgE; right circle).
Citation: The American Society of Tropical Medicine and Hygiene 95, 4; 10.4269/ajtmh.16-0348
Aggregated overview of multiple studies on the helminth/allergy interface. The areas shaded black indicate increased prevalence of allergic reactivity in the presence of helminth infection, the areas shaded white indicate decreased prevalence, and those in gray indicate no change in prevalence on clinical outcome (left circle), skin prick test (SPT; middle circle), and aeroallergen-specific IgE (asIgE; right circle).
Citation: The American Society of Tropical Medicine and Hygiene 95, 4; 10.4269/ajtmh.16-0348
Aggregated overview of multiple studies on the helminth/allergy interface. The areas shaded black indicate increased prevalence of allergic reactivity in the presence of helminth infection, the areas shaded white indicate decreased prevalence, and those in gray indicate no change in prevalence on clinical outcome (left circle), skin prick test (SPT; middle circle), and aeroallergen-specific IgE (asIgE; right circle).
Citation: The American Society of Tropical Medicine and Hygiene 95, 4; 10.4269/ajtmh.16-0348
The concept that helminth infection modulates allergic diseases emerged in the 1970s62–64 and has been debated ever since.40,65–70 As depicted in Table 1, it has often been observed that helminth infections commonly reduce the frequency of SPT reactivity and increase the levels of asIgE (Table 1 and Figure 1). This apparent dichotomy was felt to reflect the expansion of polyclonal IgE-secreting B cells, an expansion that would lead to high levels of IgE with multiple specificities leading to an inability to trigger a mast cell or basophil response. It was thought that allergens, in such conditions, could not physically cross-link the asIgE bound to the high-affinity Fc epsilon (FcɛRI) because of the multiple differing IgE antibody specificities on proximal FcɛRIs. Although theoretically possible, this concept has largely been discarded based on studies that suggest that the ratio of polyclonal to antigen-specific IgE needed to prevent basophil or mast cell degranulation rarely is achieved in vivo since it requires only cross-linking a few hundred FcɛRIs on cell membranes to trigger activation.71,72 More recent data allow us to propose other mechanisms at work in helminth infection that drive asIgE in helminth-infected populations (e.g., cross-reactive IgE) or modulate SPT positivity (e.g., IL-10) as discussed below.
Because chronic helminth infections often induce both IgE and IgG isotypes, especially IgG4 antibodies, it has been proposed that IgG can also contribute to the modulation of type I hypersensitivity responses. IgGs are usually induced in quantities 1,000- to 10,000-fold greater than those of IgE, and as such, the IgG antibodies bind antigen prior to the antigen being available to trigger an IgE-mediated effector response. This so-called “blocking phenomenon” has been explored, and two mechanisms have been identified: physical73,74 and inhibition of target cells by FcγRIIb activation by IgG complexed to antigens.74–76 Although other IgG isotypes have been implicated in physical IgE blocking, IgG4 seems to play a major role.77 It has been demonstrated that IgG can intercept allergen before it binds to IgE present on membranes of mast cells and basophils,74 and that allergen-IgG complexes can deactivate target cell by activation of the inhibitory Fc receptor (FcγRIIb), that in turn activates phosphatases in the molecular cross-linking regions of IgE shutting down FcɛRI signaling.78,79
A more unifying explanation suggests that IL-10, a primarily T-cell–derived cytokine commonly induced in chronic helminth infection,80–82 may underlie the protection from SPT positivity.11,83 Indeed, it is believed that the IL-10 modified Th2 response may be responsible for the parasite-antigen-specific tolerance imprinted on the host by helminth infection.80,84,85 Parasite-induced IL-10 or other regulatory mechanisms—that can involve cell populations such as Tregs81,86 and Bregs87–89—can increase the IgE-induced activation threshold of basophils,90 regulate T-cell91,92 and B-cell activation,92 promote IgG class switch,93 and IgG4-producing B-cell differentiation and proliferation.94 Moreover, IL-10 has been shown to drive down the production of IgE while at the same time induce isotype switching to IgG4.95,96
Despite the regulatory responses that helminth infections can induce in the host, these may not be sufficient to counteract the Th2-associated processes that mediate many allergic diseases. This puts into a framework the concept that a very delicate balance between pro- and anti-allergenic effector responses is required to maintain homeostasis. It is widely known that helminth parasites are associated with antigen-driven expansion of Th2 cells97–99 along with polyclonal T-cell activation.97–99 Interestingly, allergen extracts and helminths excretory/secretory products often share similar properties that can lead to Type 2-associated responses. For example, both are rich in proteases100 that can promote Th2 differentiation through protease-activated receptor 2101–103 directly on T cells102 or indirectly by inducing IL-33 or thymic stromal lymphopoietin production by tissue cells104,105 or IL-13 production by macrophages.106 In addition, both allergens and helminths are known to increase numbers and activity of type 2 innate lymphoid cells107–110 that license dendritic cells to promote Th2 priming in lymph nodes.111
Along with this strong, specific, and polyclonal Th2 activation induced by helminth infection, these infections also induce both polyclonal- and antigen-specific IgE production.112 Whether a result of this Th2-associated response or of some other type of response (e.g., Treg, IL-10, transforming growth factor-β), it has been observed that helminth infection causes decreases in IgG responses to parenterally-administered vaccines113 and increases in IgE responses to bystander antigens.114–117 This IgE bystander effect has been suggested to be one of the reasons that helminth parasites can promote allergic reactivity through mechanisms that include: B-cell IgE polyclonal activation; IgE potentiation in which infection creates an environment that will favor IgE production to other nonparasite antigens; and IgE cross-reactivity among parasite antigens and environmental allergens.
There has been increased interest in IgE cross-reactivity involving helminth parasites and allergens as well.116–128 We have demonstrated that helminth infection can be associated with increased IgE responses to many different allergens, especially those structurally related to parasite antigens.116 Individuals infected with filarial parasites were shown to have higher levels of IgE against HDM and cockroach extracts (that have several major allergens with homologues in filarial parasites) but not against timothy grass extract, an allergen extract with just a few minor allergen homologues in helminths.116
In more detailed studies, cross-reactivity among allergens and parasite molecules has been well described for tropomyosin,120,122,129 considered a pan-allergen.130 Tropomyosins are highly conserved across many species and cross-reactivity is not surprising from the structural point-of-view. This allergen has dominated discussions about helminth-allergen cross-reactivity, and many reviews have already discussed its implications in detail.131,132 However, studies on allergen and parasite protein sequences have found that huge numbers of allergens have both linear133 and conformational134 epitopes with significant similarity to homologous helminth proteins. The structural basis for this “allergenicity” has been inferred from bioinformatic analyses, in which it has been shown that the level of identity conservation between allergens and parasite proteins were negatively correlated with IgE prevalence to that allergen.133 Furthermore, most of the major allergens with homologues in helminth parasites show medium to low levels of conservation with helminth proteins (amino acid identities ranging from 20% to 40%),133 levels of identity deemed unlikely to be subject of antibody cross-reactivity. Nevertheless, evidences of cross-reactivity among less-conserved pairs of antigens have been demonstrated recently,116,117,120,123,133 suggesting that this may be a broader phenomenon than previously appreciated. It was noticed that extracts of the cockroach Blatella germanica (Bla g) can inhibit the binding of IgE to several Anisakis simplex allergens.118 Similarly, IgE binding to several Ascaris allergens can also be inhibited by Dermatophagoides pteronyssinus (Der p) or Blomia tropicalis (Blo t) extracts, including glutathione-S-transferase (GST).120
GSTs are major allergens of HDM,119 cockroach,135 mold,136,137 and parasites.138,139 Among the 13 classes of canonical GSTs, there are many that show very little amino acid conservation.140 Even with the small degree of sequence conservation, cross-reactivity among parasite and allergenic GST has been demonstrated formally.123 There was found to be a significant positive correlation of antiallergenic (Bla g 5, Der p 8, and Blo t 8) and antiparasite (Ascaris and filarial) GST-specific IgE levels in humans.123,138 In addition, experimental models have corroborated these findings. For example, Heligmosomoides polygyrus infection induced IgE anti-cockroach GST,123 and immunization studies with Ascaris antigens induced IgE and Th2 cells against HDM extract.117 Despite helminth protein and allergen cross-reactions leading to cross-sensitization in humans are possible,58,141–144 formal proof has not, to date, been demonstrated, especially for poorly conserved allergen-helminth proteins pairs.
Thus, the interface between helminth infection and allergic disorders reflects the delicate balance between the regulatory responses and the pro-allergenic effects of the parasites. Despite the relatively consistent finding that the presence of an active helminth infection results in lower prevalence of SPT to common environmental allergens, the fact that these same helminth infections markedly increase levels of antigen-specific IgE suggest that the complex interplay among this antigen- and allergen-specific IgE, the high affinity FcɛRI on effector cells, the regulatory and effector cytokines, and the cells at barrier sites must be studied in concert to truly understand this very complex interaction.
- 2.↑
Medzhitov R, Schneider DS, Soares MP, 2012. Disease tolerance as a defense strategy. Science 335: 936–941.
- 4.↑
Bach JF, 2002. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347: 911–920.
- 6.↑
Aravindhan V, Mohan V, Surendar J, Rao MM, Ranjani H, Kumaraswami V, Nutman TB, Babu S, 2010. Decreased prevalence of lymphatic filariasis among subjects with type-1 diabetes. Am J Trop Med Hyg 83: 1336–1339.
- 7.↑
Panda AK, Ravindran B, Das BK, 2013. Rheumatoid arthritis patients are free of filarial infection in an area where filariasis is endemic: comment on the article by Pineda et al. Arthritis Rheum 65: 1402–1403.
- 8.
Pineda MA, McGrath MA, Smith PC, Al-Riyami L, Rzepecka J, Gracie JA, Harnett W, Harnett MM, 2012. The parasitic helminth product ES-62 suppresses pathogenesis in collagen-induced arthritis by targeting the interleukin-17-producing cellular network at multiple sites. Arthritis Rheum 64: 3168–3178.
- 9.↑
Rocha FA, Leite AK, Pompeu MM, Cunha TM, Verri WA Jr, Soares FM, Castro RR, Cunha FQ, 2008. Protective effect of an extract from Ascaris suum in experimental arthritis models. Infect Immun 76: 2736–2745.
- 10.↑
Hagel I, Lynch NR, Perez M, Di Prisco MC, Lopez R, Rojas E, 1993. Modulation of the allergic reactivity of slum children by helminthic infection. Parasite Immunol 15: 311–315.
- 11.↑
van den Biggelaar AH, van Ree R, Rodrigues LC, Lell B, Deelder AM, Kremsner PG, Yazdanbakhsh M, 2000. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 356: 1723–1727.
- 12.↑
Araujo MI, Lopes AA, Medeiros M, Cruz AA, Sousa-Atta L, Sole D, Carvalho EM, 2000. Inverse association between skin response to aeroallergens and Schistosoma mansoni infection. Int Arch Allergy Immunol 123: 145–148.
- 13.↑
van den Biggelaar AH, Lopuhaa C, van Ree R, van der Zee JS, Jans J, Hoek A, Migombet B, Borrmann S, Luckner D, Kermsner PG, Yazdanbakhsh M, 2001. The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren. Int Arch Allergy Immunol 126: 321–338.
- 14.↑
Nyan OA, Walraven GE, Banya WA, Milligan P, Van Der Sande M, Ceesay SM, Del Prete G, McAdam KP, 2001. Atopy, intestinal helminth infection and total serum IgE in rural and urban adult Gambian communities. Clin Exp Allergy 31: 1672–1678.
- 15.↑
Scrivener S, Yemaneberhan H, Zebenigus M, Tilahun D, Girma S, Ali S, McElroy P, Custovic A, Woodcock A, Pritchard D, Venn A, Britton J, 2001. Independent effects of intestinal parasite infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study. Lancet 358: 1493–1499.
- 16.↑
Huang SL, Tsai PF, Yeh YF, 2002. Negative association of Enterobius infestation with asthma and rhinitis in primary school children in Taipei. Clin Exp Allergy 32: 1029–1032.
- 17.↑
Cooper PJ, Chico ME, Bland M, Griffin GE, Nutman TB, 2003. Allergic symptoms, atopy, and geohelminth infections in a rural area of Ecuador. Am J Respir Crit Care Med 168: 313–317.
- 18.↑
Cooper PJ, Chico ME, Rodrigues LC, Ordonez M, Strachan D, Griffin GE, Nutman TB, 2003. Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics. J Allergy Clin Immunol 111: 995–1000.
- 19.↑
Dagoye D, Bekele Z, Woldemichael K, Nida H, Yimam M, Hall A, Venn AJ, Britton JR, Hubbard R, Lewis SA, 2003. Wheezing, allergy, and parasite infection in children in urban and rural Ethiopia. Am J Respir Crit Care Med 167: 1369–1373.
- 20.↑
Wahyuni S, Sartono E, Supali T, van der Zee JS, Mangali A, van Ree R, Houwing-Duistermaat JJ, Yazdanbakhsh M, 2005. Clustering of allergic outcomes within families and households in areas endemic for helminth infections. Int Arch Allergy Immunol 136: 356–364.
- 21.↑
Flohr C, Tuyen LN, Lewis S, Quinnell R, Minh TT, Liem HT, Campbell J, Pritchard D, Hien TT, Farrar J, Williams H, Britton J, 2006. Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study. J Allergy Clin Immunol 118: 1305–1311.
- 22.↑
Rodrigues LC, Newcombe PJ, Cunha SS, Alcantara-Neves NM, Genser B, Cruz AA, Simoes SM, Fiaccone R, Amorim L, Cooper PJ, Barreto ML, 2008. Early infection with Trichuris trichiura and allergen skin test reactivity in later childhood. Clin Exp Allergy 38: 1769–1777.
- 23.↑
Endara P, Vaca M, Chico ME, Erazo S, Oviedo G, Quinzo I, Rodriguez A, Lovato R, Moncayo AL, Barreto ML, Rodrigues LC, Cooper PJ, 2010. Long-term periodic anthelmintic treatments are associated with increased allergen skin reactivity. Clin Exp Allergy 40: 1669–1677.
- 24.↑
Supali T, Djuardi Y, Wibowo H, van Ree R, Yazdanbakhsh M, Sartono E, 2010. Relationship between different species of helminths and atopy: a study in a population living in helminth-endemic area in Sulawesi, Indonesia. Int Arch Allergy Immunol 153: 388–394.
- 25.↑
Rujeni N, Nausch N, Bourke CD, Midzi N, Mduluza T, Taylor DW, Mutapi F, 2012. Atopy is inversely related to schistosome infection intensity: a comparative study in Zimbabwean villages with distinct levels of Schistosoma haematobium infection. Int Arch Allergy Immunol 158: 288–298.
- 26.↑
Kanobana K, Vereecken K, Junco Diaz R, Sariego I, Rojas L, Bonet Gorbea M, Polman K, 2013. Toxocara seropositivity, atopy and asthma: a study in Cuban schoolchildren. Trop Med Int Health 18: 403–406.
- 27.↑
Alcantara-Neves NM, Veiga RV, Dattoli VC, Fiaccone RL, Esquivel R, Cruz AA, Cooper PJ, Rodrigues LC, Barreto ML, 2012. The effect of single and multiple infections on atopy and wheezing in children. J Allergy Clin Immunol 129: 359–367.
- 28.↑
Mendonca LR, Veiga RV, Dattoli VC, Figueiredo CA, Fiaccone R, Santos J, Cruz AA, Rodrigues LC, Cooper PJ, Pontes-de-Carvalho LC, Barreto ML, Alcantara-Neves NM, 2012. Toxocara seropositivity, atopy and wheezing in children living in poor neighbourhoods in urban Latin American. PLoS Negl Trop Dis 6: e1886.
- 29.↑
Manuel AM, Kuljit S, Gopalakrishnan G, Suresh KG, Balraj P, 2012. The role of worm infestation in allergic rhinitis. Trop Biomed 29: 360–365.
- 30.↑
Oliveira SM, Bezerra FS, Carneiro TR, Pinheiro MC, Queiroz JA, 2014. Association between allergic responses and Schistosoma mansoni infection in residents in a low-endemic setting in Brazil. Rev Soc Bras Med Trop 47: 770–774.
- 31.↑
Davey G, Venn A, Belete H, Berhane Y, Britton J, 2005. Wheeze, allergic sensitization and geohelminth infection in Butajira, Ethiopia. Clin Exp Allergy 35: 301–307.
- 32.↑
Ponte EV, Rasella D, Souza-Machado C, Stelmach R, Barreto ML, Cruz AA, 2014. Reduced asthma morbidity in endemic areas for helminth infections: a longitudinal ecological study in Brazil. J Asthma 51: 1022–1027.
- 33.↑
Calvert J, Burney P, 2010. Ascaris, atopy, and exercise-induced bronchoconstriction in rural and urban South African children. J Allergy Clin Immunol 125: 100–105.
- 34.↑
Vereecken K, Kanobana K, Wordemann M, Junco Diaz R, Menocal Heredia L, Ruiz Espinosa A, Nunez FA, Rojas Rivero L, Bonet Gorbea M, Polman K, 2012. Associations between atopic markers in asthma and intestinal helminth infections in Cuban schoolchildren. Pediatr Allergy Immunol 23: 332–338.
- 35.↑
Souza V, Medeiros D, Sales I, Costa V, Silva A, Rizzo J, Sole D, Sarinho E, 2014. Ascaris lumbricoides infection in urban schoolchildren: specific IgE and IL-10 production. Allergol Immunopathol (Madr) 42: 206–211.