Natural immunity to Ascaris lumbricoides associated with immunoglobulin E antibody to ABA-1 allergen and inflammation indicators in children, Infect. Immun. 67

Children putatively immune to the large roundworm Ascaris lumbricoides were identified in an area of Nigeria where infection is hyperendemic. Immunity was associated with higher levels of serum ferritin, C-reactive protein, and eosinophil cationic protein, indicating ongoing acute phase or inflammatory processes. In contrast, children who were susceptible to the infection had little serological evidence of inflammation despite their high parasite burdens. Immunoglobulin G (IgG) antibody activity in all subclasses was present in high titer in most children but appeared to have no protective function. Despite exceptionally high total IgE levels, there was no evidence that atopic responses to local common allergens was associated with natural immunity to Ascaris. Among those individuals who produced IgG antibody to recombinant ABA-1 allergen of Ascaris, the naturally immune group had significantly more IgE antibody to the allergen than did those susceptible to the infection. IgE antibody responses in conjunction with innate inflammatory processes therefore appear to associate with natural immunity to ascariasis. Helminth parasites are renowned for inducing elevated levels of serum immunoglobulin E (IgE) (20, 33), but the protective role of the antibody component of this response remains debatable The large roundworm of humans, Ascaris lumbricoides, inhabits the intestine, but juvenile-stage worms undergo a tissuemigratory phase involving the liver and lungs before returning to the intestine, where they mature to large adult worms. The pulmonary phase can cause potentially lethal hypersensitivity responses in infected individuals, particularly children, and worm material is notorious for the allergic reactions that it provokes in laboratory workers (33). A. lumbricoides infects a quarter of humanity and people can remain infected for much of their lives, although at the population level, intensity of infection decreases with age after a peak within the first decade of life in high-intensity areas We have examined a range of serum factors in African children living in an area highly endemic for A. lumbricoides, using the number of worms developing to maturity as a measure of immunity status. Quantifying worm burden is superior to using the number of eggs released, because egg production is a poor indicator of the number of adult worms present (15, 18) and may miss low-level infections. The children were examined for infection on two separate occasions, and those either consistently infected or putatively immune were identified. Neither the mechanisms by which immunity to A. lumbricoides operates nor the site within the body at which it is manifest is known. Therefore, in addition to measuring of antibody in the different isotypes, we examined a range of serological markers for inflammatory responses to provide an indication of the pathological processes which might accompany immune killing of the parasites. We find that natural immunity to Ascaris is associated with IgE antibody to a major allergen of the parasite and a serum protein profile consistent with ongoing inflammatory processes. MATERIALS AND METHODS Study population. The study site was in an area of Nigeria (Ile-Ife) in which more than 80% of the school children (5 to 15 years old) were infected with intestinal nematodes, particularly A. lumbricoides (for full details, see reference 18). A group of children were treated for their intestinal nematode infections, and their worm burdens were collected and counted over a 48-h period after anthelminthic treatment (phase 1). The anthelminthic used was Ketrax (levamisole; ICI Pharmaceuticals, Macclesfield, United Kingdom), and children were given the appropriate dosage according to the manufacturer's instructions. The exercise was repeated 6 months later (phase 2), at which time blood samples were collected from 92 of the children. The children were classified as follows: category 1, those with no worms on either of the two occasions (putatively immune); category 2, those with consistently light infections (1 to 24 worms in phase 1 and 1 to 8 worms in phase 2); or category 3, those who were consistently heavily infected or susceptible, i.e., had more than the population mean plus 1 standard deviation worm burden on both occasions. The means Ϯ standard deviations of the worm burdens in phases 1 and 2 were 11.02 Ϯ 13.7 and 3.5 Ϯ 5.6, respectively. Category 3 comprised children with worm counts of Ն25 after the first treatment and Ն9 after the second treatment. There were 22, 47, and 23 children in categories 1, 2, and 3, respectively. None of the children showed overt signs o