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Repeated Treatments with Albendazole Previous studies have shown that single or multiple doses of
anthelmintic drugs have negligible effects on human cytokine
Enhance Th2 Responses to Ascaris responses to parasite antigens [6, 7] and that long-term anthel-
Lumbricoides, but Not to Aeroallergens, mintic treatments may increase allergen skin-test reactivity to
aeroallergens [8, 9]. Because programs to control geohelminth
in Children from Rural Communities infections administer anthelmintic drugs periodically over long
in the Tropics periods, it is important to determine whether anthelmintic
drugs administered over the long term have important immu-
Philip J. Cooper,1,2,3 Ana Lucia Moncayo,1 Irene Guadalupe,1 nologic effects. To investigate whether repeated anthelmintic
Susana Benitez,1,2 Maritza Vaca,1,2 Martha Chico,1,2 and treatments have important effects on immunity to parasite an-
George E. Griffin3
tigens and aeroallergens, we examined cytokine response and
1Centro de Investigaciónes FEPIS, Quinindé, Esmeraldas Province, and 2Instituto
histamine release in whole-blood samples from children living
de Microbiologia, Universidad San Francisco de Quito, Quito, Ecuador; 3Centre
BMI, body-mass index; epg, eggs per gram of stool; GM, geometric mean; t, time when observed (t ⫽ 0
is the value at baseline or the pretreatment value; t ⫽ 12 is the value at 12 months of follow-up).
a Includes allergen skin tests positive for Alternaria tenuis, cat, grass pollen mix, and fungi mix.
b Infection intensity shown excludes noninfected children.
c Directly observed treatments with single doses of 400 mg of albendazole.
americana) or to other heterologous immunological stimuli (tu- Two strengths of the present study are that selection into the
berculin and lipopolysaccharide), the treated children were dif- study was blinded to treatment status and that the treated group
ferent from the untreated children. The data provide evidence and the untreated group were similar with respect to important
that long-term anthelmintic treatment has important effects on baseline factors. A relatively large sample of children was inves-
antiparasite immunity, but not on aeroallergen-associated im- tigated, optimizing the study’s ability to detect important differ-
munity, in peripheral blood. ences. Children were selected from a large number of schools,
Untreated Treated
Immunologic
variable Subjects, no. Median (IQR) R, % Subjects, no. Median (IQR) R, %
Cytokine
Interleukin-10
Medium 102 0 (0–0) 20 95 0 (0–0) 13
SEB 102 131 (86–217) 92 95 116 (55–212) 97
Ascaris 102 0 (0–8)* 27* 95 0 (0–0) 9
Tuberculin (purified protein derivative) 102 0 (0–18)* 34 95 0 (0–0) 20
Lipopolysaccharide 102 1503 (1016–2035) 100 95 1284 (817–1949) 100
Cockroach 102 14(0–50) 64 95 22(0–122) 61
Dermatophagoides pteronyssinus 102 0 (0–221) 50 95 0 (0–278) 43
Interferon-␥
Medium 107 0 (0–0) 15 107 0 (0–0) 11
SEB 107 9961 (9160–9961) 100 107 9961 (9257–9961) 100
Ascaris 107 0 (0–2) 28 107 0 (0–28) 32
Tuberculin (purified protein derivative) 107 72 (4–389) 77 107 107 (3–521) 79
NOTE. IQR, interquartile range; R, proportion of subjects with either detectable levels of cytokine or ⬎10% histamine release; SEB, Staphylococcus
enterotoxin B.
* P ⭐ .01 (from bivariate analysis).
** P ⭐ .001 (from bivariate analysis).
thereby minimizing any systematic biases that could occur if tinuous exposure to geohelminths (i.e., as in the untreated
only a few schools were considered. The data collected were from group) may suppress parasite-specific Th2 cytokine produc-
a population in which ascariasis and trichuriasis have high prev- tion—and that repeated treatments with albendazole for 1 year
alence (defined as 肁50% [12]) and light intensity (defined as may reverse this effect. Interestingly, IgE-mediated inflamma-
⬎90% of subjects with stool egg counts of ⬍50,000 eggs per tory responses (measured by histamine release) to parasite anti-
gram [epg] for A. lumbricoides and ⬍10,000 epg for Trichuris gens were not affected by long-term treatment. Previous studies
trichiura [12]); the immunomodulating effects in populations examining the short-term effects that 2 or more doses of anthel-
with high intensities of infection may be greater, or the effects mintic drugs have on the immune response to ascariasis [6] and
may be different for other geohelminth parasites, such as hook- hookworm [7] showed that such treatment had negligible effects
worm. Because of widespread access to anthelmintic drugs and on cytokine production by parasite antigen–stimulated PBLs.
mass-treatment programs, few populations in Latin America There are 3 possible explanations for the differences between the
have high-prevalence heavy-intensity ascariasis and trichuriasis short- and long-term immunologic effects of anthelmintic
infections, and the findings of the present study may be general- drugs. First, a prolonged infection-free period may be necessary
izable to most endemic areas where these parasites predominate. to reverse the suppression of Th2 cytokines. Second, geohel-
After 12 months, repeated treatments with albendazole had not minth larvae may be the primary target of host immunity and
cured all geohelminth infections in the treated group, and the immune regulation [6, 15]. In the present study, all family mem-
prevalence of geohelminth infections had declined slightly in the bers of children in the treated group were treated also with al-
untreated group—suboptimal treatments in the treated group bendazole every 2 months. If suppression of Th2 responses were