Route of dexamethasone administration influences parasite burden in Strongyloides hyperinfection model

Abstract

Rodents infected with Strongyloides venezuelensis are experimental models applied to strongyloidiasis research. This study evaluated oral and subcutaneous dexamethasone (DEX) treatments to establish immunosuppression in an experimental model of Strongyloides hyperinfection. Rattus norvegicus Wistar were divided: G I (-): untreated and uninfected animals, G II (+): untreated and infected, G III (o -) orally treated and uninfected, G IV (o +) orally treated and infected, G V (sc -) subcutaneously treated and uninfected, G VI (sc +) subcutaneously treated and infected. For oral administration, DEX was diluted in sterile water (5 µg/ml) and made available to the animals on intervals in experimental days - 5-0, 8-13 and 21-26. For subcutaneous administration, animals received daily injections of DEX disodium phosphate (2 mg/kg). Infection was established by the subcutaneous inoculation of 3000 S. venezuelensis filarioid larvae. Groups were evaluated by egg per gram of feces and parasite females counts and IgG, IgG1 and IgG2a detection. GIV (o +) had egg peaks count on days 13 and 26 and maintained egg elimination until the last experimental day. Parasitic females recovery at day 30 was significantly higher in G IV (o +) when compared to G VI (sc +). Levels of IgG, IgG1 and IgG2a of all groups, except the positive control GII (+), were below the detection threshold. Pharmacological immunosuppression induced by oral administration of DEX produced high parasitic burden, and is a noninvasive method, useful to establish immunosuppression in strongyloidiasis hyperinfection model in rats.

Keywords: Dexamethasone; Experimental infection; Hyperinfection; Immunosuppression; Strongyloides venezuelensis.

Fig. 1

Egg per gram of feces (EPG) count on days 5, 7, 8, 13, 21, 26 and 30 of S. venezuelensis infected animal groups. Values are expressed in median and interquartile range. G II (+): untreated (≤). G IV (o +): dexamethasone orally treated (). G VI (sc +): dexamethasone subcutaneously treated (ρ). Differences were statistically significant when p < 0.05. The intergroup comparisons are represented by symbols: ^* G II (+) vs. G IV (o +), ^# GII (+) vs. G VI (sc +), ^& G IV (o +) vs. G VI (sc +)

Fig. 2

Strongyloides venezuelensis parasitic females count at day 30. Values are expressed in median and interquartile range. G II (+): untreated and infected animals. G IV (o +): orally treated and infected animals. G VI (sc +): subcutaneously treated and infected animals. Differences were statistically significant when p < 0.05. The intergroup comparisons are represented by symbols: ^& G IV (o +) vs. G VI (sc +)

Fig. 3

Detection of total IgG (A), IgG1 (B), IgG2a (C) antibodies on days 0, 8, 13, 21 and 30 by indirect ELISA. Data expressed in ELISA Index (EI) and values > 1 are considered positive. G I (−): untreated and uninfected animals. G II (+): untreated and infected animals. G III (o −): orally treated and uninfected animals. G IV (o +): orally treated and infected animals. G V (sc −): subcutaneously treated and uninfected animals. G VI (sc +): subcutaneously treated and infected animals