Outcomes in mice with abdominal angiostrongyliasis treated with enoxaparin

Abstract

Abdominal angiostrongyliasis (AA) is caused by the nematode Angiostrongylus costaricensis. Parasite-associated thrombosis of mesenteric vessels may lead to intestinal infarction, which might be prevented with anti-thrombotic agents. This study assessed the effect of enoxaparin on survival and pathological findings in Swiss mice with AA. In this experiment, 24 mice were infected with A. costaricensis (10 L3 per animal) followed by treatment with subcutaneous enoxaparin (40 mg/kg/day) or water (sham), starting from 15 days post-infection (dpi) and continued until animal death. Animals were monitored until death or sacrifice at the 50th dpi. Ten mice (42%) were dead after 36 ± 8 dpi. Of these, five (50%) were treated with enoxaparin. Animals treated with enoxaparin and sham did not differ in terms of weight loss (median, 1.3 vs. 4.2 g; P = 0.303) and macroscopical findings. Microscopically, no difference was found in regard to vascular granuloma (median grade, 2 vs. 3; P = 0.293) and presence of either vasculitis (75% vs. 100%; P = 0.217), mesenteric thrombosis (33% vs. 50%; P = 0.680), or bowel necrosis (25% vs. 50%; P = 0.400). Mice dead before the 50th dpi showed more pneumonia (90% vs. 21%; P = 0.002), bowel infarction (40% vs. 0%; P = 0.02), and purulent peritonitis (60% vs. 7%; P = 0.008) compared to survivors. Prophylactic enoxaparin in mice did not prevent tissue damage and mortality related with AA. The lower prevalence of mesenteric thrombosis and bowel infarction regardless of treatment were notorious. Frequent septic complications suggest the need of studies addressing the effect of antibiotics in AA.

Proteolytic activity in the adult and larval stages of the human roundworm parasite Angiostrongylus costaricensis

“…A published method based on a polymerase chain reaction may eventually improve our ability to diagnose the disease, although the results are still preliminary . Moreover, many studies have assessed different types of therapies with limited success, such as treatment with anthelmintic drugs (Morera & Bontempo 1985, Mentz & Graeff-Teixeira 2003, Bohrer Mentz et al 2007), anti-inflammatory drugs (Fante et al 2008) and antithrombotic agents (Rodriguez et al 2011). The present consensus is that anthelmintic drug administration is not recommended given that it usually induces the erratic migration of worms instead of killing them (Morera & Bontempo 1985).…”

Angiostrongylus costaricensisinfection in Martinique, Lesser Antilles, from 2000 to 2017

“…Anthelmintic treatment using benzimidazole-derived compounds is debatable because their larvicidal effect aggravates the inflammatory response, leading to more severe lesions, and may favor the erratic migration of adult parasites and larvae [ 39 ]. Recent studies in mouse models showed that prophylactic enoxaparin treatment does not prevent tissue damage and mortality related to abdominal angiostrongyliasis [ 54 , 55 ]. The four patients in our case series were treated with an anthelmintic as standard treatment for cases of high eosinophilia before diagnostic confirmation.…”

PCR for the Diagnosis of Abdominal Angiostrongyliasis in Formalin-Fixed Paraffin-Embedded Human Tissue

“…Finally, most of our cases compromised small and/or large bowel, particularly with the pseudotumoral form. It is characterized by severe eosinophilic infiltrate in the bowel wall, accompanied by perivascular granulomatous reaction, eventually with retention of parasitic structures such as eggs and larvae [21]. Curiously, cases of perforation were restricted to patients with small bowel lesions, as described by Graeff-Teixeira et al [3], and few cases of AA presented as acute appendicitis.…”