Abstract

BackgroundTrypanosoma cruzi is the etiological agent of Chagas disease (CD) or American trypanosomiasis, an important public health problem in Latin America. Benznidazole (BZ), a drug available for its treatment, has limited efficacy and significant side effects. Essential oils (EOs) have demonstrated trypanocidal activity and may constitute a therapeutic alternative. Our aim was to evaluate the efficacy of the EOs of clove (CEO - Syzygium aromaticum) and ginger (GEO - Zingiber officinale), administered alone and in combination with BZ, in Swiss mice infected with T. cruzi.MethodsThe animals were inoculated with 10,000 blood trypomastigotes of the Y strain of T. cruzi II by gavage and divided into four groups (n = 12 to 15): 1) untreated control (NT); 2) treated with BZ; 3) treated with CEO or GEO; and 4) treated with BZ + CEO or GEO. The treatments consisted of oral administration of 100 mg/kg/day, from the 5th day after parasite inoculation, for 20 consecutive days. All groups were submitted to fresh blood examination (FBE), blood culture (BC), conventional PCR (cPCR) and real-time PCR (qPCR), before and after immunosuppression with cyclophosphamide.ResultsClove and ginger EOs, administered alone and in combination with BZ, promoted suppression of parasitemia (p < 0.0001), except for the animals treated with CEO alone, which presented a parasitemia curve similar to NT animals. However, there was a decrease in the BC positivity rate (p < 0.05) and parasite load (< 0.0001) in this group. Treatment with GEO alone, on the other hand, besides promoting a decrease in the BC positivity rate (p < 0.05) and parasite load (p < 0.01), this EO also resulted in a decrease in mortality rate (p < 0.05) of treated mice.ConclusionsDecreased parasite load, as detected by qPCR, was observed in all treatment groups (BZ, CEO, GEO and BZ + EOs), demonstrating benefits even in the absence of parasitological cure, thus opening perspectives for further studies.

Highlights

  • Trypanosoma cruzi is the etiological agent of Chagas disease (CD) or American trypanosomiasis, an important public health problem in Latin America

  • The Essential oils (EOs) of Z. officinale alone promoted a greater reduction of parasite load, even when compared with the reference drug (BZ), which could improve the outcome of T. cruzi infection

  • The molecular analysis in this study demonstrated that qPCR has high sensitivity in the detection of T. cruzi II DNA, even surpassing Conventional polymerase chain reaction (cPCR), and evidences therapeutic failure in animals that had presented negative results by the other methods (BC and cPCR)

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Summary

Introduction

Trypanosoma cruzi is the etiological agent of Chagas disease (CD) or American trypanosomiasis, an important public health problem in Latin America. Trypanosoma cruzi is a hemoflagellate protozoan (Class Kinetoplastida, family Trypanosomatidae), and the etiologic agent of Chagas disease (CD), known as American trypanosomiasis [1] This anthropozoonosis affects more than 7 million people worldwide, and is considered a neglected and endemic tropical disease in 21 Latin American countries [2]. In the period of 2008– 2017, cases of acute CD were recorded in most Brazilian states, 95% of them were concentrated in the northern region of the country and 72% were acquired orally due to the ingestion of food contaminated with the triatomine insect vector [3] The treatment of this infection is still considered challenging, as it is restricted to two nitroderivatives, benznidazole (BZ) and nifurtimox, both of which have limited efficacy, especially in the chronic phase of the disease, in addition to severe side effects [4]. Azole derivatives, including posaconazole, demonstrating promising results for the experimental infection, had no efficacy in the human infection [16, 17]

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