Protein undernutrition reduces the efficacy of praziquantel in a murine model of Schistosoma mansoni infection

PLoS Negl Trop Dis. 2022 Jul 15;16(7):e0010249. doi: 10.1371/journal.pntd.0010249. eCollection 2022 Jul.

Abstract

Background: Undernutrition and schistosomiasis are public health problems and often occur in low and middle-income countries. Protein undernutrition can alter the host-parasite environment system and aggravate the course of schistosomiasis. This study aimed to assess the impact of a low-protein diet on the efficacy of praziquantel.

Methodology/principal findings: Thirty-day-old mice were fed with a low-protein diet, and 40 days later, they were individually infected with fifty Schistosoma mansoni cercariae. A 28-day-treatment with praziquantel at 100 mg/kg for five consecutive days followed by distilled water begins on the 36th day post-infection. Mice were sacrificed on the 64th day post-infection. We determined the parasitological burden, liver and intestine histomorphometry, liver injury, and immunomodulation parameters. Praziquantel treatment of infected mice fed with a standard diet (IN-PZQ) resulted in a significant reduction of worm and egg burdens and a normalization of iron and calcium levels. The therapy also improved schistosomiasis-induced hepatopathy and oxidative stress. The anti-inflammatory and immunomodulatory activities of praziquantel were also significant in these mice. When infected mice receiving the low-protein diet were treated with praziquantel (ILP-PZQ), the body weight loss and hepatomegaly were not alleviated, and the worm and liver egg burdens were significantly higher than those of IN-PZQ mice (P < 0.001). The treatment did not reduce the increased activities of ALT and γ-GGT, the high malondialdehyde concentration, and the liver granuloma volume. The iron and calcium levels were not ameliorated and differed from those of IN-PZQ mice (P < 0.001 and P < 0.05). Moreover, in these mice, praziquantel treatment did not reverse the high level of IL-5 and the low mRNA expression of CCL3/MIP-1α and CXCL-10/IP-10 induced by S. mansoni infection.

Conclusion/significance: These results demonstrated that a low-protein diet reduced the schistosomicidal, antioxidant, anti-inflammatory, and immunomodulatory activities of praziquantel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthelmintics* / therapeutic use
  • Anti-Inflammatory Agents / therapeutic use
  • Calcium
  • Disease Models, Animal
  • Iron
  • Liver / parasitology
  • Malnutrition*
  • Mice
  • Praziquantel
  • Schistosoma mansoni
  • Schistosomiasis mansoni* / drug therapy
  • Schistosomiasis mansoni* / parasitology
  • Schistosomiasis* / drug therapy

Substances

  • Anthelmintics
  • Anti-Inflammatory Agents
  • Praziquantel
  • Iron
  • Calcium

Grants and funding

One of the authors of this work (UMF) received the financial support of the France Government through the Cooperative and Cultural Action Service (SCAC) scholarship 959139G and the Strasbourg Institute of Parasitology and Tropical Diseases (IPPTS) to perform cytokine and RT-qPCR analyses. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.