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

• Published in: bioRxiv
• Main Authors: Joseph Bertin Kadji Fassi, Jatsa, Hermine Boukeng, Femoe, Ulrich Membe, Greigert, Valentin, Brunet, Julie, Cannet, Catherine, Kenfack, Christian Mérimé, Feussom, Nestor Gipwe, Nkondo, Emilienne Tienga, Abou-Bacar, Ahmed, Alexander Wilhelm Pfaff, Kamgang, Réné, Kamtchouing, Pierre, Louis-Albert Tchuem Tchuente
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 14.02.2022
• Subjects: Animal models; Antioxidants; Body weight; Body weight loss; CCL3 protein; Gene expression; Granuloma; Histomorphometry; Immunomodulation; Infections; Inflammation; Interleukin 5; Intestine; IP-10 protein; Iron; Liver; Low protein diet; Malondialdehyde; Nutrient deficiency; Oxidative stress; Praziquantel; Proteins; Public health; Schistosoma mansoni; Schistosomiasis; Undernutrition
• DOI: 10.1101/2022.02.14.480315

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 protein-deficient diet on the efficacy of praziquantel. Methodology/principal findings: Thirty-day-old mice were fed with a protein-deficient 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 at 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 protein-deficient 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 protein-deficient diet reduced the schistosomicidal, antioxidant, anti-inflammatory, and immunomodulatory activities of praziquantel. Competing Interest Statement The authors have declared no competing interest.