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

• Published in: PLoS neglected tropical diseases Vol. 16; no. 7; p. e0010249
• Main Authors: Kadji Fassi, Joseph Bertin, Boukeng Jatsa, Hermine, Membe Femoe, Ulrich, Greigert, Valentin, Brunet, Julie, Cannet, Catherine, Kenfack, Christian Mérimé, Gipwe Feussom, Nestor, Tienga Nkondo, Emilienne, Abou-Bacar, Ahmed, Pfaff, Alexander Wilhelm, Kamgang, René, Kamtchouing, Pierre, Tchuem Tchuenté, Louis-Albert
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 01.07.2022; Public Library of Science (PLoS)
• Subjects: Animal models; Biology and Life Sciences; Biomarkers; Body weight; Body weight loss; Calcium; CCL3 protein; Cholesterol; Cytokines; Diet; Distilled water; Dosage and administration; Effectiveness; Eggs; Feces; Gene expression; Granuloma; Granulomas; Health aspects; Health problems; High density lipoprotein; Histomorphometry; Immunomodulation; Infections; Inflammation; Interleukin 5; Intestine; Intestines; IP-10 protein; Iron; Laboratory animals; Liver; Low density lipoprotein; Low protein diet; Malnutrition; Medicine and Health Sciences; Nutrient deficiency; Nutritional status; Oxidative stress; Parasites; Praziquantel; Proteins; Public health; Schistosoma mansoni; Schistosomiasis; Testing; Therapy; Triglycerides; Tropical diseases; Undernutrition; Weight loss; Worms; Cameroon; Yaounde Cameroon; Germany
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0010249

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 36.sup.th day post-infection. Mice were sacrificed on the 64.sup.th 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 [gamma]-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-1[alpha] 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.