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

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.

Schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from Clerodendrum umbellatum Poir leaves aqueous extract in Schistosoma mansoni infection in mice.

BACKGROUND: The intensive use of Praziquantel for the treatment of schistosomiasis has raised concerns about the possible emergence of drug-resistant schistosomes. As drug treatment is an important feature of schistosome control programs, the search for alternative drugs is therefore a priority. The aim of this study was to assess the schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from Clerodendrum umbellatum Poir leaves aqueous extract. METHODS: A phytochemical screening of the fraction of C. umbellatum was conducted. The fraction was administered orally and daily to Schistosoma mansoni-infected mice (BALB/c) from the 36th day post-infection for 28 days at 100, 200 and 400 mg/kg. Praziquantel (500 mg/kg) was used as reference drug. Non-infected and infected-untreated mice served as controls. All mice were sacrificed at 65th day post-infection. Body weight, liver/body and spleen/body weights, as well as worm burden, fecal egg count, liver and intestine egg load were determined. In the plasma, levels of total protein, transaminases (ALT, AST), alkaline phosphatase and total bilirubin were monitored to assess the possibility of liver damage. Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) levels were measured in the liver as biomarkers of the oxidative stress. RESULTS: The phytochemical analysis of the fraction from C. umbellatum aqueous leaves extract revealed the presence of alkaloids, flavonoids, cardiac glycosides, phenols, saponins, tannins and terpenoids. The worm burden, fecal egg count and egg load in the liver and intestine of infected mice treated with the fraction were significantly (p < 0.001) fewer than in infected-untreated mice. Only the highest-fraction dose reduced the worm and egg burdens in a similar way as praziquantel. Hepatosplenomegaly induced by S. mansoni infection was reduced by the treatment. The liver function on infected mice was ameliorate after administration of the fraction by significant reduction of ALT activity (35.43 to 45.25%) and increase of total protein level (44.79 to 70.03%). The methanolic fraction of C. umbellatum prevents the elevated MDA level induced by the infection while significant increase in catalase activity (297.09 to 438.98%) and glutathione level (58.23 to 95.88%) were observed after treatment. CONCLUSIONS: This study disclosed the schistosomicidal, hepatoprotective and antioxidant activities of the methanolic fraction from C. umbellatum leaves aqueous. These fraction's activities were similar to those of praziquantel. This fraction can be considered as a promising source for schistosomicidal agents.

Mapping of schistosomiasis and soil-transmitted helminthiasis in the regions of Littoral, North-West, South and South-West Cameroon and recommendations for treatment.

BACKGROUND: The previous nationwide mapping of schistosomiasis and soil-transmitted helminthiasis (STH) in Cameroon was conducted 25 years ago. Based on its results, mass drug administration (MDA) of praziquantel was limited to the three northern regions and few health districts in the southern part of Cameroon. In 2010, we started the process of updating the disease distribution in order to improve the control strategies. Three of the ten regions of Cameroon were mapped in 2010 and the data were published. In 2011, surveys were conducted in four additional regions, i.e. Littoral, North-West, South and South-West. METHODS: Parasitological surveys were conducted in March 2011 in selected schools in all 65 health districts of the four targeted regions, using appropriate research methodologies, i.e. Kato-Katz and urine filtration. RESULTS: The results showed significant variation of schistosomiasis and STH prevalence between schools, villages, districts and regions. Schistosoma haematobium was the most prevalent schistosome species, with an overall prevalence of 3.2%, followed by S. mansoni (3%) and S. guineensis (1.2%). The overall prevalence of schistosomiasis across the four regions was 7.4% (95% CI: 6.7-8.3%). The prevalence for Ascaris lumbricoides was 19.5% (95% CI: 18.3-20.7%), Trichuris trichiura 18.9% (95% CI: 17.7-20.1%) and hookworms 7.6% (95% CI: 6.8-8.4%), with an overall STH prevalence of 32.5% (95% CI: 31.1-34.0%) across the four regions. STH was more prevalent in the South region (52.8%; 95% CI: 48.0-57.3%), followed by the South-West (46.2%; 95% CI: 43.2-49.3%), the North-West (35.9%; 95% CI: 33.1-38.7%) and the Littoral (13.0%; 95% CI: 11.3-14.9%) regions. CONCLUSIONS: In comparison to previous data in 1985-87, the results showed an increase of schistosomiasis transmission in several health districts, whereas there was a significant decline of STH infections. Based on the prevalence data, the continuation of annual or bi-annual MDA for STH is recommended, as well as an extension of praziquantel in identified moderate and high risk communities for schistosomiasis.

Evaluation of circulating cathodic antigen (CCA) urine-tests for diagnosis of Schistosoma mansoni infection in Cameroon.

BACKGROUND: The Kato-Katz is the most common diagnostic method for Schistosoma mansoni infection. However, the day-to-day variability in host egg-excretion and its low detection sensitivity are major limits for its use in low transmission zones and after widespread chemotherapy. We evaluated the accuracy of circulating cathodic antigen (CCA) urine-assay as a diagnostic tool of S. mansoni. In comparison, a low sensitive CCA test (CCA-L) was assessed. METHODOLOGY: THE STUDY WAS CONDUCTED IN THREE SETTINGS: two foci with single S. mansoni infections (settings A and B), and one mixed S. mansoni - S. haematobium focus (setting C). Stool and urine samples were collected from school-children on three consecutive days. Triplicate Kato-Katz readings were performed per stool sample. Each urine sample was tested with one CCA and only the first urine sample was subjected to CCA-L. Urine samples were also examined for S. haematobium eggs using the filtration method and for microhaematuria using urine reagent strips. Overall, 625 children provided three stool and three urine samples. PRINCIPAL FINDINGS: Considering nine Kato-Katz thick smears as 'reference' diagnostic test, the prevalence of S. mansoni was 36.2%, 71.8% and 64.0% in settings A, B and C, respectively. The prevalence of S. haematobium in setting C was 12.0%. The sensitivities of single Kato-Katz, CCA and CCA-L from the first stool or urine samples were 58%, 82% and 46% in setting A, 56.8%, 82.4% and 68.8% in setting B, and 49.0%, 87.7% and 55.5% in setting C. The respective specificities were 100%, 64.7% and 100%; 100%, 62.3% and 91.3%; and 100%, 42.5% and 92.0%. Mixed infection with S. haematobium did not influence the CCA test results for S. mansoni diagnosis. CONCLUSIONS/SIGNIFICANCE: Urine CCA revealed higher sensitivity than CCA-L and triplicate Kato-Katz, and produced similar prevalence as nine Kato-Katz. It seems an attractive method for S. mansoni diagnosis.

Mapping of schistosomiasis and soil-transmitted helminthiasis in the regions of centre, East and West Cameroon.

BACKGROUND: Schistosomiasis and soil-transmitted helminthiasis (STH) are widely distributed in Cameroon. Although mass drug administration (MDA) of mebendazole is implemented nationwide, treatment with praziquantel was so far limited to the three northern regions and few health districts in the southern part of Cameroon, based on previous mapping conducted 25 years ago. To update the disease distribution map and determine where treatment with praziquantel should be extended, mapping surveys were conducted in three of the seven southern regions of Cameroon, i.e. Centre, East and West. METHODOLOGY: Parasitological surveys were conducted in April-May 2010 in selected schools in all 63 health districts of the three targeted regions, using appropriate research methodologies, i.e. Kato-Katz and urine filtration. PRINCIPAL FINDINGS: The results showed significant variation of schistosomiasis and STH prevalence between schools, villages, districts and regions. Schistosoma mansoni was the most prevalent schistosome species, with an overall prevalence of 5.53%, followed by S. haematobium (1.72%) and S. guineensis (0.14%). The overall prevalence of schistosomiasis across the three regions was 7.31% (95% CI: 6.86-7.77%). The prevalence for Ascaris lumbricoides was 11.48 (95% CI: 10.93-12.04%), Trichuris trichiura 18.22% (95% CI: 17.56-18.90%) and hookworms 1.55% (95% CI: 1.35-1.78%), with an overall STH prevalence of 24.10% (95% CI: 23.36-24.85%) across the three regions. STH was more prevalent in the East region (46.57%; 95% CI: 44.41-48.75%) in comparison to the Centre (25.12; 95% CI: 24.10-26.17%) and West (10.49%; 95% CI: 9.57-11.51%) regions. CONCLUSIONS/SIGNIFICANCE: In comparison to previous data, the results showed an increase of schistosomiasis transmission in several health districts, whereas there was a significant decline of STH infections. Based on the prevalence data, the continuation of annual or bi-annual MDA for STH is recommended, as well as an extension of praziquantel in identified moderate and high risk communities for schistosomiasis.