Schistosomiasis still represents a major health problem in many tropical and subtropical countries despite continuing control efforts. Due to the unavailability of a vaccine that is practically applicable to humans, the use of chemotherapy is the mainstay of schistosomiasis-associated morbidity control. This paper attempts to review the antischistosomal drugs currently used in the treatment of intestinal schistosomiasis caused by Schistosoma mansoni. Their antischistosomal properties, advantages, and disadvantages as well as issues regarding the evidence for drug resistance and combination studies are reviewed in a simple manner. The recent trends towards the identification of specific chemotherapeutic targets for the treatment of schistosomes are also discussed briefly.
Artemether is an artemisinin derivative that is used as an antimalarial drug, especially in situations where chloroquine resistance is suspected. This compound has proved to be a good prophylactic agent against schistosomiasis japonica in China. In the present study, the therapeutic efficacies of different artemether-dosing protocols were evaluated in experimentally infected mice harbouring adult Schistosoma mansoni (Egyptian strain). Mice were treated on day 46 onwards with three dosing protocols (400 mg/kg/day for 2 days; 200 mg/kg/day for 4 days; 100 mg/kg/day for 6 days) after being infected. A number of parasitological and histopathological criteria were employed in the assessment of drug efficacies compared to infected untreated control 2 weeks post-treatment. The results of the present study suggest that artemether is efficacious against the Egyptian strain of S. mansoni with total worm reductions ranging from 40.7% to 59.7% and female worm reductions ranging from 69.3% to >90%. In addition, artemether induced significant reductions, ranging from 75.2% to 82.6%, in the liver tissue egg loads as well as significant reductions, ranging from 68.8% to 78.9% in the intestinal wall egg loads. It also induced significant alterations in the oogram pattern in the intestinal mucosa of infected mice with cessation of oviposition and increased rates of dead eggs. Antipathologic activities were also evident in the amelioration of granulomas in the liver with increased ratios of healed to active ones. In conclusion, artemether could be a promising agent in the control of schistosomiasis mansoni due to its schistosomicidal effects on female worms and to its ovicidal power as well as its potentiality in the improvement of hepatic lesions.
Schistosomiasis is a chronic parasitic disease affecting about 207 million people in the world. It still represents a major health problem in many tropical and sub-tropical countries as well as for travelers from developed countries. Control of the disease depends mainly on chemotherapy, with praziquantel becoming the exclusive drug. Extensive use of praziquantel with concerns about the possibility of drug resistance development, unavailability of an applicable vaccine, and the absence of a reasonable alternative to praziquantel all represent a real challenge. One of the suggested solutions is to exploit the advantages of compounds that proved efficacious at the experimental level with a good safety profile. These may undergo further investigations for the sake of developing their antischistosomal properties or to incorporate them in combination therapies. Chemotherapy literature is redundant with a huge number of compounds screened for their schistosomicidal properties. However, only a few of these may act as drug leads that could be promising in the development of a therapeutic reserve for schistosomiasis. The present paper reviews previous studies carried out on some of these compounds.
The title compounds (VIII), (IX), and (XI) are synthesized as shown in the reaction scheme.
There is a new trend of "back to nature" in searching for antischistosomal drugs, particularly after the concerns raised about the possible emergence of schistosome isolates resistant/tolerant to praziquantel as well as for their relative safety and fewer side effects. Many plant derivatives have been investigated for efficacy against the Egyptian strain of Schistosoma mansoni, but much attention has been paid to myrrh extract, which is a purified sap obtained from Commiphora molmol. This extract has been produced and marketed in Egypt as a pharmaceutical preparation, but with a great discrepancy in its antischistosomal activity in both experimental and clinical studies. Most previous experimental studies used myrrh in the dosing protocol of 500 mg/kg/day for five days. In the present study, we investigated the therapeutic efficacy of three low-dose myrrh protocols against experimental schistosomiasis mansoni. All these protocols showed no significant efficacy in reducing parasite burdens and tissue egg loads or in changing oogram patterns. Nevertheless, there was an amelioration of hepatic lesions, with reductions in mean counts of hepatic granulomas as well as marked healing of these granulomas.
Gastrointestinal parasites, such as helminths and protozoa, are abundant parasitic agents of livestock, particularly ruminants. The current study aims to determine the prevalence rate of parasitic infections in large ruminate animals slaughtered in the mechanical abattoir in Alexandria governorate, Egypt. The prevalence was identified through the records of parasitic infections detected in the fecal matter of large ruminate animals in addition to the recorded postmortem examination findings. Three hundred sixty-four slaughtered large ruminant animals were selected, labeled, and subjected to fecal sampling and postmortem examination. Each fecal sample was tested by three different techniques; the formalin-ether concentration, Ziehl-Neelsen hot-stained, and saturated saline flotation to diagnose all parasite types. One hundred thirty positive cases (35.71%) were determined during the fecal sample examination, and 76 cases (20.87%) were found in postmortem examination. Formalin-ether processing of fecal samples yielded the highest number of pathogens; Entamoeba species were detected in 98 fecal samples (26.69%), and Fasciola species eggs were detected in 14 samples (3.84%). The postmortem examination revealed Fasciola hepatica and F. gigantica in 13 animals (3.57%), mixed lung and liver hydatid cysts in 32 animals (8.79%), whereas liver hydatid cysts only were identified in 15 animals (4.12%). Finally, Sarcocystosis infection was detected in 3.57%. In conclusion, the parasitic infections of large ruminant animals are a leading cause of pathogenicity in large animals, leading to economic losses. Prevention and control measures must be implemented by mechanical abattoirs according to the hazard analysis critical control point system.
Combination chemotherapy of schistosomiasis mansoni has been studied previously, with praziquantel being the basis of combination. Artemether and myrrh are compounds of a natural origin that have been investigated experimentally and clinically against schistosomiasis. Artemether is used as an antimalarial drug, and has been used as a chemoprophylactic drug against Schistosoma japonicum in China whereas myrrh extract is manufactured and prescribed as an antischistosomal drug in Egypt. The present study investigated the experimental efficacy of combining artemether and myrrh using three different protocols in mice infected with the Egyptian strain of S. mansoni. Methods: Experiments were performed on 40 eight-week-old female Swiss albino mice divided into three experimental groups and one control group. Assessment of efficacy was based on a suite of parasitologic and histopathologic parameters. Parasitologic parameters included reductions in total and female worm burdens, reductions in hepatic and intestinal wall tissue egg loads, and alterations in oogram patterns in the experimental groups compared to the infected untreated control. Histopathologic parameters comprised microscopic examination of liver sections stained with hematoxylin and eosin to study the reductions in the mean counts and diameters of hepatic granulomas as well as their healing ratios compared to the control. Results: Reductions of 43.9%-58.2% in total worm burdens and 42.4%-63.7% in female worm burdens were induced. Meanwhile, significant reductions of 63.1%-77.8% in eggs per gram of small intestinal tissue and of 56.5%-66.3% in eggs per gram of liver tissue were also observed. The combination also caused alterations in the oogram pattern as well as amelioration of hepatic lesions as evidenced by increased ratios of healed granulomas in the treated groups compared to the control. Conclusion: The experimental efficacy of the artemether-myrrh combination against the Egyptian strain of S. mansoni was evident, but not to an extent that would warrant clinical trials in humans.
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