Schistosomiasis is a major neglected tropical disease that afflicts more than 240 million people, including many children and young adults, in the tropics and subtropics. The disease is characterized by chronic infections with significant residual morbidity and is of considerable public health importance, with substantial socioeconomic impacts on impoverished communities. Morbidity reduction and eventual elimination through integrated intervention measures are the focuses of current schistosomiasis control programs. Precise diagnosis of schistosome infections, in both mammalian and snail intermediate hosts, will play a pivotal role in achieving these goals. Nevertheless, despite extensive efforts over several decades, the search for sensitive and specific diagnostics for schistosomiasis is ongoing. Here we review the area, paying attention to earlier approaches but emphasizing recent developments in the search for new diagnostics for schistosomiasis with practical applications in the research laboratory, the clinic, and the field. Careful and rigorous validation of these assays and their cost-effectiveness will be needed, however, prior to their adoption in support of policy decisions for national public health programs aimed at the control and elimination of schistosomiasis.

Advances in the Diagnosis of Human Schistosomiasis

Background 
Schistosomiasis is a major endemic disease that affects hundreds of millions worldwide. Since the treatment and control of this parasitic disease rely on a single drug, praziquantel, it is imperative that new effective drugs are developed. Here, we report that phytol, a diterpene alcohol from chlorophyll widely used as a food additive and in medicinal fields, possesses promising antischistosomal properties in vitro and in a mouse model of schistosomiasis mansoni.


Methods and findings 
In vitro, phytol reduced the motor activity of worms, caused their death and confocal laser scanning microscopy analysis showed extensive tegumental alterations in a concentration-dependent manner (50 to 100 µg/mL). Additionally, phytol at sublethal doses (25 µg/mL) reduced the number of Schistosoma mansoni eggs. In vivo, a single dose of phytol (40 mg/kg) administered orally to mice infected with adult S. mansoni resulted in total and female worm burden reductions of 51.2% and 70.3%, respectively. Moreover, phytol reduced the number of eggs in faeces (76.6%) and the frequency of immature eggs (oogram pattern) was significantly reduced. The oogram also showed increases in the proportion of dead eggs. Confocal microcopy studies revealed tegumental damage in adult S. mansoni recovered from mice, especially in female worms.


Conclusions 
The significant reduction in parasite burden by this chlorophyll molecule validates phytol as a promising drug and offers the potential of a new direction for chemotherapy of human schistosomiasis. Phytol is a common food additive and nonmutagenic, with satisfactory safety. Thus, phytol has potential as a safe and cost-effective addition to antischistosomal therapy.

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Phytol, a Diterpene Alcohol from Chlorophyll, as a Drug against Neglected Tropical Disease Schistosomiasis Mansoni

Endemic in 149 tropical and subtropical countries, neglected tropical diseases (NTDs) affect more than 1 billion people annually, including 875 million children in developing economies. These diseases are also responsible for over 500,000 deaths per year and are characterized by long-term disability and severe pain. The impact of the combined NTDs closely rivals that of malaria and tuberculosis. Current treatment options are associated with various limitations including widespread drug resistance, severe adverse effects, lengthy treatment duration, unfavorable toxicity profiles, and complicated drug administration procedures. Natural products have been a valuable source of drug regimens that form the cornerstone of modern pharmaceutical care. In this review, we highlight the potential that remains untapped in natural products as drug leads for NTDs. We cover natural products from plant, marine, and microbial sources including natural-product-inspired semi-synthetic derivatives which have been evaluated against the various causative agents of NTDs. Our coverage is limited to four major NTDs which include human African trypanosomiasis (sleeping sickness), leishmaniasis, schistosomiasis and lymphatic filariasis.

https://www.mdpi.com/1420-3049/22/1/58/pdf

The Role of Natural Products in Drug Discovery and Development against Neglected Tropical Diseases

Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases.

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Antioxidants in liver health

Hepatic fibrosis (HF) is a progressive condition with serious clinical complications arising from abnormal proliferation and amassing of tough fibrous scar tissue. This defiance of collagen fibers becomes fatal due to ultimate failure of liver functions. Participation of various cell types, interlinked cellular events, and large number of mediator molecules make the fibrotic process enormously complex and dynamic. However, with better appreciation of underlying cellular and molecular mechanisms of fibrosis, the assumption that HF cannot be cured is gradually changing. Recent findings have underlined the therapeutic potential of a number of synthetic compounds as well as plant derivatives for cessation or even the reversal of the processes that transforms the liver into fibrotic tissue. It is expected that future inputs will provide a conceptual framework to develop more specific strategies that would facilitate the assessment of risk factors, shortlist early diagnosis biomarkers, and eventually guide development of effective therapeutic alternatives.

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Understanding the mechanism of hepatic fibrosis and potential therapeutic approaches.

The repeated chemotherapy of schistosomiasis has resulted in the emergence of drug-resistant schistosome strains. The development of such resistance has drawn the attention of many authors to alternative drugs. Many medicinal plants were studied to investigate their antischistosomal potency. The present work aimed to evaluate antischistosomal activity of crude aqueous extract of ginger against Schistosoma mansoni. Sixteen mice of C57 strain were exposed to 100 ± 10 cercariae per mouse by the tail immersion method; the mice were divided into two groups: untreated group and ginger-treated one. All mice were sacrificed at the end of 10th week post-infection. Worm recovery and egg counting in the hepatic tissues and faeces were determined. Surface topography of the recovered worms was studied by scanning electron microscopy. Histopathological examination of liver and intestine was done using routine histological procedures. The worm burden and the egg density in liver and faeces of mice treated with ginger were fewer than in non-treated ones. Scanning electron microscopical examination revealed that male worms recovered from mice treated with ginger lost their normal surface architecture, since its surface showed partial loss of tubercles’ spines, extensive erosion in inter-tubercle tegumental regions and numerous small blebs around tubercles. Histopathological data indicated a reduction in the number and size of granulomatous inflammatory infiltrations in the liver and intestine of treated mice compared to non-treated mice. The results of the present work suggested that ginger has antischistosomal activities and provided a basis for subsequent experimental and clinical trials.

Antischistosomal activity of ginger ( Zingiber officinale ) against Schistosoma mansoni harbored in C57 mice

2 Abstract: This investigation was designed to appraise t he ant ibilharzial efficacy of garlic. Adult male Swiss albino mi ce were a llocated i nto t wo mai n g roups; the first group was non-infected an d ki lled af ter 6 weeks, while the second one was infected with S. mansoni cercariae and divided into t wo equal halves to be sacrificed at 6 and 12 weeks post-infection. Both, the non-infected and infected groups were divided into three subgroups: I. non-treated, II. treated with 50 mg/kg of garlic extract an d III. t reated with 100 mg/kg of garlic extract. Some parasitological parameters (including worm burden, tissue egg load and hepatic granulomas count and diameter) were measured. In addition, hepatic histological examinations were performed. In non-infected mice treated with garlic (50 mg/kg), the histological changes in the inspected organ were generally mild. Concurrently, the high dose of garlic (100 mg/kg) in duced hepatocytic hypereosinophilia, vacuolation and necrosis, in addition to nuclear alterations. In infected non-treated mice, hepatic tissue manifested apparent features, including: vascular dilatation, bile ductule proliferation, periportal inflammation, granulomatous reactions and fibrosis, as well as Kupffer cel l hypertrophy and pigmentation. Besides, liver cells suffered from cloudy swelling, vacuolation and necrosis. Treating infected mice with the low dose of garlic resulted in significant parasite eradication, considerable reduction in t he num ber of ova/g t issue. In addition, a co nspicuous suppression i n granul omatous formation and diminutive histopathological ch anges were observed. C onversely, no major d ifferences w ere detected in the parasitological or histological observations following the administration of 100 mg/kg of garlic a fter infection as compared to t he non-treated infected groups. Therefore, we can conclude that garlic i n low doses has a curat ive ef fect on S. mansoni infection an d pl ays a r ole i n a meliorating its pathological consequences, a lthough at hig h doses the reversal o f t hese effects is observed.

The Effect of Garlic on Some Parasitological Parameters and On Hepatic Tissue Reactions in Experimental Schistosomiasis Mansoni

The l24-bp repetitive and highly abundant DNA sequence -used as a specific probe for the detection of Fasciola hepatica infection in snails- was tested in the detection of F. gigantica infection in Lymnaea natalensis. The probe did not show any positive peR results with Lymnaea natalensis, Phvsa aCllta, Biomphalaria alexandrina and Blilinus trucatlls or with Schistosonza mansoni, S. haematobium and Echi­ nostoma liei. However, the probe was found capable to detect F. gigantica infection within L. natalensis at very early stages of the prepatent period and at very low concentrations. Thus, the present assay is specific and sensiti ve for the detection of F. gigantica within its intermediate host. It confirmed the idea that l24-bp repetitive and highly abundant DNA sequ­ ence in Fasciola sp. genome could be used as an epidlDi,Qlogi­ cal tool for examination of fasciolosis intermediate host. The nucleic acid-based assay could eliminate both inherent uncer­ tainties and lengthy periods of time required for visual exa­ mination of the snails. Also, the assay is valuable in epizoo­ tiology of F. gigantica, vector suitability and host-parasite relationship.

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Diagnosis of Fasciola gigantica in snail using the polymerase chain reaction (PCR) assay.

Flame atomic absorption spectrometry was performed to determine the alteration of calcium concentration in the soft parts and shells of Biomphalaria alexandrina and Bulinus truncatus due to the infection with Schistosoma mansoni and S. haematobium, respectively. The results showed significant lowering in the calcium content of the shells of cercariae shedding B. alexandrina and B. truncatus relative to the calcium content in the shells of uninfected ones. In contrast, the calcium content in the soft parts of cercariae shedding snails was higher than in the soft parts of uninfected snails; the differences were statistically significant. Generally, calcium content was significantly higher in the shells than in the soft parts of the snails, regardless infected or uninfected. The results obtained and the hypothesis of hypercalcification in shells of infected snails were discussed.

Effects of Schistosoma mansoni and Schistosoma haematobium infections on calcium content in their intermediate hosts.

In this article, two strains of mice BALB/C and C57 were infected with Egyptian strain of Schistosoma mansoni. BALB/C mice appeared to harbor fewer parasites than did C57 mice. The hepatic and intestinal tissues of C57 mice were loaded with more eggs than that of BALB/C mice. Regardless the strain of mice, the number of eggs per gram of liver tissues was higher than in the intestinal tissues. Some biochemical parameters were measured in the liver of infected and non-infected mice; a significant decrease in the activities of alkaline phosphatase, catalase, glutathione-s-transferase, glutathione, and total lipids of infected mice compared to their matched control were observed. However, there was a significant increase in malondialdehyde level of infected mice compared to their matched group. Detailed discussion on the parasitological and biochemical differences between the two strains was presented.

Osama M. S. Mostafa

Papers

Antischistosomal activity of ginger ( Zingiber officinale ) against Schistosoma mansoni harbored in C57 mice

The Effect of Garlic on Some Parasitological Parameters and On Hepatic Tissue Reactions in Experimental Schistosomiasis Mansoni

Diagnosis of Fasciola gigantica in snail using the polymerase chain reaction (PCR) assay.

Effects of Schistosoma mansoni and Schistosoma haematobium infections on calcium content in their intermediate hosts.

Susceptibility of two strains of mice to the infection with Schistosoma mansoni: Parasitological and biochemical studies