Aditya Reddy

Helminths in human carcinogenesis

This review examines the salient literature on selected helminths involved in carcinogenicity in humans and updates information in an earlier review on cancer and helminths by Mayer and Fried (2007, Advances in Parasitology 65, 239-296). The earlier review was concerned with various helminths, i.e., trematodes, cestodes, and nematodes, that are definitely implicated as being carcinogenic. This review examines only those helminths, all of which turn out to be trematodes, that are definitely implicated as being carcinogenic. These trematodes are the blood flukes Schistosoma haematobium, associated with inducing human carcinoma of the urinary bladder and the liver flukes Opisthorchis viverrini and Clonorchis sinensis, associated with inducing cancer of the bile duct (cholangiocarcinoma) and cancer of the liver (hepatocarcinoma) in humans. The review examines mainly the epidemiology and pathology of these helminthic infections in humans and considers what we know about the mechanisms associated with the carcinogenicity of these three trematodes in humans.

Experimental infection of Ranapipiens tadpoles with Echinostomatrivolvis cercariae

Abstract Studies were done on laboratory-raised Ranapipiens tadpoles experimentally infected with Echinostomatrivolvis cercariae. Tadpoles exposed individually to 250 cercariae died within 24 h. They were edematous at death and their kidneys were heavily infected with metacercarial cysts. Of 20 tadpoles exposed to 100 cercariae each, 9 survived the infection, and their growth was compared for 4 weeks postinfection (p.i.) with that of 20 control tadpoles that had not been exposed to cercariae. There was a significant weekly decline in the total length and body weight of the infected versus control tadpoles. Surviving tadpoles retained their metacercarial infections in the kidneys following metamorphosis to frogs. Following exposure of tadpoles to cercariae, cercarial bodies were first seen in the kidneys by 0.5 h p.i. Metacercariae that were molding their inner and outer cyst walls were first seen at 2.3 h, and by 8.5 h the inner and outer cyst walls were clearly defined. Domestic chicks exposed to cysts aged 2.5 and 4.0 h did not become infected, whereas ovigerous adults of E. trivolvis were recovered from chicks fed 12-h-old cysts. Cercariae aged 6 to 8 h were more infective to tadpoles than were either 1- or 20-h-old cercariae. The E. trivolvis-R. pipiens tadpole model is suitable for the study of host-parasite relationships of echinostome larvae in a cold-blooded vertebrate host.

An update on the use of helminths to treat Crohn's and other autoimmunune diseases

This review updates our previous one (Reddy and Fried, Parasitol Research 100: 921–927, 2007) on Crohn’s disease and helminths. The review considers the most recent literature on Trichuris suis therapy and Crohn’s and the significant literature on the use of Necator americanus larvae to treat Crohn’s and other autoimmune disorders. The pros and cons of helminth therapy as related to autoimmune disorders are discussed in the review. We also discuss the relationship of the bacterium Campylobacter jejuni and T. suis in Crohn’s disease. The significant literature on helminths other than N. americanus and T. suis as related to autoimmune diseases is also reviewed.

The use of Trichuris suis and other helminth therapies to treat Crohn's disease

Infections with gastrointestinal (GI) nematodes are prevalent worldwide, despite the fact that anti-helminthic medications are regarded as safe, efficient, and widely available globally. In this review, we highlight the potential therapeutic benefits that may be realized through the clinical use of Trichuris suis and other helminths for Crohn’s disease (CD). Long-lived helminthic parasites are remarkable in their ability to down-regulate host immunity, protecting themselves from elimination, and also minimize severe pathological host changes. This review summarizes what is known about the underlying mechanisms that may account for the observed patterns in humans treated with helminths for CD. The Th2 arm of the immune system is emphasized as a component of primary importance in the association between the host immune system and GI nematode infections. Although GI nematode infections in humans cause significant morbidity and mortality, the existence and nature of protective mechanisms these helminths may confer remain largely unclear.

EFFECTS OF COPPER SULFATE TOXICITY ON CERCARIAE AND METACERCARIAE OF ECHINOSTOMA CAPRONI AND ECHINOSTOMA TRIVOLVIS AND ON THE SURVIVAL OF BIOMPHALARIA GLABRATA SNAILS

Copper in the form of copper sulfate (CuSO4) decreases the survival of Biomphalaria glabrata snails, but the effects of this molluscicide on Echinostoma caproni and Echinostoma trivolvis, 2 species of digeneans that use B. glabrata as intermediate hosts, are not known. Studies were done on the effects of various concentrations of CuSO4 in artificial spring water (ASW) on the survival and infectivity of E. caproni and E. trivolvis cercariae. Solutions containing 1.0, 0.1, and 0.01% CuSO4 were 100% lethal within 2 hr of exposure for both species. Time to 50% mortality in 0.001% CuSO4 was 8 hr for E. caproni and 16 hr for E. trivolvis; at 24 hr, the controls showed 50 and 65% mortality, respectively. Treatment of cercariae of both species for 0.5 hr in 0.001% CuSO4 had no effect on the ability of cercariae to form normal cysts in juvenile B. glabrata snails. However, treatment with 0.01% CuSO4 for 0.5 hr caused a significant reduction in the ability of cercariae of both species to encyst in snails. Treatment of encysted metacercariae of both species in 0.001% CuSO4 for 1 hr had no effect on subsequent excystation of these echinostomes in a trypsin–bile salts medium, whereas concentrations of 1.0, 0.1, and 0.01% CuSO4 and 1.0 and 0.1% CuSO4 decreased chemical excystation of E. caproni and E. trivolvis cysts, respectively. Survival studies on the effects of CuSO4 in Lockes solution on chemically excysted metacercariae of both species were also done. Excysted metacercariae of both species were killed by 2 hr in either 0.1 or 0.01% CuSO4 in Lockes solution. However, time to 50% mortality for both species of excysted metacercariae in 0.001% CuSO4 was approximately 5 hr. Time to 50% mortality for the controls was about 12 hr. Survival of juvenile B. glabrata snails was also examined. All B. glabrata snails were dead by 6 hr in 1 and 0.1% CuSO4 in ASW. Biomphalaria glabrata snails showed 50% mortality by about 6 hr in 0.01% CuSO4 and about 80% were still alive at 24 hr in 0.001% CuSO4. All controls were alive at 24 hr, at which time the experiment was terminated. Concentrations greater than 0.001% CuSO4 increased snail mortality, as well as that of the cercariae and excysted metacercariae of E. caproni and E. trivolvis. Our findings suggest that concentrations of copper sufficient to eliminate juvenile B. glabrata snails are also sufficient to kill the cercariae and excysted metacercariae of these digeneans but not the encysted metacercariae, which may be protected by their cyst walls.

Chemoattraction and penetration of Echinostoma trivolvis and E. caproni cercariae in the presence of Biomphalaria glabrata, Helisoma trivolvis, and Lymnaea elodes dialysate

A petri-dish bioassay was used to study the chemoattraction and penetration of the cercariae of Echinostoma trivolvis and E. caproni in the presence of snail dialysates from Helisoma trivolvis (Pennsylvania and Colorado strains), Biomphalaria glabrata, and Lymnaea elodes. Significant chemoattraction was seen with E. trivolvis cercariae in the presence of all snail dialysates released from nonperforated dialysis sacs with a molecular-weight exclusion of 12,000. Under the same conditions, E. caproni was significantly attracted to B.␣glabrata and H. trivolvis (CO strain) but not to L.␣elodes or H. trivolvis (PA strain). Dialysis sacs were perforated with needles to allow the release of snail substances of all molecular weights into the bioassay. Cercariae of both species were significantly attracted to all snail dialysates released from perforated sacs. Moreover, cercariae entered these sacs and penetrated the snails, and 24 h later the percentage of cysts per snail species ranged from 70% to 83% for E. trivolvis and from 73% to 93% for E. caproni. Dialysates released from intact sacs were extracted in choloroform-methanol (2:1) to obtain hydrophilic and lipophilic fractions. When these extracts were placed on agar plugs in the bioassay, the lipophilic fraction, but not the hydrophilic fraction, was mainly chemoattractive.

Atopic disorders and parasitic infections.

This chapter examines the relationship between atopic disorders and parasitic infections. Atopy is an exaggerated IgE-mediated Type-1 immune response in predisposed individuals. Conflicting information exists in regard to the relationship of parasitic infections and the classic allergic diseases, that is, atopic dermatitis, allergic rhinitis and asthma. Attention is paid to the explanations for these discrepancies in the literature found within both human and animal studies on atopy with particular emphasis on helminthic infections. The factors that cause only a proportion of atopic individuals to develop clinical disease have not been defined although helminths confer protection in many studies examined. Early childhood infections help induce a Th1-biased immunity and prevent the induction of the Th2 system that causes atopy. Acute parasitic infections may increase manifestations of allergy, whereas chronic infections with parasites decrease atopic predisposition. Nonetheless, a causal association between geohelminth infection and atopic disorders has not been established. Some helminthic substances, especially the cytokines, have respiratory and anti-allergic effects, and may therefore become useful as therapeutic modalities for many atopic and allergic disorders.

Infectivity and growth of Echinostoma revolutum (Froelich, 1802) in the domestic chick

Infectivity and growth studies in domestic chicks were carried out on a strain of Echinostoma revolutum isolated from Lymnaea elodes snails in Indiana, U.S.A. Of 21 chicks, each fed 40 +/- 10 cysts of Echinostoma revolutum, 16 (64%) were infected with a total of 269 (32%) worms from approximately 840 cysts. Worms were found only in the ceca and rectum at 2-14 days p.i. In vivo excysted metacercariae were obtained in the lower ileum and ceca at 4 h p.i. Excysted metacercariae averaged 0.2 mm in length and 0.02 mm2 in body area. Worm length averaged 1.3 mm on day 6, 2.3 mm on day 8 and 3.6 mm on day 14. Mean body area averaged 0.29 mm2 on day 6, 0.62 mm2 on day 8 and 1.93 mm2 on day 14. Worms first became ovigerous on day 12. Growth of E. revolutum in the chick was delayed compared to previous findings on E. trivolvis, a closely related species of 37-collar-spined echinostome in the E. revolutum complex.

Effects of snail-conditioned water from Biomphalaria glabrata on hatching of Echinostoma caproni miracidia

Abstract In vitro studies were done on Echinostoma caproni eggs with fully developed miracidia to determine the effects of snail-conditioned water (SCW) from Biomphalaria glabrata on miracidial hatching in the light. Observations were made on miracidial hatching at 4, 8, 12, 16, 20, and 24 h in multiwell chambers in the presence of SCW (experimentals) versus controls in artificial spring water (ASW). The number of hatched eggs was significantly greater (Students t-test, P < 0.05) in SCW at all times as compared with those maintained in ASW. Significantly greater hatching was also obtained when snails were maintained in intact or perforated dialysis sacs in multiwell chambers as compared with sacs without snails. Agar plugs impregnated with SCW or the hydrophilic fraction of SCW that had been extracted in chloroform-methanol (2:1) did not influence significant hatching. However, the lipophilic fraction of the SCW extract caused significant hatching. Substances in SCW significantly increase hatching of E. caproni miracidia, but details on what these compounds are remain obscure.

In vitro studies on intraspecific and interspecific chemical attraction in daughter rediae of Echinostoma trivolvis and E. caproni

In vitro pairing and aggregation studies on daughter rediae of Echinostoma trivolvis and E. caproni were done at 22 degrees C in a Petri dish bioassay containing an agar substratum and a Lockes solution overlay. Pairing or aggregation was considered positive when rediae were in contact or within 1 mm of each other. Intraspecific and interspecific pairing or aggregation occurred in the bioassay when rediae were initially placed 5 or 10 mm apart. Movement of a single redia in the bioassay to a dialysis sac containing 1-10 rediae showed that intraspecific and interspecific pairing occurred in the absence of redial tactile stimulation. Movements of single rediae in the bioassay to agar plugs impregnated with redial excretory/secretory (ES) products occurred. The lipophilic fraction of the ES products was significantly more attractive than the hydrophilic fraction. The significance of redial chemical communication is not clear.