Therapy of intestinal protozoa

doi:10.1016/j.pt.2003.09.003

Trends in Parasitology

Volume 19, Issue 11, November 2003, Pages 523-526

https://doi.org/10.1016/j.pt.2003.09.003 Get rights and content

Abstract

Protozoa that parasitize the human intestine and cause disease include Entamoeba histolytica, Giardia lamblia, Cryptosporidium parvum, Cyclospora cayetanensis, Isospora belli, and the microsporidia (which are now classified as fungi). The new and broad-spectrum agent nitazoxanide now has an Food and Drug Administration indication for the treatment of cryptosporidiosis and giardiasis in children, making C. parvum for the first time a treatable infection. Metronidazole is the standard, and in most cases effective, therapy for invasive infection due to E. histolytica and for G. lamblia infection. Cyclosporiasis and isosporiasis are treated with trimethoprim–sulfamethoxazole, whereas some isolates of Encephalitozoon intestinalis are sensitive to albendazole. Eradication of E. histolytica infection after completion of metronidazole therapy normally requires additional therapy with paromomycin, whereas cases of giardiasis refractory to metronidazole have been treated with nitazoxanide, higher doses of metronidazole, or with combination therapy with quinacrine and metronidazole.

Section snippets

Amebiasis

The global burden of disease due to amebiasis has primarily been based on stool ova and parasite exams, which are insensitive and cannot differentiate E. histolytica (Figure 1) from other morphologically identical nonpathogenic species such as Entamoeba dispar and Entamoeba moshkovskii 1, 2. Antigen detection, culture and/or PCR are much more specific and sensitive means to detect E. histolytica infection [3]. In Dhaka, Bangladesh, these techniques demonstrated that preschool children had a

Cryptosporidiosis and other spore-forming protozoa

The spore-forming protozoa (cryptosporidia, cyclospora, isospora, and the microsporidia which are now classified as fungi) are named according to the infectious spore form of the parasite which is spread in a fecal–oral manner. After ingestion of spores from contaminated food or water, sporozoites are released which invade into the intestinal epithelium where they replicate intracellularly. In humans with a normal immune system, infection with an intestinal spore-forming parasite leads to a

Giardiasis

Giardia lamblia (Figure 3) is the most common parasite identified in stool samples of individuals in the USA, present in ∼4% of stool specimens submitted to clinical laboratories. The disease is quite common in developing countries as well, especially in urban slums where a substantial number of children are infected. Water- and food-borne transmission are the most frequent mechanisms of spread, with person to person spread important in day care settings and among sexually active homosexual

Conclusion

The intestinal protozoan parasites are presently, and for the most part adequately, treated with current available medications. Important exceptions where no or inadequate therapeutic options exist include the fungal microsporidial enteropathogens and cryptosporidial infections in patients with AIDS. For many of the anaerobic protists (Entamoeba, Giardia and the sexually transmitted vaginal parasite Trichomonas), metronidazole is the drug of first choice, with attendant problems of drug

References (26)

B. Amadi
Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial
Lancet
(2002)
C.W. Hoge
Placebo-controlled trial of co-trimoxazole for cyclospora infections among travelers and foreign residents in Nepal
Lancet
(1995)
W.A. Petri
Estimating the impact of amebiasis on health
Parasitol. Today
(2000)
L.S. Diamond et al.
A redescription of Entamoeba histolytica Shaudin 1903 (amended Walker 1911) separating it from Entamoeba dispar (Brumpt 1925)
J. Eukaryot. Microbiol.
(1993)
Ali, I.K.M. et al. High prevalence of Entamoeba moshkovskii infections in children in Bangladesh. Emerg. Infect. Dis....
R. Haque
Diagnosis of amebic liver abscess and intestinal infection with the TechLab Entamoeba histolytica II antigen detection and antibody tests
J. Clin. Microbiol.
(2000)
R. Haque
Innate and acquired resistance to amebiasis in Bangladeshi children
J. Infect. Dis.
(2002)
J. Blessmann
Epidemiology of amebiasis in a region of high incidence of amebic liver abscess in central Vietnam
Am. J. Trop. Med. Hyg.
(2002)
WHO/PAHO/UNESCO report of a consultation of experts on amoebiasis
Weekly Epidemiological Report of the WHO
(1997)
S.J. Powell
Metronidazole in amoebic dysentery and amoebic liver abscess
Lancet
(1967)

J. Blessmann et al.

Treatment of asymptomatic intestinal Entamoeba histolytica infection

N. Engl. J. Med.

(2002)

J.B. McAuley

Diloxanide furoate for treating asymptomatic Entamoeba histolytica cyst passers: 14 years experience in the United States

Clin. Infect. Dis.

(1992)

J.B. McAuley et al.

Paromomycin in the treatment of mild to moderate intestinal amebiasis

Clin. Infect. Dis.

(1992)

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Therapeutic and prophylactic effects of Punica granatum peel extract versus metronidazole in murine Giardiasis intestinalis
2022, Journal of King Saud University - Science
Citation Excerpt :
Reinfection, insufficient dosage, poor immunity, drug resistance, sequestration in the biliary system, and the creation of an antioxidant network to protect oxygen-sensitive metalloenzymes are all probable reasons for Giardia therapy failure (Ansell et al., 2015). However, the majority of the medications utilized have significant adverse side effects and are therefore contraindicated (Gardner and Hill, 2001; Petri, 2003). The consumer, and the ever-increasing desire for drug-free food production, is another restraint in the use of anti-Giardia drugs (Harper and Makatouni, 2002).
Giardiasis is considered the most common protozoal infection in humans; it frequently occurs in both developing and developed countries. The present study was designed to investigate the therapeutic and prophylactic effects of Punica granatum peel methanolic extract against experimental giardiasis in comparison to metronidazole (MTZ) in mice infected with Giardia intestinalis. There were five experimental groups, as follows: G1; healthy control group, G2; infected untreated, G3; infected treated with MTZ, G4; Infected treated with pomegranate P. granatum, G5; receiving P. granatum for one week before, during induction of infection than continuous administration for another one week. Giardia cyst per gram stool 7 days and 2 weeks after treatment showed a highly statistically significant difference among the different experimental groups (G3,4,5) versus G2, while the percent reduction of mean Giardia cysts/gm stool 2 weeks after treatment showed a highly significant reduction in G3,4,5 by 92.73, 91.94, and 94.1 %, respectively. The count of Giardia trophozoites in small intestinal content showed a statistically significant difference among G3,4,5 versus G2 respectively with a highly significant reduction in G3,5 and a significant reduction in G4. The percent reduction of mean Giardia trophozoites was approximately 98.69, 58.66, and 95.96 %, respectively. Histopathological examination of small intestines sections of G3 and G4 showed improvement in the pathological lesions including slight restoration of villi/crypt ratio, with partial mucosal ulceration. There was complete healing of intestinal mucosa observable in G5, with a preserved brush border, and no trophozoites were detected. P. granatum peel methanolic extract proved to be valuable in the prevention and treatment of Giardia lamblia infection. Further studies are required to determine the effective therapeutic dose of the extract and its mechanism of action against Giardia lamblia.
Effect of magnetic field on the growth of the cultured Entamoeba histolytica isolated from patients in Palestine
2021, Experimental Parasitology
Static magnetic field (SMF) is generated in vicinity of moving charge or current passing through conductor. In this study, we aimed to investigate the effect of SMF on the growth of the cultured Entamoeba histolytica (E. histolytica) trophozoites. Different SMF strengths with maximum value equals 30 mT (mT) was applied on the E.histolytica for different periods of times: 0 h, 24 h, 48 h, and 72 h. A modified diphasic liver infusion agar medium was used for culturing E. histolytica in vitro. The results showed the successful stabilization of culture of E. histolytica trophozoites. If we kept the sample for longer time, e. g. 14 days, the growth rate decreases to zero. When applying 10 mT and 15 mT SMF on the sample, it is found that the cultivated E. histolytica trophozoites dies after 4 and 2 days respectively. The experiments suggested that the SMF inhibited the growth and the propagation of E. histolytica cells. In addition, it completely killed all the cells in a short time interval which depend on the SMF strength. It is concluded that the SMFs inhibits the growth of E. histolytica and change the morphology of these cells. Thus, we recommend to use SMF as treatment to mitigate the growth of E. histolytica.
Speculative analysis on the electronic structure, IR assignments and molecular docking of N-{4-[(4-amino-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)sulfonyl]phenyl}acetamide, an anti-amoebic agent
2020, Heliyon
An exhaustive quantum mechanical calculations on a pharmaceutically critical molecule N-{4-[(4-amino-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)sulfonyl]phenyl}acetamide have been investigated through the B3LYP/6-31G∗∗ Density Functional and HF/6-31G∗∗ Wave Function techniques. Physicochemical parameters along with the advanced electronic structure parameters like; MEP (molecular electrostatic potentials) and highest occupied & lowest unoccupied molecular orbitals (HOMO-LUMO) analysis have additionally been scanned over both methods. The computed HOMO-LUMO energy demonstrates that charge exchange takes place inside the molecule. The estimated small HOMO-LUMO energy gap, through both methods, indicates that the molecule is chemically reactive. Further, the IR vibrational spectra of the molecule have been assigned in the region 400-4000 cm⁻¹ through the DFT technique. The anticipated vibrational assignments have been compared with the experimental values accounted for in the literature. To comprehend the mode of binding, docking investigations of the molecule alongwith the co-crystallized metronidazole (MNZ) molecule were accomplished with O-acetyl-serine-sulfhydrylase (OASS) enzyme using GLIDE-SP and GLIDE-XP modules. Docking simulations and reported biological activities (IC50) demonstrate that the title molecule may act as a lead molecule for constraining the progression of Entamoeba histolytica illness.
Relational dynamics obtained through simulation studies of thioredoxin reductase: From a multi-drug resistant Entamoeba histolytica
2020, Journal of Molecular Liquids
Microbial enteric infections cause diarrhea, dysentery, and fever that constitute huge health problems worldwide. Entamoeba histolytica is a multi-drug resistant bacterial pathogen involves in instigating enteric infections. Multi-drug resistant E. histolytica is responsible for higher rate of mortality and morbidity. In the present study, a systematic in-silico pipeline applied to screen potential drug targets that are considered essential for pathogen survival. Thioredoxin reductase (TrxR) enzyme is concluded as a potential drug target bearing features of drug-ability, three-dimensional structure availability, favorable physiochemical properties, involvement in core pathways, rich interactome and broad-spectrum conservation. A library of antibacterial compounds was virtually screened against TrxR via molecular docking. The best docked complexes subjected to molecular dynamics simulation to observe dynamic behavior of complex. Root mean square deviation deduced interconversions helix-coil-helix-coil, and beta-turn-beta in TrxR and are highly flexible. Transitional changes observed in protein as a result of “relational dynamics” have a significant influence on the binding mechanism of inhibitor with in the protein cavity. Other factors: root mean square fluctuation, beta-factor and radius of gyration values show coherence with root mean square deviation results. Furthermore, crucial hydrogen bonds of residues Glu33 and Ala115 with inhibitor revealed through hydrogen bond analysis. Axial frequency distribution revealed residues Glu33 and Ala115 atoms showing high affinity for inhibitor though a minor tilting behavior was observed. Poisson Boltzmann or Generalized Born Surface Area Continuum Solvation (MM (PB/GB) SA) methods indicate van der Waal interactions as dominant interactions. These analyses revealed (1-(carboxymethyl)-4-(4-methylthiazole-5-carboxamido)-3H-pyrazol-1-ium-3-ide) as the potential lead compound. This study will facilitate researchers to discover and develop more effective leads compounds against E. histolytica.
An update on small molecule strategies targeting leishmaniasis
2018, European Journal of Medicinal Chemistry
Leishmaniasis is an infectious disease caused by various species of protozoan parasite known as Leishmania, which is transmitted to its mammalian host via bite of an infected sandfly. Clinically, Leishmaniasis appears as following four conditions: Cutaneous Leishmaniasis, Mucocutaneous Leishmaniasis, Visceral Leishmaniasis/Kala-azar, Post Kala azar dermal Leishmaniasis. Current therapies include pentavalent antimonials, Amphotericin B, Paromomycin, Miltefosine, Pentamidine, Sitamaquine. Presence of diverse survival pathways in the parasite to carry out various physiological functions has rendered targeting via drugs inefficient and troublesome. Moreover, emerging resistance mechanisms in the well-established key targets are affecting the use of current drug treatment options thus leading to treatment failure. Therefore, development of novel anti-leishmanial compounds with alternative and efficient mechanisms of actions is required to eradicate this disease. This review provides an overview of leishmaniasis along with the main emphasis on novel heterocycles reported for their anti-leishmanial activity in recent years.
An overview of azoles targeting sterol 14α-demethylase for antileishmanial therapy
2017, European Journal of Medicinal Chemistry
The azole antifungal drugs are an important class of chemotherapeutic agents with broad-spectrum of activity against yeasts and filamentous fungi, act in the ergosterol biosynthetic pathway through inhibition of the cytochrome P450-dependent enzyme sterol 14α-demethylase. Azole antifungals have also been repurposed for treatment of tropical protozoan infections including human leishmaniasis. Recent advances in molecular biology and computational chemistry areas have increased our knowledge about sterol biochemical pathway in Leishmania parasites. Based on the importance of sterol biosynthetic pathway in Leishmania parasites, we reviewed all studies reported on azoles for potential antileishmanial therapy along their structural and biological aspects. This review may help medicinal chemists for design of new azole-derived antileishmanial drugs.

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Trends in Parasitology

Abstract

Section snippets

Amebiasis

Cryptosporidiosis and other spore-forming protozoa

Giardiasis

Conclusion

References (26)

Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial

Lancet

Placebo-controlled trial of co-trimoxazole for cyclospora infections among travelers and foreign residents in Nepal

Lancet

Estimating the impact of amebiasis on health

Parasitol. Today

A redescription of Entamoeba histolytica Shaudin 1903 (amended Walker 1911) separating it from Entamoeba dispar (Brumpt 1925)

J. Eukaryot. Microbiol.

Diagnosis of amebic liver abscess and intestinal infection with the TechLab Entamoeba histolytica II antigen detection and antibody tests

J. Clin. Microbiol.

Innate and acquired resistance to amebiasis in Bangladeshi children

J. Infect. Dis.

Epidemiology of amebiasis in a region of high incidence of amebic liver abscess in central Vietnam

Am. J. Trop. Med. Hyg.

WHO/PAHO/UNESCO report of a consultation of experts on amoebiasis

Weekly Epidemiological Report of the WHO

Metronidazole in amoebic dysentery and amoebic liver abscess

Lancet

Treatment of asymptomatic intestinal Entamoeba histolytica infection

N. Engl. J. Med.

Diloxanide furoate for treating asymptomatic Entamoeba histolytica cyst passers: 14 years experience in the United States

Clin. Infect. Dis.

Paromomycin in the treatment of mild to moderate intestinal amebiasis

Clin. Infect. Dis.

Cited by (101)

Therapeutic and prophylactic effects of Punica granatum peel extract versus metronidazole in murine Giardiasis intestinalis

Effect of magnetic field on the growth of the cultured Entamoeba histolytica isolated from patients in Palestine

Speculative analysis on the electronic structure, IR assignments and molecular docking of N-{4-[(4-amino-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)sulfonyl]phenyl}acetamide, an anti-amoebic agent

Relational dynamics obtained through simulation studies of thioredoxin reductase: From a multi-drug resistant Entamoeba histolytica

An update on small molecule strategies targeting leishmaniasis

An overview of azoles targeting sterol 14α-demethylase for antileishmanial therapy