Blastocyst, a distinctive stage of a mammalian embryo. It is a form of blastula that develops from a berrylike cluster of cells, the morula. A cavity appears in the morula between the cells of the inner cell mass and the enveloping layer. This cavity becomes filled with fluid. The blastocyst. כל מה שרציתם לדעת על: לפני כחודש התחלתי להרגיש גירודים בפי הטבעת, לאחר ביקור אצל רופא משפחה קיבלתי הפניה לבדיקת צואה. תוצאות ראשוניות אבחנו כי אני נושא את הטפיל Blastocystis hominis. השאלה שלי, האם יכול להיות כי הטפיל הנ'ל אחראי.

Abstract

Blastocystis is a highly controversial protozoan parasite. It has been variably regarded as a commensal and pathogen. Scientists have for decades wondered whether it is truly an enteropathogen and if it is observed in symptomatic patients whether treatment is required because patient recovery and improvement has been noted even without any treatment. Though associated with self-limiting infection, treatment is warranted in many patients due to persistence of symptoms. This particularly holds true for children and adults who are immuno compromised. Several drugs have been used to treat Blastocystis but each one of them has produced widely variable rates of clinical cure and eradication of the parasite from the feces. Based on the studies carried out in vitro and clinical responses obtained in patients, metronidazole appears to be the most effective drug for Blastocystis infection. However, the therapy is complicated due to different dosages and regimens adopted and the unresponsiveness to treatment observed in several sections of the population studied. Recently, the finding of different subsets of Blastocystis exhibiting resistance to metronidazole and associated with variable degrees of symptoms has underscored the importance of typing the subsets of the parasite in order to foretell the clinical response and the need to treat. Till date, the mode of action of the drugs used and the mechanism of resistance is not entirely known and is a topic of speculation. Other drugs with anti Blastocystis activity and used in therapy includes trimethoprim sulfamethoxazole and nitazoxanide. Several other compounds have also been evaluated for the treatment either alone or in combination with the first or second line drugs. A lot of interest has also been generated on the role of probiotics particularly Saccharomyces boularrdii and other natural food compounds on eradication of the parasite. This review provides a comprehensive overview of antimicrobials used to target Blastocystis and discusses the issues pertaining to drug resistance, treatment failure, reinfection, and the current views on treatment modalities.

INTRODUCTION

Blastocystis presents a great challenge to biologists seeking to describe its taxonomy and for parasitologists and clinicians who have struggled for many decades to determine whether it is truly an enteropathogen.[] Despite being one of the most common human intestinal protozoans in the developing countries, current knowledge about this parasite is incomplete and contradictory. Several issues are still unresolved and much debated regarding this parasite such as the clinical relevance, pathogenicity and the need for treatment.[] In 1916, a study described blastocystosis as “an infection that is difficult to get rid of” although treatment has been available and used for several decades.[,4] Patients infected with Blastocystis frequently present with gastrointestinal complaints and are treated with the intention to eradicate the parasite. However, an accumulating body of data on treatment modalities indicates that successful antimicrobial eradication of Blastocystis is far from straight forward.[] In a study from Taiwan on 100 patients who had Blastocystis in the feces, all patients improved without specific treatment for Blastocystis. Further, on stool examination within 1 year of follow-up, the parasite was undetectable in 91.2% of patients despite their having no specific antiprotozoal treatment.[] Little is known about the organism's metabolic processes, and conclusive animal models are lacking for cause- and-effect relationship.[] As a result of this uncertainty surrounding its pathogenic role, large scale treatment trials are also lacking. Treatment of symptomatic patients is often warranted despite the self-limiting nature of the infection.[] Recent data also suggest that Blastocystis causes symptoms frequently. Therefore, therapy should be limited to patients with persistent symptoms subsequent to a complete work up for alternative etiologies.[] Further, studies reporting therapeutic improvement concomitant with parasite clearance in symptomatic patients substantiates the pathogenic role of the organism and hence, the need for treatment.[]

This review provides a comprehensive overview of antimicrobials used to target Blastocystis and discusses issues pertaining to drug resistance, treatment failure, re-infection and the current views on treatment modalities.

Tatsuya Suda, 59, pleaded to a single felony in Orange County Superior Court, Santa Ana, in a deal with the district attorney’s office, also included paying more than $400,000 in. Tatsuya suda.

THERAPEUTIC OPTIONS

To date a number of antimicrobial agents have been used to treat Blastocystis infection. This includes metronidazole, nitazoxanide, trimethoprim-sulfamethoxazole (TMP-SMX), paramomycin, iodoquinol, ketoconazole, secnidazole, emetine, tinidazole, and the probiotic Saccharomyces boulardii. Table 1 depicts the common drugs used and the treatment regimens.[]

Table 1

Drugs and dosage schedules for treatment of B. hominis

In instances where treatment is warranted, metronidazole is the most frequently prescribed antibiotic.[] With metronidazole, a high proportion of patients achieve clinical remission (88%) and a 6 month fecal clearance (80%).[11] Though considered for first line treatment, the success of eradicating the parasite with this drug has been reported to be anywhere between 0% and 100%.[,] Metronidazole is prescribed in various dosage regimens ranging from 250 mg to 750 mg 3 times a day for 10 days, to 1.5 g/day for 10 days. It has been used alone or in combination with other drugs such as paramomycin or cotrimoxazole.[] There is extensive variation in treatment response to metronidazole.[] Accurate prediction of a response is difficult in individual patients.[] In a placebo controlled treatment trial of Blastocystis infection with metronidazole administered at a dosage of 1.5 g/day for 10 consecutive days, it was observed that diarrhea improved, and there was parasitic clearance from the stools at 1 month following therapy. However, an extension of follow-up at 6 months resulted in an elevated occurrence of parasitological relapses in the metronidazole treated group, both symptomatic, and asymptomatic. Therefore, it is suggested that metronidazole may be ineffective in achieving complete eradication possibly due to resistance. Surprisingly, in the placebo treated group there was a sporadic spontaneous clearance of the parasite from stools and this was more evident at 6 months evaluation.[]

In all placebo controlled studies, successful treatment is indicated by the resolution of symptoms in association with the partial or complete eradication of the organisms. However, with metronidazole, microbiological resolution is found only in 80% of treated patients.[,] There are many reasons attributed to this. Treatment confers an enhancement in the reproductive potential of the parasite and thus, the treated parasite reverts to becoming granular with the release of reproductive granules that account for the increased number of parasites in microscopy and cultures encountered sometimes in the post treatment phase.[] The cysts forms in addition to being genetically heterogeneous are resistant to the cytotoxic effect of the drug.[,]

Resistance to metronidazole was first reported as early as 1991, thus, undermining its value as a first line treatment.[,] It has been noted that this drug is effective for certain patients but does not provide complete eradication for others, particularly those with severe infection. This variation in treatment response suggests the existence of resistant subtypes of the parasite. Currently no in vitro and in vivo data unequivocally supports this.[] The unresponsive patients are perhaps infected with the resistant subtypes.[,] In a study by Constantine Vassalos et al., it was concluded that Blastocystis species subtype 3 is the most predominant and intra subtype differences in subtype 3 morphotype exists in relation to their pathogenic potential. Transition from vacuolar to amoeboid form reflects the progression from an asymptomatic to symptomatic state. Hence, searching for amoeboid forms may be helpful before antiprotozoal treatment is attempted.[] It is also possible that the apparent failure of treatment is due to patient non-compliance, differing pharmacokinetic properties of drugs and inactivation of the drug by the normal bacterial flora.[,] Recent studies have indicated that the human isolates of Blastocystis from different geographical locations possess varying degrees of resistance to metronidazole. This implies that an efficient drug or drug combinations at a proper dosage must be instituted in order to eliminate the parasite.[,] One clinic has reported successful treatment with a combination of secnidazole, nitazoxanide, and furazolidone. However, it is to be noted that all three drugs are not currently available in many countries.[] A 2006 text described an USA patient returning from Nepal with chronic Blastocystosis who was treated without success over a period of 3 years with iodoquinol, paramomycin, doxycycline, albendazole, tinidazole, ornidazole, quinacrine, nitazoxanide, rifaximin, furazolidone, cotrimoxazole, itraconazole, ketoconazole, and various combinations of these drugs.[17] One recent study on metronidazole resistance and subtype dependent variation in drug susceptibilities of Blastocystis revealed that subtype 7 and subtype 4 are resistant to metronidazole and also exhibit cross resistance to tinidazole, indicating that new unknown mechanisms of activation and/or resistance may be involved.[] Nasirudeen et al., reported that metronidazole induces programed cell death in Blastocystis and apoptosis like features are observable in growing axenic cultures. The central vacuole of Blastocystis acts as a repository where apoptotic bodies are stored before being released into the extracellular space. Little is known about the organism's metabolic processes, although one study has identified the role of mitochondrion like organelles in the reduction of ferrodoxins in subtype 7 that plays a role in the conversion of metronidazole into its active state.[,]

Association between Blastocystis and irritable bowel syndrome (IBS) has been suggested in the recent literature. One study on IBS patients, revealed 60% resistance to 0.1 mg/ml of metronidazole while another Indonesian study observed resistance at 1.0 mg/ml metronidazole.[,] In at least 10% of IBS patients, Blastocystis cannot be successfully treated. This can be either due to resistance or defective clearance secondary to decreased humoral and cellular immune functions.[]

TMP-SMX has been shown to have good effects on the cure rate and the clinical symptoms in patients with Blastocystis infection. It is considered to be superior to metronidazole in the treatment without the side-effects.[23] This drug is suggested as an alternative particularly if symptoms persist after treatment with metronidazole.[24] TMP-SMX is safe to use in pregnant women and is cheaper in terms of cost.[23] Whether the drug has a direct effect on the parasite itself or kills the essential intestinal bacteria for the survival of Blastocystis is not clear.[23] In a study carried out in Turkey by Ok et al., it was demonstrated that patients treated with TMP-SMX experienced 100% recovery.[] In another study, treatment with TMP-SMX for 7 days, only 97.3% of cases showed clinical improvement.[] More recently, it has been opined that there is no advantage of TMP-SMX over placebo in the treatment of recurrent abdominal pain caused by Blastocystisin children. The eradication rate in children is 35% compared to 44% with metronidazole as second line treatment. It is assumed that TMP/SMX leads only to a reduction in the number of Blastocystis and not to permanent eradication.[] Research on subtype dependent variation in susceptibility revealed higher susceptibility of Blastocystis to TMP-SMX ratio of 1:2 than to a ratio of 1:5. At this ratio, it was observed that there is no subtype dependent variation in susceptibility and 95-100% of cases achieved eradication[] In contrast Moghaddam et al., reported only 22% eradication of the parasite on treatment with TMP-SMX.[] In Human immunodeficiency virus infected patients the prophylactic use of TMP-SMX leads to a decreased detection rate of Blastocystis.[]

Nitazoxanide, a 5-nitro thiazole, broad spectrum antiparasitic agent is found to have potent activity against Blastocystis.[,] In children, the achievable clearance rates are 97-100% on treatment with this drug. It is well-tolerated with no serious adverse effects.[] Metronidazole treatment failures in Blastocystis may well respond to nitazoxanide.[] In vitro, Blastocystis subtype 7 has been found to be significantly more susceptible to nitazoxanide than subtype 4, though both are considered to be nonhuman subtypes. A placebo controlled trial of nitazoxanide 500 mg twice daily for 3 days reported a clinical and parasitological cure of 86%.[] Paramomycin, a broad spectrum aminoglycoside antibiotic was useful to successfully treat Blastocystis associated cutaneous lesions particularly urticaria.[] In some studies, it has exhibited superior performance in comparison to metronidazole. With an eradication rate of 77%, treatment with paramomycin appears significantly more effective than treatment with metronidazole (38%) or no treatment (22%).[] Treatment failure was suspected in one out of three patients in a study, and this patient was subsequently successfully treated with metronidazole.[,] Curiously, an early in vitro study revealed that paramomycin was not inhibitory to the parasite. Since, it is bactericidal it might act by the destruction of the gut bacterial flora essential for Blastocystis survival.[] Mirza et al., have reported that paramomycin has no activity against the nonhuman subtypes of Blastocystis.[]

Other drugs that are found to have variable efficacy on Blastocystis are tinidazole, ornidazole, secnidazole, ketoconazole, pentamidine, furazolidone, quinine, iodoquinol, iodochlorhydroxyquin, and emetine.[,] The activity of emetine against Blastocystis has been evaluated in 3 previous in vitro studies. While two studies reported its effectiveness, Zierdt et al., reported strain-to-strain variation in the susceptibility of the parasite to the drug.[] It has also been observed that emetine resistance occurs along with metronidazole resistance thereby suggesting that multidrug resistant phenotypes might be present in the parasite. Clinically, however, emetine has limited use because of its severe side effects. Blastocystis subtype 4 is resistant to emetine and variably susceptible to quinacrine and mefloquine. Furazolidone is another drug with anti Blastocystis activity and to date no subtype dependent variation has been observed for this drug.[]

Cysteine proteases play an important role in the cell cycle and pathophysiology of Blastocystis and induce up regulation of pro-inflammatory cytokines. This finding suggests a potential role for cysteine proteases inhibitors as a therapeutic option for Blastocystis isolates resistant to conventional agents.[,]

S. boulardii is a non-pathogenic yeast and has proven effective in gastrointestinal diseases with predominant inflammatory component, indicating its role in interference with cellular signaling pathways and it is marketed as a dietary supplement. It regulates the intestinal microbial homeostasis, interferes with the ability of pathogens to colonize and infect the mucosa, modulates local and systemic immune responses, stabilizes gastrointestinal barrier functions and induces enzymatic activity favoring absorption and nutrition.[] In a randomized single blinded clinical trial in symptomatic children who had Blastocystis positive stools, both clinical and parasitological cure rates were 94.4% in comparison with 73.3% achieved in the metronidazole treated group. These findings challenge the existing guidelines for treatment.[]

A few traditional Chinese medicinal herbs have also been examined for in vitro activity against Blastocystis (Brucea javanica and Coptis chinensis). Their inhibitory activity was not as great as with similar concentrations of metronidazole. As an adjunct, dietary management strategies like introduction of high fiber and lactose free diet is shown to improve clinical signs and symptoms.[24]

There have been several studies examining the use of alternative agents for the treatment of Blastocystis infection. Blastocystis isolates from IBS patients mostly genotype-1 have demonstrated increased susceptibility to garlic at 0.01 mg/ml. Other investigational agents such as ginger, black pepper, and white cumin did not have significant inhibitory effect in drug susceptibility assays.[]

In summary, a variety of drug treatment options are available for Blastocystis infections [Table 1]. Metronidazole appears to be the most effective drug for Blastocystis chemotherapy despite some evidence for treatment failure. In such circumstances, TMP-SMX and nitazoxanide may be considered as second choice drugs. Treatment should be instituted if the diarrhea is persistent and no other causative pathogen is identified in fecal specimens. Future studies should investigate the association between genotypes and variations in drug susceptibility. The mechanisms of action and the mode of resistance to each of the drug has to be evaluated further.[] Genome analysis of the species and application of modern techniques, such as microsatellites, microarrays and differential display coupled with proteonomics and bioinformatics analysis are more likely to elucidate the differences in pathogenicity, virulence and response to treatment.[] The development of new therapeutic options to counter antimicrobial resistance requires the use of high through put screening tools.[]

Footnotes

Source of Support: Nil

Conflict of Interest: None declared

REFERENCES

Blastocystis hominisby Drugs.com. Last updated on Jan 29, 2019. Disease ReferenceOn this page.OverviewBlastocystis hominis is a microscopic organism that sometimes is found in the stools of people who have ingested contaminated food or water.

It can be found in healthy people who aren't having digestive symptoms, and it's also sometimes found in the stools of people who have diarrhea, abdominal pain or other gastrointestinal problems.Researchers don't fully understand the role Blastocystis hominis plays, if any, in causing disease. Certain forms of the organism might be more likely to be linked to an infection with symptoms. Most commonly, blastocystis simply lives in a person's digestive tract without causing harm.Blastocystis hominis, also known as blastocystis spp or Blastocystis hominis infection, usually clears on its own. Dinosaur simulator value list. There are no proven treatments for these infections. SymptomsSigns and symptoms possibly associated with Blastocystis hominis include:.

Watery diarrhea. Nausea. Abdominal pain.

Bloating. Excessive gas (flatulence). Loss of appetite. FatigueWhen to see a doctorSee your doctor if you have signs and symptoms, such as diarrhea or cramps, that last longer than three days.

CausesBlastocystis is a parasite — a microscopic single-celled organism (protozoan). Many protozoans normally live in your gastrointestinal tract and are harmless or even helpful; others cause disease.It's not clear whether blastocystis causes disease. Most people who carry the organism have no signs or symptoms, but it's also found in people who have diarrhea and other digestive problems. Blastocystis often appears with other organisms, so it's not known whether it causes disease.Experts suspect that blastocystis gets into the digestive system when people eat contaminated food or are exposed to the stool of a contaminated person, such as when changing a diaper in a child care setting. Rates of the organism in stool increase where there's inadequate sanitation and poor personal hygiene. Blastocystis hominisBlastocystis is a microscopic single-cell organism (protozoan) that lives in the digestive tract. Many protozoans normally live in the digestive tract and are harmless or even helpful, but some cause disease.

Risk factorsBlastocystis hominis is common, and anyone can have the organism in his or her stools. You might be at higher risk if you travel or live where sanitation is inadequate or where the water might not be safe or if you handle contaminated animals, such as pigs and poultry. ComplicationsIf you have diarrhea associated with Blastocystis hominis, it's likely to be self-limiting.

However, anytime you have diarrhea, you lose vital fluids, salts and minerals, which can lead to dehydration. Children are especially vulnerable to dehydration. PreventionYou might be able to prevent Blastocystis hominis or other gastrointestinal infection by taking precautions, especially while traveling in high-risk countries. Watch what you eatThe general rule of thumb is this: If you can't boil it, cook it or peel it — forget it. Avoid food from street vendors.

Don't eat soft-cooked eggs. Avoid unpasteurized milk and dairy products, including ice cream. Avoid raw or undercooked meat, fish and shellfish.

Steer clear of moist food at room temperature, such as sauces and buffet offerings. Eat foods that are well-cooked and served hot. Stick to fruits and vegetables that you can peel yourself, such as bananas, oranges and avocados. Stay away from salads and fruits you can't easily peel, such as grapes and berries. Avoid frozen pops and flavored ice. Skip salsa and other condiments made with fresh ingredients.Don't drink the waterWhen visiting high-risk countries, keep the following tips in mind:.

Avoid unsterilized water — from tap, well or stream. If you need to drink or wash fruits or vegetables in local water, boil it for at least three minutes and let it cool to room temperature. Avoid ice cubes or fruit juices made with tap water.

Keep your mouth closed while showering. Use bottled water to brush your teeth. Make sure hot beverages, such as coffee or tea, are steaming hot.Feel free to drink canned or bottled drinks in their original containers — including water, carbonated beverages, beer or wine — as long as you break the seals on the containers yourself. Wipe off any can or bottle before drinking or pouring.You can chemically disinfect water with iodine or chlorine.

Iodine tends to be more effective, but limit its use, because too much iodine can be harmful to your body. Take precautions against passing a parasite to othersIf you have Blastocystis hominis or another gastrointestinal infection, good personal hygiene can help keep you from spreading the infection to others:.Wash hands with soap and water frequently, especially after using the toilet and before, during and after handling food. Rub soapy, wet hands together for at least 20 seconds before rinsing. Lather the backs of your hands and between your fingers. Dry your hands well with a clean towel.If soap and water aren't available, use an alcohol-based hand sanitizer that contains at least 60 percent alcohol. Wash hands well after changing a diaper, especially if you work in a child care center, even if you wear gloves.DiagnosisThe cause of your diarrhea might be difficult to diagnose. Even if Blastocystis hominis is found in your stool, it might not be causing your symptoms.

More commonly, it suggests you've been exposed to contaminated food or water that contains other organisms that can cause gastrointestinal symptoms.Your doctor likely will take your medical history, ask you about recent activities, such as traveling, and perform a physical exam. A number of lab tests help diagnose parasitic diseases and other noninfectious causes of gastrointestinal symptoms:. Stool (fecal) exam. This test looks for parasites or their eggs. Your doctor might give you a special container with preservative fluid for your stool samples. Refrigerate — don't freeze — your samples until you take them to your doctor's office or lab. Endoscopy.

If you have symptoms, but the fecal exam doesn't reveal the cause, your doctor might request this test. After you're sedated, a doctor, usually a gastroenterologist, inserts a tube into your mouth or rectum to look for the cause of your symptoms. You'll need to fast beginning the night before the test. Blood tests. A blood test that can detect blastocystis is available but not commonly used. However, your doctor might order blood tests to look for other causes of your signs and symptoms.TreatmentIf you have Blastocystis hominis without signs or symptoms, then you don't need treatment.

Mild signs and symptoms might improve on their own within a few days.Potential medications for treating Blastocystis hominis include:. Antibiotics, such as metronidazole (Flagyl) or tinidazole (Tindamax).

Combination medications, such as sulfamethoxazole and trimethoprim (Bactrim, Septra, others). Anti-protozoal medications, such as paromomycin or nitazoxanide (Alinia)Response to medication for Blastocystis hominis varies greatly from person to person.

And because the organism might not be the cause of your symptoms, improvement might be due to the medication's effect on another organism. Preparing for an appointmentYou'll likely see your primary care doctor. However, in some cases, you might be referred to someone who specializes in either infectious disease or in digestive system disorders (gastroenterologist).Here's some information to help you get ready for your appointment.

What you can doBe aware of pre-appointment restrictions.