DOCSLIB.ORG

An Important Advance in Anti-Parasitic Therapy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
An Important Advance in Anti-Parasitic Therapy Am. J. Trop. Med. Hyg., 68(4), 2003, pp. 382–383 Copyright © 2003 by The American Society of Tropical Medicine and Hygiene EDITORIAL NITAZOXANIDE: AN IMPORTANT ADVANCE IN ANTI-PARASITIC THERAPY A. CLINTON WHITE, JR. Infectious Diseases Section, Department of Medicine, Baylor College of Medicine, Houston, Texas The field of anti-parasitic drugs has had a shaky history. maceuticals, Inc. (Marietta, GA) and focused on develop- The major pharmaceutical companies have increasingly fo- ment of the drug for treatment of cryptosporidiosis in ac- cused their drug development efforts on the major markets, quired immunodeficiency syndrome. Controlled trials began with potential annual sales of at least $100 million. This has shortly after the advent of effective anti-retroviral therapies. not worked well for development of anti-parasitic drugs. Most The trials were abandoned due to poor enrollment and the patients develop parasitic infections due to poverty. Thus, Food and Drug Administration rejected an application based while there may be millions of cases in developing countries, on uncontrolled studies. the number able to support the high prices of branded drugs Rather than abandon their efforts, Romark launched an is small. A few new drugs have come into the market. For impressive series of controlled trials. No other agent has example, mefloquine, albendazole, ivermectin, and atova- proven efficacy in the treatment of cryptosporidiosis. How- quone-proguanil have all come to the U.S. market since 1990. ever, a placebo-controlled study of nitazoxanide in cryptospo- However, even this limited number of new drugs is somewhat ridiosis demonstrated significant clinical improvement in deceiving. Mefloquine and atovaquone-proguanil are largely adults and children with mild illness.4 Among malnourished supported by their use in malaria prophylaxis. In this case, the children in Zambiawithchronic cryptosporidiosis, athree- millions of wealthy Western tourists provide a substantial day course of therapy not only led to clinical and parasitologic market for these high-price drugs. In addition, the U.S. mili- improvement, but also improved survival.5 In Zambia5 and in tary initiated the development of mefloquine, and safety data astudy conducted in Mexico, 6 nitazoxanide was not success- for atovaquone was supported by its development for treat- ful in the treatment of cryptosporidiosis in advanced infection ment of Pneumocystis pneumonia, for which there was a sub- with human immunodeficiency virus at the doses used. How- stantial market in the U.S. Ivermectin has never had a large ever, it was effective in patients with higher CD4 counts.6,7 market for human diseases. However, its development and Also, higher doses seem to have some effect in uncontrolled manufacture were supported by the lucrative market as a and unpublished studies. In treatment of giardiasis, nitazox- prophylaxis for canine heartworms. anide was superior to placebo and comparable to metronida- Between 1990 and 2000, the number of anti-parasitic drugs zole.7 Nitazoxanide was successful in the treatment of metro- available for human use in the United States actually shrank. nidazole-resistant giardiasis.8 Studies have suggested efficacy Diethylcarbamazine (DEC), quinacrine, and niclosamide in the treatment of cyclosporiasis, isosporiasis, and amebiasis. were withdrawn from the U.S. market. Eflornithine was her- There have also been several controlled trials of nitazox- alded as the “resurrection” drug for its dramatic effects in anide for treatment of infection with intestinal helminths.9 As West African trypanosomiasis, yet its sole manufacturer shown in the study by Diaz and others in this issue of the stopped production. Finally, praziquantel was withdrawn journal, nitazoxanide is effective against Ascaris, Trichuris, from the U.S. market. It appeared that there was actually a and Hymenolepis.10 However, some patients require repeated “disappearing arsenal” of anti-parasitic drugs.1 dosing. Other controlled trials have demonstrated some ac- Some of these problems have been reversed in response to tivity against chronic fascioliasis, for which there is no cur- political pressure. Eflornithine itself was resurrected. The rently licensed therapy available.11 However, the response drug proved an effective topical depilatory, thus ensuring that rates are lower than those described with triclabendazole. In the base compound was being manufactured. In response to all studies, nitazoxanide has been extremely well tolerated pressure led by World Health Organization, and Médicins with adverse effects similar to placebo. San Frontière, the manufacturer agreed to formulate some Studies have suggested a number of possible indications for drug for intravenous use and make it available for treatment treatment of specific parasites. Given its broad anti-parasitic of trypanosomiasis.2 Praziquantel was re-instated when the spectrum, it is tempting to use nitazoxanide empirically. Can marketing company realized that the public relations losses nitazoxanide be used as an alternative to albendazole or me- from withdrawing the drug out-weighed the cost savings from bendazole in mass chemotherapy of intestinal helminths? Be- ending production. fore this could be done, it will be important to confirm its In this context, the development of nitazoxanide is quite activity against hookworm species. It will also be important to remarkable. Nitazoxanide was originally discovered in the know whether it can be safely used in a variety of patient 1980s by Jean François Rossignol at the Pasteur Institute. groups (e.g., Are there adverse effects in onchocerciasis and Initial studies demonstrated activity versus tapeworms.3 In Loa loa infections seen with DEC in Africa?). vitro studies demonstrated much broader activity. Dr. Ros- In both developing and developed countries, intestinal pro- signol subsequently led the preclinical and clinical develop- tozoans are important causes of persistent and chronic diar- ment of albendazole and halofantrine. He co-founded Ro- rhea. It is difficult to identify specific causes with currently mark Laboratories, with the goal of bringing nitazoxanide to available tests. Multiple stool examinations may be needed to market as an anti-parasitic drug. Initial studies in the United identify Giardia. Cryptosporidium requires specialized tests States were conducted in collaboration with Unimed Phar- (modified acid fast or fluorescent stains), which are not uni- 382 NITAZOXANIDE 383 formly performed by all laboratories unless requested. Anti- 3. Rossignol JF, Maisonneuve H, 1984. Nitazoxanide in the treat- gen-detection assays may improve the diagnostic yield, but ment of Taenia saginata and Hymenolepis nana infections. Am can be expensive and are underused. Currently, cryptospo- J Trop Med Hyg 33: 511–512. 4. Rossignol JF, Ayoub A, Ayers MS, 2001. Treatment of diarrhea ridiosis is underdiagnosed. The cost and inconveniences of caused by Cryptosporidium parvum: aprospective random- multiple stool examinations will usually be greater than the ized, double-blind, placebo-controlled study of nitazoxanide. J cost of treatment. Can nitazoxanide be used empirically in- Infect Dis 184: 103–106. stead of aggressively pursuing a parasitologic diagnosis? A 5. Amadi B, Mwiya M, Musuku J, Watuka A, Sianongo S, Ayoub A, Kelly P, 2002. Effect of nitazoxanide on morbidity and comparison of empirical therapy versus pursuing diagnosis mortality in Zambian children with cryptosporidiosis: a ran- and specific treatment should be compared in post-travel di- domised controlled trial. Lancet 360: 1375–1380. arrhea. 6. Rossignol JF, Hidalgo H, Feregrino M, Higuera F, Gomez WH, Finally, pre-clinical studies have suggested significant activ- Romero JL, Padierna J, Geyne A, Ayers MS, 1998. A double- ity of nitazoxanide against some bacterial pathogens, includ- ‘blind’ placebo-controlled study of nitazoxanide in the treat- ment of cryptosporidial diarrhoea in AIDS patients in Mexico. ing Campylobacter, Clostridium difficile, and Helicobacter py- Trans R Soc Trop Med Hyg 92: 663–666. lori. Will these observations translate into clinical efficacy? 7. Ortiz JJ, Ayoub A, Gargala G, Chegne NL, Favennec L, 2001. Controlled trials are clearly indicated. If nitazoxanide proves Randomized clinical study of nitazoxanide compared to met- effective for these indications, the potential market associated ronidazole in the treatment of symptomatic giardiasis in chil- with these common infections may provide a major source of dren from northern Peru. Aliment Pharmacol Ther 15: 1409– 1415. revenue that will help insure drug availability. For now, we 8. Abboud P, Lemee V, Gargala G, Brasseur P, Ballet JJ, Borsa- should celebrate the arrival of an important new addition to Lebas F, Caron F, Favennec L, 2001. Successful treatment of the anti-parasitic arsenal. metronidazole- and albendazole-resistant giardiasis with nita- zoxanide in a patient with acquired immunodeficiency syn- Clin Infect Dis 32: Author’s address: A. Clinton White, Jr., Infectious Diseases Section, drome. 1792–1794. Department of Medicine, Baylor College of Medicine, 1 Baylor Plaza, 9. Gilles HM, Hoffman PS, 2002. Treatment of intestinal parasitic 535 EA, Houston, TX 77030, Telephone: 713-798-6846, Fax: 713-798- infections: a review of nitazoxanide. Trends Parasitol 18: 95– 0681, E-mail: [email protected] 97. 10. Diaz E, Mondragon J, Ramirez E, Bernal R, 2003. Short report: epidemiology and control of intestinal parasites with nitazox- REFERENCES anide in children in Mexico. Am J Trop Med Hyg 68: 384–385. 11. Favennec L, Jave Ortiz J, Gargala G, Lopez Chegne N, Ayoub A, 1. White AC Jr, 2000. The disappearing arsenal of antiparasitic Rossignol JF, 2003. Double-blind, randomized, placebo- drugs. N Engl J Med 343: 1273–1274. controlled study of nitazoxanide in the treatment of fascioliasis 2. Wickware P, 2002. Resurrecting the resurrection drug. Nat Med in adults and children from northern Peru. Aliment Pharmacol 8: 908–909. Ther 17: 265–270..
Load more

Recommended publications
  • Efficacy and Tolerability of Quinacrine Monotherapy and Albendazole Plus Chloroquine Combination Therapy in Nitroimidazole-Refractory Giardiasis: a Tropnet Study
    Klinik für Infektiologie & Spitalhygiene Efficacy and tolerability of quinacrine monotherapy and albendazole plus chloroquine combination therapy in nitroimidazole-refractory giardiasis: a TropNet study Andreas Neumayr, Mirjam Schunk, Caroline Theunissen, Marjan Van Esbroeck, Matthieu Mechain, Manuel Jesús Soriano Pérez, Kristine Mørch, Peter Sothmann, Esther Künzli, Camilla Rothe, Emmanuel Bottieau Journal Club 01.03.21 Andreas Neumayr Background on giardia treatment: • 1st-line treatment: 5-nitroimidazoles: metronidazole (1957), tinidazole, ornidazole, secnidazole • cure rate of 5NIs in 1st-line treatment: ~90% • in the last decade, an increase of 5NI-refractory giardia cases has been observed in travel medicine clinics across Europe: Hospital for Tropical Diseases, London: 2008: 15% --> 2013: 40% 70% of 5NI-refractory cases imported from India • 2nd-line treatment: effectiveness of a 2nd round with a 5NI: ~17% alternative drugs: albendazole, mebendazole, nitazoxanide, quinacrine, furazolidone, chloroquine, paromomycin 2012 TropNet member survey: 53 centres use 39 different treatment regimens, consisting of 7 different drugs in mono- or combination-therapy in various dosages and durations JC 01.03.21 Nabarro LE et al. Clin Microbiol Infect. 2015;21:791-6. • by 2013, there were only 13 reports of 2nd-line therapy for giardiasis (8 case series, 5 individual case reports): n=110 Cure rates Albendazole 6/32 18.7% Paromomycin 5/17 29.4% Nitazoxanide 2/5 40.0% Albendazole + 5-NI 42/53 79.2% Quinacrine 19/21 90.5% Quinacrine + 5-NI 14/14 100% Quinacrine + Paromomycin 2/2 100% • 2013: TropNet "GiardiaREF" study kick-off: Study on efficacy and tolerability of two 2nd-line regimens in nitroimidazole-refractory giardiasis: Quinacrine JC 01.03.21 Meltzer E et al.
    [Show full text]
  • Safety and Efficacy of Nitazoxanide-Based Regimen for the Eradication of Helicobacter Pylori Infection: a Systematic Review and Meta-Analysis
    Original Article Gastroenterol Res. 2020;13(6):260-268 Safety and Efficacy of Nitazoxanide-Based Regimen for the Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis Umair Iqbala, g, Harshit S. Kharaa, Daud Akhtarb, Yirui Huc, Hafsa Anward, Khwaja F. Haqe, Hafiz U. Siddiquif, Marika K. Bergenstocka, Matthew J. Shellenbergera Abstract eradication regimens revealed a pooled eradication rate of 85% (95% CI: 69-94%) without heterogeneity. In a subgroup analysis, highest Background: Helicobacter pylori (HP) is the most common cause of eradication rates were achieved with levofloxacin, doxycycline, nita- gastritis worldwide. Clarithromycin-based triple therapy or bismuth- zoxanide and proton pump inhibitor with a pooled eradication rate of based quadruple therapy is usually considered the first-line treatment, 92% (88-95%). however with around 30% failure rate for both regimens. Drug re- Conclusion: Nitazoxanide-based regimen is safe and effective in the sistance of clarithromycin and metronidazole is a growing concern eradication of HP infection. It is also successful as a salvage therapy in some parts of the world. Therefore, there is a need for effective in patients who have failed prior treatments. eradication regimen for HP. Nitazoxanide, a bactericidal thiazolide antibiotic, has been shown to be effective in HP infection. We con- Keywords: Nitazoxanide; Helicobacter pylori; Eradication regimen; ducted a systematic review and meta-analysis to evaluate the efficacy Meta-analysis of nitazoxanide-based regimen for the eradication of HP. Methods: We have searched PubMed, Embase, Ovid Medline and Cochrane library database from inception to December 9, 2020 to identify studies that utilized nitazoxanide in the treatment regimen Introduction for HP eradication.
    [Show full text]
  • Treatment Outcomes with Nitazoxanide in Immunocompetent
    dicine & Me S l u a r ic g e p r o y r T Ali and Kumar, Trop Med Surg 2015, 3:4 Tropical Medicine & Surgery DOI: 10.4172/2329-9088.1000198 ISSN: 2329-9088 Research Article Open Access Treatment Outcomes with Nitazoxanide in Immunocompetent Adults Naive Patients with Cryptosporidiosis; Do We Need Combination Therapy with Paromomycin or Azithromycin? Sajjad Ali1* and Sunil Kumar2 1Chairman Infection Prevention and Control Department, Department of Internal Medicine/Infectious Diseases, Sultan Bin AbdulAziz Humanitarian City Hospital, Riyadh, Saudi Arabia 2Department of Infectious Diseases, Sindh Institute of Urology and Transplantation, Karachi, Pakistan *Corresponding author: Sajjad Ali, Chairman Infection Prevention and Control Department, Department of Internal Medicine/Infectious Diseases, Sultan Bin AbdulAziz Humanitarian City Hospital, Riyadh, Saudi Arabia, Tel: 00966115620000; E-mail: [email protected] Received date: September 16, 2015, Accepted date: October 16, 2015, Published date: October 19, 2015 Copyright: © 2015 Sajjad, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. Abstract Introduction: Human cryptosporidiosis is caused by infection with Cryptosporidium. Nitazoxanide has shown activity against cryptosporidium. The objective of this study is to see treatment outcomes with 7 days of nitazoxanide in immunocompetent adult patients diagnosed with cryptosporidiosis and to consider combination therapy which includes nitazoxanide with paromomycin or azithromycin? Study Design: This cross sectional study was conducted at Sindh Institute of Urology and Transplantation, Karachi Pakistan. Patients were not enrolled with prior diagnosis of cryptosporidiosis and/or had taken Nitazoxanide, Paromomycin or Azithromycin in last 4 weeks prior their diagnosis.
    [Show full text]
  • PRESCRIBING INFORMATION These Highlights Do Not Include All the Information Needed to Use ALINIA ______DOSAGE FORMS and STRENGTHS ______Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ALINIA _____________ DOSAGE FORMS AND STRENGTHS ______________ safely and effectively. See full prescribing information for ALINIA. ALINIA Tablets: 500 mg (3.1) ALINIA for Oral Suspension: 100 mg/5 mL (3.2) ALINIA® (nitazoxanide) tablets, for oral use ALINIA® (nitazoxanide) for oral suspension ___________________ CONTRAINDICATIONS ___________________ Initial U.S. Approval: 2002 Hypersensitivity (4.1) __________________ _________________ INDICATIONS AND USAGE ___________________ ADVERSE REACTIONS ___________________ ALINIA is an antiprotozoal indicated for the treatment of diarrhea caused by The most common adverse reactions in ≥2% of patients were abdominal pain, Giardia lamblia or Cryptosporidium parvum (1). headache, chromaturia, and nausea (6.1). Limitations of Use: ALINIA has not been shown to be effective for the treatment of diarrhea To report SUSPECTED ADVERSE REACTIONS, contact Romark at caused by C. parvum in HIV-infected or immunodeficient patients (1). 813-282-8544 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. ___________________ ____________________ _______________ DOSAGE AND ADMINISTRATION ______________ DRUG INTERACTIONS ALINIA Tablets should not be administered to pediatric patient 11 years of Competition for binding sites may occur when administered concurrently with age or younger (2.1). other highly plasma protein-bound drugs with narrow therapeutic indices. Dosage for treatment of diarrhea caused by G. lamblia or C. parvum (2.1): Monitor for adverse reactions (7). Age Dosage Duration ______________ USE IN SPECIFIC POPULATIONS _______________ 5 mL of ALINIA for Oral Suspension Pediatric Patients: Safety and efficacy of ALINIA for Oral Suspension in 1-3 years (100 mg nitazoxanide) every 12 hours with food pediatric patients less than one year of age has not been studied (8.4).
    [Show full text]
  • Tapeworm Infection1.Qxd
    Page 1 of 2 TAPEWORM infection Drug Adult dosage Pediatric dosage — Adult (intestinal stage) Diphyllobothrium latum (fish), Taenia saginata (beef), Taenia solium (pork), Dipylidium caninum (dog) Drug of choice: Praziquantel1,2 5-10 mg/kg PO once 5-10 mg/kg PO once Alternative: Niclosamide3* 2 g PO once 50 mg/kg PO once Hymenolepis nana (dwarf tapeworm) Drug of choice: Praziquantel1,2 25 mg/kg PO once 25 mg/kg PO once Alternative: Nitazoxanide1,4 500 mg PO once/d or bid x 3d5 1-3yrs: 100 mg PO bid x 3d5 4-11yrs: 200 mg PO bid x 3d5 — Larval (tissue stage) Echinococcus granulosus (hydatid cyst) Drug of choice:6 Albendazole7 400 mg PO bid x 1-6mos 15 mg/kg/d (max. 800 mg) x 1-6mos Echinococcus multilocularis Treatment of choice: See footnote 8 Taenia solium (Cysticercosis) Treatment of choice: See footnote 9 Alternative: Albendazole7 400 mg PO bid x 8-30d; can be 15 mg/kg/d (max. 800 mg) PO in repeated as necessary 2 doses x 8-30d; can be repeated as necessary OR Praziquantel1,2 100 mg/kg/d PO in 3 doses x 100 mg/kg/d PO in 3 doses x 1 day then 50 mg/kg/d in 1 day then 50 mg/kg/d in 3 doses x 29 days 3 doses x 29 days * Availability problems. See table below. 1. Not FDA-approved for this indication. 2. Praziquantel should be taken with liquids during a meal. 3. Niclosamide must be chewed thoroughly before swallowing and washed down with water.
    [Show full text]
  • Antiparasitic Treatments in Pregnant Women: Update and Recommendations E Boitel, Guillaume Desoubeaux
    Antiparasitic treatments in pregnant women: Update and recommendations E Boitel, Guillaume Desoubeaux To cite this version: E Boitel, Guillaume Desoubeaux. Antiparasitic treatments in pregnant women: Up- date and recommendations. Médecine et Maladies Infectieuses, Elsevier Masson, In press, 10.1016/j.medmal.2018.09.008. hal-02439523 HAL Id: hal-02439523 https://hal.archives-ouvertes.fr/hal-02439523 Submitted on 17 Jan 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Médicaments antiparasitaires chez la femme enceinte : actualités et recommandations Antiparasitic treatments in pregnant women: update and recommendations E Boitel1, G Desoubeaux1,* 1CHU de Tours, Parasitologie – Mycologie – Médecine tropicale, 37044 Tours - France *Corresponding author: [email protected] Service de Parasitologie – Mycologie –Médecine tropicale Hôpital Bretonneau, Bâtiment B2A 1er étage 2 boulevard Tonnellé 37044 CHU de Tours Cedex 9 - FRANCE Téléphone : +33(0)2 47 47 39 27 Fax : +33(0)2 47 47 80 82 Mots clés : hypotrophie ; morts fœtales in utero ; mutagénicité ; tératogénicité ; paludisme Keywords: fetal death; low birth weight; mutagenicity; teratogenicity; malaria RESUME Les parasitoses constituent une importante cause de morbi-mortalité dans le monde, et plus particulièrement dans les pays à faibles ressources où la prévalence de telles infections est très élevée.
    [Show full text]
  • A Randomized Study Comparing Levofloxacin, Omeprazole, Nitazoxanide, and Doxycycline Versus Triple Therapy for the Eradication O
    1970 ORIGINAL CONTRIBUTIONS nature publishing group see related editorial on page 1976 A Randomized Study Comparing Levofl oxacin, Omeprazole, Nitazoxanide, and Doxycycline versus Triple Therapy for the Eradication of Helicobacter pylori STOMACH STOMACH P. Patrick Basu , MD 1 , 2 , Krishna Rayapudi , MD 2 , Tommy Pacana , MD 2 , Niraj James Shah , MD 2 , Nithya Krishnaswamy , MD 2 and Molly Flynn , PharmD 3 OBJECTIVES: Resistance to standard Helicobacter pylori (HP) treatment regimens has led to unsatisfactory cure rates in HP-infected patients. This study was designed to evaluate a novel four-drug regimen (three antibiotics and a proton pump inhibitor (PPI)) for eradication of HP infection in treatment-naive patients. METHODS: Patients with a diagnosis of HP gastritis or peptic ulcer disease confi rmed using endoscopy and stool antigen testing were eligible for inclusion in this study. All patients underwent a washout period of 6 weeks from any prior antibiotic or PPI usage. Patients were then randomized to either levofl oxacin, omeprazole, nitazoxanide, and doxycycline (LOAD) therapy for 7 days (LOAD-7) or 10 days (LOAD- 10), including levofl oxacin 250 mg with breakfast, omeprazole 40 mg before breakfast, nitazoxanide (Alina) 500 mg twice daily with meals and doxycycline 100 mg at dinner, or lansoprozole, amoxicillin, and clarithromycin (LAC) therapy for 10 days, which included lansoprozole 30 mg, amoxicillin 1 g with breakfast and dinner, and clarithromycin 500 mg with breakfast and dinner. HP eradication was confi rmed by stool antigen testing at least 4 weeks after cessation of therapy. RESULTS: Intention-to-treat analysis revealed signifi cant differences ( P < 0.05) in the respective eradication rates of the LOAD therapies (88.9 % (80 / 90) LOAD-10, 90 % (81 / 90) LOAD-7, 89.4 % (161 / 180) for combined LOAD) compared with those receiving LAC, 73.3 % (66 / 90).
    [Show full text]
  • Parasitic Infections (1 of 14)
    Parasitic Infections (1 of 14) 1 Patient presents w/ signs & symptoms suggestive of GI parasitic infection 2 DIAGNOSIS No ALTERNATIVE Is a GI parasitic infection DIAGNOSIS confi rmed? Yes Protozoal or helminthic infection? Protozoal Infection Helminthic Infection A Rehydration & nutrition B Prevention PHARMACOLOGICAL PHARMACOLOGICAL THERAPY FOR THERAPY FOR PROTOZOAL HELMINTHIC INFECTIONS INFECTIONS ©See page 3 MIMSSee page 3 B1 © MIMS 2019 Parasitic Infections (2 of 14) 1 SIGNS & SYMPTOMS OF GI PARASITIC INFECTIONS GI Symptoms • Abdominal pain, diarrhea, dysentery, fl atulence, malabsorption, symptoms of biliary obstruction Nonspecifi c Symptoms • Fever, malaise, fatigue, anorexia, sweating, wt loss, edema & pruritus • Some patients may be asymptomatic PARASITIC INFECTIONS PARASITIC 2 DIAGNOSIS Clinical History • Attempt to elicit a history of possible exposure, especially for helminthic infections, eg eating undercooked meat, source of drinking water, swimming in fresh water where certain parasites may be endemic • Knowledge of the geographic distribution of parasites is helpful in the diagnosis of patients Host Susceptibility Factors in GI Parasitic Infections • Nutritional status • Intercurrent disease • Pregnancy • Immunosuppressive drugs • Presence of a malignancy Physical Exam Findings • Pallor • Hepatomegaly • Ascites • Ileus • Rectal prolapse Lab Tests Microscopic Exam of Stools • Fundamental to the diagnosis of all GI infections - A minimum of 3 stool specimens, examined by trained personnel using a concentration & a permanent stain
    [Show full text]
  • Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study Combined with Docking for Mechanistic Insight
    Send Orders for Reprints to [email protected] Current Computer-Aided Drug Design, 2015, 11, 21-31 21 Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study Combined with Docking for Mechanistic Insight Thomas Scior*,1, Jorge Lozano-Aponte1, Subhash Ajmani2, Eduardo Hernández-Montero3, Fabiola Chávez-Silva4, Emanuel Hernández-Núñez4, Rosa Moo-Puc5, Andres Fraguela-Collar3 and Gabriel Navarrete-Vázquez4 1Laboratorio de Simulaciones Moleculares Computacionales, Facultad de Ciencias Químicas, BUAP, Puebla, Puebla 72000, México 2Department of Computational Chemistry, Jubilant Biosys Limited, #96, Industrial Suburb, 2nd Stage, Yeshwanthpur, Bangalore - 560 022, India 3Posgrado en Matemáticas, Facultad de Ciencias Físico Matemáticas, BUAP, Puebla, Puebla 72000, México 4Laboratorio de Química Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, México 5Unidad de Investigación Médica Yucatán, Unidad Médica de Alta Especialidad del Centro Médico Nacional Ignacio García Téllez, IMSS Mérida, Yucatán 97000, México Abstract: In view of the serious health problems concerning infectious diseases in heavily populated areas, we followed the strategy of lead compound diversification to evaluate the near-by chemical space for new organic compounds. To this end, twenty derivatives of nitazoxanide (NTZ) were synthesized and tested for activity against Entamoeba histolytica parasites. To ensure drug-likeliness and activity relatedness of the new compounds, the synthetic work was assisted by a quantitative structure-activity relationships study (QSAR). Many of the inherent downsides – well-known to QSAR practitioners – we circumvented thanks to workarounds which we proposed in prior QSAR publication. To gain further mechanistic insight on a molecular level, ligand-enzyme docking simulations were carried out since NTZ is known to inhibit the protozoal pyruvate ferredoxin oxidoreductase (PFOR) enzyme as its biomolecular target.
    [Show full text]
  • Analysis of US FDA-Approved Drugs Containing Sulfur Atoms
    Top Curr Chem (Z) (2018) 376:5 https://doi.org/10.1007/s41061-018-0184-5 REVIEW Analysis of US FDA‑Approved Drugs Containing Sulfur Atoms Kevin A. Scott1,2 · Jon T. Njardarson1 Received: 20 November 2017 / Accepted: 5 January 2018 / Published online: 22 January 2018 © Springer International Publishing AG, part of Springer Nature 2018 Abstract In this review, we discuss all sulfur-containing FDA-approved drugs and their structures. The second section of the review is dedicated to structural analy- sis and is divided into 14 subsections, each focusing on one type of sulfur-contain- ing moiety. A concise graphical representation of each class features drugs that are organized on the basis of structural similarity, evolutionary relevance, and medical indication. This review ofers a unique and comprehensive overview of the struc- tural features of all sulfur-containing FDA-approved drugs to date. Keywords Sulfonamide · Thioether · Sulfoxide · Sulfone · Sulfate · Sulfur heterocycle Abbreviations 6-APA 6-Aminopenicillanic acid ADP Adenosine diphosphate cGMP Cyclic guanosine monophosphate COX-2 Cyclooxygenase-2 GERD Gastroesophageal refux disease GPCR G protein-coupled receptor HIV Human immunodefciency virus mRNA Messenger RNA NSAID Nonsteroidal anti-infammatory drugs SMN1 Survival motor neuron 1 This article is part of the Topical Collection “Sulfur Chemistry”, edited by Xuefeng Jiang. * Jon T. Njardarson [email protected] 1 Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA 2 Department of Pharmacology
    [Show full text]
  • Challenges of Antibacterial Discovery Lynn L
    CLINICAL MICROBIOLOGY REVIEWS, Jan. 2011, p. 71–109 Vol. 24, No. 1 0893-8512/11/$12.00 doi:10.1128/CMR.00030-10 Copyright © 2011, American Society for Microbiology. All Rights Reserved. Challenges of Antibacterial Discovery Lynn L. Silver* LL Silver Consulting, LLC, 955 S. Springfield Ave., Unit C403, Springfield, New Jersey 07081 INTRODUCTION .........................................................................................................................................................72 The Discovery Void...................................................................................................................................................72 Class Modifications versus Novel Classes.............................................................................................................72 BACKGROUND............................................................................................................................................................72 Early Screening—a Brief and Biased Philosophical History .............................................................................72 The Rate-Limiting Steps of Antibacterial Discovery ...........................................................................................74 The Multitarget Hypothesis ....................................................................................................................................74 ANTIBACTERIAL RESISTANCE ..............................................................................................................................75
    [Show full text]
  • 2-Amino-1,3,4-Thiadiazoles As Prospective Agents in Trypanosomiasis and Other Parasitoses
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE Acta Pharm. 70 (2020) 259–290 Review https://doi.org/10.2478/acph-2020-0031 2-Amino-1,3,4-thiadiazoles as prospective agents in trypanosomiasis and other parasitoses GEORGETA SERBAN Parasitic diseases are a serious public health problem af fect ing Pharmaceutical Chemistry hundreds of millions of people worldwide. African trypano- Department, Faculty of Medicine somiasis, American trypanosomiasis, leishmaniasis, malaria and Pharmacy, University of Oradea and toxoplasmosis are the main parasitic infections caused by 410028 Oradea, Romania protozoan parasites with over one million deaths each year. Due to old medications and drug resistance worldwide, there is an urgent need for new antiparasitic drugs. 1,3,4-Thiadiazoles have been widely studied for me di cal applications. The chemi- cal, physical and pharmaco kinetic properties recommend 1,3,4-thiadiazole ring as a target in drug development. Many scientific papers report the antiparasitic potential of 2-amino- -1,3,4-thiadiazoles. This review presents synthetic 2-amino- -1,3,4-thiadiazoles exhibiting antitrypanosomal, antimalarial and antitoxo plasmal acti vi ties. Although there are insufficient results to state the quality of 2-amino-1,3,4-thiadiazoles as a new class of antiparasitic agents, many reported derivatives can be considered as lead compounds for drug synthesis and a pro- mise for the future treatment of parasitosis and provide a valid strategy for the development of potent antiparasitic drugs. Keywords: 2-amino-1,3,4-thiadiazoles, antiparasitic activity, anti- Accepted October 24, 2019 trypanosomal activity, antimalarial activity, antitoxo plas mal Published online November 18, 2019 activity, inhibitory concentration INTRODUCTION Human parasitic diseases are caused by organisms of different sizes and shapes, from unicellular organisms (protozoa) to large-sized worms.
    [Show full text]