Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new biltricide research articles will be listed here shortly after becoming available to us.
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Medical research on biltricide
J Parasitol. 2008 Apr; 94(2): 537-41
Sabra AN, Botros SS
The stability of praziquantel (PZQ)-insusceptible S. mansoni isolates and the possible selection of PZQ-insusceptible parasites upon applying therapeutic pressure were examined over several life cycle passages (snails to mice). To test isolate stability, 3 PZQ-susceptible and 7 PZQ-insusceptible isolates were used to establish infection in mice, and they were passaged each for 2-5 life cycles. After each passage, 6 groups of mice were used to assess the PZQ dose at which the worm burden was decreased by 50% (ED50). Five of them were treated with doses of PZQ (12.5, 25, 50, 100, and 200 mg/kg for 5 days) 7 wk after infection; the last group represented infected, but untreated, controls. Possible selection of PZQ-insusceptible parasites under therapeutic pressure was examined by subjecting 1 PZQ-susceptible and 1 PZQ-insusceptible S. mansoni isolate to therapeutic pressure by PZQ for 8 passages. After the final passage, PZQ ED50 was estimated. All PZQ-susceptible S. mansoni isolates showed stable susceptibility to PZQ (mean PZQ ED50 = 85 mg/kg) over all passages. Two of the 7 PZQ-insusceptible S. mansoni isolates (847 and ER5) showed normal sensitivity to PZQ in 1-2 passages (although not the last passage, and without a declining ED50 profile), whereas the remaining passages kept a sustained insusceptibility to the drug (mean PZQ ED50 = 217 mg/kg). Worm maturity and sex were irrelevant to variability in drug ED50 within an individual isolate over different passages, revealing the heterogeneous nature of the parasite. Therapeutic pressure for limited life cycle passages did not result in a significant increase in drug ED50. The fact that reversion of some of the PZQ-insusceptible S. mansoni isolates to normal drug-sensitive state is not long lasting and that the therapeutic pressure by PZQ in the field is not comparable with that in the laboratory (unlimited), make monitoring the response of patients to the drug in the field an integral part of schistosomiasis control measures.
Schistosoma haematobium (Egyptian strain): rate of development and effect of praziquantel treatment.
J Parasitol. 2008 Apr; 94(2): 386-94
Botros SS, Hammam OA, El-Lakkany NM, El-Din SH, Ebeid FA
This study investigates the development of the Egyptian strain of Schistosoma haematobium and the resultant immunohistopathology and biochemical changes in organs affected. In addition, the response of different developmental stages of S. haematobium worms to praziquantel (PZQ) was examined. Schistosoma haematobium-infected hamsters were classified into 4 groups and were treated at day 35, 55, 75, and 95 postinfection (PI), respectively. Each group was subdivided into 3 subgroups. Two of them were treated orally with PZQ (300 mg/kg or 500 mg/kg divided equally on 2 consecutive days), and the third group was left without treatment. Treated groups were killed 20 days posttreatment. Infection with S. haematobium became patent 73 days PI; tissue egg load and worm fecundity were higher at 95 days and maximal 115 days PI, with an oogram pattern comparable to that in Schistosoma mansoni infection. In the liver, small cellular granulomas were observed 75 days PI, with preponderance of CD4+ T-cell phenotypes. In the urinary bladder, only submucosal focal Brunn's-nest formation and angiogenesis without typical granulomas were observed. Ninety-five and 115 days PI, confluent granulomata with multiple eggs in the center were observed in the liver and urinary bladder, with a preponderance of CD8+ positive T cells in the liver and hyperplasia of the urinary bladder epithelium with cystitis cystica and papillae formation. One hundred percent worm eradication was recorded with the higher dose of PZQ in animals treated 75 and 95 days PI. In conclusion, in spite of the long prepatent period of the Egyptian strain of S. haematobium, sensitivity to PZQ was recorded soon after infection. Granulomata were similar to those of S. mansoni in the livers and urinary bladders, but they were confluent with multiple eggs in the centers, hyperplasia of the urinary bladder urothelium with cystitis cystica, papillae, and Brunn's-nest formation predictive of malignant changes with no hepatocyte dysplasia.
Enterobiasis: a neglected infection in adults.
Southeast Asian J Trop Med Public Health. 2008 Mar; 39(2): 213-6
Sato M, Sanguankiat S, Pubampen S, Kusolsuk T
In this study, adult patients were treated with praziquantel to expel intestinal flukes. Unexpectedly, dozens of adult Enterobius vermicularis worms with disfigured morphology, which had not been detected on fecal examination using Kat's modified thick-smear technique, were expelled from 6 of 33 patients.
Long-term evaluation of patients with hydatidosis treated with albendazole and praziquantel.
Int J Immunopathol Pharmacol. 2008 Apr-Jun; 21(2): 429-35
Haralabidis S, Diakou A, Frydas S, Papadopoulos E, Mylonas A, Patsias A, Roilides E, Giannoulis E
Hydatidosis is a usually asymptomatic chronic disease. In most patients who undergo surgery, hydatidosis is not resolved due to high recurrence rate. However, long-term treatment with albendazole has been found to have a significant efficacy that has been further improved when albendazole is combined with praziquantel and fat-rich diet. In this study a retrospective evaluation of the outcome of hydatidosis in 70 patients, was performed. In group A, a combined chemotherapy of albendazole plus praziquantel was given after surgical removal of cysts. In group B chemotherapy alone was administered without surgery. Sera of all patients were assayed for IgG, IgM, IgA and IgE antibodies by ELISA. In addition, ultrasonography (US) and/or computerized tomography (CT) scans were performed every 3 months for 18 months, and then, each year until the end of follow-up. The difference between the two kinds of treatment used in the present study was found to be not significant, nor was the difference of the shrinkage and extended calcification of the HCs between the two groups. However, the difference of the shrinkage of the HCs of more than 80%, as well as the extended calcifications of the cysts between the two groups were found to be statistically significant. In all patients high levels of IgG and IgA were detected, while IgE in group A and/or IgM in group B were marginally detected above the background level throughout the study. Level of IgG was strongly fluctuated and significantly decreased at 11.7 years after the end of chemotherapy, or at 8.5 years after relapses in group A, while was dramatically decreased at 3.6 years after the termination of chemotherapy in group B. Relapses occurred in 11.4% of patients within the first six months after end of chemotherapy. After additional chemotherapy with albendazole for 3-6 months, all of them were considered cured at 8.5 years of follow up.
[Defining an ethics for preventive trials]
Bull Soc Pathol Exot. 2008 Apr; 101(2): 85-9
Chippaux JP
Preventive trials (to prevent from infection) or prophylaxis trials (to avoid consequences of the disease) differ from other clinical trials as they apply to healthy subjects or subjects considering themselves as such: the latter do not ask for intervention even less for trial. Moreover, it is generally an experiment which aims at validating a public health intervention, the individual character of which could appear as secondary regarding the collective interest. It concerns many tools or methods: preventive or prophylactic vaccines and drugs, condoms, impregnated bed nets, etc. The field of implementation of preventive trials is large and covers routine immunization (EPI), large-scale control or eradication of endemic diseases or epidemics, for which the concept of individual risk is generally better understood. Preventive trials imply ethical obligations (high individual or collective benefits and absence of risks as there is no immediate therapeutic compensation), methodological adaptations (because the number of subjects is considerably larger than for therapeutic trials) and a sensitive valorization towards a large population who is not asking for the recommended intervention. As regard the benefits, it is also necessary to consider the costs in comparison with the expected efficacy The methodological constraints are important because the demonstration of both safety and efficacy requires a very large number of subjects to validate the product. It is often necessary to use indirect or substitutive markers and indicators (title of protective antibodies rather than definite clinical protection) which need a preliminary validation. Before carrying out a preventive or prophylactic trial, it is advisable to specify the objectives in order to assess the real profits and absence of risks during the trial and after the implementation of the tested product. Preventive trials require a phase of technological transfer to guarantee the application of the validated tools for the benefit of the population at stake. In this respect, if trials for prevention are now well codified both on ethical and methodological aspects, trials for prophylaxis (filariasis with ivermectin, schistosomiasis with praziquantel, malaria with intermittent "preventive" treatment or HIV with antiretroviral treatment, for example) still remain a difficult issue at both ethical and methodological levels.
Prog Urol. 2008 May; 18(5): 327-329
Fall PA, Berthe H, Diao B, Ndoye AK, Odzebe AS, Dangou JM, Diagne BA
Vulvar localisation of schistosomiasis is a rare presentation. We report a case of a woman of 20years old hospitalised for a vulvar mass of six months. That mass progressively increased in volume and was tender. It was accompanied by frequency and dysuria. The patient had a history of swimming in fresh water and hematuria when she was eight years old. Initial clinical examination found a good general state, there was a mass involving the clitoris and the small lips. This painless mass had a cauliflower appearance and was soft with a large implantation. Pathology exam of the mass revealed a vulvar schistosomiasis with an important amount of living eggs. A tumour removal with a plasty of small lips was performed. Additionally, praziquantel was administered orally. Vulvar localisation of schistosomiasis might suggest a malignant tumour. Only pathological examination can assess the diagnosis.
DNA-based vaccines protect against zoonotic schistosomiasis in water buffalo.
Vaccine. 2008 Jul 4; 26(29-30): 3617-25
Da'dara AA, Li YS, Xiong T, Zhou J, Williams GM, McManus DP, Feng Z, Yu XL, Gray DJ, Harn DA
Schistosomiasis japonica is an endemic, zoonotic disease of major public health importance in China where water buffaloes account for approximately 75% of disease transmission. Interventions that reduce schistosome infection in water buffaloes will enhance their health simultaneously reducing disease transmission to humans. While chemotherapy has proved successful, it requires continued time consuming and expensive mass treatments. A more sustainable option would be development of vaccines that reduce transmission of S. japonicum from bovines to replace bovine chemotherapy. We performed two randomized double blind trials in water buffaloes to determine if DNA vaccines encoding triose-phosphate isomerase (SjCTPI), or the tetraspanin 23kDa integral membrane protein (SjC23), alone or fused to bovine heat shock protein 70 (Hsp70) could induce a level of immunity conducive to long-term sustainable control. Groups of water buffaloes (15/group) received three intramuscular injections, 4 weeks apart. Booster immunizations were co-administered with a plasmid DNA encoding IL-12. Four weeks after the last injection, water buffaloes were challenged with 1000 cercariae, and vaccine efficacy analyzed 8 weeks later. Water buffaloes vaccinated with SjCTPI-Hsp70 or SjCTPI plasmids had worm burdens reduced by 51.2% and 41.5%, respectively. Importantly, fecal miracidial hatching was reduced by 52.1% and 33.2% respectively compared to control vaccinated water buffaloes. Vaccination with SjC23-Hsp70 and SjC23 plasmids reduced worm burdens by 50.9% and 45.5%, respectively, and fecal miracidial hatching by 52.0% and 47.4%. A mathematical model of schistosome transmission predicts that schistosome vaccines capable of reducing water buffaloes' fecal egg output by 45%, alone or in conjunction with praziquantel treatment, will lead to a significant reduction in transmission of schistosomiasis. Both DNA vaccines tested here exceed this hypothetical level. Indeed, mathematical modeling of SjCTPI-Hsp70 and SjC23-Hsp70 alone and in conjunction with human chemotherapy showed a significant reduction in transmission almost to the point of elimination.
Pulmonary paragonimiasis with coincidental malignant mesothelioma.
Intern Med. 2008; 47(11): 1027-31
Yamazaki M, Ohwada A, Miyaji A, Yamazaki H, Nara T, Hirai S, Fujii H, Uekusa T, Suzuki M, Iwase A, Takahashi K
A 72-year-old man patient was referred to our institution for evaluation and treatment of right pleural effusion. Eosinophilic pleural effusion and peripheral eosinophilia were identified during the course of hospitalization. Pulmonary paragonimiasis was confirmed by the presence of paragonimus-specific IgG antibodies for Paragonimus (P.) westermani and P. miyazakii in his serum. Although Praziquantel, a highly effective agent for the treatment of lung flukes was repeatedly administered, the pleural effusion did not subside and the patient's condition gradually deteriorated until his death due to circulatory insufficiency. Postmortem examination revealed malignant mesothelioma of the sarcomatous type encasing the right lung and heart. Cardiac involvement accompanied with old and recent-onset myocardial ischemic changes resulted in death of this patient. Here, we report a very rare case of malignant mesothelioma with a concomitant infection of parasitic lung fluke.
Antimicrob Agents Chemother. 2008 Jun 2;
Martins-Leite P, Gazzinelli G, Alves-Oliveira LF, Gazzinelli A, Malaquias LC, Correa-Oliveira R, Teixeira-Carvalho A, Silveira AM
The objective of the present study was to test the hypothesis that treatment of schistosomiasis mansoni with praziquantel can alter significantly the immune response of patients and generate a reversal of the level of fibrosis. Peripheral blood mononuclear cell (PBMC) samples were collected from, and abdominal ultrasound examinations conducted on, volunteers infected with Schistosoma mansoni and living in an area endemic for the disease, prior to and one year after treatment with praziquantel. Subjects were classified into groups according to the pathology presented (i.e. fibrosis absent, incipient, moderate or severe). PMBC were stimulated with soluble antigens from schistosome eggs (SEA) and the production of the cytokines gamma interferon (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interleukin-4 (IL-4), IL-10, and IL-13 determined. The chemotherapy was effective in reducing morbidity, particularly in individuals presenting severe fibrosis. When cytokine production in post-treatment PBMC cultures stimulated by SEA was categorized as low or high, significant differences in the distribution of IL-13 levels were established between groups presenting of not presenting fibrosis. Comparison of pre- and post-treatment SEA-induced cytokine levels in individuals that had experienced no change in the grade of fibrosis following chemotherapy, revealed that IFN-gamma decreased in subjects with fibrosis, whilst IL-10 decreased in individuals with and without fibrosis. The data suggest that chemotherapy is effective in reducing the morbidity of the disease, and that the level of IL-13 may be a useful indicator of the persistence of fibrosis following treatment.
Ann Trop Med Parasitol. 2008 Jun; 102(4): 335-46
Gutman J, Fagbemi A, Alphonsus K, Eigege A, Miri ES, Richards FO
Both Schistosoma haematobium and S. mansoni are endemic in Nigeria. Since 1999 the ministries of health of Plateau and Nasarawa states, assisted by The Carter Center, have provided mass drug administrations with praziquantel to villages where >20% of the school-aged children tested with urine dipsticks have been found to have haematuria (presumed to be caused by S. haematobium). The current extent of S. mansoni in Nigeria remains relatively unknown because the tests needed to detect human infection with this parasite are difficult to perform in many endemic areas. In a cross-sectional survey involving 924 children, the prevalence of S. mansoni was determined in 30 villages (in four local government areas) that had been excluded from mass praziquantel administrations because the prevalence of haematuria in their school-aged children had been found to be