A Paragonimiasis Patient with Allergic Reaction to Praziquantel and Resistance to Triclabendazole: Successful Treatment after Desensitization to Praziquantel

Paragonimiasis is an infectious disease caused by trematodes of the genus Paragonimus. This trematode can be treated successfully with praziquantel in more than 90% of the cases. Although praziquantel is generally well tolerated, anaphylactic reactions to this drug have been reported in a few cases. We report here a 46-year-old Korean female with paragonimiasis, presumed to be due to Paragonimus westermani, who displayed an allergic reaction to praziquantel and resistance to triclabendazole treatment. The patient was successfully treated with praziquantel following a rapid desensitization procedure. Desensitization to praziquantel could be considered when no alternative drugs are available.

Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni

The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7 percent for Group 1 and 83.9 percent for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage.

Potential relation ibetween the appearance of biomphalaria alexandrina- biomphalaria glabrata hybrid in the irrigation system and the evolution of resistance to praziquntel lyeatment in Egypt

In the last decade, partial resistance to Praziquantel [PZQ] in treatment of schistosomiasis appeared in some villages in Egypt. This happened following the invasion of the irrigation system by hybrid snails of the indigenous, vector snail Biomphalaria alexandrina and the introduced Biomphalaria glabrata. The objective of this study was to investigate if the distribution of the hybrid snails in the irrigation system represents a factor, between others, which is related to the appearance of [PZQ] resistance. Therefore, three groups of mice were infected with Schistosoma mansoni cercariae obtained from infected B. alexandrina, B.glabrata and hybrid snails. Six weeks later, the animals were treated with.the usual curative dose of PZQ [500mg/kg body weight for two consecutive days] and sacrificed two weeks post-treatment. The results showed that worms reduction in the group infected with cercariae from hybrid snails was significantly less than that in the other two groups 86.1% versus 95.1% and 92.8%, respectively. The number of dead ova in the same group was also less, being 81.5% versus 97.5%, and 95.1% respectively. The numbers of ova/g liver was 56.6%, in the same group while 64.2 and 70.9 in the other two groups. The reduction in numbers of ova/g intestine was 81.9% in this group versus 86.1% and 88.4% in the other two groups.The present results give indication that the appearance of PZQ resistance against schistosomiasis in Egypt may return at least partially to the wide distribution of the hybrid Biomphalaria snails in this country

Efficacy of Randia nilotica methanol extract against Schistosoma mansoni infection in mice

Schistosomiasis is an important parasitic disease in the tropics. Emergence of praziquantel-resistence strains urged the need for new drugs. To scientifically evaluate the effectiveness of a plant [Randia nilotica] used traditionally to treat Schistosomiasis Albino mice were experimentally infected with single dose of 150 cercariae of the Sudan strain of Schistosoma mansoni. All the cercariae penetrated the shaved tail of the mouse. The mice were treated with single i.p [intraperitoneal] dose of 1 ml of R. nilotica methanol extract [prepared from fruit part of the plant] in concentration of 5000 ppm and double doses through the same route of administration with 1 ml of R. nilotica methanol extract in concentrations of 1000 and 500 ppm. This resulted in total worm burden reductions at 87% 76% 68% respectively. The reductions in female worm burden were 99%, 97%, and 95% respectively. Oral administration with the same concentrations [single dose of 5000 ppm and double doses of 1000 and 500 ppm] resulted in total and female worm burden reductions. There was obvious reduction in the number of eggs in liver and intestinal tissues of the treated mice and improvement of their health when compared with the control group. We conclude that the methanol extract of R. nilotica is effective against Schistosoma mansori

short review of some pharmacological, therapeutic and toxicological properties of praziquantel in man and animals

Praziquantel is the current drug of choice against many trematodes and cestodes in both man and animals. This article summarizes the main pharmacological, therapeutic and toxicological properties of the drug, especially that have been reported during the last 10 years. In most cases, the effectiveness and safety of the drug have been confirmed, although there are currently concerns about the resistance/decreased effectiveness of the drug to certain Schistosome isolates, and also about the mutagenicity of the drug

Therapeutic evaluation of sustained-releasing praziquantel (SRP) for clonorchiasis: Phase 1 and 2 clinical studies

Sustained-releasing praziquantel (SRP) tablet was designed for single dose treatment regimen of clonorchiasis. A previous pre-clinical study confirmed its sustained-releasing characteristics and a better cure rate than conventional praziquantel (PZQ). In this clinical study, the pharmacokinetics of this SRP tablet were investigated in human volunteers (phase 1; 12 volunteers), and its curative efficacy was examined in clonorchiasis patients (phase 2; 20 volunteers). In the phase 1 clinical study, blood concentrations of both tablets showed wide individual variation. The AUC(last) of SRP was 497.9+/-519.0 ng.hr/ml (mean+/-SD) and PZQ of 628.6+/-695.5 ng.hr/ml, and the AUC(inf) of SRP was 776.0+/-538.5 ng.hr/ml and of PZQ 658.6+/-709.9 ng.hr/ml. C(max) values of SRP and PZQ were 90.7+/-82.2 ng/ml and 214.9+/-251.9 ng/ml, and T(max) values were 3.42+/-1.43 hr and 1.96+/-1.23 hr, respectively. SRP tablets showed similar AUC values, but lower C(max) and longer T(max) values than PZQ. In the phase 2 study, SRP at 30 mg/kg (single dose) achieved a 60% cure rate and a 95.5% egg reduction rate. The cure rate of a single dose SRP was unsatisfactory compared with that of the conventional PZQ dose, but much better than that achieved by a single dose PZQ.

Comparative study of the hepatotoxic, genotoxic and carcinogenic effects of praziquantel distocide and the natural Myrrh extract Mirazid [R] on adult male albino rats

Praziquantel [PZQ] is widely and effectively used in the control of bilharziasis which constitutes a major endemic health problem in Egypt. However, recent studies recommended that the drug must be re-evaluated because of its potential carcinogenicity and genotoxicity. Mirazid is a new natural anti-schistosomal drug formed of myrrh extract and considered to be a safe drug. This work was conducted to evaluate and compare hepatotoxic, genotoxic and carcinogenic effects of PZQ und mirazid on adult male albino rats by assessment of serum levels of ALT, AST and bilirubin, histopathological study of the liver and cytogenetic study of bone marrow cells. 100 adult male albino rats were equally divided into 4 groups: group I negative control, group II control rats received distilled water, group III received weekly single oral dose of PZQ [1500 mg/kg] for 6 weeks and group IV received daily oral dose of mirazid [500mg/kg] for 6 weeks. At the end of the study, 10 rats of each group were investigated by assessment of the levels of AST, ALT, and bilirubin. After scarification, liver sections were examined by light microscopy. Another 10 rats of each group were submitted to cytogenetic examination. It was found that praziquantel induced a significant increase in the mean values of AST, ALT and bilirubin with areas of hyaline degeneration, fatty changes, dysplasia and necrosis in the liver sections. It also induced a significant increase in the incidence of chromosomal aberrations as polyploidy, fragment, deletion and ring chromosome as compared with control group. Mirazid induced an insignificant increase in the mean values of AST, ALT and bilirubin with a normal hepatic tissue and an insignificant increase in the incidence of chromosomal aberrations as compared with the control group. On comparing both drugs, praziquantel induced a significant hepatotoxic, genotoxic and carcinogenic effects. It was concluded that praziquantel is considered to be a hepatotoxic, genotoxic and carcinogenic drug. On the other hand, mirazid seemed to be a safe and promising antiparasitic drug, free from hepatotoxic, genotoxic and carcinogenic effects

Investigation of Induced biochemical and histopathological parameters of acetonitril extract of Jatropha carcus in albino rats

Toxicological and histopathological investigations were carried on the acetonitrile extract from J. Carcus in comparison with praziquantel, the known anti-schistosomal drug. On a constant weight dose bases [single dose of 50 mg/kg body weight injected orally to albino rats], the acetonitrile extract from J. carcus showed mild toxicological parameters, biochemical parameters as well as histopathological profile in comparison with the control. However, these side effects were nonsignificant compared with the severe side effects caused by praziquantel

Anthelmintics: a review.

Helminths infect 25% of the world's population. In the last 50 years specific, safe and effective anthelminitic drug therapy for various parasitic infestations have been developed. The population of the developing countries across the globe suffers not only as a direct result of these infections but due also to co-morbidity such as anemia, malnutrition and reduced immunity status. Earlier anthelmintic drugs suffered from serious drawbacks such as hepatotoxicity and required specific preparation of the patient before treatment such as 12-hour fasting and pre-post purging caused considerable inconvenience to the patient. However, successive discoveries were born out of rationale approach that contributed to the effective, more specific and more easily tolerated drugs i.e. benzimidazoles, piperazine derivatives, avermectins, pyrazinoquinoline, etc. The present approach is to identify the causative parasite on the basis of stool examination and as a result of this approach, different drugs are prescribed for different parasitic infections. Examples include thiabendazole for cutaneous larva migrans, mebendazole for ascariasis, trichiuriasis and hookworm, albendazole for inoperable cases of cystic hydatid disease, DEC for Toxocara induced visceral larva migrans and loiasis, ivermectin for onchocerciasis, praziquantel for schistosomiasis and niridazole for Dracunculus medinensis. The cure rates with these drugs is also high e.g. thiabendazole produces a cure-rate of 98% in cutaneous larva migrans while mebendazole gives cure rate of 76-95% in ascariasis, trichiuriasis and hookworm infestations. A cure rate of 96% is produced by praziquantel in schistosomiasis. Most of these drugs have broad-spectrum anthelmentic effect. The present review aims at evaluating the currently available anthelmintics with respect to their efficacy and adverse effects. Steps to prevent impending helminthic drug resistance are also discussed.

Esquema corto de Praziquantel para el tratamiento de la neurocisticercosis parenquimatosa / Short regimen of Praziquantel for the treatment of parenclymatose neurocysticercosis

Objetivo. La terapia para la neurocisticercosis parenquimatosa con praziquantel (PZQ) de 15 días ha mostrado ser efectiva. Las concentraciones en plasma y líquido cefalorraquídeo (LCR) del PZQ son más elevadas después de dos horas de su administración. Nosostros pensamos que el mantenimiento de concentraciones elevadas de PZQ por seis horas pudieran ser una terapia cisticida adecuada para estos pacientes. Métodos. Tratamos 30 pacientes con neurocisticercosis parenquimatosa con tres dosis orales de 25 mg por kg de peso de PZQ con intervalos de dos horas. Ellos recibieron dexametasona 10 mg intramuscular por tres días consecutivos a la administración del PZQ. Resultados. En 21 pacientes desaparecieron los quistes, en siete hubo una desaparición de 30 a 60 por ciento y dos pacientes permanecieron sin cambios. Del número total de quistes, hubo una tasa de desaparición de 70.7 por ciento. Dos pacientes presentaron crisis convulsivas, seis cefalea y otros más náusea. Ningún paciente cursó con convulsiones durante el tratamiento con antiepilépticos. Conclusión. El costo y el tiempo de administración del PZQ se reducen significativamente y la inflamación que sigue a la destrucción del parásito es tratada secuencialmente

efficacy and side effect of some antiparasitic drugs in normal and S. mansoni infected mice

The present work aims to study the schistosomicidal and side effects of two antibilharzial drugs, the Praziquantel and Anthiomaline beside Fasinex which is used in this field for the first time and was effective in the treatment of fascioliasis. For this purpose, eight groups each of 30 mice were selected, then four groups were infected with S. mansoni cercariae. The treatment started at seven weeks postinfestation when the eggs were detected in the faeces for groups [I, II and III]. Praziquantel, [7.5 mg / mouse] and Fasinex [0.02 ml/mouse] were given per os as a single dose while Anthiomaline [6.5 mg / mouse] was given intramuscularly 3 injections / week for three weeks. The sacrifice of 8 mice for each group was carried out at one week post - treatment for worm load and biochemical analysis of SGOT and SGPT and after four weeks for histopathological examination of the liver and counting worms. The results showed that Praziquantel reduced the worm load by 97.65% and 99.73% at one and four weeks post treatment and had no destructive effect on normal liver function or hepatic-tissues. Also, it improved the liver function and the pathological picture of the liver, leaving only fibrosed egg granulomes, in the infected mice. Anthiomalin reduced the worm load by 81.86% and 96.27% after the same periods. It had slight destructive effect on the liver function in both normal and infected mice [elevation of SGOT and SGPT, also produced some swelling, vacuolation and hydropic changes in the hepatocytes of these groups]. Fasinex reduced the worm load by 52% and 60.33%. It had slight destructive effect in the liver function for normal and infected groups, but the drug had no toxic effect on the liver tissues in these groups

Effect of praziquantel on sex hormone level in murine schistosomiasis mansoni

Changes in sex hormonal levels were studied in Schistosoma mansoni infected and praziquantel treated mice [400 x 2 mg/kg], drug control and in normal control groups. It was observed that schistosomiasis lead to increase in the level of testosterone, progesterone and 17 beta-estradiol, 60 and 70 days post-infection in male and female mice, respectively. In praziquantel treated group the level of testosterone was lowered 10, 20 and 30 days post-treatment, progesterone and 17 beta-estradiol fell 30 days post treatment after primary rise. The mechanism of recorded changes was discussed in details

effects of treatment with praziquantel on hearing

Praziquantel is a commonly used broad spectrum antihelminthic drug. It has totally replaced the antimonial compounds in the treatment of schistosomiasis. In this work 109 patients were included to study the audiometric changes produced by the drug in the routine treatment regimen for schistosomiasis. Pretreatment pure tone audiograms were obtained for all patients on air and bone conduction. They were then repeated after 24 hours of treatment, one week and one month after treatment. Eight patients out of 109 developed marked significant changes in their audiogram, defined as more than 15 dB from previous readings. The results concluded that praziquantel treatment can cause mild audiometric changes mainly in the higher frequencies for a transient period which was followed by a return to normal hearing. Full audiological assessment to all patients undergoing treatment with praziquantel is highly recommended

Praziquantel therapy in neurocysticercosis.

Neurocysticercosis is being recognised more often now, because of advances in radio-imaging. No treatment was available for this disease till about a decade back. Praziquantel has provided new hope. From India, there are very few published reports on experience with this drug. Nine cases of neurocysticercosis are being presented, where praziquantel therapy has been tried. Five patients with tumour syndrome and one patient with a meningoencephalitic syndrome have shown a favourable response. In 3 patients with epilepsy syndrome, it is difficult to assess the role of this drug in their management. The relevant data have been presented and analysed.

effect of praziquantel treatment on the liver functions, worm burden, and granuloma size using two drug regimen in murine schistosoma mansoni infection

The effect of single dose of praziquantel [400 mg/kg] or two doses on two consecutive days was studied in mice infected with S. mansoni. With the single dose there was improvement in the serum protein pattern, towards pre-infection values and a transient rise in serum transminases which soon declined to normal Improvement was more evident after using two doses of praziquantel [P < 0.001]. Worms were eradicated by 70%, 77% and 80% after the single dose and by 88%, 92% and 95% after two doses. Granuloma size was reduced by 50%, 54% and 60% after single dose and by 58% and 73% respectively after 10, 20, and 30 days from treatment

The treatment of neurocysticercosis with praziquantel.

Twenty-five patients with cerebral cysticercosis admitted to the Bangkok Hospital for Tropical Diseases from March 1987 to November 1989 were studied. The patients had a mean age of 41 +/- 5 years with a mean body weight of 57 +/- 4 kgs. Male to female ratio was 1.5:1. Eight patients (32%) gave a history of having taeniasis with a mean duration of 3.6 years before having symptoms of cerebral cysticercosis. Six patients (24%) also had subcutaneous cysticercosis with a duration of 20 +/- 8 months. The important clinical symptoms were headache, focal seizure, epilepsy and dementia. Fourteen patients (56%) had headache, 12 patients (48%) had focal seizure and four patients (16%) had a mild degree of dementia. Baseline study included routine blood examination, biochemical tests, cerebrospinal fluid for routine examinations and immunological study. Biopsy of subcutaneous cysts, plain films of soft tissue and computerized tomography of brain. Praziquantel was given orally at a dosage of 45 mg/kg/day in 3 divided doses at 4-5 hour interval for 15 days. Patients who were taking anti-epileptic drugs before were permitted to continue their medications. The evaluation of results of treatment was done a year post treatment, ten patients (40%) were asymptomatic, 12 patients (48%) had much clinical improvement, their epileptic attack was controlled by 1-2 tablets of phenobarbital (1/2 g) at bedtime. Two patients (8%) had mild headache. One patient (4%) was not improved. Those patients with dementia were not improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Tratamento da neurocisticercose com praziquantel / Treatment of neurocysticercosis with praziquantel

Vinte e sete pacientes com neurocisticercose foram tratados com praziquantel, utilizado em doses progressivamente crescentes até alcançar 50 mg/kg/dia, por período de 21 dias, associado a dexametasoma. Os doentes foram avaliados clínica e laboratorialmente durante o tratamento e, aqueles que completaram um ano de evoluçäo, repetiram os testes imunofluorescência e ELISA neste período. Cefaléia foi o sintoma encontrado mais freqüentemente durante o tratamento, ocorrendo em 37% dos pacientes; 18,5% dos doentes apresentaram hipertensäo intracraniana, um deles evoluindo para o óbito; 25,9% dos enfermos tiveram que suspender o praziquantel antes de completar o tratamento, devido ao surgimento de complicaçöes importantes. Nos exames laboratoriais realizados no sétimo dia de tratamento, 33,3% dos pacientes apresentaram anormalidades, sendo leucocitose a mais freqüente. No período de um ano, 72,2% dos enfermos tiveram melhora do quadro clínico, enquanto os testes imunológicos tornaram-se näo-reagentes no soro em 45,4% dos doentes e no LCR em 42,8%. Entretanto, nem sempre houve coincidência da melhora clínica com a apresentaçäo dos testes imunológicos näo-reagentes. No presente trabalho, näo é possível afirmar que os testes imunológicos näo-reagentes, assim como a melhora clínica dos pacientes, sejam conseqüentes à eficácia do tratamento com o praziquantel. Devido à grande freqüência e gravidade das complicaçöes deste tratamento, os pacientes devem ser avaliados individualmente quanto aos ...