Treatment of Opisthorchis viverrini and intestinal fluke infections with Praziquantel.

The study was carried out from September to November 1997 in Phrae Province of northern Thailand. A total of 95 adult patients with Opisthorchis-like ova in their stools were randomly treated with two different manufactured Praziquantels. Group 1, consisting of 49 patients, received a single dose of 40 mg per kg Praziquantel manufactured by the Thai Government Pharmaceutical Organization. Group 2 (46 patients) received Biltricide at the same dosage. Haplorchis taichui, H. yokogawai, Echinostome spp., O. viverrini, Taenia saginata and Enterobius vermicularis were expelled in the stools after treatment. Minute intestinal flukes were detected in 64% of patients. O. viverrini was found in lower proportion of 17%. By formalin-ether concentration examination one stool specimen from each patient, the cure rate in both groups on the 30th day of treatment was 100%. The side effects of the two different Praziquantel treatments were mild with no significant difference. Praziquantel, regardless of its manufacture, proved effective against O. viverrini and other minute intestinal flukes (H. taichui, H. yokogawai and Echinostome spp).

Opisthorchiasis and intestinal fluke infections in northern Thailand.

Four hundred and thirty-one residents from 16 provinces in northern Thailand who had previously been found positive for Opisthorchis viverrini or Opisthorchis viverrini-like eggs were given praziquantel 40 mg/kg. The stool was collected for 4 to 6 times and examined for adult worms. The prevalence of Opisthorchis viverrini in this group was 11.6%. Intestinal flukes, Haplorchis taichui and Haplorchis yokogawai, were predominantly found in 63.11% and 10.44% respectively. Other intestinal flukes (Centrocestus caninus, Echinostoma malayanum, Haplorchis pumilio, Phaneropsolus bonnei, Plagiorchid flukes, Prosthodendrium molenkampi and Stellantchasmus falcatus) were also found in small numbers.

Pharmacokinetics of praziquantel in patients with opisthorchiasis.

The pharmacokinetics of praziquantel was investigated in 9 Thai male patients with asymptomatic opisthorchiasis (stool positive) and 9 patients (6 males, 3 females) with moderately advanced infection (hepatomegaly). The geometric means of the pretreatment Opisthorchis viverrini egg count in these patients were 2,950 vs 4,468 eggs per gram of stool. The results indicate the impairment of metabolism of praziquantel in the moderately advanced stage opisthorchiasis. The pharmacokinetics of the drug in these patients during the acute infection was markedly altered when compared with that after recovery and in patients with early stage of the infection. The clearance rate (Cl/f) was significantly reduced [medians and ranges of 106 (43-242) vs 192 (112-692) and 171 (133-427) ml/min/kg] and the t1/2z and MRT were prolonged [t1/2z: 3.8 (2.0-6.2) vs 2.7 (1.7-4.3) and 2.3 (1.7-2.8) hours; MRT: 6.2 (3.2-11.0) vs 4.6 (2.7-6.2) and 4.5 (2.9-5.1) hours]. In addition, AUCo-alpha was significantly greater [6.0 (2.5-15.6) vs 3.5 (0.6-6.0) and 3.9 (1.6-5.0) micrograms hour/ml].

A new intestinal fluke, Plagiorchis harinasutai n.sp.

Dilution-sedimentation examination of stool specimens from four opisthorchiasis patients treated with praziquantel led to the discovery of six Plagiorchis worms. This is the first known report of plagiorchis infection in man in Thailand. The morphological features differed from those of previously described Plagiorchis species indicating that these worms belong to a new species, which we designated as Plagiorchis harinasutai n.sp. in honour of Professor Chamlong Harinasuta, former Dean of the Faculty of Tropical Medicine, Mahidol University, Bangkok. The holotype is held at the Museum and Reference Centre. Paratypes are held in the Bangkok School of Tropical Medicine, Faculty of Tropical Medicine, Mahidol University.

Ultrasonographic study of the biliary system in opisthorchiasis patients after treatment with praziquantel.

Ultrasonographic examination of the liver and biliary system using a portable ultrasound unit was performed in 1987 in 647 opisthorchiasis patients who had been treated with praziquantel during 1981 to 1986. Treatments was repeated annually in those reinfected. The reinfection rate was 53.9% in the first year and gradually declined. Ultrasonographic findings were normal in 80.6% of subjects. The most common abnormal finding was liver enlargement (14.8%), followed by dilatation of the gallbladder (3.5%), sludge formation (2.1%) and thickening of the wall of the gallbladder (1.0%). Gallstones were found in 7 cases (1.0%). Dilatation of intrahepatic bile ducts was detected in one subject (0.1%). The incidence of gallstones in treated patients was similar to that reported in a large necropsy series of the general population. Prospective studies will be needed to further investigation the association between opisthorchiasis, treatment and gallstone formation.

Effect of praziquantel treatment on antibody levels and lymphoproliferative responses in patients with opisthorchiasis.

The purpose of this study was to explore alternative method(s) to monitor the efficacy of anthelmintic treatment of patients with opisthorchiasis. Therefore, in our initial attempt, we studied the changes in antibody levels and lymphoproliferative responses in O. viverrini infected patients before and 2 months after successful praziquantel treatment. The results showed that although a substantial reduction of the antibody levels occurred after such a treatment, it did not occur in all patients. In those showing reduction, the final level were still above 2 standard deviations of the normal mean value. The reduction was more profound for IgG antibody. With regard to the IgA antibody isotype, the reduction was not as marked. In contrast, IgE antibody levels in most patients not only failed to decline, but instead, showed a tendency to be elevated after praziquantel treatment. Unlike the antibody levels, there was no alteration in the lymphoproliferative response to PHA stimulation and therefore this parameter is not useful for our intended objective. It was suggested that studies of a more specific O. viverrini component may be more reliable than the current method of parasitological examination of eggs in the feces of suspected individuals.

Clinical field trial of praziquantel in opisthorchiasis in Nong Rangya Village, Khon Kaen Province, Thailand.

A clinical field trial of praziquantel was carried out in Nong Ranya Village, Amphoe Ban Phai, Khon Kaen Province, with a population of 309 individuals, and 94% prevalence rate of opisthorchiasis. A mass treatment was carried out using a single dose of praziquantel at 40 mg per kg body weight. Acceptance for treatment was 91%. Follow-up stool examinations performed on days 14 and 60 gave prevalence rates of 20.5% and 22.2% respectively. Side effects including dizziness, headache, abdominal discomfort, nausea, vomiting, diarrhoea, lassitude, arthralgia, sleepiness, cramps and hot sensation were the complaints from 80% of adults and 40% of children. All of these were mild and transient except in one adult female who had severe diarrhoea and required intravenous fluid infusion.

Studies on the chemotherapy of human opisthorchiasis: effective dose of praziquantel in heavy infection.

Ninety-six patients who had heavy Opisthorchis viverrini infection were studied. Egg count per gram of faeces ranged from 10,800 to 139,000 (mean 26,044.3). Praziquantel 50 mg per kg body weight was given after a morning meal. 68 patients completed the follow up period of 60 days. The cure rate was 97.0%. The side-effects occurred in 61 patients (89.7%). The common side effects were diarrhoea, dizziness, sleepiness, epigastric pain, headache, nausea and anorexia. These side-effects were mild and transient. 62 patients (91.2%) showed clinical improvement, and 20 patients were symptom free on day 60.

Treatment of Opisthorchiasis viverrini in hamsters with albendazole.

Efficacy of many drugs against Opisthorchis viverrini in man were shown by the percentages of egg reduction and the absence of egg in faeces. In some cases, however, the eggs reappeared after a period of time. The pathological changes of the bile duct could cause partial or even complete obstruction of the bile passages, thus resulting in the occurrence of natural egg reduction. Albendazole, a broad spectrum anthelmintic was used to treat opisthorchiasis viverrini in hamsters. At dosage of 100 mg per kg body weight twice daily for three consecutive days, the drug yielded an average of 81.5% of worm reduction at four months after medication. In this study complete cure was not obtained.

Increased efficacy of liposomes-encapsulated praziquantel in treatment of opisthorchiasis in hamsters.

An increased efficacy of liposomes-encapsulated praziquantel was observed in the treatment of hamster opisthorchiasis. A single intracardial dose of 1.5 mg/kg of encapsulated praziquantel is as effective as an intracardial dose of 30 mg/kg or an oral dose of 100 mg/kg of free praziquantel. The suppressing activity of both free and liposomes-encapsulated praziquantel significantly decrease as the infection times increase from 1 to 5 weeks, suggesting that the young liver flukes are more susceptible to praziquantel than the adult flukes.

Mass treatment of opisthorchiasis in Northeast Thailand.

In an attempt to control opisthorchiasis, a single dose of 40 mg/kg of Praziquantel was given to 666 people in the three villages of Nam Pong Water Resource Development Project, Khon Kaen, Northeast Thailand. The results showed a cure rate after 1 month was 95.9%. The side effect was minimized by alternation of the time of treatment from after breakfast to after dinner. The use of Praziquantel for the mass treatment in control of opisthorchiasis is possible. However, to achieve the objective of control programme other measures such as environmental sanitation improvement, health education and change in eating habits must be integrated into the programme.

Field trial of praziquantel in human opisthorchiasis in Thailand.

Praziquantel is an excellent drug for treatment against Opisthorchis viverrini infection. Sixty cases of Opisthorchis viverrini infection were treated with Praziquantel, 3 x 25 mg/kg body weight for one day, except one case that was retreated with the same regimen at one month after the first treatment, and the cure rate was 100.0% at one year after the treatment. The side effects of the drug were headache, lassitude, sleepiness, and diarrhoea, but most of these were only in mild degree. Other laboratory findings showed no abnormal changes.

Treatment of Opisthorchis viverrini with mebendazole.

Thirty-six hospitalized Thais (21 males, 15 females, 9 to 63 years of age) with Opisthorchis viverrini infection were treated with mebendazole in dosages of 20 mg/kg body weight for 4 weeks and 30 mg/kg body weight for 3 or 4 weeks. The drug was found to be effective when given in dosages of 30 mg/kg body weight for 3 to 4 weeks only a few eggs being found in the stool of one of 27 persons at 3 or 4 weeks post-treatment. In follow-up examination at 6 months, only two of 15 persons available were positive. These could have been reinfection, however. Side effects were essentially absent, except one person who vomited on the first day of treatment. The drug could be used in a mass treatment campaign because of effectiveness, low toxicity, and action against other helminthic infections.

Studies on the chemotherapy of human opisthorchiasis: III. Minimum effective dose of praziquantel.

A clinical trial of praziquantel was carried out in patients with opisthorchiasis using low dosages with 30 and 60 days follow-up. In group III, 30 patients treated with praziquantel 25 mg per kg body weight bid, for one day yielded a cure rate of 88%. In group IV, 12 patients received 25 mg per kg body weight in a single dose and gave a cure rate of 44 %. In group V, 55 patients received 40 mg per kg body weight in a single dose and yielded a cure rate of 91%. Mild and transient side effects were present in 54%, these included abdominal pain, lassitude, headache, dizziness, nausea, diarrhoea, myalgia and tachycardia. Clinical improvement was observed in most of the patients after one month and 33% of them were clinically cured in two months. The recommended dose of praziquantel for the treatment and control of opisthorchiasis in the endemic area is a single dose of 40 mg per kg body weight after meals.

Studies on the chemotherapy of human opisthorchiasis: II. Clinical trial of niclofolan.

A clinical trial of Niclofolan on human opisthorchiasis was carried out in 60 patients admitted to the Hospital for Tropical Diseases. Two dosage regimen, 2 mg and 3 mg per kg body weight repeated after a 72 hour interval was administered to 31 and 4 patients respectively. Comparative evaluation with the placebo group of 25 patients was made by the Stoll count on day 20, 40 and 60 after treatment. On day 60 percentage egg reduction of the treated and the placebo groups were similar. Mild and transient side effects such as nausea, anorexia, myalgia and arthralgia were recorded in all 3 groups but more severe in the higher dosage group. In this study, Niclofolan failed in reducing the egg production of Opisthorchis viverrini.

Studies on the chemotherapy of human opisthorchiasis in Thailand: I. Clinical trial of praziquantel.

Praziquantel (Embay 8440) was found to be effective in eliminating egg of Opishtorchis viverrini. from the stools of 49 patients. Two regimens were used: Group I patients received 25 mg/kg body weight three times daily after meals for two consecutive days: and Group II patients received 25 mg/kg body weight three times daily after meals for one day. In both groups eggs were not detected in the faeces by day 60 and up to 4-8 months post treatment. Mild transient side effects were present in approximately 80% of patients of Group I, with milder side effects reported in Group II. Severe diarrhoea was present on day 0 in one patient from each group. Side reactions included headache, dizziness, myalgia and lassitude, however, no laboratory evidence of toxicity was detected.