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.     

The clinico-epidemiological characteristics of opisthorchiasis foci in the Yamalo-Nenets Autonomous Okrug and the treatment results with praziquantel]

A clinical and epidemiological study of opisthorchiasis foci in the Yamalo-Nenets Autonomous Okrug was carried out. 764 people were surveyed, including 473 aborigines of the north, 207 denizens, and 84 migrants. Opisthorchiasis infection rate in villages was 40.5-45.7%. The intensity of infection was lower than 200 eggs per g faeces. The modelling of opisthorchiasis prevalence performed after Muench showed the highest correlation with the "simple" and "reversible" models. Factors determining the infection spread and limiting its intensity and those influencing the effect of chemotherapy were defined. Theoretically determined radical suppressive low-dose praziquantel chemotherapy was carried out. The efficacy of the drug, 25, 30, 40 and 50 mg/kg, varied from 76.5 to 92.0% (mean 88.1%), and the decrease of the egg density was more than 60%. The incidence of side effects of the therapy averaged 45.3%.     

Clinico-immunologic indices of various patient contingents in a focus of chronic opisthorchiasis. 3. Dynamics of the indices following praziquantel treatment

Studies of the time course of the immune status characteristics after praziquantel treatment and of the nature of its side-effects on various groups of opisthorchiasis patients in the focus established significant differences in their immune response to specific treatment. The lack of alterations in the T- and B-immunity systems in aboriginal population of the focus may suggest its tolerance to helminthic antigens. The trend towards cellular immunity stimulation and a significant increase in the levels of circulating immune complexes and specific antibodies in the serum were observed in aboriginal population of the focus. The comers showed significant initial alterations of the immunity status before treatment, pointing to their sensitization to parasitic antigens. Suppression of the infection normalizes several cellular and humoral immunity characteristics--the number of T-helpers, T-lymphocytes, B-lymphocytes, Th/Tc indices, T-lymphocyte functional activity, thus eliminating immune depression. The increased IgG, CIC and specific antibody levels significantly exceeding the normal level, occurrence or enhancement of allergic reactions point to the necessity of performing a desensitizing therapy and using effective cholagogic drugs in the multimodality treatment to rapidly eliminate the parasitic antigen.     

Prasiquantel treatment of patients under ambulatory conditions in an opisthorchiasis focus in the Komi-Permyak autonomous area

90 Opisthorchis felineus invaded patients were subjected to prasiquantel treatment. Single doze of the drug (40 mg/kg) was administered under ambulatory conditions. Treatment efficacity 6 months after administration attained 85.9%. Side-effects were observed in 89.7% of patients, the neurotropic effects' rate being 85.4%. Lower side-effects' rate was established in case of prasiquantel administration with milk. Positive clinical effect of prasiquantel treatment was observed in 69.3% patients.     

Anthelmintic therapy of opisthorchiasis in patients with active tuberculosis]

Study was based on the clinical and laboratory follow up of 34 patients with active pulmonary tuberculosis in 12 of whom it was concurrent with opisthorchiasis. The clinical course of the combined pathology and immunopathogenesis were evaluated by the monocytic interleukin-1 capacity to regulate the immune T-system status. In conditions when the course of tuberculosis is aggravated by opisthorchiasis invasion, the number of cases of antibacterial therapy intolerance increases and prognosis of the diseases deteriorates, it is expedient to use the anthelminthic therapy with a new preparation biltricide which also has an immunomodulating action. It was shown that the antibacterial and anthelminthic therapy had a favourable clinical and immunologic effect.     

Differences in the dynamics of the eosinophilia, blood immunoglobulin E and the level of circulating immune complexes in patients with chronic opisthorchiasis treated with different doses of praziquantel]

Sixty patients with a chronic Opisthorchis felineus infection were administered one-day therapy with praziquantel in doses 25, 40, or 60-75 mg/kg b. m. The former two doses of the drug did not much improve the levels of the examined immunologic parameters. In patients treated with the highest dose of praziquantel a significant decrease of the total and specific IgE and CIC levels, reaching that in the reference groups, was observed in 6-8 months after the treatment, this indicating a 92% efficacy of the drug in this group of patients.     

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.     

The effect of various factors on the immune status of patients with chronic opisthorchiasis. 2. Changes in immunologic indices in patients with chronic opisthorchiasis undergoing chloxyl treatment for various lengths of time

Most immunological characteristics became practically normal 7-9 months after a single chloxyl treatment course in patients with chronic cholecystocholangitic opisthorchiasis. The patients who required repeated chemotherapy showed more profound and steady immune disturbances.     

Paragonimiasis: diagnosis and the use of praziquantel in treatment

Paragonimiasis was diagnosed in eight patients: five with sputum specimens positive for characteristic ova and three with only stool specimens positive for ova. Clinical symptoms, roentgenograms and serologic findings appeared to correlate with severity of disease. All eight patients were treated with praziquantel (oral dose, 75 mg/kg of body weight daily for two consecutive days). Of seven patients who completed the treatment, six had ova-negative sputum and stool specimens by day 90; the seventh patient's specimens became ova negative by day 120. The eighth patient, who had failed to respond to prior treatment with bithionol, could not tolerate the daily dosage of 75 mg/kg because of nausea. Although he received the same total dose (150 mg/kg) over four days his specimens remained ova positive on day 90. Adverse effects included nausea (two patients), headache (one patient), and urticaria (two), the last effect possibly secondary to release of antigen from drug-damaged parasites. A review of the epidemiology, clinical presentation, and treatment of pulmonary paragonimiasis is presented.     

Controversies in the use of antimicrobials for the prevention and treatment of Lyme disease

Summary Unanswered questions in the management of patients with Lyme disease or those who have hadIxodes tick bites include: Is antimicrobial therapy effective in preventing Lyme disease during the incubation period of the infection? Which oral agents are most effective in treatment of Lyme disease? Are macrolides efficacious? And, for how long a time period should antimicrobial therapy be given? Potentially useful insights into these questions can be gained by examining experience with other spirochetal infections. Using this information, in conjunction with existing data from recent studies on Lyme borreliosis, tentative answers to these questions can be formulated. Based on this analysis, it would be anticipated that a short course of antibiotic therapy, perhaps even a single dose, will be effective in preventing Lyme disease after a tick bite. Beta-lactam antibiotics such as amoxicillin, and tetracycline preparations, such as doxycycline, are the mainstays of oral therapy for treatment of active infection. Macrolides are less effective, but their utility is likely to be improved if they are given in maximal dosage. There is no convincing evidence for extending treatment of early Lyme disease beyond 14 days. There is also no evidence that longer therapy is more efficacious for other manifestations of Lyme disease, although this issue deserves further study.

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Kontroversen in der präventiven und therapeutischen Anwendung von Antibiotika by Lyme-Krankheit

Zusammenfassung Folgende Fragen sind in der Behandlung von Patienten mit Lyme-Krankheit oder Personen nach Zeckenstich noch ungelöst: Kann die Lyme-Krankheit durch Antibiotikatherapie während der Inkubationszeit der Infektion verhütet werden? Welche oralen Substanzen sind in der Therapie der Lyme-Krankheit am effizientesten? Sind Makrolide wirksam? Wie lange sollte eine Antibiotikatherapie durchgeführt werden? Erfahrungen mit anderen durch Spirochäten verursachten Krankheiten bieten möglicherweise brauchbare Erkenntnisse zu diesen Fragen. In Verbindung mit verfügbaren Daten aus neuen Studien zur Lyme-Borreliose erlauben diese Informationen möglicherweise eine vorläufige Antwort. Demnach ist davon auszugehen, daß eine Kurzzeittherapie, eventuell mit einer Einzeldosis, die Lyme-Krankheit nach Zeckenstich verhindern kann. -Laktam-Antibiotika wie Amoxicillin und Tetracycline wie Doxycyclin sind die wichtigsten Substanzen für die orale Behandlung der aktiven Infektion. Makrolide sind weniger wirksam, doch kann ihre Effizienz wahrscheinlich verbessert werden, wenn sie in Höchstdosis verabreicht werden. Es gibt keine überzeugenden Daten dafür, daß eine Verlängerung der Therapie der frühen Lyme-Krankheit über 14 Tage hinaus von Vorteil ist. Auch fehlt es an Beweisen dafür, daß eine längerdauernde Therapie bei anderen Manifestationsformen der Lyme-Krankheit die Ergebnisse verbessert, doch bedarf dieses Thema weiterer Untersuchungen.

     

Choosing drug use measures for treatment outcome studies. I. The influence of measurement approach on treatment results

Drug use is measured in a number of different ways in drug treatment outcome studies. Different measures of outcome may yield different results, making comparison across studies difficult. The utility, sensitivity, and level of measurement of five categories of measures are reviewed. It is suggested that research focus on examining the properties of existing drug use measures, on developing methods of evaluating timing and sequence in the relapse process, and on standardizing measurement approaches across studies.