Antiparasitic Therapy Research Articles

Linguatuliasis in Germany

Linguatuliasis in Germany

Cord Blood Screening for Congenital Toxoplasmosis in Northwestern Switzerland, 1982–1999

In the absence of mandatory nationwide toxoplasmosis screening during pregnancy in Switzerland, the Basel region introduced cord blood screening in 1982. From 1982 to 1999, 64,622 cord blood samples (>90% of all neonates) collected in Basel region obstetric units were screened for toxoplasma specific immunoglobulin (Ig) G, M and A antibodies using commercial kits. Neonates with relevant results (IgG titers > or =300 IU/mL, or > or =200 IU/mL in the Abbott Toxo IMX system, and/or positive IgM or IgA antibodies) were monitored until clarification of infection status. From 1991 onward, retrospective maternal and follow-up data on these children were also collected by questionnaire. Despite increasing maternal age, seroprevalence for toxoplasmosis decreased steadily from 53% (1982-1985) to 35% (1999). During the same period, the prevalence of congenital toxoplasmosis declined from 0.08% to 0.012%. IgM and/or IgA antibodies were present with the Platelia Toxo test (enzyme-linked immunosorbent assay; sanofi pasteur; Bio-Rad) in the cord blood samples of 17 of 18 infected neonates born between 1986 and 1999, regardless of maternal treatment in pregnancy. Vertical transmission rates in 69 women with proven or suspected primary infection between 1991 and 1999 were 3.9% with, compared to 27.7% without, antiparasitic treatment during pregnancy. Toxoplasma seroprevalence and congenital toxoplasmosis incidence declined markedly in northwestern Switzerland from 1982 to 1999. Our data provide no conclusive evidence that maternal antiparasitic therapy in pregnancy affects vertical transmission because the treatment group also included women with suspected but unproven primary infection during pregnancy. Because toxoplasma specific IgA/IgM antibodies in cord blood identified almost all infected children, screening at birth may be more cost effective than during pregnancy.

Chemotherapeutic targets for antiparasitic therapy

Despite the worldwide importance of parasitic diseases, antiparasitic chemotherapy is faced with spreading resistance and a lack of interest from pharmaceutical companies. In recent years, however, powerful new research techniques, such as high-throughput screening and advanced proteomics, have emerged and allowed the identification of new molecules and potential targets. In addition, some new antiparasitic drugs benefited from antiretroviral and anticancer research. Since parasites share many metabolic routes with their hosts, efficient drugs must reach them without being harmful to the patient, and in this respect, selectivity is a key parameter. In this review, we cover the most important chemotherapeutic targets thus far identified within the complex host-parasite relationships.

Ascaris lumbricoides como causa de vómitos incoercibles en una gestante de 13 semanas

Ascaris lumbricoides is the largest intestinal nematode and can reach up to 40 cm. It is a human parasite. A lumbricoides is widespread in tropical and subtropical regions with an estimated worldwide prevalence of over one thousand million people. Nearly all infected individuals present few worms and are asymptomatic. Symptoms occur when pulmonary hypersensitivity or intestinal complications appear. The presence of parasitosis should be considered in the differential diagnosis of cases of incoercible vomiting and other gastrointestinal symptoms, especially in pregnant women from endemic areas. We present a case of A lumbricoides in a 13-week pregnant woman from Ecuador who had been resident in Spain for 3 months and who presented incoercible vomiting. She received antiparasitic therapy with favorable outcome.

Encephalopathy After Bone Marrow Transplantation

Encephalopathy After Bone Marrow Transplantation

1453 Does antiparasitic therapy alter the course of seizure disorder and resolution of lesions in neurocysticercosis patients? A follow-up study for more than 5 years in 300 patients

1453 Does antiparasitic therapy alter the course of seizure disorder and resolution of lesions in neurocysticercosis patients? A follow-up study for more than 5 years in 300 patients

DNA topoisomerases in life and death: implications in kinetoplastid protozoa.

Current biomedical research has its focus on the search for newer intervention strategies to control public health impact of parasitic diseases. The dramatic advances of molecular and cellular biology in recent times have provided opportunities for discovering and evaluating molecular targets for drug designing, which now form a rational basis for the development of improved anti parasitic therapy. DNA topoisomerases, the "cellular magicians" involved in nearly all biological processes governing DNA, have emerged as one such biological target. Over the last two decades, interest in topoisomerases has expanded beyond the realm of the basic science laboratory into the clinical arena. This review aims at providing a comprehensive insight into the biology of DNA topoisomerases and also focus on its evolution as a drug target in the unicellular kinetoplastids.

Antiparasitic therapy for viable cysts may help seizure control in patients with neurocysticercosis.

Antiparasitic therapy for viable cysts may help seizure control in patients with neurocysticercosis.

Time course of coagulation parameters, cytokines and adhesion molecules in Plasmodium falciparum malaria.

We studied 38 patients with malaria tropica over a period of 5 days during antiparasitic therapy. Serum or plasma levels of interleukin (IL) 1beta, IL-6, IL-10, tumour necrosis factor-alpha (TNF-alpha), the soluble vascular adhesion molecule (sVCAM) and the soluble intracellular adhesion molecule (sICAM) were determined by enzyme-linked immunosorbent assay. Protein C and antithrombin III activity were analysed by chromogenic tests and protein S activity by a clotting test. Antithrombin III, protein C and protein S activity was significantly lower in patients with severe malaria and displayed a highly significant increase in activity over the time of evaluation. Levels of sVCAM and sICAM were increased for the whole study period, but no significant differences were found between severe and mild malaria cases. Serum IL-1beta, IL-6 and IL-10 levels were significantly higher in patients with severe malaria, whereas no significant differences were found for TNF-alpha. IL-6 and IL-10 decreased significantly over 5 days during schizontocidal therapy. Our data show an impairment of the coagulation system which correlates with pro-inflammatory cytokines and therefore with the severity of the disease.

A Trial of Antiparasitic Treatment to Reduce the Rate of Seizures Due to Cerebral Cysticercosis

Neurocysticercosis is the main cause of adult-onset seizures in the developing world. Whether therapy with antiparasitic agents results in improved seizure control has been questioned because of the lack of adequate, controlled studies. We conducted a double-blind, placebo-controlled trial in which 120 patients who had living cysticerci in the brain and seizures treated with antiepileptic drugs were randomly assigned to receive either 800 mg of albendazole per day and 6 mg of dexamethasone per day for 10 days (60 patients) or two placebos (60 patients). The patients were followed for 30 months or until they had been seizure-free for 6 months after the doses of the antiepileptic drugs had been tapered. The efficacy of treatment was measured as the decrease in the number of seizures after treatment. In the albendazole group, there was a 46 percent reduction in the number of seizures (95 percent confidence interval, -74 to 83 percent) during months 2 to 30 after treatment. This reduction, which was not statistically significant, was composed of a nonsignificant reduction of 41 percent in the number of partial seizures (95 percent confidence interval, -124 to 84 percent) and a significant 67 percent reduction in the number of seizures with generalization (95 percent confidence interval, 20 to 86 percent). Most of the difference in the number of partial seizures was attributable to a few patients who had many seizures during follow-up. The proportions of patients who had partial seizures during follow-up were similar in the two groups (19 of 57 in the albendazole group and 16 of 59 in the placebo group), but the patients in the placebo group had a greater tendency to have seizures with generalization (22 of 59, vs. 13 of 57 in the albendazole group; risk ratio, 1.63; 95 percent confidence interval, 0.91 to 2.92). More of the intracranial cystic lesions resolved in the albendazole group than in the placebo group. With the sole exception of abdominal pain, side effects did not differ significantly between the two groups. In patients with seizures due to viable parenchymal cysts, antiparasitic therapy decreases the burden of parasites and is safe and effective, at least in reducing the number of seizures with generalization.

INTESTINAL PARASITIC INFECTION AND TOTAL SERUM IgE IN ASYMPTOMATIC ADULT MALES IN AN URBAN SLUM AND EFFICACY OF ANTIPARASITIC THERAPY

Malnutrition is thought to potentiate the polyclonal stimulation of IgE by parasites. This diminishes immunity due to the decrease in specific anti-parasitic IgE. Prevalence of intestinal parasitic infections in chronically undernourished, asymptomatic adult males from a slum and efficacy of anti-parasitic therapy and its effect on total serum IgE were evaluated. Stool specimens from 51 subjects were examined. Anti-helminth and anti-protozoan therapy consisted of oral, single dose albendazole (400mg) and tinidazole (2g) respectively. Total serum IgE was measured. 23 (45.1%) subjects were positive. Albendazole and tinidazole cleared intestinal parasites but had no significant effect on total serum IgE levels.

Diagnosis, treatment and control of Taenia solium cysticercosis.

Taenia solium taeniasis/cysticercosis is now recognized as a major public health problem in most developing countries because of its association with seizures. Major advances in the diagnosis and epidemiology of taeniasis/cysticercosis have occurred in recent years. However, despite abundant literature on the subject, many questions remain unanswered including the role of anti-parasitic therapy and the potential for long-term control or elimination of the disease in field conditions following active interventions. Recent advances have included improved knowledge of the availability and optimization of diagnostic tools for the tapeworm stage, a better understanding of the meaning of antibody serology, the introduction of antigen detection assays, a consensus on the use of antiparasitic medication, awareness of inflammation and chronic scars around calcified cysts, population-based neuroimaging studies, application of control measures, and progress in the development of a pig vaccine. Neurocysticercosis is now much better understood than it was a few years ago. Infection and disease are now classified in terms of parasite viability, resulting in multiple and diverse clinical entities, each of which has a proper prognosis and management. As a result of this, the interpretation of diagnostic assays and imaging examinations is much more coherent. New aspects of this interesting disease have been recognized, mainly in relation to the frequency of calcified neurocysticercosis and its potential association with symptomatic relapses. Consensus diagnostic and treatment schemes have been proposed, and promising alternatives for control are currently being tested in several countries.

Immunopathogenesis of toxoplasmosis.

Toxoplasmosis is a ubiquitous infection affecting 500 million persons around the world, with a range of incidence 12%-90%, increasing with age, education, crowding and sanitary habits. Cats are the definitive host. Infection is primarily congenital but acquired ocular infection has been documented. The review focuses on the immunopathogenesis of toxoplasmosis with emphasis on the eye problem due to its morbidity. The response to infection correlates with both parasitic and retinal antigens. The clinical picture and histopathology is a reflection of the immune response which constitutes early humeral response which presents both systemically and locally primary infection and is elevated with reactivation. This is followed by the cellular response, varying from low grade monocular infilterate a total tissue destruction with response of live parasites especially in immuno-compromised patients. Penetration of the parasite and its enclosure within the parasitophorous vacuole and its eneyst all make its eradicatier impossible. This reflects the variability of antiparasitic therapy that include folate antagonists, macrolides, hydroxy naphthoquindones and fluoroquinolones. Use of corticosteroid should be limited to severe reactions and should be associated with specific therapy.

Management of neurocysticercosis.

Neurocysticercosis is a common cause of neurological disease in developing countries and a major cause of epilepsy worldwide. A unique characteristic of human neurocysticercosis is that the living parasite is very well tolerated in human brain, so symptoms and clinical disease primarily result from death of the organism and accompanying inflammatory reaction in the human CNS. Among the diverse clinical manifestations of human neurocysticercosis, seizures are the most common, but other clinical problems occur, depending upon the localisation and viability of the parasite. Although both praziquantel and albendazole are effective agents, there is controversy about their role in several forms of the disease. Systematic reviews have pointed out the limited quality of available data on therapy. At a recent international conference convened to develop guidelines for treatment of this disease, areas of consensus and disagreement on the role of antiparasitic therapy were discussed. It was clear to all that cysticercosis cannot be regarded as a single disorder; treatment needs to be modified based on the location and number of cysticerci and the host response. There was a strong consensus that there is no role for antiparasitic drugs in patients with only calcified lesions. Studies suggest that patients with single enhancing lesions will do well regardless of antiparasitic therapy. Antiparasitic drugs are contraindicated in patients with cerebral oedema (cysticercal encephalitis). Most experts strongly recommend antiparasitic therapy in patients with multiple subarachnoid cysticerci or giant cysticerci. In patients with ventricular cysticerci, endoscopic removal is the preferred therapy. However, recent evidence suggests that placement of a ventricular shunt followed by antiparasitic therapy is an acceptable alternative. Standard treatment for localization-related epilepsy is effective for seizures caused by cysticercosis. In general, seizures are easily controlled in this illness. While many controversies regarding the treatment of patients with neurocysticercosis were not resolved at the international consensus conference, participants did conclude that controlled prospective studies are required to define optimal therapy for the infection and that treatment of infected individuals must be individualised.

Atypical presentations of ocular toxoplasmosis.

The diagnosis of ocular toxoplasmosis is based most often on the presence of characteristic clinical findings, which include focal retinochoroiditis, an adjacent or nearby retinochoroidal scar, and moderate to severe vitreous inflammation. However, a variety of less common, "atypical" presentations may be unfamiliar to clinicians, delaying both diagnosis and treatment. Patients who are immunocompromised or elderly may, for example, present with large, multiple and/or bilateral lesions. Other unusual manifestations include punctate outer retinal toxoplasmosis, retinal vasculitis, retinal vascular occlusions, rhegmatogenous and serous retinal detachments, a unilateral pigmentary retinopathy mimicking retinitis pigmentosa, neuroretinitis and other forms of optic neuropathy, and scleritis. Although in the past most cases of ocular toxoplasmosis were considered to result from reactivation of a congenital infection, it is now believed that postnatally acquired infection accounts for many cases of this disease. With appropriate use of antiparasitic therapy, the visual prognosis for patients with both typical and atypical forms of ocular toxoplasmosis may be good.

The role of stage-specific oligonucleotide primers in providing effective laboratory support for the molecular diagnosis of reactivated Toxoplasma gondii encephalitis in patients with AIDS.

The switch from bradyzoites to tachyzoites is the fundamental pathogenic event that leads to Toxoplasma gondii encephalitis (TE) in patients with AIDS. Distinction between these stages is difficult, particularly when specific treatment has been started. A new approach consisting of a nested PCR (n-PCR) assay was performed on cerebrospinal fluid (CSF) specimens collected from AIDS patients with TE before or after antiparasitic therapy was initiated, to assess the efficacy of primer sets which amplify target sequences expressed on bradyzoites (SAG4 and MAG1), tachyzoites (SAG1) or both stages (B1) of T. gondii. CSF specimens were obtained from 46 patients with AIDS, of whom 27 had TE (16 first episode, 11 relapse) and 19 had other AIDS-related brain lesions (AIDS-OBL) in the absence of TE. CSF specimens from 26 HIV-negative and immunocompetent patients were also checked. All samples were tested with different primer pairs targeting the B1, SAG-1, SAG-4 and MAG-1 genes. With B1, 75% of patients with first episodes of TE were positive, compared with 36.3% of those with relapse of TE and 5.2% of those with AIDS-OLB. The SAG1 gene yielded positive values in 28.7% and 45.4% of patients with first episodes of TE or relapse of TE, respectively, and in none of the controls. With the SAG4 and MAG1 genes, 72.7% of patients with relapse of TE were detected, compared with 25% of patients with first episodes of TE and 5.2% with AIDS-OLB. None of the HIV-negative subjects showed positive PCR reactions. These results demonstrate that specific primers for the genes SAG4, MAG1 and SAG1 may be useful in AIDS patients with relapse of TE, in whom the use of PCR targeting the B1 gene may fail to detect DNA, especially when prophylaxis or treatment has been started.

Neurocysticercosis--5 years' experience at the Clinic for Infectious Diseases

Neurocysticercosis (NCC) is the most common parasitic disease with wide distribution which is caused by larval forms of Taenia Solium. Our aim was to: show the most common clinical manifestations of patients with NCC and their importance in diagnosing this disease; examine the value of serologic diagnostic methods in blood and cerebrospinal fluid; to emphasize the value of radiological diagnostic methods--CT and MRI of the brain, in relation to the applied protocol of therapy, as well as the impact of anti-parasitic therapy on the outcome of this disease. 13 patients with NCC (from 35 to 63 years of age, median age 49; 61.5% male and 38.5% female) were treated at the Clinic of Infectious Diseases in Novi Sad during a five-year period. Two patients had a positive epidemic data of parasitic diseases of the intestinal tract in childhood. The most common clinical manifestation was headache in 61.5% of patients, and generalized convulsions and hemiparesis in 46.2%. Meningeal inflammation was present in 27.3% of patients. Two of five patients had positive ELISA test for cysticercosis in the serum and cerebrospinal fluid. CT and MRI findings confirmed parenchimal form of NCC in 30.8% of patients, while calcifications were found in 69.2% of patients. All patients were treated with Albendazole, 800 mg a day, in two doses, 30.76% of patients had a favorable outcome of the disease, 53.7% of patients were discharged with complications, and one patient died. The most common manifestation of NCC in our patients was headache, followed by general convulsions and hemiparesis. Radiological diagnostic methods--CT and MRI--proved to be most valuable both in diagnostics and follow-up of lesions. All our patients were treated with Albendazole; Dexamethasone was applied in patients with severe inflammatory reaction, and anti-convulsive drugs in patients with convulsions.

Ophthalmological findings in children with congenital toxoplasmosis. Report from a Swedish prospective screening study of congenital toxoplasmosis with two years of follow-up

Congenital toxoplasmosis may lead to severe visual impairment or neurological sequelae in the child. The authors studied the severity of the primary and late ophthalmological dysfunction during a prospective incidence study of congenital toxoplasmosis in the Stockholm and Skane counties. Blood collected on phenylketonuria (PKU) cards from 40,978 consecutively born children were investigated for antitoxoplasma antibodies. Children with verified congenital toxoplasmosis were treated for 12 months with antiparasitic therapy and followed ophthalmologically, neurologically and serologically every third month. Three children had congenital toxoplasmosis. Two of these were asymptomatic at birth and would have escaped early detection without screening. One child had unilateral severe visual impairment and CNS involvement. The incidence of congenital toxoplasmosis was less than 1:10,000. The authors conclude that neonatal screening is important to diagnose asymptomatic infected children with congenital toxoplasmosis as treatment has been shown to reduce long-term sequelae. Ophthalmological investigations should start early and continue in co-operation with pediatricians.—Thomas J. Liesegang.

Atypical Parasitic Migration and Necrotizing Sacral Myelitis due to Serratospiculoides amaculata in a Prairie Falcon (Falco mexicanus)

An adult, wild-caught, female prairie falcon (Falco mexicanus) was presented with the chief complaint of anorexia. Radiographic findings included increased densities within the air sacs, and coelomic endoscopy revealed numerous slender worms within the air sacs and on the serosal surfaces of the ovary, oviduct, liver, proventriculus, and ventriculus. The bird seemed to improve for a short period of time with antiparasitic therapy (ivermectin and fenbendazole) and supportive care. Twenty-one days after initial presentation, the bird became recumbent with increasing pelvic limb neurologic deficits and was euthanized. On histopathologic examination, mature nematodes and larvated eggs identified as Serratospiculoides amaculata were found within the subdural space of the distal thoracolumbar and synsacral spinal cord and within the coelomic cavity. This case suggests that S. amaculata can cause clinically significant lesions in its falconiform host with potentially fatal results.

Short regimen of praziquantel in the treatment of single brain enhancing lesions

Twenty-six patients with single enhancing brain lesion (SEL) were openly assigned to receive single-day praziquantel therapy ( n=14), or not ( n=12). From 14 treated patients, complete resolution was found in 11, partial resolution in two, and the remaining case was later diagnosed as an arteriovenous malformation. Side effects presented in only one patient and remitted in the same day with symptomatic treatment. Conversely, the lesions persisted unchanged in six of 12 patients in the non-treatment group. Untreated patients with persisting lesions were prescribed praziquantel treatment. After this, SELs disappeared in three cases, other diagnoses (brain tuberculoma and arteriovenous malformation) were made in two, and one was not evaluated. When analyzed in regard to the baseline serology, resolution of lesions on computed tomography was found in 13 (complete=12, partial=1) of 14 seropositive patients, whereas it only happened in six (complete=5, partial=1) of 12 seronegative patients. Serological screening defines a subset of SEL patients with good prognosis. If antiparasitic therapy is to be used in patients with SEL, and we cannot find a strong argument against it, single-day praziquantel is the regimen of choice based on duration, costs, and minimal side effects.