Clinical and immunologic follow-up study of patients with neurocysticercosis after treatment with praziquantel.

In a prospective study, 17 Brazilian patients with parenchymatous neurocysticercosis were monitored for a period of 12 months after treatment with praziquantel. Taenia solium-specific IgG antibodies, interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, neopterin, and soluble interleukin-2 receptor (sIL-2R) were measured in serum and CSF before starting the therapy, on the last day of treatment, 5 weeks after treatment, and 3, 6, and 12 months after treatment. The most common symptoms and signs found in patients before treatment were headache, neck stiffness, and seizures. Six months after commencement of therapy, 13 of the 17 patients were free of complaints. Clinical normalization was paralleled by a significant decrease (p < 0.05) in the amount of intrathecally produced anti-T solium IgG 1 year after treatment. IL-1 beta was undetectable in serum at all times, whereas in the CSF it was within the normal range during the whole study period. The mean concentration of sIL-2R in the CSF was 65 kU/l (normal, < 50 kU/l) 5 weeks after treatment, whereas in all subsequent investigations sIL-2R was undetectable. The median CSF neopterin level was slightly elevated before treatment (6.8 nmol/l). One year after treatment, it had dropped by 69% (p < 0.001) to a median value of 2.1 nmol/l. The size of planimetrically measured focal cystic brain lesions on CT correlated with the amount of intrathecally synthesized anti-T solium IgG at the end of the study (r = 0.89, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

T cell phenotype alterations in hepatosplenic schistosomiasis mansoni normalize after chemotherapy.

Peripheral blood T cell phenotypes, CD3-induced mitogenesis and soluble IL 2 receptor and CD8 in sera were studied in intestinal and hepatosplenic Schistosomiasis mansoni before and three to six months after therapy with praziquantel. Fifteen pairs matched for intensity of infection were analyzed and compared with local, non-infected age-matched controls. CD3+ cell counts were lower in untreated hepatosplenic schistosomiasis (median 1040 cells/microliters; 95% confidence interval 608-1269) compared to controls (1534; 1264-1620). This difference was largely accounted for by immature CD1+/CD3-cells circulating in these patients (median 388/microliters, 252-474). The frequency of CD1+ T cells in circulation decreased drastically after chemotherapy. Similar, but less marked, alterations were seen in intestinal schistosomiasis. Lymphocyte proliferation initiated by agonistic anti-CD3 monoclonal antibody was severely impaired in hepatosplenic patients, who had suffered haemorrhagic complications, but not in the cases of incipient hepatomegaly. Soluble CD8 antigen circulated in increased amounts in hepatosplenic schistosomiasis. Remarkably, a negative correlation between CD3-induced mitogenesis and circulating levels of CD8 was noted in these patients. Whereas CD3-induced mitogenesis in hepatosplenic schistosomiasis normalized after therapy, circulating IL 2R and CD8 antigen in hepatosplenic patients still exceeded control levels. The results demonstrate disturbances of CD3 and CD8 expression and/or T cell maturation in hepatosplenic schistosomiasis. Imbalanced CD4/CD8 ratios and an increased IL 2R/CD8 turnover may reflect an inhibitory circuit within the T cell compartment.

Differences in drug response of Plasmodium falciparum within an area of the Amazon region.

Clinical characteristics of patients with falciparum malaria, as well as sensitivity of Plasmodium falciparum to chloroquine and mefloquine, were investigated in 2 distinct strata within the same geographical area of the Amazon Basin. One stratum was the population living along the road, the other that living along the river, both near Rio Branco, capital of Acre State, Brazil. The clinical features did not differ between the 2 strata. Full in vitro sensitivity of P. falciparum to mefloquine was observed in both areas. However, significant differences in chloroquine sensitivity were observed between the 2 strata. EC50 values for chloroquine were 0.8484 mumol/litre for parasite isolates from the road stratum (E) and 0.4638 mumol/litre for parasite isolates from the river stratum (R). EC90 values were 2.8095 and 1.2549 mumol/litre in strata 'E' and 'R', respectively. Continuous drug pressure over years in area 'E' and relatively low drug pressure in area 'R' were presumably responsible for these differences.

Immunological alterations in uncomplicated Plasmodium falciparum malaria. Relationship between parasitaemia and indicators of macrophage activation.

Numerical alterations of circulating lymphocytes were investigated in 37 Brazilian patients with uncomplicated Plasmodium falciparum malaria and in a group of 15 healthy controls. The number of CD4+ T helper/inducer cells was significantly lower in patients than controls, whereas absolute numbers of CD8+ suppressor/cytotoxic T cells did not differ between the groups. TNF and neopterin levels were markedly increased in the plasma of patients and remained slightly elevated after chemotherapy with clindamycin. Neopterin, but not TNF levels, were significantly correlated with parasitaemia. TNF was inversely related to monocyte counts. Interferon gamma could not be detected in the plasma of control subjects and was observed in only one patient. We conclude that in uncomplicated falciparum malaria the distribution of phenotypes of circulating lymphocytes are altered slightly and that the high plasma levels of TNF and neopterin indicate excessive release of these molecules by activated macrophages and the activation of cellular immune mechanisms during the infection.

Sequelae after infection with Trichinella spiralis: a prospective cohort study.

It is still a matter of debate whether or not infection with Trichinella spiralis is followed by long lasting sequelae. A common source epidemic of trichinosis which occurred in Bitburg, FRG, in October 1982 gave us the opportunity of performing a controlled cohort study (171 patients and 51 controls). 145 patients and 44 controls completed the 3 year follow-up. Complaints persisted in 36% of patients aged less than 30 years and in 100% of patients aged greater than 50 years. Complaints in order of frequency were: muscular complaints 84%, ocular complaints 63%, cardiac complaints 48%, cephalgia 43%, neurological complaints 35%, gastrointestinal complaints 18%, m fatigue and weakness 18%, oedema 12% and fever less than 1%. IgG antibodies to T. spiralis were still present in all but 5 patients 3 years after infection. IgM antibodies were either low or absent. In our patients the frequency and pattern of complaints and the correlation to the specific antibody response provide evidence that trichinosis causes long-lasting disease. Yet, from our data we were unable to draw conclusions as to the causative pathophysiological mechanisms.

Immunodiagnosis of human anisakiasis by use of larval excretory-secretory antigen.

L3 larvae of Anisakis simplex, isolated from freshly caught herrings were cultured in Medium 199 at different temperatures to obtain excretory-secretory (ES) antigen. Larvae have been cultured in vitro for a period of 11 months. A crude extract of A. simplex larvae was compared with ES antigen obtained under 4 different culture conditions for the determination of IgG and IgE antibodies by ELISA and a modified RAST, respectively. 1 serum from a patient with histopathologically proved anisakiasis and 4 samples from persons with presumptive clinical disease were positive in the ELISA. Two sera were positive in the RAST. A combination of both tests is suggested for the serodiagnosis of human anisakiasis.

Human exposure to volatile halogenated hydrocarbons from the general environment.

The objective of this study was to assess individual human exposure to volatile halogenated hydrocarbons (VHH) under normal environmental conditions by means of biological monitoring, i.e. by the measurement of these compounds or their metabolites in body fluids, such as blood, serum, and urine. Blood samples of 39 normal subjects without known occupational exposure to these agents were examined for the occurrence of VHH. The following compounds were present in quantifiable concentrations in 60 to 95% of the blood samples examined: chloroform (median 0.2 microgram/l; range less than 0.1-1.7 microgram/l), 1,1,1-trichloroethane (median 0.2 microgram/l; range less than 0.1-3.4 micrograms/l), tetrachloroethylene (median 0.4 microgram/l; range less than 0.1-3.7 micrograms/l). Trichloroethylene could be detected in 31% of all blood samples (median less than 0.1 microgram/l; range less than 0.1-1.3 microgram/l). In addition, the levels of trichloroacetic acid (TCA) were determined in serum and 24-h urine samples of 43 and 94, respectively, normal subjects. TCA was present in measurable concentrations in all serum and urine samples examined. The median of the TCA levels in serum was 21.4 micrograms/l (range 4.8-221.2 micrograms/l) and in urine 6.0 micrograms/24 h (range 0.6-261.4 micrograms/24 h). The results are discussed in relation to data from the literature on human exposure to VHH from the general environment, i.e. via air, food, and water. The upper normal limits calculated from the results of this investigation can be used to detect even minor excessive exposures to VHH.

Immune response in patients during and after Plasmodium falciparum infection.

The kinetics of indicators of lymphocyte activation were determined in non- and semiimmune patients with uncomplicated Plasmodium falciparum infection and in control subjects in Acre, Brazil. Delayed type hypersensitivity (DTH) to seven recall antigens was weakest in nonimmune patients. Both patient groups differed significantly from controls on admission (P less than .001 for both) and improved considerably after clindamycin therapy. Total serum IgG and IgM, but not antimalarial antibodies, were highest in nonimmune patients compared with semiimmune patients and controls during acute malaria. Immunoglobulin levels normalized after chemotherapy. A striking decrease of CD4+ peripheral blood lymphocytes, normalizing after chemotherapy, was seen in both patient groups, and was more pronounced in nonimmune patients. A slight increase in interleukin-2 receptor (IL-2R)-bearing cells was found in nonimmune patients. In addition, soluble plasma IL-2R was significantly elevated in them (P less than .001) and to a lesser extent in semiimmune patients. These findings were paralleled by significantly decreased IL-2 concentrations in plasma (P less than .001) during the acute phase of malaria, suggesting pronounced general immunosuppression in nonimmune malaria patients.