The effect of metrifonate in mixed Schistosoma haematobium and Schistosoma mansoni infections in humans.

In order to examine the effect of metrifonate, 156 patients with mixed Schistosoma haematobium and mansoni infection were randomly divided into three groups and treated with metrifonate (twice 10 mg/kg body weight), oxamniquine (60 mg/kg) and praziquantel (40 mg/kg), respectively. The output of S. haematobium and S. mansoni ova were quantitatively assessed in urine and stool. Application of metrifonate resulted in a similar reduction of S. haematobium and S. mansoni eggs in the urine, whereas no effect on egg excretion was observed in the stool irrespective of the parasite species. In contrast, oxamniquine influenced the output of S. mansoni ova in stool and urine, but showed no effect on S. haematobium egg excretion. praziquantel was equally effective against both parasite species. The chemotherapeutic effects were not of transient nature since the number of ova of both parasite species remained unchanged five months after treatment. The results clearly indicate that metrifonate acted exclusively on adult worms located in the perivesical plexus irrespective of the parasite species.

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.

Intermittent chemotherapy with trichlorfon (metrifonate) reverses proteinuria, hematuria, and leukocyturia in urinary schistosomiasis: results of a three-year field study.

Trichlorfon (metrifonate) was given intermittently to 37 schoolboys with urinary schistosomiasis living in a hyperendemic area of the Sudan. Patients were followed up for three years. Initially, 10 mg of trichlorfon/kg of body weight was administered; this dosage was repeated 14 days and 16 months later. Patients still excreting eggs after 24 months received a fourth dose. At month 24, 61% and at month 36, 56% of the patients had no detectable egg excretion; the others showed severe reduction of egg output. The number of ova excreted was always paralleled by a combined scale of hematuria, leukocyturia , and proteinuria, as assessed by urine analysis reagent strips. Quantitative urine analysis at month 36 revealed pathological findings in only eight individuals. Thus, trichlorfon given three or four times in a dose of 10 mg/kg of body weight spaced over a period of two years was highly effective in reducing parasite load and disease in children living under hyperendemic conditions.

Proteinuria, hematuria, and leukocyturia in children with mixed urinary and intestinal schistosomiasis.

Quantitative parasitological assessment and quantitative analysis of proteinuria, hematuria, and leukocyturia were carried out in 182 Sudanese schoolboys with mixed urinary and intestinal schistosomiasis. Pathological proteinuria was found in 73% of patients (median = 380, 95% confidence limits = 200 to 500 mg/liter). The median protein/creatinine ratio was 0.54. SDS polyacrylamide gel electrophoresis showed an excretion of albumin, transferrin, and IgG consistent with a postrenal pattern of proteinuria. Pathological erythrocyturia occurred in 84% of patients (median = 255, 95% CL = 95 to 629 cells/microliter) and leukocyturia in 77% of patients (median = 148, 95% CL = 93 to 246 cells/microliter). Phase contrast microscopy revealed intact erythrocytes, suggestive of postrenal hemorrhage. Proteinuria, erythrocyturia, and leukocyturia correlated significantly with the ova excretion in the urine, but not with egg excretion in the stool. Oxamniquine reduced ova excretion in the stool but did not influence pathological urine findings. In patients treated effectively with Praziquantel or Metrifonate, pathological PU, EU, and LU decreased markedly 1 month post treatment. PU in severely proteinuric patients reached physiological values 5 months post therapy. We suggest that the proteinuria, erythrocyturia, and leukocyturia in mixed schistosomiasis were of postrenal origin.

Re-infection in human schistosomiasis mansoni: a prospective field study 18 months after praziquantel therapy.

Twenty-eight Zairean patients with Schistosoma mansoni infection were investigated and treated with praziquantel. Of these, 22 were re-examined 18 months later and 13 were found to be re-infected. Eighteen uninfected Zaireans were monitored concurrently to control for variations unrelated to schistosomiasis. Pathophysiological changes related to liver fibrosis were assessed by the determination of serum cholylglycine and procollagen-III-peptide. Circulating T-cell subsets were quantitated, and shedded T-cell antigens were measured in sera. In patients initially presenting with hepatomegaly, the biochemical indicators for egg-induced immunopathology became normal after therapy and remained normal even after re-infection, when the parasite load attained about 50% of the pretreatment level. Among T-cell phenotypes, CD4+ cells transiently increased by three months after treatment, but after 18 months the CD4/CD8 ratios both in patients then re-infected and in those not re-infected had reverted to the respective balances which had been observed at the start of the investigation. Both soluble CD8 antigen and interleukin 2 receptor in patients' sera were significantly elevated throughout the study period. The results indicate a dissociation of factors regulating fibrogenesis and immunomodulation after treatment and re-infected.

Relationship between intensity of infection and immunomodulation in human schistosomiasis. I. Lymphocyte subpopulations and specific antibody responses.

Cellular and humoral immune responsiveness in 44 Sudanese children with schistosomiasis was studied and related to the intensity of infection. The parasite load was quantitated by accurate assessment of the excretion of ova of S. mansoni and S. haematobium in stool and urine, respectively. Lymphocyte subpopulations (T3+, T4+, T8+, TAC+, HNK1+, Ia+, SIg+, LGL+, ANAE+) as well as specific IgE and IgG antibodies to adult schistosome antigens were determined. The relationships existing between intensity of infection and cellular and humoral immune responsiveness revealed a distinct pattern of anti-parasite immunity: The percentage of pan-T cells (T3+) and the T helper (T4+):T suppressor (T8+) ratio were inversely correlated to the intensity of infection. In contrast, the percentage of T suppressor cells positively correlated to the parasite load. Ia+, TAC+, HNK1+ and T4+ cell counts did not show a significant relationship to worm burden. Specific IgE and IgG antibodies to S. mansoni and S. haematobium adult worm antigen clearly increased with the parasite load. The dichotomy of decreased T cell parameters and increased antibody response in heavily infected individuals represents a unique feature in helminthic infections.

Relationship between intensity of infection and immunomodulation in human schistosomiasis. II. NK cell activity and in vitro lymphocyte proliferation.

Natural killer (NK) cell activity against K-562 targets and lymphoproliferative responses to Con A, interleukin-2 (IL-2) and Con A + IL-2 were examined in a group of 41 Sudanese children suffering from schistosomiasis mansoni and haematobium. The results were correlated to the intensity of infection as determined by enumeration of parasite ova in urine and stool. NK cell activity measured at three effector to target cell ratios was significantly depressed in the patient group as compared to a German control group. Impairment of NK cell activity showed a direct relationship with the patients' parasite load. Furthermore lymphoproliferation to Con A, IL-2 and Con A + IL-2 was depressed in the group of patients. Interestingly the costimulation effect of IL-2 expressed as coefficient of delta ct/min(Con A + IL-2)/delta ct/minCon A correlated significantly to the intensity of infection suggesting that lymphocytes from heavily infected patients were defective in producing appropriate amounts of IL-2 in response to Con A. Our findings support the concept that heavy infections with S. mansoni and/or S. haematobium induce a peculiar dichotomy of cellular and humoral immune parameters. Whereas T cell-dependent cellular immune responsiveness and NK cell function decrease with increasing worm burden specific IgE and IgG antibody responses increase.

Immune response in chronic Schistosomiasis haematobium and mansoni. Reversibility of alterations after anti-parasitic treatment with praziquantel.

Peripheral blood mononuclear cells from Sudanese children heavily infected with Schistosoma haematobium and S. mansoni were examined for lymphocyte subpopulations, for mitogen and antigen responsiveness, and for natural killer (NK) cell activity before and 5 months after treatment with praziquantel. The humoral immune response was simultaneously investigated by determination of parasite-specific IgG and IgE antibodies, IgE-containing circulating immune complexes, and circulating schistosome antigen. A single dose treatment with praziquantel (40 mg/kg) resulted in a normalization of numerical imbalances in lymphocyte subpopulations, a significant increase in the blastogenic response upon stimulation with adult worm antigen, phytohaemagglutinin (PHA), and concanavalin A (Con A), and restoration of natural killer (NK) cell-mediated lysis of K562 targets. These findings were paralleled by a remarkable decrease in parasite-specific IgE antibodies, IgE-containing circulating immune complexes, and circulating schistosome antigen. The results indicate that the modulation of immune responses in chronic schistosomiasis is associated with active infection and is reversible after successful chemotherapy.

Efficacy of oxamniquine, praziquantel and a combination of both drugs in Schistosomiasis mansoni in Brazil

Conduziu-se um ensaio clínico para comparar a eficácia de uma combinaçäo em baixo doses de oxamniquine (7,5 mg/kg) mais praziquantel (20 mg/kg) com ambas as drogas - oxamniquine (15 mg/kg) e praziquantel (40 mg/kg) - empregadas isoladamente, no tratamento da esquistossomose mansônica em uma área endêmica do nordeste brasileiro. Os medicamentos foram administrados, aleatoriamente, por via oral, a 91 pacientes. Seis e doze meses depois do tratamento 89% dos admitidos no ensaio foram reexaminados segundo os métodos de Kato-Katz (dez lâminas) e MIF (um grama de fezes). Os índices de cura alcançados, representando a ausência de ovos nas fezes em todos os controles durante o acompanhamento parasitológico individualizado dos pacientes, foram de 81,8%, 81,2% e 67,6% com, respectivamente, o praziquantel, a oxamniquine e a combinaçäo. A reduçäo do número de ovos eliminado por grama de fezes nos casos näo curados, variou de 93,8-96,8% com o praziquantel, 32,5-97% com a oxamniquine e 76,9-99,5% com a combinaçäo. Concluiu-se que os três regimes terapêuticos, nas doses utilizadas, däo resultados similares e satisfatórios no tratamento da esquistossomose mansônica näo complicada, no Brasil