Bacterial strains isolated from blood cultures of Nigerian children with cerebral malaria.
Explore the source record for details and available documents.
Bacteremia↗
Biomedical subjects
U Bienzle
Publications and source records attributed to U Bienzle.
Anti-HAV seroprevalence in German travellers and hepatitis A vaccination in immune subjects.
Explore the source record for details and available documents.
Adolescent↗
Sensitivity of HIV antibody detection in saliva.
To assess the sensitivity and specificity of HIV antibody detection in saliva we tested matched serum and saliva samples from HIV-infected and uninfected individuals. Saliva specimens were collected by two different devices of the Salivette system and stored at different temperatures. Samples were tested for HIV antibodies by two commercially available enzyme-linked immunosorbent assays (ELISAs; Wellcome, Biotest). HIV antibodies were detected in 98.5% (Wellcome) and 97.8% (Biotest) of the saliva samples (standard Salivettes) from 135 seropositive individuals. Using the Salivettes flavoured with citric acid the sensitivity was only 22.9%. No reactions in ELISA were found in saliva from HIV-seronegative individuals. Salivary HIV-specific IgA was detected in 90% of seropositive individuals. All positive saliva samples stored at room temperature were still reactive after 20 days; of those stored at 37 degrees C, 23 out of 24 were positive when retested on day 5. Sensitivity of HIV antibody detection in saliva samples dried onto filter paper was 100% when a minimum of 100 microliters of saliva was used. HIV antibody testing in saliva is an efficient tool for large scale epidemiological studies when standard Salivettes are used for sample collection. Saliva samples can be stored in Salivettes or dried onto filter paper for several days at room temperature and under tropical conditions (37 degrees C).
Enzyme-Linked Immunosorbent Assay↗
Selective damage of hippocampal neurons in murine cerebral malaria prevented by pentoxifylline.
The effect of pentoxifylline, a phosphodiesterase inhibitor, was investigated on the development of cerebral malaria in Plasmodium berghei K 173 infected C57/B16 mice. No significant differences occurred in the course of parasitemia and survival time after infection between control mice and pentoxifylline treated mice. Moreover, no differences were observed between the groups with respect to the occurrence of cerebral malaria. The only striking difference was that pentoxifylline treatment selectively prevented neuronal cell damage in the sector CA1 of the hippocampus. These findings are in contrast to previous studies, where pentoxifylline prevented cerebral malaria in P. berghei ANKA infected CBA/Ca mice, another widely used model of cerebral malaria. Obvious differences exist between these models.
Animals↗
Immunochemotherapy of visceral leishmaniasis: a pilot trial of sequential treatment with recombinant interferon-gamma and pentavalent antimony.
The clinical, parasitological, hematological, and serological evolution of visceral leishmaniasis in Brazilian patients was assessed during treatment with human recombinant interferon-gamma (rIFN-gamma; 0.1 mg/m2 i.m. days 1-14) followed by pentavalent antimony (Sbv; 10 mg/kg days 22-28). At day 30, 6 patients had improved, 2 had slightly improved, and 1 patient had deteriorated. IFN-gamma was well tolerated in the dose tested and may be very effective as an adjunct to conventional therapy with antimony.
Adolescent↗
Trichinosis: a prospective controlled study of patients ten years after acute infection.
The existence of chronic trichinosis as a disease entity is still a matter of debate. For 10 years after an outbreak of infection with Trichinella spiralis, we conducted a prospective controlled study of the patients involved. At the termination of this investigation, we undertook clinical, biochemical, serological, immunologic, neuroradiological, radiological, and psychological studies of 128 originally infected persons and 16 controls. The categories of symptoms most often documented in persons who had been infected were muscular (90%), ocular (59%), neurological (52%), and psychological (52%). Impaired muscle strength (56%), conjunctivitis (55%), and impaired coordination (32%) were the clinical manifestations most frequently encountered. Thirty-eight percent of the 128 originally infected patients still had IgG antibodies to T. spiralis after 10 years. Magnetic resonance imaging of the brain revealed no abnormalities. No calcifications of residual larvae were detected by mammography or muscle biopsy. The level of performance in psychometric tests was lower in the originally infected population than in the general population. Although patients who had had trichinosis differed significantly from controls in terms of a variety of parameters even after 10 years, we found insufficient evidence on which to conclude that chronic trichinosis exists as a distinct entity.
Adult↗
Interference by antimalarial drugs with the in-vitro production of reactive nitrogen intermediates by murine macrophages.
The production of reactive oxygen intermediates (ROI) by host macrophages has long been recognized as an important defense mechanism against microorganisms. More recently, reactive nitrogen intermediates (RNI), also produced by activated macrophages, have been shown to be part of the host's first line of defense against malaria. In the present in-vitro study we have investigated the effects of antimalarial drugs on RNI production by murine macrophages stimulated by interferon-gamma (IFN-gamma) and/or malaria antigen, and on ROI production induced by phorbol myristate acetate. At concentrations exceeding the peak serum levels achieved with therapeutic dosages, chloroquine, in a dose-dependent manner, inhibited IFN-gamma- and malaria antigen-induced RNI production. Quinine, at a concentration of 10 mg/L also caused a significant reduction in IFN-gamma and malaria antigen-induced RNI synthesis; this concentration was well within the therapeutic range. High concentrations of artelinate significantly inhibited IFN-gamma-induced RNI production but clindamycin had no effect on RNI synthesis. In contrast, halofantrine, in concentrations attainable with therapeutic dosages, significantly enhanced IFN-gamma-induced RNI production. ROI production by murine macrophages was unaffected by the antimalarial drugs over the same concentration ranges. It remains to be determined whether these in-vitro effects of antimalarial drugs on RNI production also influence the clinical and parasitological response in patients with malaria.
Animals↗
Production of interleukin-6 by human and murine mononuclear leukocytes stimulated with Plasmodium antigens is enhanced by pentoxifylline, and tumor necrosis factor secretion is reduced.
When pentoxifylline was present during stimulation of human mononuclear leukocytes with Plasmodium falciparum exogenous antigens, an increase in interleukin-6 production was observed simultaneously with a reduction of tumor necrosis factor secretion. Similar results were obtained in murine macrophages stimulated with P. vinckei antigens. This indicates the independence of interleukin-6 and tumor necrosis factor secretion in response to malaria antigens.
Animals↗
Curing of chloroquine-resistant malaria with clindamycin.
A randomized comparative trial for treating adult patients with Plasmodium falciparum malaria was performed in Lambarene, Gabon. Forty-two patients received chloroquine (25 mg/kg for 48 hr) and 38 patients received clindamycin (5 mg/kg twice a day, for five days). Chloroquine treatment cured 15 patients (36%). Twenty patients (48%) showed recrudescent malaria by day 28 of follow-up (RI resistance) and seven patients (17%) showed persistent parasitemia after chloroquine treatment (RII/III resistance). In contrast, clindamycin treatment cured 37 of 38 patients (97%) and only one (3%) showed a recrudescence by day 28 (P < 0.001). Although the parasite clearance time was significantly longer after clindamycin treatment (median five days, range 3-6) than after chloroquine treatment (median four days, range 2-8) (P < 0.01), no differences were seen in the duration of symptoms after chemotherapy. In both treatment groups, no severe side effects occurred. Clindamycin can be used as a safe alternative to achieve radical cure in semi-immune adult patients with chloroquine-resistant P. falciparum malaria in Central Africa.
Adolescent↗
Malaria antigen and cytokine-induced production of reactive nitrogen intermediates by murine macrophages: no relevance to the development of experimental cerebral malaria.
The in vitro production of reactive nitrogen intermediates (RNI) by murine macrophages was evaluated in response to heat-stable malaria antigen and cytokines. Malaria antigen, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) induced RNI production in macrophages in a dose-dependent way. RNI production steadily increased over a 2-day period and was enhanced when the malaria antigen was co-incubated with IFN-gamma and/or TNF. RNI production induced by either IFN-gamma or malaria antigen or a combination of the two was suppressed by pentoxifylline in a dose-dependent manner. Pentoxifylline did not significantly influence TNF-induced RNI production. L-N-monomethyl arginine reduced malaria antigen, IFN-gamma and TNF-induced RNI production when these reagents were used in combination or alone. An anti-TNF monoclonal antibody (mAb) reduced IFN-gamma-induced RNI production, but did not significantly alter the malaria antigen-induced RNI synthesis by macrophages. The influence of inhibitors of nitric oxide synthase, L-N-monomethyl arginine and N omega-nitro-L-arginine, was studied in experimental cerebral malaria. They did not exert any significant effect on the development of cerebral malaria in Plasmodium berghei ANKA-infected CBA/J mice.
Animals↗
Interferon-gamma induced lethality in the late phase of Plasmodium vinckei malaria despite effective parasite clearance by chloroquine.
A combination therapy was tested consisting of chloroquine and interferon-gamma (IFN-gamma) in the late phase of blood-stage Plasmodium vinckei malaria in BALB/c mice. When mice were treated with three times 300 micrograms chloroquine at 24-h intervals starting at a parasitemia of 30%-50%, only 5 of 14 mice (36%) died 2-4 days after initiation of therapy. However, when infected mice received chloroquine plus 1 microgram IFN-gamma at the same time, 14 of 18 mice (78%) died 0.5-3 days after start of therapy (p < 0.05) despite clearance of parasitemia. The histopathology from mice dying after combination therapy revealed interstitial leukocyte infiltration of lung tissue, severe liver cell necrosis and kidney tubular necrosis. Pretreatment of P. vinckei-infected mice with pentoxifylline, a phosphodiesterase inhibitor, led to a significant decrease of IFN-gamma-induced lethality (p < 0.05). In contrast, pretreatment with neutralizing antibodies to tumor necrosis factor or with L-N-monomethyl arginine, the latter an inhibitor of the nitric oxide synthase, significantly increased lethality (p < 0.05).
Animals↗
Antibody response in Plasmodium vinckei malaria after treatment with chloroquine and adjuvant interferon-gamma.
The antibody response of mice infected with Plasmodium vinckei after treatment with chloroquine either alone or in combination with interferon-gamma (IFN-gamma) was determined. Sequential serum samples were drawn from BALB/c mice receiving either 240 micrograms chloroquine on the day of infection or 120 micrograms chloroquine plus 10(4) units IFN-gamma daily for 11 days beginning on day 3 prior to infection. Mice treated with additional IFN-gamma showed an early induction of IgG2a response and a reduction in IgG1 antibodies as detected by the immunofluorescence technique at between 10 and 16 days after infection as compared with mice treated with chloroquine alone. Thus, IFN-gamma may partly exert its antimalarial activity via the induction of IgG2a antibody formation. At 4-6 weeks after infection, when mice from both groups resisted homologous re-infection, the predominant antibody isotypes found in both groups were IgG1 and IgG2a. Serum samples obtained from mice in both treatment groups at 6 weeks after infection were used for serum transfer experiments. When parasitised erythrocytes were preincubated with such immune serum, a retardation of the course of parasitaemia by 2 days was observed.
Animals↗
Inhibition of endotoxin-induced macrophage tumor necrosis factor expression by a prostacyclin analogue and its beneficial effect in experimental lipopolysaccharide intoxication.
Tumor necrosis factor (TNF), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. A stable prostacyclin analogue (iloprost) was investigated for its ability to interfere with TNF secretion of lipopolysaccharide (LPS)-stimulated macrophages. It could be demonstrated by bioassays that LPS-induced TNF production was suppressed in a dose-dependent manner when macrophages were treated with iloprost at the time of LPS stimulation. Northern blot analysis revealed that iloprost inhibited TNF production at the transcription level. In vivo, endotoxin-induced mortality rates in galactosamine-sensitized mice could be significantly (P less than .05) reduced by iloprost administration. It is assumed that prostacyclin modulates endotoxin-induced and TNF-mediated inflammation in septic shock.
Animals↗
A comparative study of four serological methods for diagnosis of acute and chronic Chagas' disease in Brazilian patients.
Complement fixation (CF), indirect immunofluorescence (IFAT), latex agglutination (LA) and the enzyme-linked immunosorbent assay (ELISA) were applied to assess the diagnostic value of antibody determination in Brazilian patients with acute or chronic Chagas' disease. Patients with various forms of leishmaniasis and healthy individuals from the endemic region were used as specificity controls. Whereas LA, IFAT and ELISA identified 81% of acutely ill patients, CF had no diagnostic potential in this phase of the disease. In later stages CF showed a sensitivity of 69% as compared to 100% for LA, IFAT and ELISA, irrespective whether patients presented clinically as chronic asymptomatic or chronic symptomatic cases. Cross-reactivity with anti-leishmania antibodies was observed in 23%, 38% and 77% of serum samples in LA, ELISA and IFAT, respectively, but not in CF.
Acute Disease↗
Interferon-gamma treatment in mice experimentally infected with Trichinella spiralis.
Interferon-tau (IFN-tau) treatment of Trichinella spiralis-infected BALB/c mice was investigated. The therapeutic regimen consisted of daily intraperitoneal injection of 10(4) U murine IFN-tau for 7 days, starting at 2 weeks post-infection. Striated muscle samples (diaphragm, thigh) were collected at 4, 8 and 12 weeks after infection. The muscle larval burden, the degree of encystation and the digestion of T. spiralis larvae were investigated. Furthermore, immunohistochemical studies of the inflammatory cell infiltrate around encysted larvae were performed. The results demonstrated an influence of IFN-tau treatment on the CD4+ and CD8+ subset distribution during the immune response but revealed no difference in the degree of encystation or digestion of encapsulated larvae as compared with control values.
Animals↗
Interferon-gamma enhances the effect of antimalarial chemotherapy in murine Plasmodium vinckei malaria.
Most nonimmune patients with Plasmodium falciparum infection are no longer cured by such standard antimalarial drugs as chloroquine. Thus, alternative treatment regimens are necessary. A combination therapy was tested consisting of a subcurative dose of chloroquine and interferon-gamma (IFN-gamma) in BALB/c mice with lethal Plasmodium vinckei malaria. Treatment with either agent alone prolonged median survival by 1-2 days compared with placebo-treated mice. However, a combination of 80 micrograms of chloroquine given at the time of infection plus 1 x 10(4) units of IFN-gamma/day for 11 days (starting 3 days before infection) cured 83% of infected mice. Moreover, these mice showed solid immunity when challenged with the homologous strain of P. vinckei. However, when these mice were infected with the heterologous strain of Plasmodium berghei, the same degree of parasitemia developed as did in P. berghei-infected control mice. Thus, the combination of chemotherapy with the cytokine IFN-gamma leads to substantial improvement of antimalarial treatment and to a rapid development of strain-specific immunity in murine P. vinckei malaria.
Animals↗
Pentoxifylline prevents murine cerebral malaria.
Pentoxifylline, a widely used methylxanthine, was tested for its capacity to prevent cerebral malaria (CM) in Plasmodium berghei ANKA-infected CBA/Ca mice. Nine of 12 control mice developed neurologic signs and died from CM approximately 2 weeks after infection. All 12 mice treated with daily intraperitoneal pentoxifylline (1 mg) for 10 days after infection did not develop CM. All surviving mice developed high parasitemia and severe anemia and died 2 weeks later without neurologic signs. In pentoxifylline-treated mice, serum tumor necrosis factor (TNF) bioactivity was nondetectable, whereas control mice had high TNF levels on day 6 after infection. These findings were supported by in vitro investigations of malaria antigen-induced TNF synthesis. Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed. These findings make pentoxifylline a potential candidate for study as a supportive agent in human CM.
Animals↗