Plasmodium falciparum malaria acquired in Berlin, Germany.
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Biomedical subjects
Publications and source records attributed to U Bienzle.
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The immunogenicity, reactogenicity, and safety of an inactivated hepatitis A vaccine were assessed in anti-HIV positive homosexual men. Fourteen anti-HIV positive (group 1) and 20 anti-HIV negative (group 2) men received vaccine (containing 720 ELISA units of hepatitis A antigen per dose) intramuscularly at 0, 1, and 6 months. Twelve unvaccinated anti-HIV positive men (group 3) were included as controls to evaluate disease progression. Seroconversion (anti-hepatitis V virus (HAV) > or = 20 mlU/ml) was higher in group 2 than group 1 at months 2 (100% vs. 73%) and 7 (100% vs. 77%). Group 2 had higher antibody titres than group 1 at months 1 (201 vs. 92 mlU/ml) and 7 (1,687 vs. 636 mlU/ml). The decline in CD4+ cells between months 0 and 7 was similar in groups 1 and 3 (6.4% vs. 16.2%), showing no evidence for harmful effect of the vaccine on the course of HIV infection. This hepatitis A vaccine appears safe, well tolerated, but less immunogenic in HIV positive homosexual men.
This study investigated differences in prevalence and determinants of HIV infection, and in recent risk behaviour (previous 6 months) among injecting drug users (IDUs) who are in contact with different types of services for IDUs in Berlin. Participants (n = 557) were recruited from drug-free long-term treatment centres, a storefront agency and a syringe exchange bus. HIV seroprevalence was lowest (3.9%) at the treatment centres, and highest among IDUs at the storefront agency (20.7%). In logistic regression, independent risk factors for HIV infection were duration of injecting drug use, borrowing syringes in prison, sex with HIV-positive partners, and prostitution. Syringe sharing in prison was the most important independent determinant of HIV infection among all three subpopulations of IDUs. Participants entering long-term treatment were most likely, and IDUs at the syringe exchange bus were least likely to have borrowed and passed on syringes in the previous 6 months. In logistic regression, site of recruitment was independently associated with recent borrowing of syringes, but not with condom use. Injection of drugs other than heroin only, and injecting in prisons, were also independent predictors of recent borrowing. The results indicate that IDUs entering treatment form an important target group for health education. There is a need for AIDS prevention measures in prisons. The comparatively low levels of recent injection risk behaviour among IDUs at the syringe exchange bus suggest that this type of intervention may be effective in harm reduction.
In a randomized trial, a high dosage chloroquine monotherapy (45 mg/kg over 3 days) was compared with combination regimens of sulfadoxine/pyrimethamine and chloroquine/clindamycin for treating Gabonese school children with Plasmodium falciparum malaria. In chloroquine treated patients only 32% were ultimately cured. In contrast, more than 90% of patients were cured after treatment with either combination regimen.
In a randomized trial, a three-dose quinine monotherapy was compared with short-term combination regimens of quinine-clindamycin and quinine-doxycycline for treating adult Gabonese patients with Plasmodium falciparum malaria. In quinine-treated patients, only 38% were ultimately cured. In contrast, more than 90% of patients were cured after treatment with either combination regimen.
In a randomized trial, a 4-day quinine-clindamycin regimen was compared with the standard 7-day quinine regimen for 100 Gabonese children (50 children in each group) with severe Plasmodium falciparum malaria. In each group, only one patient died. Parasite clearance and fever clearance times were significantly shorter in the quinine-clindamycin group (P = 0.03 and P = 0.01, respectively) than in the quinine group, and significantly more recurring fever episodes occurred in the quinine group than in the quinine-clindamycin group shortly after initial fever clearance and parasite clearance (P < 0.001).
After 4 hours of stimulation of human mononuclear leukocytes in the presence of 300 ng/ml exogenous Plasmodium falciparum antigens, the ICAM-1 expression increased variably from 15% to 375%. Simultaneously, an increase of IL-1 mRNA production could be observed in Northern blot hybridizations with a specific cDNA gene probe for human IL-1 alpha labelled with digoxigenin. Furthermore, the reactive oxygen intermediates (ROI) production was also found to be enhanced in similar conditions. Additionally, when the levels of soluble ICAM-1 (sICAM-1) in plasma of 122 patients with P. falciparum or Plasmodium vivax malaria were analyzed in an enzyme immunoassay (EIA), significant sICAM-1 increases were found, more pronounced in patients with P. falciparum malaria, in comparison with healthy controls and with the same patients 4 weeks after chemotherapy. The presented results indicate that the expression of ICAM-1 may also be upregulated by exogenous Plasmodium antigens besides cytokines like IL-1 during the acute phase of malaria, with subsequently elevated sICAM-1 concentrations in blood.
A cross-sectional study was carried out to identify risk factors for seropositivity for antibodies against hepatitis C virus (HCV) and to assess to the distribution and determinants of HCV genotypes among intravenous drug users (IVDUs). The study population consisted of 405 IVDUs. Serum specimens were tested for seromarkers for HCV, for human immunodeficiency virus (HIV), for hepatitis B virus (HBV) and for syphilis. HCV RNA determination by polymerase chain reaction (PCR) and virus typing were performed in a subsample of anti-HCV-positive specimens (n=135). Of the IVDUs, 83% were anti-HCV-positive, 18% HIV-infected, and 58% HBV (anti-HBc)-positive. Longer duration of intravenous drug use, syringe sharing in prison, and higher number of IDVU sex partners were independent risk factors for anti-HCV positivity. GCV RNA was detected in 76% of anti-HCV-positive IVDUs. HCV genotypes 1 (49%) and 3 (44%) were most commonly found. All the type 3 isolates were identified as subtype 3a, and 95% of the type 1 isolates as subtype 1b. In logistic regression analysis, HCV type 3a viraemia was significantly associated with lack of HIV infection and a higher number of sex partners. The results indicate that preventive measures are needed to reduce syringe sharing among IVDUs in prisons. Sexual contacts with other IVDUs may play a role in the HCV epidemic among IVDUs. In Germany, HCV type 3a infection appears to be much more common among IVDUs than among other HCV risk groups such as transfusion recipients or haemophiliacs.
Cytokine regulation was compared in three groups of Gabonese patients with Plasmodium falciparum malaria before and after therapy; adults with uncomplicated malaria, children with uncomplicated malaria, and children with severe malaria. Plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, TNF receptors (TNF R), and the TNF/TNF R ratios were significantly higher in severe malaria compared with uncomplicated malaria. High plasma levels of all immunoregulatory molecules were associated with slow cure after therapy. In all patients, phytohemagglutinin-induced cytokine production was depressed on admission compared with convalescence. A significant difference was the higher TNF production capacity in patients with severe malaria on day 2 and day 5 compared with that in patients with uncomplicated malaria. In contrast to IL-6 and IL-8, a high TNF production capacity during the acute phase of malaria predicted a rapid clinical and parasitologic cure in the patients. These findings illustrate the dual role of TNF in the protection and pathology of malaria.
OBJECTIVES: To examine changes of risk behaviour and its determinants as well as risk factors for HIV infection in intravenous drug users (IVDU) with particular attention to imprisonment and its risk patterns. SETTING: In 1993 a multisite cross-sectional study was carried out by standardized questionnaires and blood/saliva samples in which 612 IVDU from Berlin were enrolled. RESULTS: Multifactorial analysis revealed that the most important risk factor for HIV infection was needle-sharing in prison. In total, 353 IVDU (58%) reported reduced risk behaviour; changes related more to injection behaviour than sexual practices (91 versus 68%). Important determinants for needle-sharing during the last 6 months were intravenous drug use in prison, duration of drug-taking history, and knowledge of a negative HIV test. The most frequently reported reasons for current needle-sharing were having shared needles with only one regular partner (45%) and imprisonment (26%). CONCLUSION: Information campaigns and other prevention measures appear to have produced risk awareness in IVDU, and as a consequence, a reduction in risk behaviour. The situation in prisons (no sterile injecting equipment, no effective disinfectants), however, is counteractive to prevention measures implemented outside prisons. An important task for future strategies should be to enable IVDU to avoid HIV transmission while in prisons.
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High levels of interleukin 1 alpha (IL-1 alpha) were detected in vitro, in murine peritoneal macrophages stimulated with Plasmodium vinckei exogenous antigens, and in vivo, in sera of P. vinckei-parasitized mice. Moreover, high production of IL-1 alpha mRNA could be detected by in situ hybridization analysis in spleen sections of mice during the course of P. vinckei malaria. The observed IL-1 alpha gene expression in the spleen was associated with the accumulation of F4/80+ macrophages in the red pulp and in the marginal zone of follicles, as well as with the relative proportions of Mac-1+ cells in the spleen and the capacity of spleen cells to produce reactive oxygen intermediates during murine malaria.
A cohort of 148 Cameroonian children infected with Schistosoma haematobium was followed before praziquantel therapy and 1, 2, 3, 5, and 12 months thereafter. Egg output, the reagent strip index (RSI, a pathological marker), and circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine were quantified. At enrollment, the median level of egg output was 365/10 mL of urine; 97% of children had a positive RSI; CAA was detected in serum from 76% of children and in urine from 64%; and CCA was detected in serum from 55% of children and in urine from 87%. Two months after chemotherapy, egg output and RSI had decreased significantly; reinfection later developed in parallel with increases in the serum and urine concentrations of CAA and the urine concentrations of CCA. The measurement of CAA and CCA is useful for diagnosis, evaluation of disease severity, and follow-up of chemotherapy in individuals infected with S. haematobium.
Multidrug resistance of Plasmodium falciparum is becoming common in Africa. In a randomized trial, four short-term regimens were compared for treating uncomplicated P. falciparum malaria in children 4-15 years old in Gabon. One hundred thirty patients received chloroquine (25 mg/kg over 48 h; group C), chloroquine (as above) plus clindamycin (5 mg/kg every 12 h for 6 doses; group CCl), quinine (12 mg/kg every 12 h for 6 doses; group Q), or quinine (as above) plus clindamycin (as above; group QCl). In group C, only 9% of patients were cured by day 28, 44% showed recrudescent malaria (RI), and 47% showed intermediate or high-grade resistance (RII/RIII). In group CCl, 70% of patients were cured and 30% showed recrudescences. In group Q, 32% were cured and 68% showed recrudescences. In group QCl, 88% were cured and 12% showed recrudescences after day 14. All treatment regimens were well tolerated. Thus, the combination of clindamycin with chloroquine or quinine enhances parasite clearance and improves response to therapy.
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Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. In Lambarene, Gabon where chloroquine-resistant malaria is prevalent, a randomized comparative trial with three regimens for treating P. falciparum malaria in adults was performed. One hundred two patients evaluated received either a new micronized formulation of halofantrine (8 mg/kg every 6 hr in three doses) (group H) or chloroquine (25 mg/kg for a 48-hr period) plus clindamycin (5 mg/kg every 12 hr in six doses) (group CC1), or chloroquine (as above) plus doxycycline (2 mg/kg every 12 hr in six doses) (group CD). All treatment regimens were well-tolerated. In group H, 100% of the patients were cured, and in group CC1, 97% of the patients were cured by day 28 of follow-up. In group CD, a significantly lower cure rate of 75% (P < 0.01) and a slower parasite clearance was observed, but only low grade (RI) resistance occurred.
The sensitivity of Plasmodium falciparum to chloroquine, mefloquine, quinine, halofantrine, and sulfadoxine/pyrimethamine has been investigated at Lambaréné, in the Gabonese rain forest, between April and September 1992. WHO standard micro in vitro tests were performed. Of 43 isolates tested for response to chloroquine all were resistant to the drug with mean EC 50 and EC 90 values of 1.86 and 4.18 mumol/l blood, respectively, indicating the highest degree of resistance ever reported from Central Africa. With sulfadoxine/pyrimethamine 19 out of 27 isolates showed 90% inhibition of schizont maturation at a pyrimethamine concentration of at least 75 nmol/l blood medium mixture, indicating 30% of resistance to sulfadoxine/pyrimethamine. In contrast all isolates tested were fully inhibited by mefloquine at 3.2 mumol/l blood (40 isolates), quinine at 5.12 mumol/l blood medium mixture (41 isolates) and halofantrine at 3 nmol/l blood medium mixture (40 isolates) indicating full sensitivity to these drugs. A significant positive correlation was found between responses to quinine and mefloquine. The response to halofantrine was positively correlated with the responses to quinine and mefloquine, in the case of chloroquine and halofantrine an inverse relationship was observed. Compared with previous data from Gabon, the findings suggest a substantial increase of chloroquine resistance, in contrast to reports from neighbouring countries, which show stabilising or even declining chloroquine resistance patterns.
The ability of rural health personnel to recognise AIDS related symptoms and signs according to the WHO clinical case definition (CCD) and its modified Rwandan version was tested in 4141 clinically suspected cases in South-Rwanda. The sensitivities of these CCDs for AIDS in adults were 33% (36%), the specificities 78% (76%), and the positive predictive values (ppv) 46%. For AIDS in children the sensitivities of the CCDs were 13% (16%), the specificities 94% (90%), and the ppv 44% (38%). While the specificities did not differ from those found in studies conducted by trained physicians, the low sensitivities and predictive values demand improvement of the training of the health personnel to diagnose AIDS related symptoms and signs, especially where laboratory tests are not available.