Biomedical subjects
Publications and source records attributed to S Caligaris.
The Indian Ocean provides a unique opportunity to curb the HIV epidemic in its nascent phase through strengthening STI control programmes. Making effective and appropriate health services available should be regarded as the first priority for STI control in the region and, whenever possible, core groups should be identified and targeted to interrupt transmission within such networks.
A previously unreported CD8(+)CD28(+)CD11b(+) T cell subset occurs in healthy individuals and expands in patients suffering from primary viral infections. In functional terms, these cells share the features of naive/memory CD8(+)CD28(+)CD11b(-) and terminally differentiated effector CD8(+)CD28(-)CD11b(+) subpopulations. Like CD28(-) cells, CD28(+)CD11b(+) lymphocytes have the ability to produce IFN-gamma, to express perforin granules in vivo, and to exert a potent cytolytic activity. Moreover, these cells can respond to chemotactic stimuli and can efficiently cross the endothelial barrier. In contrast, like their CD11b(-) counterpart, they still produce IL-2 and retain the ability to proliferate following mitogenic stimuli. The same CD28(+)CD11b(+) subpopulation detected in vivo could be generated by culturing naive CD28(+)CD11b(-) cells in the presence of mitogenic stimuli following the acquisition of a CD45RO(+) memory phenotype. Considering both phenotypic and functional properties, we argue that this subset may therefore constitute an intermediate phenotype in the process of CD8(+) T cell differentiation and that the CD11b marker expression can distinguish between memory- and effector-type T cells in the human CD8(+)CD28(+) T cell subset.
The quantitative buffy coat (QBC) parasite detection method is a sensitive and specific tool for the diagnosis of malaria parasites. It is also useful for the diagnoses of other hemoparasites, including Trypanosoma, Babesia, and Leptospira. We report a case of relapsing fever diagnosed by this technique in a short-term traveler from Senegal. The diagnosis was confirmed by the standard Giemsa hemoscopy and by the identification of significant titers of antibodies to Borrelia spp. of tick-borne relapsing fevers by specific immunofluorescence and Western blot tests. The QBC technique seems to be useful in the diagnosis of tick-borne relapsing fever in blood samples and should be included in the management of fever in the traveler returning from tropical regions.
The tolerability of and adherence to intermittent short-term rifabutin-isoniazid preventive treatment was assessed in subjects dually infected with Mycobacterium tuberculosis and the human immunodeficiency virus (HIV). In a randomised, open-label, phase II pilot study, 44 subjects received either rifabutin 300 mg and isoniazid 750 mg twice weekly for 3 months (group A, n = 16) or the same regimen with rifabutin at 600 mg (group B, n = 14), or isoniazid 300 mg/day for 6 months (group C, n = 14). Three, two and four subjects in groups A, B, and C, respectively, did not complete their treatment (one case of flu-like syndrome in group B; one methadone withdrawal syndrome in group A; and patient decision in two cases in group A and four in group C). Overall, adverse events were reported by four, nine, and seven subjects in groups A, B and C, respectively. Intermittent combined rifabutin + isoniazid for 3 months had lower default rates than daily standard isoniazid for 6 months. The regimen with rifabutin at 300 mg dose compared favourably to standard isoniazid, and warrants larger efficacy studies to assess its role for the prevention of latent tuberculosis in HIV-infected subjects.
An increasing proportion of malaria cases in Italy is observed in immigrants revisiting their country of origin, but little specific research work has been carried out in this field. All malaria cases occurring from 1990 to 1998 at the Reference Clinic for Infectious and Tropical Diseases in Brescia were prospectically evaluated to compare clinical outcome in migrant and non-immune cases. No difference was observed between parasitaemia at diagnosis and time to clearance of peripheral parasitaemia. Clinical presentation was milder in migrants than in non-immunes, with an OR for severe malaria of 0.27 (c.i. = 0.09-0.84) (p = 0.01). Fever clearance time was significantly shorter in migrants (3.0 days, SD = 1.2) than in non-immunes (4.3 days, SD = 1.7) (p < 0.001). Among immigrants, the proportion of severe cases was higher in residents since 2 years or less (12.5%) compared to residents since 2 to 5 years (3.3%) and residents since more than 5 years (0.9%) (p = 0.02). The proportion of malaria cases who had used chemoprophylaxis was significantly lower among immigrants (30/272, 11.0%) compared to non-immunes (41/74, 55.4%) (p < 0.001). In a population based malaria KAP analysis among 504 migrants from malaria endemic countries, correct knowledge of malaria risk was reported by 351 (69.5%). Of 170 subjects who reported at least one visit back to the home country, 30 (17.6%) had sought pre-travel advice, 24 (14.1%) had started chemoprophylaxis and 7 (4.1%) had completed it during the last visit. Of 140 migrants who failed to seek pre-travel advice, 73 (52%) were unaware of malaria risk, 56 (40%) did not know how to protect themselves, and 11 (8%) refused to use protective measures. Migrants account for a significant proportion of imported malaria cases in industrialised countries. Clinical presentation is milder compared to non-immune subjects. The proportion of migrants who adopt malaria protective measure while returning home is very low, due to both unawareness of risk and inappropriateness of medical advice.
Placental malaria is recognized as a common complication of malaria in pregnancy in areas of stable transmission, and is particularly frequent and severe in primigravidae. Many hypotheses, based on a systemic or local failure of the immunological response to malaria, have been proposed to explain the 'preference' of the parasites for replication in the placenta. Some of the hypotheses are briefly reviewed here, with a particular focus on the discovery of an uncommon subpopulation of Plasmodium falciparum which can adhere and massively sequester in the placenta. Histologically, placental malaria is characterized by the presence of parasites and leucocytes within the intervillous spaces, pigment within macrophages, fibrin deposits and trophoblasts, proliferation of cytotrophoblastic cells and thickening of the trophoblastic basement membrane. The exact mechanisms leading to placental changes and determining the observed impairment of materno-foetal exchange are incompletely understood. Parasites are unlikely to be directly responsible for the placental pathology, but leucocytes, through the production of non-chemotactic cytokines, might be associated with the thickening of the trophoblastic basement membrane, and might cause a mechanical blockage of oxygen and nutrient transport across the placenta. There is sound epidemiological evidence that placental malaria determines low birthweight, mainly mediated by intrauterine growth retardation, and increases the risk of death and disease during the first year of life. Antimalarial chemoprophylaxis significantly reduces placental malaria and prevents the development of low birthweight. It is likely that, in areas of high endemicity, the placenta is where the drama of maternal malaria is mostly played. A deeper understanding of the mechanisms involved in this process is of key importance in the design of protective interventions which are effective and acceptable during the gestation period.
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One hundred fifty-three blood samples from patients positive for the human immunodeficiency virus (HIV) were analyzed by polymerase chain reaction (PCR) to detect the presence of Mycobacterium avium. Samples were collected from patients who also had blood cultures performed by a radiometric method. Blood samples were centrifuged on a Ficoll-Hypaque gradient to purify peripheral blood mononuclear cells. The purified cells were washed and incubated with a resin, boiled to release mycobacterial DNA, and then amplified. Polymerase chain reaction products were detected by a nonisotopic method. A 123 base-pair (bp) insertion sequence, namely IS6110, from Mycobacterium tuberculosis complex was also included in the reaction as an internal control of Taq polymerase activity to exclude the presence of enzyme inhibitors. This IS6110 fragment can be distinguished from the 383 bp target product on ethidium bromide-stained agarose gel and may also be used in a colorimetric assay. Such results were compared with the results of culture and indicated that the assay is as sensitive as bacteriological methods, though faster.
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Programmed cell death or apoptosis has been shown to play a central role in CD4+ T cell depletion following HIV infection. Because most apoptotic signals are delivered through T cell receptor stimulation, we investigated whether T cell depletion in AIDS is a stochastic phenomenon or if it preferentially affects T cell subsets defined by their interaction with superantigens. To address this problem we have taken advantage of the exclusive property of superantigens to trigger T cells expressing selective sets of T cell receptor V beta elements. Here we report that CD4+ T cells from HIV-infected patients can proliferate in vitro to T cell receptor mobilization by some superantigens, but not others. Furthermore, the failure of T cells to respond to some superantigens was shown to be due to an active cell death process that differentially affected T cells capable of interacting with different superantigens. The selective programmed cell death priming of T cells responsive to particular superantigens, observed in this study, suggests that T cell depletion in HIV infection is not simply due to the cytopathic effect of the virus. The possible link between programmed cell death and T cell receptor variable regions suggested by the present experiments may help to better define current models of AIDS pathogenesis.
In July 1990, the in vitro chemosensitivity of 22 isolates of Plasmodium falciparum was assessed by an isotopic semi-microtest in Yaounde, Cameroon. Out of them, 54.5% were resistant to chloroquine, 28.6% to amodiaquine, 4.8% to quinine and 4.5% had a decrease of sensitivity to mefloquine. A strong positive correlation between the IC50 of the antimalarial drugs compared by pairs was detected.
We carried out an electron-microscopy study on in vitro cultures of Plasmodium falciparum, whose general ultrastructural features are consistent with previous reports. In addition, whorled membrane-vesicles systems involving parasite and host-cells, never described to our knowledge up to now. As far as the parasite is concerned, these membraneous systems appear to be related to its growth and its connection with the external medium, with the possible involvement of Maurer's clefts. As for the erythrocyte, surface vesicles prove to be related to plasmodial infection in long-term in vitro culture. Richness in membranous structures of the complex host-parasite varies according to the metabolic demand of the plasmodium (i.e. on the life-cycle stage) and is influenced by external factors, possibly being a marker of drug action.
Leptospirosis, anthropo-zoonosis ubiquitously widespread, is a social and economic problem still to be solved. The experimental and therapeutic employment of many antibiotics has largely been tested "in vitro" and "in vivo". In the following research we tried to evaluate, by experimental "in vitro" method, the sensitivity difference of three serovar strains of Leptospira interrogans to two macrolides, Erythromycin and Josamycin, compared with Penicillin. From standard cultures, previously treated with serial dilution of these antibiotics, the MIC and MSC, as quantitative parameters, have been stated. For the qualitative evaluation of the damages induced at ultrastructural level by the drug activity. Electron Microscopy investigations were performed on specimens from cultures treated for 6 hr with twice and tenfold the MSC. The present research confirms the good sterilizing efficaciousness "in vitro" of the tested macrolides (MSC less than 1 mcg/ml) and their different activity pathway.
In the present morphological study, we used electron microscopy (EM) to evaluate the activity of three quinolines upon Plasmodium falciparum strains cultured in vitro. The drugs (namely chloroquine, mefloquine and a new active substance, SF6606) showed common cellular targets (i.e. feeding process, protein synthesis, membrane formation and utilisation) but gave rise to different morphological features. EM as a tool is able to reveal a variety of drug-induced alterations, but it does not seem to supply evidence of a definite mechanism of action. Nevertheless, our observations suggest that each drug acts via several mechanisms, possibly linked to different degrees of parasite susceptibility.
We carried out a research on hospitalized cases of imported malaria in Lombardy in the period 1981-1985 to characterize the risk factors and the clinical features of this phenomenon and to identify its trend in comparison with the previous quinquennium (Carosi et al., 1983). 1) Prevalent factors of risk are: the P. falciparum etiology (68%), the african origin of the strains, the work motivated travelling (56%) and a long period of stay (56%) in the summer-autumnal season (62%). On the contrary, in the previous quinquennium, short periods of stay during winter season prevailed. 2) As far as the chemoprophylaxis is concerned, it has been adopted in 55% of the cases, but only in 14 cases it was correct. In 52% of the cases, symptoms were noted within 20 days of re-entry, and in 17% of the cases they started abroad. In 62% of the cases a correct diagnosis was made within 10 days from the onset of symptoms and in 72% fever disappeared within 48 hours after therapy. Data show an inversion of the trend of the previous quinquennium and evidentiate a wider use of chemoprophylaxis and a more effective therapeutic action by the Sanitary Structure in Lombardy. The Authors stress the need for improvement in malaria control programs by Italian industries working in Developing Countries (roads and dams construction) and the increasing prophylactic problems related to che widespread extent of chloroquine resistant P. falciparum strains in Africa. Our causistry shows the outcome of 14 falciparum malaria cases in spite of correct chloroquine chemoprophylaxis.
The traditional IgM-ELISA has a better sensibility and specificity than IgM-IFA when these two tests are performed on whole sera, but in many cases (sera titer values of greater than 200 I.U./ml) the presence of IgM antitoxoplasma antibodies can be detected only after purification of IgM fractions. The separations of IgM fractions avoids either false positive results due to the rheumatoid factors or antinuclear antibodies, and false negative results due to the competition between IgG and IgM antibodies. The present investigation has shown that antibody titers obtained by IgM-IFA and traditional IgM-ELISA correlate well with DS-IgM-ELISA and IgM-ISAGA performed on whole serum. The false negative results that frequently occur with IgM-IFA and traditional IgM-ELISA performed on whole sera having sera titer values of greater than 200 I.U./ml in IgG IFA are avoided when the same sera were tested by DS-IgM-ELISA and IgM-ISAGA. All the sera which gave positive results by DS-IgM-ELISA were also positive when tested with IgM-ISAGA. Our researches demonstrate the high specificity and sensitivity of IgM-ISAGA and DS-IgM-ELISA performed on whole serum.
The present investigation has shown that antibodies titers obtained by IgM-IFA performed on pure IgM-fractions, obtained by gel-filtration method, correlate well with DS-IgM-ELISA. False negative IgM-IFA results that frequently occurs with sera having greater than or equal to 200 I.U./ml by IgG-IFA, were not observed with DS-IgM-ELISA: and the 98% of sera positive only after separation of IgM fraction with IgM-IFA, are also positive with DS-IgM-ELISA performed on whole serum.
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