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Biomedical subjects

M Micoud

Publications and source records attributed to M Micoud.

At least 19 recordsLinked to original sources

[Cytomegalovirus infection in pregnant women. Seroepidemiological prospective study in 1,018 women in Isere].

Cytomegalovirus (CMV) is the leading cause of viral congenital infections. In children, the consequences may be severe, especially in case of maternal primary infection during pregnancy. A prospective study was carried out in the department of Isère, in 1,018 pregnant women, in order to establish the seroprevalence of CMV, the frequency of primary infections during pregnancy and the associated risk factors. The overall seroprevalence was 51.5%; it increased significantly with age, parity, and low socioeconomic status. It was higher in women born in the South of France (51.6%) than in those born in the North (37.4%). Among a total of 878 women with serological follow-up, 7 primary infection cases (0.8%) were observed. Seventeen women (1.9%) presented border IgM values in the first serum, and these values were not related to recent infection. Extrapolation of the results to the whole department of Isère, suggests that each year about 100 pregnant women would be concerned by CMV primary infection, with 2 or 3 cases of death or severe sequelae in children. In light of these results, the interest of serological screening is discussed.

Adult

[Visceral localizations of cat-scratch disease in an immunocompetent patient].

Locoregional expression of cat scratch disease is well known, but despite advances in microbiology over the last 10 years leading to the description of two new bacteria (Afipia felis, Bartonella henselae) the infective agent responsible for cat scratch syndrome remains unknown. Until the 80s, only one systemic disease was attributed to infection with a germ in the Bartonella genus: trench fever. With the onset of the AIDS epidemic, new clinical syndromes caused by Bartonella bacteria have been described: bacillary angiomatosis, hepatic peliosis, cases of recurrent septicemia, cases of endocarditis, etc. More recently, atypical forms of cat scratch disease including systemic diseases have been reported in immunocompetent subjects. Although quite rare (1% of the cases), such types of expression can raise questions as to diagnosis both in terms of clinical signs and in terms of bacteriological findings. Clinical and experimental data do not provide a clear direction for treatment but would suggest that prolonged use of aminoglycosides is useful.

Adult

Rifabutin versus placebo in combination with three drugs in the treatment of nontuberculous mycobacterial infection in patients with AIDS.

The aim of this double-blind, randomized, placebo-controlled, 12-week study was to assess the efficacy of rifabutin (450 or 600 mg/d) in the treatment of disseminated nontuberculous mycobacterial infection in patients with AIDS. Companion drugs in both arms of the study were ethambutol, clofazimine, and isoniazid. Because of low accrual, the study was prematurely terminated when a total of 382 patients had been enrolled, of which 200 were eligible (i.e., their specimens were culture-positive for Mycobacterium avium complex [MAC] or Mycobacterium xenopi at baseline) and 102 were evaluable (i.e., they were eligible, were treated for a minimum of 6 weeks, and had at least one culture assessment after baseline). The original protocol called for a total of 220 evaluable patients. At week 12, rifabutin treatment was associated with higher, although nonsignificant, rates of bacteriologic conversion than was the placebo arm, with regard to both the eligible patients (25% vs. 18%) and the evaluable patients (45% vs. 38%). Corresponding median times to culture conversion were 42 vs. 63 days (eligible patients) and 43 vs. 69 days (evaluable patients). No significant difference was observed in clinical improvement, mortality, or toxicity between the two treatment arms. The addition of rifabutin to a triple-drug regimen may contribute to the clearance of disseminated MAC infection in patients with AIDS, without causing additional toxicity.

AIDS-Related Opportunistic Infections

Toxoplasma gondii surface antigen-1 in sera of HIV-infected patients as an indicator of reactivated toxoplasmosis.

The major surface antigen from the proliferative form of Toxoplasma gondii (P-30 of SAG-1) was chosen as a target for exploration of Toxoplasma gondii reactivation in sera from immunocompromised patients. Samples were obtained from 37 HIV-infected subjects with lymphocyte levels of CD4+ < 200/mm3. The prevalence of IgG antibodies to Toxoplasma gondii was 64.9%. Ten patients had clinical symptoms of reactivated toxoplasmosis; eight of these had Toxoplasma encephalitis. The SAG-1 epitopes were found as circulating antigen in five cases with an immunocapture enzyme immunoassay (EIA). The EIA was improved with an IgG1 monoclonal antibody to SAG-1 and a streptavidinbiotin amplification. The sensitivity, specificity and positive predictive value were 30, 92 and 60%, respectively. The SAG-1 levels were compared with different biological parameters such as HIV p24 antigen, beta 2 microglobulin, CD4+ cell count and IgG antibodies to Toxoplasma gondii. The levels of SAG-1 in these patients were significantly higher than those in the 75 healthy control persons with or without a chronic Toxoplasma gondii infection. Therefore, SAG-1 may be involved as a marker of reactivated toxoplasmosis in HIV-infected patients.

AIDS-Related Opportunistic Infections

[Azithromycin and genital infections].

The lower genital tract infections due to Chlamydia trachomatis are frequent, essentially occurring in young patients, with possible complications and severe sequela, particularly in women where the sterility risk is one of the major consequences. If an effective treatment could be systematically proposed, a good compliance (easy administration and good toleration) is one of the key factor to success. In this context, the azithromycin displays numerous advantages. The azithromycin in vitro activity on Chl. trachomatis strains is permanent with MIC comprised between 0.06 and 0.125 micrograms/ml, with an activity equivalent to those of other macrolides, to tetracyclines and quinolones. Different animal models allow to demonstrate the curative activity of the azithromycin administered as a single dose, at dosage regimen equivalent to those used in man, and a prophylactic activity on the salpingitis onset in provoked Chl. trachomatis infections. Several comparative clinical studies with azithromycin administered as a 1 g single dose displayed very satisfactory results with 98% of bacterial eradication, identical to those obtained with reference treatment. On the other hand, restrictions to the product use are a less constant activity against Neisseria gonorrhoeae and a lack of efficacy on Mycoplasma hominis. The efficacy on Treponema pallidum remains to be clinically tested.

Adult

Vitamin, trace element and peroxide status in HIV seropositive patients: asymptomatic patients present a severe beta-carotene deficiency.

We have investigated whether nutritional status and peroxidation process are associated with the degree of development of HIV infection. This was done by measuring the status of vitamins (E, A and beta-carotene), of antioxidant trace elements (zinc, selenium) and lipid peroxide levels (lipid hydroperoxides and thiobarbituric acid reactants) in HIV-seropositive patients at CDC II and CDC IV stages and in comparison with normal subjects. There was a decrease in vitamin and trace element levels related to the severity of disease. The most dramatic decrease, however, was seen for carotenoids (0.94 +/- 0.46 mumol/l) and beta-carotene (0.24 +/- 0.14 mumol/l vs. 0.56 +/- 0.29 mumol/l) whose stage II levels were only half the normal value. Paradoxically, lipid peroxidation was higher at stage II than at stage IV. This can be attributed to an overproduction of oxygen radicals by polymorphonuclears in stage II. This deficiency in antioxidant status, often found in patients suffering from peroxidative diseases, may have important consequences on cellular immunity. Furthermore, the concomitant overproduction of free radicals may also affect HIV multiplication.

Adult

Antioxidant status and lipid peroxidation in patients infected with HIV.

Deficiency in antioxidant micronutrients have been observed in patients with AIDS. These observations concerning only some isolated nutrients demonstrate a defect in zinc, selenium, and glutathione. An increase in free radical production and lipid peroxidation has been also found in these patients, and takes a great importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1 replication secondary to free radicals overproduction. We have assessed different studies, trying to obtain a global view of the antioxidant status of these patients. In adults we observe a progressive decrease for zinc, selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II. However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal value. To understand if these decreases in antioxidant and increases in oxidative stress occur secondary to the aggravation of the disease or, conversely, are responsible for it, we undertook a longitudinal survey of asymptotic patients. The preliminary results of this evaluation are presented. Paradoxically, lipid peroxidation is higher at stage II than at stage IV. This may be consecutive to a more intense overproduction of oxygen free radicals by more viable polymorphonuclear (PMN) at the asymptomatic stage. The free radicals production and lipid peroxidation seem secondary to a direct induction by the virus of PMN stimulation and cytokines secretion. N-Acetyl cysteine or ascorbate have been demonstrated in cell culture to be capable of blocking the expression of HIV-1 after oxidative stress and N-acetyl cysteine inhibits in vitro TNF-induced apoptosis of infected cells. In regard to all these experimental data, few serious and large trials of antioxidants have been conducted in HIV-infected patients, although some preliminary studies using zinc or selenium have been performed. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants. The more promising candidates for presenting synergistic effects when associated with N-acetyl cysteine seem to be beta-carotene, selenium and zinc.

Acquired Immunodeficiency Syndrome

Changes in the dominant Epstein-Barr virus type during human immunodeficiency virus infection.

Two types of Epstein-Barr virus (EBV), EBV-1 and EBV-2, were identified on the basis of DNA sequence divergence in the genes for nuclear proteins EBNA 2, 3a, 3b and 3c. In the present study, we conducted an immunological and genomic analysis in a human immunodeficiency virus (HIV)-infected population to determine the prevalence of the two types, and whether the identified type was stable over years. The EBNA-2 serotyping and genotyping showed that HIV-infected patients were highly infected by EBV-2, and that the dominant strain was mostly retained. However, during a follow-up study, a change in the dominant viral strain was observed in two patients. A first HIV-positive patient (patient A), although having a stable level of anti-EBNA-2A and -2B antibodies, showed a change in the genotype and antigen produced in spontaneously established lymphoblastoid cell lines (LCL). The sequence analysis of LCLs confirmed the emergence of the EBV-2 type population. A strain from a second HIV-positive patient (patient B) was clearly identified as EBV-2: the genotype from a saliva sample and from sequential LCLs belonged to EBV-2, as well as the antigen produced from LCLs, and serum antibodies. After a 5-year continuous EBV-2 infection, a reactivation of the EBV-1 strain was observed. In both cases, sequence analysis of the EBNA-2 gene showed, only with EBV-1, the presence of EBV variants related to the B95-8 prototype. Two mutations (at nucleotides 49212 and 49304) were found in both patients A and B, whereas an additional mutation (at nucleotide 49237) was characteristic of the patient A. No mutation relative to the prototype B95-8 strain was observed in a subsequent analysis of this EBNA-2 region from LCLs obtained from two HIV-negative patients predominantly infected by EBV-1. Therefore, we speculate that these mutations may be EBV-1 mutations specifically occurring during HIV infection.

Antigens, Viral

[Bacillary angiomatosis related to Rochalimaea quintana. Anatomoclinical and ultrastructural study of cutaneous localizations in AIDS].

We report a case of bacillary angiomatosis in a 53-year-old homosexual man with acquired immunodeficiency syndrome (AIDS). Pathological and bacteriological studies of cutaneous nodules led to the identification of a rickettsia: Rochalimaea quintana. This observation prompted us to relate the clinical presentation of cutaneous and visceral forms of this disease. Histopathological patterns are also considered. They usually consist in a lobular proliferation of capillaries with plump and sometimes epithelioid endothelial cells. Polymorphonuclear cells, histiocytes and necrotic areas may be present. The most characteristic feature is the presence of interstitial, granular and amorphous clusters of bacteria. Diagnostic problems can be raised with Kaposi's angiosarcoma which can be associated with bacillary angiomatosis. Two types of Rochalimaea have so far been isolated in this disease i.e., R. henselae which is the most frequently involved, and R. quintana. The usefulness of making such a diagnosis resides in the sensitivity of bacillary angiomatosis to antibiotics, emphasing the need to carefully look for the presence of bacterial clusters when atypical angioproliferative lesion appears in patients with AIDS.

AIDS-Related Opportunistic Infections

Trimethoprim-sulfamethoxazole versus aerosolized pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia: a prospective, randomized, controlled clinical trial. LFPMI Study Group. Ligue Française de Prévention des Maladies Infectieuses.

The objective was to compare the efficacy and tolerance of monthly aerosolized pentamidine versus trimethoprim-sulfamethoxazole (TMP-SMX) to prevent the first episode of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients. In an open, prospective, randomized multicentric clinical trial, HIV-infected patients (n = 214) with CD4 cell counts < 200/mm3 or 20% without a history of PCP or cerebral toxoplasmosis were randomized to receive for at least 2 years aerosolized pentamidine (300 mg monthly) or low-dose daily TMP-SMX (400-80 mg). The mean follow-up was 578 days. The two groups (except for gender) were homogeneous for age, risk group for HIV infection, initial CD4+ lymphocyte count, and mean follow-up. The PCP rate per year of observation using an intent-to-treat analysis was 3.1% and 1.3% in the groups treated with pentamidine and TMP-SMX, respectively (p > 0.05). Moderate or severe clinical and biological side effects were observed in five patients on pentamidine and 33 on TMP-SMX (p < 0.05). Nineteen episodes of cerebral toxoplasmosis were diagnosed during the study. The analysis showed no significant difference in time of development of toxoplasmosis, but only one patient was actually treated with TMP-SMX. Survival was not significantly different in the two groups. Low-dose daily TMP-SMX or monthly aerosolized pentamidine effectively prevented a first episode of PCP in HIV-infected patients, but aerosolized pentamidine was better tolerated. However, TMP-SMX is less costly and should have a preventive effect for toxoplasmosis.

AIDS-Related Opportunistic Infections

[Neuromeningeal listeriosis in adults. Clinical aspects and contribution of cotrimoxazole in monotherapy].

A series of 28 patients suffering from neuromeningeal listeriosis is reported. This disease is consecutive to infection by Listeria monocytogenes--an ubiquitous and opportunistic Gram-positive bacillus--and has become a public health problem: its incidence is increasing and its prognosis is very severe despite the development of new bacteriological identification methods. Human beings are contaminated by food, which explains the frequent outbreaks of epidemics which are widely publicized, the infection being one of the consequences of the unprecedented development of the food industry and the cold food chain. The predominant clinical picture is one of non-specific meningoencephalitis. In about 50 percent of the cases the subjects infected are "immunodepressed" and/or more than 60 years' old. The diagnosis is difficult since the bacteriological identification is delayed (direct examination of the cerebrospinal fluid is rarely positive) and this fluid may be sterile (hence the value of blood cultures). A probability treatment therefore must be initiated before the diagnosis is confirmed if an unfavourable outcome is to be avoided. In Listeria monocytogenes infection cotrimoxazole administered alone seems to be a better antibacterial therapy than the reference ampicillin-aminoside combination.

Adolescent