Varicella-zoster virus encephalitis in acquired immunodeficiency syndrome: report of four cases.

Four patients with acquired immunodeficiency syndrome, a 27-year-old female intravenous drug abuser and three males (two drug addicts aged 27 and 33 years and a 40-year-old homosexual) presented with a rapidly progressive encephalopathy. Two had generalized varicella-zoster virus skin infection, one had had a regressive thoracic zoster rash 7 months previously and one had no history of cutaneous eruption. Neuropathological examination revealed, in each case, multifocal necrotic changes with numerous, intranuclear Cowdry type A inclusion bodies in glial cells, endothelial cells, macrophages and neurons, within and around the lesions. These inclusion bodies were stained positively for varicella-zoster virus by immunocytochemistry and contained herpes virus nucleocapsids by electron microscopy. Molecular biology using the polymerase-chain-reaction method demonstrated viral genome. In one case, zoster-induced non-inflammatory vasculopathy involved medium sized leptomeningeal vessels and was associated with circumscribed areas of cortico-subcortical infarction. In another case, varicella-zoster virus encephalitis was associated with human immunodeficiency virus encephalitis and a secondary cerebral lymphoma. Multinucleated giant cells expressing human immunodeficiency virus proteins in their cytoplasm, were found in the lymphomatous deposits and in the varicella-zoster virus necrotic lesions. In these latter lesions, Cowdry type A inclusion bodies could be seen in the nuclei of some multinucleated giant cells confirming previous observations of MGCs co-infected by HIV and CMV, and supporting the hypothesis that DNA viruses interact with HIV, thus increasing its effect.

Differences in the respiratory burst of human polymorphonuclear leukocytes induced by virulent and avirulent Legionella pneumophila serogroup 1.

Two strains of Legionella pneumophila of different virulence were examined for their influence on the metabolic oxidative activity of human polymorphonuclear leukocytes. The leukocytes exhibited decreased rates of oxygen consumption and diminished chemiluminescence activity following phagocytosis of a virulent strain of L. pneumophila serogroup 1. In contrast, phagocytosis of its multipassaged derivative rendered avirulent, was accompanied by increased rates of both oxygen consumption and chemiluminescence activity. Although no differences were observed in oxygen uptake induced by the virulent legionellae compared to leukocytes at rest, statistically significant differences were observed in the chemiluminescence responses. These observations were not unexpected, since the luminol-enhanced chemiluminescence assay, is more sensitive than the oxygen uptake assay. In spite of decreased metabolic activity of PMN in the presence of virulent legionellae, electron microscope studies showed higher numbers of intracellular L. pneumophila than the avirulent subtype. Thus, virulent and avirulent L. pneumophila can be differentiated on the basis of oxygen consumption and chemiluminescence assays.

[Neuropathologic study of 135 adult cases of acquired immunodeficiency syndrome (AIDS)]. / Etude neuropathologique de 135 cas adultes de syndrome d'immuno-déficience acquise (SIDA).

The central nervous system was examined in 135 adult AIDS patients who died between August 1982 and December 1990. Twenty two brains showed non-diagnostic changes including microglial nodules, discrete myelin pallor with reactive astrocytosis, mineralization of blood vessels and granular ependymitis. In 105 brains with specific changes, toxoplasmosis was the most frequent finding (55 cases) manifested by multifocal necrotic lesions or diffuse pseudo-encephalitic process. Other opportunists included cytomegalovirus (21 case), progressive multifocal leukoencephalopathy (1 cases), cryptococcosis (6 cases), mycobacterium avium intracellulaire (2 cases), varicella-zoster virus (2 cases), aspergillosis (1 case) and multiple bacterial microabscesses (1 case). Multinucleated giant cells were found in 52 cases. In 40 cases, they were widely disseminated throughout the brain and in 39 cases, they were associated with diffuse or multifocal white matter changes. Fifteen cases had a cerebral lymphoma, 9 hepatic encephalopathy, 1 centropontine myelinolysis and 1 focal pontine leukoencephalopathy. Three cases had a cerebral haemorrhage due to disseminated intravascular coagulation, antithrombin therapy and amyloid angiopathy. Spinal changes in 13 cases included vacuolar myelopathy (7 cases), HIV myelitis (1 case) and ganglio-radiculitis (1 cases), cytomegalovirus myelo-radiculitis (1 case) secondary spread from a lymphoma (1 case) and spinal infarcts due to disseminated intravascular coagulation (1 case). These lesions were frequently atypical and various combinations of all these pathologies were encountered in the same brain, sometimes in the same area and occasionally in the same cell. Chronological variations in the incidence of some complications could be related to changes in treatment.

Isolation, purification and partial analysis of the lipopolysaccharide antigenic determinant recognized by a monoclonal antibody to Legionella pneumophila serogroup 1.

Monoclonal antibody II-6-18 recognizes a serogroup-1-specific Legionella pneumophila antigenic determinant which has been shown to be virulence-associated. We previously reported the physicochemical characterization by means of a quantitative fluorometric assay of monoclonal antibody II-6-18 binding to L. pneumophila, and its implications concerning the nature of the antigen. We describe here the isolation and the purification of the antigen by chemical and immunological methods, followed by its partial chemical analysis. The results demonstrate that the epitope--an immunodominant carbohydrate which includes a fucosamine-like residue--is part of the cell wall lipopolysaccharide (LPS). It is localized in the polysaccharide moiety of the LPS which contains KDO, rhamnose, mannose, glucosamine and an unidentified aminodideoxyhexose X1, but no heptose. The aminodideoxyhexose X1 could be fucosamine and is probably the immunodominant residue in the epitope, localized, at least partially, at the end of the polysaccharide chain.

Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease.

Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients.

Comparative postantibacterial activities of pefloxacin, ciprofloxacin, and ofloxacin against intracellular multiplication of Legionella pneumophila serogroup 1.

The inhibitory and postantibacterial activities of pefloxacin, ciprofloxacin, and ofloxacin against virulent Legionella pneumophila serogroup 1 were evaluated in cell-free and cellular models. In the absence of macrophages (with the tissue culture medium alone), bacterial numbers remained unchanged at 24 h in the presence of 0.1 microgram of pefloxacin, ciprofloxacin, or ofloxacin per ml and 1.0 microgram of pefloxacin per ml, whereas they were reduced in the presence of 1.0 microgram of ciprofloxacin or ofloxacin per ml. Experiments to evaluate the postantibacterial effects of these drugs were therefore performed with concentrations of 0.1 microgram/ml. In the cell-free model, brief exposure (1 h) of bacteria to each antimicrobial agent resulted in a transient decrease in numbers followed by logarithmic growth. In the cellular model, all three drugs (at 0.1 and 1.0 microgram/ml) inhibited the intracellular multiplication of L. pneumophila. The intracellular postantibacterial effects of 0.1 microgram of pefloxacin, ciprofloxacin, and ofloxacin per ml, which were left in contact with L. pneumophila-infected human macrophages for 24 h, were evaluated at various times after removal of the drugs. Pefloxacin was found to exhibit a significant inhibitory effect at 72 h, whereas following the removal of ciprofloxacin and ofloxacin, rapid bacterial multiplication occurred, leading to the destruction of the macrophage monolayer within 48 h. Thus, while pefloxacin, ciprofloxacin, and ofloxacin all inhibited the multiplication of L. pneumophila in human monocyte-derived macrophages, only pefloxacin exhibited a prolonged postantibacterial effect.

T activation marker evaluation in ARC patients treated with AZT. Comparison with CD4+ lymphocyte count in non-progressors and progressors towards AIDS.

Reductions in the percentage and absolute number of CD4+ lymphocytes, as well as abnormally high levels of activated peripheral T lymphocytes (CD3+ HLA-DR+ phenotype) and an increased proportion of CD8+ cells coexpressing the CD57 surface antigen (involved in natural killer activity) have been reported in HIV infection and associated with disease progression. We prospectively measured these subsets of lymphocytes in 34 patients with advanced AIDS-related complex (ARC) treated with azidothymidine (AZT). Peripheral blood lymphocyte phenotyping was performed before treatment, then at weeks 12 and 24. A striking fall in the proportion of activated T lymphocytes from baseline was observed (P less than 0.001) at week 24. In contrast, the percentage of CD4+ cells showed a slight and transient rise at week 12 (P less than 0.05). No modification in levels of CD8+ or CD8+ CD57+ cells was detected during the study. Of the 34 patients, 11 developed AIDS, and 23 remained AIDS-free during 51 weeks of follow-up. Similar patterns of change in CD4+ and HLA-DR+ CD3+ lymphocytes were found in the AIDS progressors and nonprogressors. Likewise, HIV p24 antigenaemia showed parallel decreases in both groups of patients. Although changes in CD4+ cells, p24 antigenaemia and HLA-DR-reactive T lymphocytes were not predictive of clinical outcome, large differences existed between the two groups prior to the initiation of therapy. The short-term onset of AIDS was associated with lower CD4+ cell numbers, higher levels of serum p24 antigen and a greater proportion of activated T lymphocytes. Our results suggest that the possible interest of T lymphocyte activation markers, in conjunction with conventional phenotyping, should be investigated further.

[Nosocomial Legionnaires' disease in children. Preventive measures]. / Maladies des légionnaires nosocomiale chez l'enfant. Mesures de prévention.

Two immunocompromised children, aged 3 years and 1 1/2 month, developed an hospital-acquired Legionnaire's disease. In one case, Legionella pneumophila serotype 1 was identified by culture in pleural fluid; LP1 was isolated in all the warm water samples in the hospital. Clinical, epidemiological data and laboratory findings are discussed.

[Lyme disease: biological diagnosis and treatment]. / Maladie de Lyme: diagnostic biologique et traitement.

In daily practice the diagnosis of Lyme disease is confirmed in the laboratory by serological tests the specificity and sensitivity of which are not fully satisfactory. There are false-positive results due to antibodies directed against antigens others than Borrelia burgdorferi, but the main problem is that most people living in endemic areas have specific antibodies while being, and remaining, asymptomatic. In addition, the sensitivity of the current tests is mediocre at the onset of the disease. A negative serology therefore should not exclude definitively a diagnosis of Lyme disease, just as a positive serology should not compulsorily lead to this diagnosis in patients with atypical clinical signs. The treatment of Lyme disease aims at eradicating the organisms, including those wHich infest the central nervous system. Beta-lactam antibiotics seem to be particularly suitable for this purpose: amoxycillin is used in ambulatory patients, and ceftriaxone is probably the most effective treatment of severe neurological manifestations of the disease.

[Negativity of Borrelia burgdorferi serology in scleroderma en plaques]. / Négativité de la sérologie pour Borrelia burgdorferi dans la sclérodermie en plaques.

The occurrence of morphea has been attributed to Borrelia, burgdorferi infection, but the relationship between localised scleroderma and borreliosis remains controverted. Antibodies directed against B. burgdorferi were looked for in 21 patients (18 female and 3 male, aged from 8 to 63 years) whose disease had been present for 6 weeks to 13 years. One patient had a single morphea, two had monomelic scleroderma and 18 had multiple localised morpheas. The search for antibodies was conducted in these 21 patients and in 200 blood donors from the Paris region by indirect immunofluorescence techniques, using the CDC method where only antibody titers of 1/256 or more are significant. Serology was lower than 1/256 in 20 cases and equal to 1/256 in one case. Among the 200 blood donors, five (2.5%) had antibody titers of 1/256 or more. None of the patients studied had been exposed to tick bite due to their occupation or place of residence. We therefore found no evidence of a link between B. burgdorferi infection and morphea in the Paris region.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of zidovudine in 365 consecutive patients with AIDS or AIDS-related complex.

Zidovudine (AZT) is of some benefit for selected patients with AIDS-related complex (ARC) or AIDS treated for up to 24 weeks. The activity and toxicity of oral AZT, 200 mg 4-hourly when possible, was evaluated in 365 consecutive patients with ARC (80) or AIDS (285) followed up for a mean of 31 weeks (range 2-52). A transient increase in body weight, Karnofsky index, and CD4 cell count was observed during the first months of therapy. However, by 6 months, these values had returned to their pretreatment levels and several opportunistic infections, malignancies, and deaths occurred. These disappointing results were partly related to the haematological toxicity of the drug, which led to interruption of treatment in many patients. Thus the benefits of AZT are limited to a few months for ARC and AIDS patients. At least for the most severely affected patients, reduced dosage of AZT may increase the therapeutic index.

Efficacy of intravenous spiramycin in the treatment of severe Legionnaires' disease.

Spiramycin is a 16-membered macrolide that has been shown in cell and animal models to be active against Legionella spp. The activity of the injectable form of spiramycin was evaluated in the treatment of severe Legionnaires' disease in seven immunocompromised and three previously healthy patients. Seven of the ten patients were cured. Three patients died primarily from the underlying disease or from intercurrent complications. This result and the better tolerance of spiramycin compared with 14-membered macrolides suggest that spiramycin may be a suitable alternative to erythromycin for the treatment of Legionnaires' disease.

Comparison of spiramycin and erythromycin in the treatment of experimental guinea pig legionellosis.

Spiramycin was compared with erythromycin in a guinea pig model of severe Legionella pneumophila serogroup 1 infection. Male guinea pigs weighting 264-321 g were infected by the intraperitoneal route with 1.2 x 10(7) virulent L. pneumophila serogroup 1. Forty eight h after infection, animals that had lost greater than or equal to 9% of their body weight were randomly assigned to receive 48, 54 and 72 h after infection intraperitoneal injections of (1) distilled water (n = 20), (2) erythromycin lactobionate, 30 mg/kg per injection, (n = 22) or (3) the injectable form of spiramycin adipate, 30 mg/kg per injection (n = 22). Animals were observed daily for 15 days. All infected animals treated with distilled water died within four days of infection. Of the 22 animals treated with spiramycin, 10 (45.5%) died, and of the 22 animals treated with erythromycin, 11 (50.0%) died of disseminated L. pneumophila infection. In this animal model of very severe L. pneumophila infection, the injectable forms of erythromycin and of spiramycin gave similar results. Spiramycin should therefore be considered for the treatment of Legionnaires' disease in man.

Monoclonal antibody reactivity as a virulence marker for Legionella pneumophila serogroup 1 strains.

Using a panel of nine monoclonal antibodies, we subgrouped 85 environmental and 129 clinical Legionella pneumophila serogroup 1 isolates from Paris, France. Patients were unlikely to be epidemiologically linked either with each other or with the 44 sampled environmental sites (14 air conditioning systems and 30 buildings) that were selected at random in the Paris area. According to their monoclonal antibody patterns, isolates belonged to 14 subgroups. Monoclonal antibody 2 recognized 121 (93.8%) of 129 clinical isolates and 30 (35.3%) of 85 environmental isolates (P less than 10(-9)). Of the eight patients infected with L. pneumophila not recognized with monoclonal antibody 2, seven were immunocompromised; only 46.3% of the 121 patients infected with L. pneumophila reactive with monoclonal antibody 2 were immunocompromised (P = .02). We conclude that monoclonal antibody 2 can be used as a marker for the more virulent strains of L. pneumophila serogroup 1.