Chronic Q fever. Ninety-two cases from France, including 27 cases without endocarditis.

OBJECTIVE: Chronic Q fever is seldom recognized; before 1989, only 234 cases had been reported in the literature. The 92 cases of chronic Q fever collected at the French National Reference Center for Rickettsioses from 1982 through 1990 represent the largest series ever reported. PATIENTS: The patients included in the study were diagnosed between July 31, 1982, and August 1, 1990, at the French National Reference Center for Rickettsioses as having chronic Q fever by the following criteria: presence of antibody against Coxiella burnetii phase I antigen at a titer greater than or equal to 800 for IgG and 50 for IgA by the indirect immunofluorescence test. Epidemiologic, clinical, laboratory, and treatment data were collected from 39 different collaborative hospitals throughout France. MAIN OUTCOME MEASURE: For each serologically selected patient, a computerized questionnaire was utilized to record 188 different items of demographic, epidemiologic, clinical, laboratory, and therapeutic data, which were analyzed. RESULTS: Chronic Q fever occurs more frequently in city dwellers than in rural inhabitants, and exposure to domestic ruminants and raw milk is an important feature. Immunocompromising conditions (20.2%) and underlying heart disease (88.4%) or vascular disease are the most important risk factors to consider in potential cases of chronic Q fever. The mortality in these patients with endocarditis was high (23.5%). The clinical spectrum of 84 patients included 57 cases of endocarditis, three cases of vascular prosthesis infection, three cases of aneurysmal infection, three cases of osteoarthritis, four cases with lung localizations, nine asymptomatic cases, three cases of hepatitis, and two cases with cutaneous forms of the disease. CONCLUSIONS: In patients with unexplained fever, negative blood cultures, and a history of underlying vascular or cardiac disease, Q fever should be considered.

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.

Change in transaminases in hepatitis C virus- and HIV-coinfected patients after highly active antiretroviral therapy: differences between complete and partial virologic responders?

Patients with HIV and hepatitis C virus (HCV) coinfection have more severe hepatitis-related disease than do patients with HCV infection alone. Highly active antiretroviral therapy (HAART) with protease inhibitor appears to restore pathogen-specific immune responses, especially in patients with persistent undetectable HIV viral load. To evaluate the potent impact of immune restoration induced by HAART on the course of HCV-related disease, HCV viremia and levels of transaminases were compared between two groups of patients: 10 HIV/HCV-coinfected patients with persistently undetectable HIV viremia (group A) and 12 HIV/HCV-coinfected patients with persistent detectable HIV viremia. No difference was detected in HCV viral load in either group. An increase in transaminases was found only in patients with persistent undetectable HIV viral load, which was correlated with the increase in CD8+ T cells. This may suggest that the restoration of CD8+ T cell cytotoxicity could lead to an enhancement of hepatitis C-related disease in HCV/HIV-coinfected patients receiving HAART.

Chronic Q fever: diagnosis and follow-up.

Sera from 40 patients (25 men, and 15 women) with clinical features compatible with the diagnosis of chronic Q fever were received. Total or partial clinical data were available. All of them had serological evidence of chronic Q fever (IgG class anti-phase I titer greater than 800). The final diagnosis was vascular infection in four cases (with two positive cultures for Coxiella burnetii), bone infection in two patients (one positive culture), chronic hepatitis in one patient, and endocarditis in 32. The last patient had an isolated fever with a chronic Q fever serologic profile. Among the 32 with endocarditis, valve replacement was performed in 59%, and valve cultures were positive in 14/18 patients. Twenty-nine of these patients had previously known valvulopathy; 23 were exposed to cattle, sheep or goats; and four had an immunocompromised situation. Ten patients died; two before any treatment, five of cardiac failure during or a few weeks after surgery, and three during the medical treatment. For antibiotic treatment, tetracycline alone was employed in seven cases. For the other patients, combined therapy including tetracycline and another drug (rifampin, fluoroquinolones, cotrimoxazole, or erythromycin) was initiated. Three patients were considered to be completely cured.

The polymerase chain reaction for the detection of HIV-1 genomic RNA in plasma from infected individuals.

HIV (human immunodeficiency virus) viraemia in serum or plasma of HIV-infected individuals was investigated by the polymerase chain reaction assay (PCR) in combination with reverse transcription to detect HIV-1 genomic RNA. Before PCR, plasma or serum was ultracentrifuged, precipitated virions were then treated with a RNase-free DNase, and a cDNA from the HIV-1 genomic RNA was synthesized. Thirty-three fresh plasma and seven sera from either HIV-1 antibody-positive individuals or patients treated with AZT were tested. Plasma from three patients were assayed 3 or 6 months apart. Twelve sera from HIV-1 antibody-negative individuals were used as negative control. PCR was performed with primers in LTR, gag and env regions: 11 of 40 samples were positive with three primer pairs, 16 with two primer pairs and 11 with only one primer pair. PCR on HIV-1 genomic cDNA was positive in 38 out of the 40 plasma or serum samples (95%), regardless of the clinical stage of the infection: HIV-1 was detected in 14 of the 15 untreated subjects and in 24 of the 25 AZT-treated patients. HIV p24 antigen was detected in the serum of 38% of subjects (15 of 40). The results suggest that this method is suitable for the detection of viral particles in plasma or serum from HIV-1-infected individuals irrespective of antiviral treatment.

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.

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.

[Study of a brucellosis epidemic in a horticultural school]. / Etude d'une épidémie de brucellose dans une collectivité scolaire horticole.

An epidemiological survey was conducted after the observation of 4 cases of acute brucellosis in an horticultural school. Of a total number of 215 attendants, eventually exposed to a single contamination, 65 cases of brucellosis were thus identified. The source of contamination was probably a practical lesson where the pupils studied a bovine gravid uterus. More stringent regulations are needed in order to avoid further similar epidemics.

[Clinical trial of an antipneumococcal vaccine in elderly subjects living in institutions]. / Essai clinique du vaccin antipneumococcique chez des personnes âgées vivant en institution.

Pneumococcal vaccine effectiveness was assessed in a randomized trial among 1,686 old people (mean age: 74, standard deviation: 4 years) living in 24 geriatric hospitals and 26 homes for the aged in our district; 937 were vaccinated with Merck-Sharp and Dohme pneumococcal vaccine (14 serotypes). The 749 others composed the reference group. This study was performed during 2 years, since December 1980. Both groups were randomized after a two-criteria stratification: by clinical risk assessed before the study, and by type of homes for the aged. Forty pneumonias were diagnosed, with 13 proved pneumococcal etiology. The incidence of pneumonia was significantly reduced in the vaccinated group (p less than 10(-4) but the mortality rate was not modified. We concluded in favor of the effectiveness of pneumococcal vaccine: etiological fraction 77.1% (51.2%-89.3% confidence limits, 95% risk) in the population we studied. The incidence of pneumococcal-proved pneumonia was not significantly reduced.

[Human salmonellosis and turtles in France]. / Salmonelloses humaines en rapport avec les tortues aquatiques dans le déparement de l'Isère.

Two immunosuppressed children were infected with Salmonella, due to turtles living in water. So we investigated the carriage of Salmonella among those animals. Among the 95 investigated animals, 10 were carrying Salmonella (Arizonae, Rissen, Pomona and Blockley). The water of 6 containers out of 20 contained Salmonella. Comparing our data to others in the litterature, we conclude that human salmonellosis, acquired from turtles are not, by now, a major problem in France. Nevertheless, a number of those animals are carrying Salmonella. So an epidemiological survey is necessary, and immunosuppressed patients should avoid contact with those animals.

[Treatment of Listeria monocytogenes meningoencephalitis with cotrimoxazole in monotherapy]. / Traitement des méningo-encéphalites à Listeria monocytogenes de l'adulte par le cotrimoxazole en monothérapie.

L. monocytogenes meningo-encephalitis are still a therapeutic problem, with most of the time a poor prognosis. In vitro, cotrimoxazole has about the same bactericidal activity as the ampicillin-aminoglycoside combination. So we treated 8 patients with L. M. meningoencephalitis with cotrimoxazole alone, with a mean duration of treatment of 13 days. All patients recovered without sequellae from their infectious episode.

[First intention treatment with josamycin in primary acute pneumopathies of infectious origin in adults]. / Traitement de première intention par josamycine au cours des pneumopathies aiguës primitives d'origine infectieuse chez l'adulte.

In a prospective study 128 community acquired pneumoniae were treated with a macrolide (josamycin) by oral route. Patients improved in 94 p. 100 (113). Complications were as following: 2 deaths, 2 sequels, 3 failures. Authors discuss macrolides effectiveness in acute pneumoniae, particularly pneumococcal ones. They conclude macrolides are a good choice in first intention in acute pneumoniae of adults.

[Spinal leptomeningeal tumor spread disclosing a pineocytoma]. / Essaimage tumour leptomeninge spinal révélateur d'un pineocytome.

A 39-year-old female was admitted to the hospital because of a sudden meningeal syndrome followed by diplopia, cervical, dorsal and sciatic nerve pains, and right peripheral facial palsy. Cerebrospinal fluid obtained by lumbar puncture showed a protein level at 23 g/l. Myelography and magnetic resonance imaging (MRI) were in favor of a lumbar arachnoiditis. A meningeal biopsy revealed a tumour infiltration with foci of cells that were stained with anti-glial fibrillary acidic protein antibody. Cerebral MRI was performed to search for a central nervous system (CNS) primary tumour, and disclosed a pineal mass. Five months after the onset of the disease, the patient worsened her clinical state and died. Necropsy confirmed the presence of a pineocytoma with astrocytic differentiation and diffuse leptomeningeal spread. This exceptional occurrence leads us to discuss about primary tumours of the CNS with leptomeningeal spread.

[Economic benefit of using antibiotics prophylactically in cesarean sections with little risk of infection]. / Bénéfice économique de l'antibioprophylaxie dans les césariennes dépourvues de haut risque infectieux.

A randomised double trial was carried out in 266 women who had Caesarean without any high risk of infection in order to study the efficacy of prophylactic antibiotics given during the operation. One group received 1 gram of cefotetan when the cord was being clamped and the other had an injection of placebo under the self-same conditions. Apart from studying the clinical efficacy, evaluation of the economics of the treatment was carried out using, as parameters, the length of stay in hospital and the cost of the antibiotics which were prescribed after the operation. The following results were obtained: 75% of the Caesarean operations carried out in the Maternity Units of the University Regional Hospital Centre were without high risk of infection. Prophylactic antibiotics are proficient because they reduce post Caesarean morbidity due to: endometritis, superficial and deep abscesses and septicaemia. 12.5% in the group who had antibiotics developed infections as against 26% in the placebo group. Post Caesarean infections which required antibiotics cost on an average for each Caesarean 16 francs in the groups who received antibiotics as against 52 francs in the groups that received the placebo. Even including the cost of the antibiotics given prophylactically the costs of antibiotics (prophylactic and curative) was higher in the antibiotic group than in the placebo group. The length of hospital stay was significantly reduced in the group that received prophylactic antibiotics.

[Cytomegalovirus infection in pregnant women. Seroepidemiological prospective study in 1,018 women in Isere]. / Infection à cytomégalovirus chez la femme enceinte. Etude séro(-)épidémiologique prospective chez 1,018 femmes en Isère.

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.

[Visceral localizations of cat-scratch disease in an immunocompetent patient]. / Localisations viscérales de la maladie des griffes du chat chez un sujet immunocompétent.

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.

[Cerebral and pulmonary miliary tuberculosis in an immunocompetent patient: aggravation in an adequately treated patient]. / Miliaire tuberculeuse cérébrale et pulmonaire chez un patient immunocompétent: aggravation sous traitement adapté.

BACKGROUND: Extrapulmonary localizations are observed in 20% of tuberculosis cases, mainly in immunosuppressed patients. Prognosis is poor in case of relatively uncommon cerebral localizations and miliary dissemination, especially if treatment is initiated in late stages. We report a case of disseminated tuberculosis associated with cerebral and pulmonary localizations in an immunocompetent patient. THe disease progressed despite adapted treatment. CASE REPORT: A young immunocompetent man with an uneventful history developed miliary tuberculosis with pulmonary localizations visualized on the computed tomography (CT) of the thorax. Brain CT was normal, but magnetic resonance imaging revealed several intracranial lesions. The disease course was marked by development of neurological symptoms and progression of the cerebral lesions after one month of treatment. No evidence of therapeutic failure (insufficient dosing, non-compliance, primary resistance) could be identified. DISCUSSION: Magnetic resonance imaging provides a more precise evaluation of tuberculosis lesions in the brain. Early antituberculosis therapy associated with corticosteroids can improve prognosis. Clinicians should be aware that cerebral lesions may continue to progress despite appropriate treatment, a course which is not satisfactorily explained by any current pathogenic hypothesis.

[Neuromeningeal listeriosis in adults. Clinical aspects and contribution of cotrimoxazole in monotherapy]. / Listériose neuroméningée de l'adulte. Aspects cliniques et apport du cotrimoxazole en monothérapie.

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.

[Hepatitis C virus infection in internal medicine and infectious diseases departments in France. Preliminary results of a national epidemiological survey]. / Infection par le virus de l'hépatite C dans les services de médecine interne et les services de pathologie infectieuse en France. Résultats préliminaires d'une enquête épidémiologique nationale.

OBJECTIVES: In order to know the number and the main clinical features of patients with hepatitis C virus (HCV) infection, we conducted a national epidemiological study of patients followed in Internal Medicine and in Infectious Diseases departments in France. METHODS: For each patient with HCV infection seen between 13/03 and 13/04/1995 (in- or out-patients), a chart was completed. RESULTS: The response rate was about 30% with 2002 charts being analyzed. There were 59% males and 39% females, with a peak of frequency between 25 and 40 years, including 1241/2002 (62%) patients. Most patients were of French origin (85.7%). We found that 1436/2002 (72%) patients came from provinces of southern France and Paris. In 10% of cases the diagnosis was made during the study period. A route of transmission was identified in 86.4%, mainly drug abuse 60.4% and blood product transfusion 19.3%. At the time of diagnosis, main clinical features were: no symptom 47%, liver biological abnormalities 52%, cirrhosis 7.4%, cryoglobulinemia 2.7%, auto-immune disease 3%, hepatocellular carcinoma 0.85%. We frequently found a viral co-infection: HIV 56.1%; HBV 22.2%. A confirmation RIBA test was done in 67.8%, measurement of viremia in 33.4%, genotyping in 6.7% and liver biopsy in 28.7% of cases. Finally, 407 (20.3%) patients received a specific anti-HCV treatment. CONCLUSION: These preliminary results underscore: 1) the large percentage of the population with HCV infection followed outside of hepatogastroenterology departments in France. 2) the high probability that the HCV epidemic is underestimated as we noted 10% of new diagnosis during the study period. 3) the requirement for a multidisciplinary approach for these HCV patients.

[Experience with an "isolation unit" for patients infected with multi-resistant bacteria. Retrospective study of 49 patients]. / Expérience d'une "unité d'isolement" dans la prise en charge de patients porteurs de bactéries multirésistantes. Etude rétrospective sur 49 patients.

OBJECTIVES: Perform a retrospective analysis of care in a hospital "isolation unit" for patients infected with multirestant bacteria (MRB), i.e. meticillin-resistant staphylococcus aureus (SAMR), broad spectrum beta-lactamase secreting enterobacteria. (BLSE). PATIENTS AND METHODS: Forty-nine patients infected with MRB were cared for in our hospital isolation unit between January 1, 1996 and January 1, 1997. Each patient was in a separate room equipped with a sink and soap distributor, single-use towels, and individual material for patient care (stethoscope, mobile equipment, writing material, etc.). The personnel were given special training in the prevention of nosocomial infections. At admission, and in all patients, bacteriological samples to search for SAMR were acquired from nasal discharge, urine, perineal swabs, wounds and bed sores. Wound, urine and fecal samples were also taken to search for BLSE. Search for other sites of infection depended on the clinical situation. The management protocol in the isolation unit included: isolation, daily antiseptic baths, topical application of antibiotics or antiseptics on all bacteriologically proven sites of SAMR infection, selective decontamination of the digestive tract for patients with BLSE positive stools. Systemic antibiotics were given case by case. RESULTS: Mean duration of stay in the isolation unit was 17 days for SAMR infections and 14 days for BLSE infections. Mean delay to sterilization of the infected sites varied depending on the localization: 2.3 days for blood and 19.4 days for stools. Seven patients died. After leaving the isolation unit, the bacteriological course was followed in 23 patients: there were 7 cases of recurrence at least one site within a mean delay of 34.5 days. CONCLUSION: Use of isolation units provides an interesting solution for health care centers to control spread of multiresistant bacteria. Considering the endemic state of multiresistant bacteria infections in French hospitals, each health care unit should have correctly equipped facilities for isolating infected patients.