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AQFThe authors present the guidelines of the French Society of ENT and Head and Neck Surgery (SFORL) regarding the management of Bell's palsy in adults. After a literature review by a multidisciplinary workgroup, guidelines were drawn up based on retrieved articles and group-members' experience, then read over by an independent group to edit the final version. Guidelines were graded A, B, C or "expert opinion" according to decreasing level of evidence. Thorough ENT and neurological clinical examination is recommended in all patients presenting with peripheral facial palsy to confirm diagnosis of Bell's palsy. MRI with gadolinium enhancement should explore the entire course of the facial nerve, if possible within the first month. ENMG should be performed to assess prognosis for recovery. In confirmed Bell's palsy, corticosteroid therapy should be implemented as early as possible (ideally within 72h) at a dose of 1mg/kg/day for 7-10 days. Antiviral therapy should be associated to steroids in patients with severe and early-onset disease and in Ramsay-Hunt syndrome. Isolated antiviral therapy is not recommended. To date, there is no evidence that surgical facial nerve decompression provides benefit.

Background Treatment of hookworm-related cutaneous larva migrans (HrCLM) with a single dose of oral ivermectin has not been adequately evaluated to date. Response rates reported in three large studies varied from 77% to more than 95%. Objectives We evaluated the efficacy of ivermectin in the treatment of HrCLM. Methods We retrospectively studied all returning travellers with HrCLM who consulted in our institution. Patients were then treated with a single, 200 μg/kg dose of ivermectin, orally. Results Sixty-two travellers (35 female, 27 male, mean age 35.6 years) with HrCLM and creeping dermatitis were included. Six patients (10%) also had associated hookworm folliculitis. Fifty-nine patients (95%) completely responded with one ivermectin dose. The response rate was 98% in the 56 patients presenting with only creeping dermatitis and 66% in the six patients presenting with additional hookworm folliculitis (P = 0.02). Conclusion The efficacy of a single dose of oral ivermectin is higher in patients with only creeping dermatitis than in those with associated hookworm folliculitis.

Oxidative stress is now recognized as accountable for redox regulation involving reactive oxygen species (ROS) and reactive nitrogen species (RNS). Its role is pivotal for the modulation of critical cellular functions, notably for neurons astrocytes and microglia, such as apoptosis program activation, and ion transport, calcium mobilization, involved in excitotoxicity. Excitotoxicity and apoptosis are the two main causes of neuronal death. The role of mitochondria in apoptosis is crucial. Multiple apoptotic pathways emanate from the mitochondria. The respiratory chain of mitochondria that by oxidative phosphorylation, is the fount of cellular energy, i.e. ATP synthesis, is responsible for most of ROS and notably the first produced, superoxide anion (O(2)(;-)). Mitochondrial dysfunction, i.e. cell energy impairment, apoptosis and overproduction of ROS, is a final common pathogenic mechanism in aging and in neurodegenerative disease such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Nitric oxide (NO(;)), an RNS, which can be produced by three isoforms of NO-synthase in brain, plays a prominent role. The research on the genetics of inherited forms notably ALS, AD, PD, has improved our understanding of the pathobiology of the sporadic forms of neurodegenerative diseases or of aging of the brain. ROS and RNS, i.e. oxidative stress, are not the origin of neuronal death. The cascade of events that leads to neurons, death is complex. In addition to mitochondrial dysfunction (apoptosis), excitotoxicity, oxidative stress (inflammation), the mechanisms from gene to disease involve also protein misfolding leading to aggregates and proteasome dysfunction on ubiquinited material.

Objective . – To determine if asymptomatic stable chronic hyperlactatemia in human immunodeficiency virus (HIV)-infected patients under highly active antiretroviral therapy (HAART, including nucleoside analog reverse transcriptase inhibitors (NRTI)) could be improved by antioxidant supplementation. Design . – To match two groups of patients taking NRTI for at least 24 months: 15 without and 15 with antioxidant supplementation (vitamin E, β-carotene, N -acetylcysteine, selenium, Gingko biloba extracts and nutritional supplements). For both the groups, the supplementation by antioxidants or its lack was carefully assessed. Venous lactatemia, blood oxidative stress markers (plasma lipid peroxidation, enzymatic and non-enzymatic antioxidants), CDC revisited classification, CD4 count and viral load, NRTI (with or without stavudine) and other antiretroviral drugs used, lipoatrophy, central fat accumulation were assessed. Results . – Patients were not statistically different with respect to the CDC classification, CD4 count, viral load and characteristics of antiretroviral therapy. Blood oxidative stress markers, i.e. vitamin E, vitamin A and β-carotene tended to be higher in the supplemented group. The difference observed in venous lactate concentration between the two groups was significant (1.37 ± 0.10 vs. 1.82 ± 0.19 mmol/l in the supplemented and non-supplemented groups, respectively P = 0.04). Conclusion . – Antioxidant supplementation improves the asymptomatic stable chronic hyperlactatemia observed in HIV-infected patients taking HAART including NRTI for a long time. Controlled studies are needed to demonstrate the efficacy of this supplementation on mitochondrial toxicity observed during HAART and the possible usefulness of its combination with mitochondrial cofactors like carnitine, riboflavine, coenzyme Q, α-lipoic acid.

Septic arthritis due to Mycobacterium kansasii is rare; only 40 cases have been published. A French national inquiry revealed the occurrence of 10 new cases between 1992 and 1997 (8 men and 2 women: mean age, 37 years; range, 25-54 years). Seven had an underlying condition: AIDS (n = 4), chronic skin psoriasis and AIDS (n = 2), or a renal transplant (n = 1). Trauma to the joint, use of intra-articular corticosteroid(s) I month to 2 years after the event, and chronic skin psoriasis were risk factors. The mean interval between appearance of the first symptoms of arthritis and the diagnosis was 5 months. Monarthritis was localized to the knee (n = 4), wrist (n = 3), finger (n = 1), elbow (n = 1), or ankle (n = 1). The main diagnostic procedure was culture of a synovial biopsy specimen. In all cases, debridement was associated with antimycobacterial treatment. Three patients died of AIDS during treatment, and another is still undergoing treatment; the other 6 patients were cured. M. kansasii infection should be considered in all cases of indolent arthritis with any of the following risk factors: local trauma, local or systemic corticosteroid therapy, chronic skin psoriasis, and immunodepression, especially that due to human immunodeficiency virus infection.

We report a case of box-jellyfish related envenomation in a 40 year old tourist that occurred in Sihanoukville, Cambodia, in the Gulf of Thailand. Symptoms that appeared within a few minutes associated intense pain, hand edema and large edematous and erythematous flagellations in the stung skin areas. Antibiotics and corticosteroids were delivered. Inflammatory signs and skin lesions disappeared within 15 days followed by crusts then scars. Jellyfish at risk for humans are generally found in tropical seas and their geographic distribution seems to spread. As it is difficult to prevent this kind of accident, travelers should be aware of the first acts to perform, such as appropriate cleaning of the wound, the interest of vinegar usage, the administration of analgesics and corticosteroids in case of significant inflammatory signs.

The emergence of multi-resistant bacteria (MRB) in developing countries (DCs) is a worrying phenomenon at regional and international levels with a risk of international spread through travelers. The French guidelines recommend a systematic screening in case of hospitalization, for the travelers who have been repatriated and for those with a history of hospitalization in a foreign country during the past year. A simple travel in DCs is not considered as a risk factor for colonization or infection with a MRB. We report the case of a 56-year-old man with acute prostatitis and epididymitis due to Extended-spectrum β-lactamase-producing Escherichia coli. He was returning from Southeast Asia with no history of hospitalization or recent use of antibiotics. However, he had unprotected sex during his travel. This case report leads us to discuss the different ways of acquiring this resistant bacterium during travel as well as the usefulness of expanding the screening of carriage for MRB in all travelers in case of hospitalization.

Ecthyma gangrenosum (EG) starts as an erythematous or purpuric macule, papule or plaque that develops into a haemorrhagic bulla, which becomes a necrotic black sore. EG is usually a cutaneous manifestation of Pseudomonas aeruginosa infection but other microbial agents can be involved.Four patients (three women and one man, mean age: 36 years) with fever and cutaneous black sores characteristic of EG were hospitalized. Three were cardiac transplant recipients treated with immunosuppressant drugs and one had end-stage acute myeloid leukaemia. All had cutaneous necrotic black sores. Blood cultures isolated in one case P. aeruginosa and Candida albicans. Bacteriological culture of cutaneous swabs from necrotic lesions revealed C. albicans and P. aeruginosa in two cases, respectively. The cutaneous black sores healed with appropriate antimicrobial treatment. Three patients were cured but the patient with leukaemia died despite therapy.These four cases illustrate the clinical polymorphism of EG and the broad spectrum of aetiologies. While EG is primarily considered a cutaneous manifestation of P. aeruginosa infection, other microbial agents such as C. albicans may be responsible, as in two of our cases.

Between 1983 and 1989, we cared for 56 patients with tuberculosis and human immunodeficiency virus (HIV) infection. In 37 patients (66%), tuberculosis occurred before any other AIDS-defining disease (group 1); in 10 (18%) it occurred during the same month as another AIDS-defining disease (group 2); and in 9 (16%), after the diagnosis of AIDS (group 3). Tuberculosis was entirely pulmonary in 14 patients (25%), entirely extrapulmonary in 9 (16%), and both pulmonary and extrapulmonary in 33 (59%). The frequency of extrapulmonary involvement was similar in patients from group 1 and from groups 2 and 3 (combined): 76% versus 74%. Needle biopsy of the liver revealed hepatic involvement in 18 patients (32%). The mean CD4 lymphocyte count was 232/mm3 when tuberculosis was entirely pulmonary, and 243/mm3 when extrapulmonary disease was present (difference not significant). In group 1, the onset of both pulmonary and extrapulmonary tuberculosis occurred at the same stage of HIV infection, 12 and 10 months, respectively, before any other AIDS-defining disease. Treatment, planned to last 1 year, was highly effective, despite frequent side-effects. Among the 32 patients who completed treatment, relapse of tuberculosis occurred in 2 (6%) with a mean follow-up of 16 months (0-53 months) after completion. Our results suggest that pulmonary tuberculosis should be included in the criteria for diagnosis of AIDS.

We report the case of a retroviral rebound syndrome associated with parotid gland enlargement in a chronically HIV-infected man.

Human African trypanosomiasis (sleeping sickness), an endemic disease, is currently reemerging in Africa with an estimated incidence of 45,000 new cases per year. It is caused by Trypanosoma brucei subspecies and transmitted by day-biting tsetse flies.We report a case of West African trypanosomiasis due to Trypanosoma brucei gambiense involving a Frenchman living in Libreville, Gabon. The patient presented with fever and polyadenopathies as well as two skin ulcerations highly suggestive of trypanosomiasis. Microscopic examination of cutaneous and peripheral blood smears confirmed the diagnosis of haemolymphatic infection with T. b. gambiense with trypanosomal chancres. Examination of the cerebrospinal fluid was normal. The patient was successfully treated with pentamidine isethionate.Recognition of cutaneous manifestations may allow a rapid diagnosis of African trypanosomiasis that is essential for timely and efficient treatment and survival.

Tuberculosis (TB) is frequent in human immunodeficiency virus (HIV) infected patients, but its treatment is hampered by adverse events and paradoxical reactions.To examine the impact of HIV infection and other factors on the risk and spectrum of adverse events related to anti-tuberculosis treatment in a prospective cohort study conducted between January 2003 and August 2004.Of 105 patients treated for TB, 30 were HIV-infected. The overall incidence of adverse events was 122.5 +/- 18.5 per 100 patient-years (py) and the incidence of severe adverse events was 45.2 +/- 11.3/100 py. Age50 years (OR 2.2, 95%CI 1.01-4.8, P = 0.046) and HIV infection (OR 3.9, 95%CI 2.1-7.5, P0.001) were independently associated with a higher risk of adverse events. Hepatitis (30.5/100 py) and neuropathy (28.6/100 py) were the most frequent adverse events. Hepatitis C virus infection was associated with hepatitis (OR 4.2, 95%CI 1.2-15.0, P = 0.028) and neuropathy with HIV infection (OR 3.8, 95%CI 1.1-13.7, P = 0.040).Adverse reactions to anti-tuberculosis drugs are frequent. HIV infection and age50 years are factors associated with such reactions, while hepatitis C virus infection is a risk factor for hepatitis.

Quantitative monitoring of human cytomegalovirus (HCMV) is currently used in the follow-up of immunosuppressed patients.To investigate whether real-time PCR quantification (QPCR) of HCMV DNA could replace pp65 antigenemia.We compared HCMV QPCR on whole blood (WB) and on plasma with a pp65-antigenemia assay on 192 samples. Afterwards, we tested 1310 samples from 308 immunosuppressed patients both by antigenemia assay and QPCR on WB.The first study comparison showed that QPCR results on WB and plasma were significantly correlated with antigenemia. QPCR on WB was more sensitive than QPCR on plasma or antigenemia, detecting 31 and 49 additional positive samples, respectively. During the second comparison, QPCR on WB and antigenemia were again correlated (r=0.70; p0.0001), but QPCR detected 244 additional positive samples. HCMV DNA was detected earlier than pp65 antigen (median difference: 14 days; range: 7-30). One, 5, 10, 50 and 100 pp65-positive cells/200,000 leukocytes corresponded to 439, 1531, 2623, 9150 and 15,671 HCMV DNA copies/mL of WB, respectively, but this equivalence differed according to the sub-group of patients considered.QPCR on WB is the most sensitive method for the monitoring of HCMV infection in immunosuppressed patients.

We prospectively studied the prevalence and the clinical forms of adverse cutaneous reactions associated with the main antiseptics used in France, the incidence of which is not well known.Patients were included by 773 French dermatologists from May to June 2003. The 8 first consecutive adult patients for whom ambulatory treatment with a cutaneous antiseptic was prescribed were included. Patients were evaluated at inclusion and after treatment, either in person or by telephone. All reported adverse cutaneous reactions were validated by two independent experts.3,403 patients (61% women, 39% men; mean age: 47) were included. Antiseptics were indicated for ambulatory surgery (45%), technical procedures (33%), and in combination with other treatments for various dermatoses, wounds and burns (12%). The 6 most widely used treatments (96% of prescriptions) were hexamidine (37%), chlorhexidine-benzalkonium (28%), chlorhexidine-alcohol (16.5%), aqueous chlorhexidine (7%), polyvidone iodine (6%) and hexamidine-chlorhexidine (1.8%). The antiseptic was prescribed for application by dabbing (57%) or spraying (40%), twice daily for a mean 10 days (3-30 days). A transient burning sensation was noticed by 4 to 7% of the patients, without any significant difference between antiseptics. Twelve adverse events were reported: contact dermatitis in 9 patients, persistent burning sensation in 2 and yellow discoloration of the skin in one. This latter case, caused by the colour of the antiseptic, cannot be considered as an adverse event. Furthermore one patient with contact dermatitis should have not been included because he had a history of cutaneous reaction related to the use of the same antiseptic. Therefore only 10 cutaneous reactions were eventually taken into account (overall prevalence=2.9 per thousand, ranging from 0% to 0.5% according to the antiseptic). There was no significant difference in terms either of the antiseptic used or the site of the treated lesion. A history of contact dermatitis was associated with a significant risk of adverse reaction (OR=7.2; CI 95: 2.0-26.4; p=0.007). The median time from onset of treatment to appearance of contact dermatitis was 4 days (0-90 days). The condition resolved following discontinuation of treatment; spontaneously in 5 patients and with dermocorticoid therapy in 5 others.The results of this study give a precise idea of how the antiseptics are used by French dermatologists in clinical practice in outpatients and how often their use is complicated by the occurrence of adverse cutaneous reactions. The low rate of such reactions (2.9 per thousand) in our study is thus in contrast with the impression given by the large number of publications related to this complication. It also tempers the high rates of sensitisation to various antiseptics found in selected at-risk patients. The most common adverse event observed was contact dermatitis and a history of this condition conferred a significant risk of cutaneous reaction.Although cutaneous antiseptics are well tolerated with a low prevalence of adverse reactions, generally mild, they should nevertheless be prescribed with caution in patients with a history of contact dermatitis.

Bioterrorism is defined by the intentional or threatened of microorganisms or toxins derived from living organisms to cause death or diseases in humans, animals or plants on which we depend. The other major point is to generate fear in the population. More than 180 pathogens have been reported to be potential agents for bioterrorism. The following is an overview of several agents that could be involved in a biological attack.

Schistosomiasis is a tropical helminthic infection, observed in travelers as well as local populations. It is most often due to Schistosoma mansoni or Schistosoma haematobium and can be diagnosed at the invasive phase. Migration of the schistosomulae (larvae) in the body leads to acute parasitic toxemia, which includes a hypersensitivity reaction and circulating immune complexes. The invasive stage occurs generally 2 to 6 weeks after the exposure and combines fever, asthenia, faintness and headaches. Other signs include diarrhea, dry cough, dyspnea, urticarial rash, arthralgia, myalgia, and enlargement of liver and spleen. Although rare, neurological and cardiac complications may be fatal. This diagnosis should be considered in travelers returning from the tropics with compatible clinical signs and delayed hypereosinophilia, if they report exposure in an endemic area. It is later confirmed by seroconversion for schistosomiasis and then by observation of schistosome eggs in stool or urine (according to species). The standard treatment of acute schistosomiasis with praziquantel is ineffective and can aggravate clinical outcome during this phase. Corticosteroid treatment is recommended for serious forms with neurological or cardiac manifestations.

The use of the smallpox virus as a biological weapon is very old. Confronted with a high probability of a current bioterrorist menace, counteracting strategies have been developed. One of the principle aims relies on the vaccination of teams dedicated to the management of persons infected and the stocking of vaccine for the whole population of a country. Following worldwide eradication of the disease, preventive vaccination was topped in 1978 in France for the primo-vaccination, and in 1984 for repeat vaccinations. The various strains used in the first generation vaccinations are weakened living vaccine, the natural host and origin of which is unknown. Second and third generations vaccines are under study; the principle objective is to obtain efficacy with a minimum of side effects. There are two types of adverse events, generally observed with the first generation vaccines: the first, extremely rare, can be life-threatening; the others, more frequent (10 to 15% of patients) are benign. In emergency situations, in the presence of smallpox, there should be no absolute contraindications to vaccination. In the bioterrorist context, massive vaccination campaigns of the population are unadvisable (because of the considerable risk of death and severe adverse events) in the absence of any real permit, in each case, definition of the vaccinal strategy to be adopted.

Acute schistosomiasis, called safari's fever in Africa and Katayama fever in Japan, is an immunoallergic reaction due to transcutaneous penetration of infective cercaria. We report the collective case of seven young adults spending holidays in Mali.An eighteen years-old girl presents fever, headache, diarrhoea and abdominal pains at return from Dogon country (south of Mali). After turned down malaria and with the notion of bathing in fresh water followed by pruritus, we think to safari's fever. So we alarm all other members of the group. All can be treated to avoid chronic schistosomiasis.These observations recall that acute schistosomiasis is a real danger for tourists when bathing in fresh water in endemic areas of Africa. Education of travellers is necessary. Occurrence of safari's fever should alert physicians to prevent chronic schistosomiasis.

Stonefish (Synanceja verrucosa) sting has been known for a long time to be a medical hazard. It is a common cause of severe marine envenomation. Immediate complications (collapsus, pulmonary oedema) have been described extensively. Late complications (oedema, tissue necrosis) have not been studied in details although they are common and a cause of invalidity and pain. We have observed six travellers with complications of stonefish sting over a 10 year-period in our department. All the patients were coming back from the Indo-Pacific maritime region. They presented with cutaneous abcess (in one) or necrotic complications (foot ulcers in two, cellulitis in three) associated with painfull oedema in two and lymphangitis in three. Surgery has been performed in four patients, two of them undergoing many operations. Two had long term sequelae. Such complications could be avoided. Appropriate initial treatment (i.e., neutralization of the venom by hot water, disinfection, antivenom and antibioprophylaxis) seems to be able to reduce late complications. Antivenom is indicated in severe systemic manifestations which are life threatening and in case of crucial pains. Prevention is the most important part of therapy and relies on appropriate information of the travellers.

Lymph node tuberculosis is the most frequent form of extrapulmonary tuberculosis, especially in immunocompromised patients. We have studied patients with proven lymph node tuberculosis in the Department of Infectious Diseases at Pitié-Salpêtrière Hospital, Paris, between January 1997 and January 2002. Clinical presentation, microbiological diagnosis and treatment were analyzed in 13 HIV infected and 19 non-HIV infected patients. A risk factor for tuberculosis was present in all cases (HIV infection, immigration, life in community, poverty, past history of tuberculosis and IVDU). The median duration between the onset of symptoms and diagnosis was longer for HIV infected (2 months) compared with non-HIV infected patients (1 month). At the time of the diagnosis, general symptoms were present in50% of patients of both groups. In HIV infected patients, abdominal lymph node involvement was more frequent (P0.05). All the non-HIV infected and 85% of HIV infected patients had peripheral adenopathies. A pulmonary tuberculosis was noted in more than half of the cases (53% non-HIV and 69% HIV patients). Inflammatory parameters and liver function tests were frequently abnormal in both groups. Hyponatremia was more frequent in HIV patients (P0.05). TB skin testing was more frequently positive and phlyctenular in non-HIV infected patients (P0.05). In this study, direct examination of the needle aspirate from infected lymph nodes was rarely positive; cultures were more frequently positive after biopsy compared to needle-aspiration. The median duration of treatment was 9 months for the two groups (6-24 months). Three HIV infected patients were infected by mycobacteria resistant to at least one antibiotic (isoniazid, 1; rifampicin, 1; isoniazid, streptomycin, etambutool, 1). All the patients recovered.

Résumé Propos et points forts. – Le syndrome respiratoire aigu sévère (SRAS) a récemment été reconnu comme étant associé à une infection virale émergente, hautement contagieuse et pouvant être mortelle. Actualités. – À fin juin 2003, plus de 8500 cas d’infections humaines et 800 décès ont été rapportés dans 30 pays. L’agent responsable de cette infection a été identifié comme étant un nouveau coronavirus. La présentation clinique, les anomalies biologiques et radiologiques, ainsi que l’évolution et le traitement des patients infectés par ce virus sont décrits dans cet article. Perspectives et projets. – La recherche de thérapeutiques efficaces et de vaccins est en cours d’évaluation.

Contrary to patients exhibiting cellular immunodepression, legionellosis is rare in HIV-infected patients. We report 4 cases.Four men aged 41 to 48 were infected by HIV-1. Three of them were treated with antiretroviral therapy. The clinical and biological manifestations were unspecific. Evolution was favourable with adapted antibiotic therapy (erythromycine for three patients and ciprofloxacine for the fourth).Legionella pneumophila serotype Lp1 remains the principle etiological agent. Frequent use of contrimoxazole in prophylaxis against pneumocystosis and toxoplasmosis, macrolides, rifamycines and fluoroquinolones in the preventive and curative treatment of mycobacterioses, and the relative conservation of monocyte/macrophage function and immune repair with efficient antiretroviral therapy, may explain the low prevalence of this disease in HIV infections.

Seven patients (four men, three women, mean age 31 years), all returning from the tropics, presented with pruritic folliculitis and creeping eruption. The folliculitis consisted of 20-100 follicular papules and pustules confined to a particular area of the body, mainly the buttocks. The creeping eruption consisted of two to 10 serpiginous or linear burrows 1-5 cm long located either in the same area or in a different area from the folliculitis. Five patients were cured with one to three courses of ivermectin (one course in two cases, two courses in two cases and three courses in one case) and two patients were cured with a 3-day regimen of albendazole. Folliculitis should be added to the dermatological manifestations of cutaneous larva migrans. Treatment is more difficult than in classical forms of cutaneous larva migrans.

OF NEW CLINICAL DEMONSTRATIONS: Since the use of HAART, morbidity and mortality in HIV-infected patients have decreased dramatically. But increased survival in these patients is associated with other diseases (malignant diseases, inflammatory reactions after initiation of HAART) and with drug toxicity (lipodystrophy, mitochondrial toxicity). TRANSMISSION AND REVELATION: Despite widespread information on HIV, new HIV-infected patients with an AIDS-defining illness are still detected. At present, heterosexuality is the most frequent risk factor for HIV-infection (51%). Pneumocystis pneumonia remains the most common opportunistic illness in HIV-infected patients (28%).

Q fever is a worldwide zoonosis but is not often a common cause of fever among travellers returning from the tropics. We report a case of acute Q fever, revealed by a pneumonia and acquired by a traveller in French Guyana. The chest radiography showed alveolar opacities and pleural effusion. Biological abnormalities were elevated liver enzyme levels and thrombocytopenia. The patient improved or the third day of antibiotic treatment. She mentioned that 3 other people she lived with during her trip had been diagnosed with Q fever. A common source outbreak was then suspected. They all stayed in the same farm in French Guyana. Animal exposure occurred there, in particular with a goat and a dog (both were parturient). The disease was probably transmitted by airborne dust to our patient, as no other vectors of transmission were found. Since the clinical presentation of Q fever is not specific, in order for the physician to diagnose it, he must have an awareness of the disease. Our case emphasised that looking for risk factors of Coxiella burnetii exposures is particularly important. Amongst them, the most important seems to be contact with farm animals. The clinician should thus try to trace such a possible contact when treating a case of traveler's Q fever.

To describe the epidemiological characteristics of primary central nervous system lymphoma (PCNSL) and the evolution of the incidence of this lymphoma in HIV-infected patients with a more than 17-year follow-up.Eighty cases of PCNSL were analyzed from a data base of 2,263 AIDS subjects followed from 1983 to 1999 (3.5% of the patients with AIDS). At the time of diagnosis, PCNSL was the first AIDS defining event in 36% of the cases, median CD4 count was 9/mm3 (0-134); 82% of the patients were given antiretroviral therapy (HAART = 0). Only eight cases of PCNSL were observed after 1996 (median HIV RNA level: 250,000 copies/mL (24,000-1,500,000)). The incidence was 39 per 100 patients-year in 1991 and decreased to 1.9 in 1999. At the end of the study, 78 patients had died (98%). The median survival was one month before 1996 ([0-27], n = 72), and was ten months after ([0-44], n = 8). Two patients were still alive 38 and 44 months after diagnosis. After 1996, survival was increased in patients with good response to antiretroviral treatment and in patients with high CD4 count at the moment of diagnosis.After the introduction of HAART (1996), the incidence of PCNSL has decreased drastically and survival was increased.

A COMMON SITUATION: Among HIV-infected patients treated with antiretroviral regimens, 20% to 50% escape therapeutic control. The principal factors predictive of treatment failure are low CD4 counts and high viral load prior to institution of the antiretroviral treatment. Several virological and pharmacological mechanisms are implicated.Genotyping is particularly useful to optimize treatment in HIV-infected patients who escape therapeutic control, irrespective of the therapeutic strategy. A committee of experts has developed a scheme for adapting treatment to the very complex results of genotyping tests. The benefit of phenotyping remains to be established.Serum concentrations of antiretroviral agents should be determined and adapted in order to maximize the treatment effect. However, to manage therapeutic escape, the only method with a proven impact is genotyping. The possible usefulness of regular drug assays for adjusting treatment doses in case of therapeutic escape remains to be assessed in prospective trials.

Advances in HIV/AIDS therapy have been rapid and profound.In developed countries the epidemic infection has stabilized and there are dramatic decreases in morbidity and mortality resulting from the use of intensive but expensive therapies. HIV patients who have detectable viral loads and/or evidence of immunologic dysfunction should be treated with a potent combination antiretroviral regimen. Currently, this consists of two nucleoside reverse transcriptase inhibitors with at least one protease inhibitor, or a non-nucleoside reverse transcriptase inhibitor, or another combination with adequate potency. Current therapies do have limitations, including side effects, cross-resistance, adherence challenges, and drug interactions.Drug resistance is a major factor contributing to the failure of antiretroviral therapy: the ability to predict clinical response to therapy on the basis of genotype and/or phenotype depends on knowledge of appropriate data for defining drug resistance. Moreover, careful selection and monitoring of combination drug therapy along with individualized rather than standard dosage regimens may minimize the pharmacological problems and help ensure optimum antiviral activity. Further developments include new drugs, vaccine, cytokine-, and gene therapy-based treatment strategies.

We report the case of a patient with leukocytoclasic vasculitis that disclosed active pulmonary tuberculosis. This patient had no signs of systemic vasculitis. The clinical course was favorable with anti-tuberculosis drugs alone. There has been no recurrence at 8 months. Vasculitis associated with tuberculosis is uncommon. The pathophysiological mechanism remains uncertain. No immunosuppressor treatment is needed and the vasculitis generally regresses with treatment of the infection.

Severe falciparum malaria usually occurs in nonimmune patients, namely children in endemic areas or travelers returning from tropical areas. It generally has one of two outcomes: rapid death or cure without sequelae. Neurologic sequelae have been reported in children but have not been described in detail in adults. The purpose of this study was to determine the clinical spectrum, neuroimaging aspects and long-term outcome of these sequelae. We describe six imported cases of severe malaria with neurologic sequelae in adults, seen in a Parisian university hospital over a 10-year period. The most striking findings were neuropsychological disorders, in particular memory impairment and diffuse white matter damage on magnetic resonance imaging. Only three of the patients had made a full recovery after 6 months.

IMMUNITY: The anti-infectious effect of the spleen in general and its anti-malarial effect has been known for a long time. This effect is associated, among other functions, with the spleen's capacity to filter and destroy erythrocytes parasitized by plasmodies or altered by various physical (heat...) or chemical factors. In addition, splenic immunity, which associates specific and nonspecific humoral and cellular effector mechanisms is no longer a question of debate.There remains nevertheless one aspect of the question to be elucidated: the probable interaction between this immunity and other (genetic...) factors of the malarious host. CELL FUNCTIONS: This article summarizes current knowledge in connection with: a) participation of various cell populations in the mechanisms of splenic filtration and phagocytosis and b) genesis of a repertory of B and T lymphocytes, plasmodio-specific memory cells. During an infection, lymphocytes, monocytes and macrophages are recruited from peripheral blood and, in cooperation with cells known as "barrier" cells, increase the capacity of splenic filtration/purge and phagocytosis. In addition, the appearance of B and T lymphocytes with specific memory of P. falciparum result from hypermutation in VH genes (for B lymphocytes) or from clonal selection (for T lymphocytes). The folicular dendritic cells accomplish a reserve function. By constantly releasing the antigen, these cells would contribute to maintaining immune memory or to stimulating naive cells. Further studies are necessary to better understand the role of the splenic microcirculation and to identify parasite components which stimulate the protective response of the spleen against plasmodies.

We have recently seen a worldwide explosion of infectious diseases: emerging diseases like the HIV/AIDS pandemic, or old diseases like cholera, tuberculosis, diphteria, plague, yellow fever, dengue, or malaria. These reemerging diseases are on the surge because of multiple factors: environmental changes, transformation of ecosystems, ongoing socioeconomic degradation and deterioration of public health systems in many countries. The increasing bacterial resistance to antibiotics or virologic resistance to antiviral drugs are becoming a serious problem today. This global danger needs a global response. There must be a cooperation between the different actors in the field of public health. The general practitioner should look for good therapeutic compliance, control vaccinations, and give his patients health education, including prevention of HIV and other sexually transmitted diseases.

The primary HIV infection is the period of time following HIV inoculation. Its manifestations are diverse. We present here some clinical cases: a mononucleosis-like syndrome with fever, angina, lymphadenopathy and skin rash, a frequent picture, with among other signs, flu-like symptoms, lymphocytic meningitis and facial paresis. In presence of those nonspecific clinical pictures, it is important for the primary health care physician to consider primary HIV infection, detect a history of exposure and order HIV-tests including p24-antigenemia. On one side, an early treatment blocks replication and dissemination of HIV in the body and brings an amelioration of prognosis. On the other side, the patient is particularly infectious during this phase and should take appropriate preventive measures.

NEURON DEATH: Major progress in our understanding of the pathophysiology of neurodegenerative diseases has greatly benefited from the convergence between work devoted to reactive oxygen species (including nitric oxide) and programmed cell death, or apoptosis, and exitotoxicity. LATERAL AMYOTROPHIC SCLEROSIS: The discovery of a mutation in the copper-zinc superoxide dismutase gene in patients with lateral amyotrophic sclerosis has made it possible to analyze the events leading to neuron death in transgenic mice. An overload of reactive oxygen species accelerates apoptosis and oxidative stress is implicated in excitotoxicity which is a hyperstimulation of excitatory amino acides (glutamate, aspartate) producing neuron death. OTHER CHRONIC CONDITIONS: Based on evidence from the mouse model, apoptosis, excitotoxicity and oxygenated free radicals could play a causal role in other neurodegenerative diseases including HIV-related encephalopathy, Parkinsonís disease and Alzheimerís disease.

Cerebrospinal fluid (CSF) and plasma HIV-1 RNA levels were prospectively measured by the Roche Amplicor Monitor polymerase chain reaction assay in 30 HIV-1 infected patients without central nervous system opportunistic infections. All participants completed a global neuropsychological battery consisting of Mattis Dementia Rating Scale. Additional tests were used to better characterize the type of cognitive changes with a specific reference to frontal lobe function. The neuropsychological evaluation confirmed the subcortical pattern of cognitive dysfunction. CSF and plasma HIV-1 RNA levels were significantly correlated. No correlation was detected with either blood or CSF RNA levels and the global cognitive status, but when stratified in three cognitive subgroups, higher CSF HIV-1 RNA levels were observed in the more cognitively impaired subjects. Our results provide further evidence that plasma and CSF HIV-1 RNA level cannot be used as a reliable diagnostic marker for HIV-1 associated cognitive disorders. Only longitudinal studies will determine whether a high CSF HIV-1 level could be a risk factor for HIV-1 dementia.

The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P.05 and P.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P.0001). HIV seropositivity (P.0001), alcohol consumption (50 g/d, P =.0002), age at HCV infection (25 years old, P.0001), and severe immunosuppression (CD4 count/=200 cells/microL, P.0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (50 g/d), CD4 count (/=200 cells/microL), and age at HCV infection (25 years old) (P. 0001, respectively) were associated with a higher fibrosis progression rate. HIV seropositivity accelerates HCV-related liver fibrosis progression. In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate.

Protease inhibitors (PIs) are recently introduced drugs that have improved the survival of HIV-infected patients when given in combination with two reverse transcriptase inhibitors. The HIV-1 protease gene is naturally highly polymorphic. Selection pressure due to IP use can result in major or minor resistance-associated mutations (RAMs). This study investigated whether presence before IP therapy of minor RAMs on the protease gene predicts the virological response. Of the 58 PI-naive patients included in the study, 12 had received two nucleoside reverse transcriptor inhibitors, 14 had received indinavir, 16 ritonavir, and 28 saquinavir-SGC. Viral load was measured on D0 (prior to PI initiation) and at M3 and M6 (Roche Monitor 1.5 with 200 and 20 copies/ml as the thresholds). The protease gene was fully sequenced on D0 using the ABI 377 automatic sequencer after RNA amplification by nested RT-PCR. None of the viral strains exhibited major mutations, but 57 of 58 (98%) had at least one minor mutation (median number of substitutions, 4), 60% had 1 to 4 substitutions, and 40% had 5 to 9 substitutions. Substitutions seen with a prevalence20% were located at codons 15, 35, 37, 41, 63, and 77. Numbers of substitutions at M3 and M6 were not correlated with viral load or the nature of the PI used, and neither were they significantly different between patients with more or fewer than 20 copies/ml. These data suggest that the protease genotype at PI initiation does not predict the efficacy of a regimen including a PI and is of no assistance in deciding whether or not to include a PI in a triple combination regimen.

DATA FAVORING IMMUNE RECONSTITUTION: Multiple drug therapies for HIV infection have enabled a major reduction in the viral load, higher CD4 counts, and a lower incidence of opportunistic infections and tumor formations, and subsequently lower hospitalization rates and mortality. TWO STAGES OF CD4 RECONSTITUTION: In HIV-positive patients with advanced stage disease treated with a protease inhibitor associated with 2 nucleoside analog reverse transcriptase inhibitors and followed prospectively, it has been observed that CD4 counts rise considerably, with a rapid increase during the first 2 months followed by a slower but still positive slope over a period of 18 months. Discordant results have however also been observed suggesting an ineffective anti-viral effect or a retarded immune reconstitution. SEVERAL MECHANISMS: The lymphocyte amplification observed during the early phase corresponds to re-circulation of CD4 and CD8 lymphocytes which had been sequestered in lymphoid organs; most of these CD4 lymphocytes are memory cells. A second phase corresponds to a more moderate and progressive rise in naive CD4 cells which originate from an unknown source. This biphasic reconstitution of CD4 lymphocytes is associated with a correction of the chronic lymphocyte overactivation. PARTIAL IMMUNE RECONSTITUTION: With treatment, the capacity to respond to known antigens reappears. This restored capacity is secondary to the amplification of CD4 memory cells and appears prior to the expansion phase of naive cells. The response remains moderate and is only observed against antigens from microorganisms highly prevalent during advanced stage infection.

HIV-associated neurocognitive disorders are mainly reported during the late stages of the disease, in deeply immunosuppressed patients Clinically, they present as a subcortical cognitive impairment, dominated by reduced psychomotor speed and memory deficit. Encephalic magnetic resonance imaging shows in most cases a diffuse leucoencephalopathy, and there is often a poor correlation between clinical status and neuroradiological findings. The diagnostic and prognostic value of HIV load in blood and cerebrospinal fluid is currently under investigation. Finally, the efficacy of new antiretroviral drugs on HIV dementia remains uncertain.

NEW THERAPEUTIC VECTORS: Liposomes are nontoxic biodegradable lipid particles which can vehicle drug compounds to the site of action, thus limiting the risk of general toxicity. WITH AMINOGLYCOSIDES: Liposome vectors for aminoglycosides, particularly amikacin, have been developed. Oto- and hepatic toxicity can be limited allowing the use of higher doses for longer periods. WITH AMPHOTERICIN B: Liposomal amphotericin B is now available and appears to give interesting results both in terms of efficacy and tolerance. OTHER APPLICATIONS: Capsular forms of other antibiotics such as ciprofloxacin are being studied. An encapsulated anticytomegalovirus agent, foscamet, is also be explored. In cancerology, liposomes could be developed to deliver toxic agents such as doxorubicin for example. The high cost of these therapeutic vectors does however limit their current use.

TWO WELL-KNOWN AGENTS: Although the activity of amantadin and rimantadin against type A Myxovirus influenzae are well known, use is still limited. These agents only have a moderate curative effect and, though they are more effective for prophylaxis, can only be used in cases with a certain positive diagnosis, which is difficult to obtain. In addition, questions remain concerning tolerance which is not always excellent, particularly for amantadin.This compound belongs to a new class. It specifically inhibits the neuraminidase in type A and B Myxovirus influenzae. Given by the nasal route, zanamivir has been shown to be effective compared with placebo, reducing the duration and intensity of flu symptoms and with a very satisfactory tolerance profile. GS4104: Studies are in the preliminary phases for this agent which is a powerful inhibitor of the influenzae A and B virus neuraminidase. It has been found to be active in mouse and rodent models.Vaccination remains the only effective tool today. These new compounds can only be seen as complementary agents to be used in combination with vaccination regimes.

FREQUENT MUTATIONS: Associated with the high turnover rate of the HIV, frequent inverse transcriptase errors lead to a wide range of possible mutations. Certain mutations can modify the response to antiretroviral agents. The development of resistant strains is mediated by the selection pressure of antiretroviral agents and occurs at a very variable rate depending on the antiretroviral agent used. TO LOWER THE RISK OF RESISTANCE: Persistent replication, whatever the cause, favors the emergence of resistant mutants. Thus the antiretroviral treatment must be initiated early and with the most powerful protocol possible in order to reduce viral replication as quickly as possible. CONTRIBUTION OF VIROLOGY TESTS: It is not always possible to predict the efficacy of antiviral agents from phenotyping and genotyping results. Their use is currently limited to cases of treatment failure. Their contribution in everyday clinical practice remains to be defined.