[Liposomal amphotericin B treatment of cutaneous leishmaniasis contracted in Djibouti and resistant to meglumine antimoniate]. / Traitement par amphotéricine B liposomale d'une leishmaniose cutanée contractée à Djibouti et résistante à l'antimoniate de méglumine.

Pentavalent antimony (PA) compounds remain the main therapeutic agents of cutaneous leishmaniasis (CL). CL infection resistant to PA is difficult to cure, limited by severe side effects and requiring a long course treatment of parenteral administration of recommended second line drugs. We report a case of CL unresponsive to meglumine antimoniate contracted in Djibouti, successfully treated with a short course treatment of AmBisome. In this case the subject had a recurrent thick crusted erythematous lesion on his left elbow associated with spreading micropapula on arms and thorax. The diagnosis of CL was confirmed by direct examination and genomic amplification by PCR of skin samples, cultures were negative. A short course treatment of parenteral AmBisome (18 mg/kg) has lead to clinical cure with no side effects and no relapse. In our hospital, the high cost of medication was counterbalanced by easiest administration, reduction of hospitalization duration, absence of adverse events and a gain of comfort. For this patient, a short course treatment of AmBisome proved to be a suitable alternative to traditional drugs used in CL resistant to PA.

[Splenic rupture in infectious disease: splenectomy or conservative treatment? Report of three cases]. / Ruptures de rate au cours des maladies infectieuses: splénectomie ou traitement conservateur? A propos de trois cas.

INTRODUCTION: Spontaneous splenic ruptures are rare but life-threatening complications of infectious diseases. Splenectomy is still the treatment of choice but numerous recent reports have documented favorable outcome with conservative treatment. EXEGESIS: We report three cases of splenic rupture occurring respectively with infectious mononucleosis, P. vivax infection and dengue fever. Diagnosis, treatment and indications are reviewed, an approach to management is suggested. The study included three military men respectively aged 23, 24 and 35 years, admitted for acute abdominal pain in the left upper quadrant. The abdominal computed tomography confirmed partial rupture (splenic hematoma) in the first two cases, and an hemoperitoneum in the dengue case. Splenic ruptures can reveal or complicate an evolving infection. Rupture can happen spontaneously or as a result of trauma, which may be minor and unnoticed. The typical presentation is acute, but progressive forms are described. The diagnosis is made by ultrasound and CT scan. Splenectomy dogma tends to be supplanted by conservative treatment. Non-operative management can be successful if appropriate criteria and a long period of follow-up are applied in carefully selected cases. When an operative approach is selected, conservative surgical treatment is attractive. Splenectomy should be reserved for patients with uncontrollable rupture or with recurrent splenic bleeding. CONCLUSION: Spontaneous splenic rupture are uncommon in infectious diseases. A multidisciplinary management is necessary. A conservative treatment should be considered in selected, closely monitored patients.

Unusual presentation of typhoid fever: cutaneous vasculitis, pancreatitis, and splenic abscess.

We report a case of typhoid fever with an unusual presentation: prolonged fever with cutaneous vasculitis, pancreatitis, and splenic abscess. This is the first case of cutaneous leukocytoclastic vasculitis associated with Salmonella typhi. The diagnosis was made upon isolation of S. typhi in blood cultures, and after ruling out other causes of leukocytoclastic vasculitis. The outcome was favourable with antibiotics alone without surgery.

Role of hepatitis E virus in sporadic cases of acute and fulminant hepatitis in an endemic area (Chad).

Forty-one patients with acute or fulminant hepatitis and 86 control patients were entered into a study of sporadic, acute, and fulminant hepatitis in the N'Djamena area of Chad in 1993. Acute hepatitis B was diagnosed in nine (22%) patients and acute hepatitis E in 27 (66%) patients. No acute hepatitis A was observed and 10% of the patients had serologic markers of hepatitis C virus (HCV) infection. Dual acute hepatitis B and E were observed in four patients (10%) and acute HEV infection was associated with chronic hepatitis B surface antigen carriage in 16 (39%). Epidemiologic findings concerning HBV from Chad suggest that these patients had undiagnosed chronic liver disease due to HBV, with acute deterioration caused by superimposed HEV replication. Moreover, it is obvious that in developing countries only the most severe cases of hepatitis are seen in hospital settings and a large proportion of them are related to superinfection with HBV and HEV. Antibody to HEV was observed in 22% of the control patients. This observation and the fact that epidemic and sporadic cases of HEV are observed in Chad indicates that HEV is highly endemic in this country.

[Resistance to chloroquine and cycloguanil of Plasmodium falciparum in patients arriving in France after travel in Africa without chemoprophylaxis]. / Résistance à la chloroquine et au cycloguanil de Plasmodium falciparum chez des patients arrivant en France après un voyage en Afrique sans chimioprophylaxie.

The in vitro susceptibility of chloroquine and the genomic profile of dihydrofolate reductase (DHFR) codon 108 was determined against african isolates of P. falciparum (Pf) from imported malaria cases without previous drug intake by an isotopic microtest or PCR + RFLP. Pf resistance to chloroquine or to the DHFR inhibitor was present in 49% and 46% of isolates, respectively. Pf drug resistance was more frequent in permanent than in seasonal malarial transmission areas and chloroquine plus DHFR resistance reached 28% in years 1995-97. Updating the guidelines for the prevention of malaria in travellers to Africa is necessary.

Lack of chronic immune activation in HIV-infected chimpanzees correlates with the resistance of T cells to Fas/Apo-1 (CD95)-induced apoptosis and preservation of a T helper 1 phenotype.

Chimpanzees are one of the few species, along with humans, susceptible to persistent HIV-1 infection. However, HIV-infected chimpanzees do not exhibit the marked immune system alterations seen in humans and remain relatively resistant to AIDS. In humans, HIV infection leads to unresponsiveness of T cells in response to TCR stimulation, associated with increased T cell death by apoptosis. In an effort to understand some of the mechanisms used to limit lentivirus infection in African nonhuman primates, we compared apoptosis in infected humans vs chimpanzees in CD4 and CD8 T cells in relation with the expression of Bcl-2 and Fas molecules. The intensity of apoptosis in CD4 and CD8 T cells from infected chimpanzees was very low, was not inducible by several TCR-dependent activators, and was comparable to that detected in noninfected chimpanzees. Moreover, CD45RO+ and HLA-DR+ subsets, which were shown to exhibit ex vivo a high propensity to undergo apoptosis in infected humans, were not modified in infected chimpanzees. Interestingly, in contrast to the situation found in infected humans, Fas ligation by agonistic Abs or recombinant human Fas ligand on CD4 and CD8 T cells from infected chimpanzees did not induce apoptosis in these subsets even when Bcl-2 was down-regulated. Finally, this resistance to apoptosis was associated with the predominance of CD3 T cells with a Th1 phenotype. Together these observations argue for a strong relationship among the absence of chronic immune stimulation in HIV-1-infected chimpanzees, the normal control of lymphocyte survival, and the resistance to disease progression.

[Antibiotic sensitivity of aerobic gram-negative bacilli isolated from severe infections in 1992: results of a French multicenter study. Groupe d'Etude d'Infections à bacilles à Gram Négatif (GEIGN)]. / Sensibilité aux antibiotiques des bacilles à Gram négatif aérobies isolés d'infections sévères en 1992: résultats d'une étude multicentrique française. Groupe d'Etude d'Infections à bacilles à Gram Négatif (GEIGN).

OBJECTIVES: Antibiotic susceptibility of 649 gram-negative bacilli involved in severe infections and isolated in 18 teaching hospitals from January to December 1992 was evaluated. METHODS: Minimal Inhibitory Concentrations were determined by agar dilution method for piperacillin, piperacillin+ tazobactam and imipenem, and by a microdilution method for 11 other antibiotics (amoxicillin, amoxicillin + clavulanic acid, cefotaxime, ceftazidime, aztreonam, ticarcillin, ciprofloxacin, fosfomycin, tobramycin, gentamicin, amikacin). Criteria of Comité Français de l'Antibiogramme de la Société Française de Microbiologie were followed for interpretation. Betalactamases were identified by isoelectric focusing and overproduction of cephalosporinase was defined by the resistance phenotype. The main species isolated were Escherichia coli (45%), Pseudomonas aeruginosa (14%), Klebsiella pneumoniae (7.8%), Salmonella spp. (7.5%), Enterobacter cloacae (4%) and Klebsiella oxytoca (4%). Most of the strains were isolated from blood culture (72.3%), respiratory tract (11.4%) and intraabdominal infections (8.6%). Most of the enterobacteria isolates were susceptible to imipenem, aztreonam, amikacin and ciprofloxacin (percentages of susceptibility were respectively 99.3, 98, 98.3 and 96.3); in most of cases clavulanic acid did not entirely restore sensitivity to amoxicillin of penicillinase-producing strains. Among 89 P. aeruginosa strains, 82% were susceptible to imipenem and ceftazidime, 81% to the association piperacillin + tazobactam and 51% to ticarcillin. Resistance rates are very high for Acinetobacter baumannii except for imipenem. CONCLUSION: Production of TEM-type penicillinase and over-production of the chromosomal cephalosporinase are the most widely observed mechanisms of resistance (respectively 22% and 9% of 649 strains). Prevalence of extended spectrum betalactamases was low (1%) and essentially observed for K. pneumoniae.

[Infectious hazards in military personnel in operations.]. / Les risques infectieux chez les militaires en opération.

Military personnel in operations have always paid a high toll to infections, particularly epidemics. Currently, 40 000 servicemen serve overseas in various missions and operations of various durations in various countries. Infectious hazards persist in spite of the implementation of preventive measures. They are primarily due to poor sanitation, promiscuous living conditions, and the operational situation : bacterial diarrhea, amoebiasis, viral hepatitis A and E are relatively frequent. Others are due to the tropical environment ; malaria remains a concern due to its chemoresistance ; bilharziosis can also cause small epidemics, cutaneous leishmaniasis is not rare in Guyana. Exceptional but serious infections are observed. Infectious hazards associated with warfare are reviewed : biological warfare, infections of wounded, burnt and irradiated soldiers.

Short report: polymerase chain reaction detection of hepatitis E virus in north African fecal samples.

Epidemics of enterically-transmitted non-A, non-B hepatitis were described in 1983-1984 involving French soldiers in Chad and in 1979-1980 in residents of Algeria. Hepatitis E virus (HEV) was subsequently implicated by serology. In this study, the presence of HEV in patient stool specimens from both outbreaks and from sporadic cases in residents of Chad (1994) was documented. This virus was detected in fecal suspensions by antibody capture of the virus and reverse transcriptase-polymerase chain reaction amplification of the viral RNA in the 3' end of open reading frame 2. Two of five epidemic cases from Chad (1983-1984) were positive, as well as one of five sporadic cases from Chad (1994), and two of three epidemic cases from Algeria (1979-1980). Of these 13 patients, 12 had detectable anti-HEV IgG in their serum. These results confirmed that HEV was the cause of hepatitis in at least five of these 13 patients.

Role of beta 2-glycoprotein I in the anticardiolipin antibody affinity for phospholipid in autoimmune disease.

The binding capacity to cardiolipin and the functional affinity of affinity-purified anticardiolipin (aCL) IgG of patients with autoimmune disease have been compared with those of individuals with malaria and acquired immunodeficiency syndrome (AIDS). The binding of autoimmune IgG aCL was enhanced gradually by the incorporation of increasing amounts of beta 2-glycoprotein I (beta 2GPI) into the assay, in contrast to that of patients with infectious diseases. In addition, there were significant reductions of functional affinity in autoimmune disease, but not in malaria or in AIDS. These results indicate that beta 2GPI requirement for binding to the target antigen varies inversely with functional affinity in autoimmune disease when beta 2GPI was present, and suggest that IgG aCL are more heterogeneous in this type of disorder than in patients with infectious disease.

[Diagnosis of cerebro-meningeal infections after travel abroad]. / Diagnostic des infections cérébro-méningées au retour d'un voyage outre-mer.

Cerebromeningitis after travel abroad is often acute and febrile and is a serious event. The most frequent and severe cause is pernicious malaria due to Plasmodium falciparum; diagnosis is rapid by thick blood film and thin blood smear; it requires specific emergency treatment. Many other aetologies exist but they are rare; they must nonetheless be considered, keeping in mind that cosmopolitan infections can be favoured by travel conditions.

Hepatitis type E in a French population: detection of anti-HEV by a synthetic peptide-based enzyme-linked immunosorbent assay.

Four synthetic peptides were used to develop an ELISA for detecting hepatitis type E infections. Antibodies to HEV were detected in 54 of 64 patients present during two outbreaks previously recognized as being due to hepatitis E virus. Those patients included French soldiers stationed in Chad at the time, and Algerian civilians residing in Algeria and considered as positive controls. Anti-HEV were also detected in 3 out of 74 cases of sporadic non-A, non-B, non-C hepatitis in France, and in 2 out of 150 anti-HAV-IgM-positive sporadic cases, also in France, but in none of 278 healthy adults from the general French population. Among a total of 34 anti-HEV-positive cases in French subjects, 32 were shown to be associated with travel outside of western Europe; in two cases, however, HEV transmission appeared to have taken place in Europe. Using this ELISA, a rapid drop in anti-HEV antibodies to undetectable levels following the acute phase of the disease was observed in a high proportion of the infected subjects. Thus, the present test would appear to be more suitable for diagnostic purposes than for epidemiological investigations.

Circadian rhythms of circulating NK cells in healthy and human immunodeficiency virus-infected men.

Antiviral immunity involves NK cells, which circulate rhythmically every 24 hours. We have investigated circadian and 12-hour rhythms in the peripheral count of circulating NK cells in 15 men infected with human immunodeficiency virus (HIV) and 13 healthy controls. We analyzed three phenotypes using double-labeling with monoclonal antibodies and flow cytometry assessment: CD3- CD16+, CD3-CD57+, and CD2+CD3-. A statistical validation of time-dependent differences was achieved if significance (p < 0.05) was validated both with analysis of variance and cosinor. The circadian rhythm had a similar asymmetric waveform for the three phenotypes and is homogeneous on an individual basis. The circulating NK cell count peaked in the early morning and was low at night. A circadian rhythm and a circahemidian harmonic characterized all phenotypes in healthy subjects. We considered two groups of HIV-infected men: those who were asymptomatic (eight) and those with acquired immune deficiency syndrome (AIDS) (seven). Circadian changes in NK cell count were similar in both subgroups and in healthy controls. The circadian pattern was also consistent among individual patients. Asymptomatic HIV-infected men (early-stage disease) exhibited more pronounced 12-hour rhythmicity than did patients with AIDS or controls. The circulation of NK cells does not appear to share the same synchronizer(s) as other circulating T- or B-lymphocyte subsets. Thus, HIV infection gradually abolished circadian rhythmicity in circulating T and B cells, whereas it did not disturb that in NK cells.

Mapping of linear B cell epitopes on open reading frames 2- and 3-encoded proteins of hepatitis E virus using synthetic peptides.

Hepatitis E virus (HEV) is the causative agent of non-A, non-B hepatitis which is transmitted by the fecal-oral route and occurs principally in the form of large epidemics and outbreaks in developing countries. Two overlapping synthetic peptides corresponding to overlapping DNA sequences of the ORF 3 of HEV genome were found to be immunoreactive with sera from patients involved in two epidemics of enterically transmitted non-A, non-B hepatitis. The results suggested the existence of two distinct epitopes. The four synthetic peptides representing these two epitopes from Burma and Mexico strains of hepatitis E virus, were used to investigate anti-HEV reactivities. HEV antibodies were detected in 84-88% of HEV-infected individuals according to the peptide used. The results suggest that a peptide-based ELISA can provide an accurate tool for the diagnosis of acute hepatitis type E.