Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus.

Alterations in the circadian time structure of the secretion of several hormones were investigated in 13 male patients infected with human immunodeficiency virus (HIV). Seven were asymptomatic (classified CDC II, according to the criteria of the Atlanta Centers for Disease Control), and 6 had acquired immunodeficiency syndrome (CDC IV). Ten healthy males volunteered as controls. Plasma levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), cortisol, testosterone, ACTH, and beta-endorphin were determined by RIA in blood samples obtained every 4 h from 0830-0830 h the next morning. Data were analyzed both by two-way analysis of variance and the cosinor method. Circadian rhythms were statistically validated for each of the six hormones in each of the three groups of subjects. Compared with the control subjects, mesors (24-h adjusted means) were significantly higher for cortisol and lower for DHEA, DHEA-S, and ACTH (P less than 0.001 for all four hormones) in all HIV-infected patients. Plasma testosterone mesors were similar in controls and CDC II patients, but decreased significantly in the CDC IV patient group (P less than 0.05). Analysis of the circadian rhythms of plasma hormone levels clearly indicated an altered adrenal hormonal state in HIV-infected male patients, even during the asymptomatic period of the infection. For instance, plasma cortisol at 0430 h was more than twice as high in HIV-infected patients as it was in time-qualified controls. Although patients already had elevated plasma cortisol and lowered adrenal androgen levels at this stage, hypogonadism was not observed, as gauged by plasma testosterone concentrations. We speculate that the primary hormonal defect in HIV-infected patients is increased cortisol secretion resulting from circadian-varying stimulation of the adrenal cortex by a factor other than pituitary ACTH. This factor might be a stimulating substance secreted primarily by infected immune cells. Excess cortisol would lower adrenal androgen secretion by shifting adrenal steroid biosynthesis toward glucocorticoids and decreasing pituitary ACTH secretion via a negative feedback mechanism.

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.

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.

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.

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.

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.

[Acute epidemic non-A, non-B hepatitis: clinical study of 38 cases seen in Chad]. / Hépatite aiguë non-A, non-B épidémique: étude clinique de 38 cas observés au Tchad.

An epidemic of acute non-A, non-B hepatitis (NANBH), observed in 38 young French soldiers in Chad, presumed to be waterborne, allowed to describe the clinical picture of the disease. The main features of this entity were compared with those observed during previously described outbreaks of waterborne NANBH encountered in North Africa and in Asia as well as with 85 cases of viral type A hepatitis of various other geographical origins, observed during the same period of time. Similarities between the clinical features of the disease within every water-transmitted NANBH epidemic center were suggestive of a particular nosologic entity among the non-parenterally transmitted cases of NANBH. In young male subjects, the course of the disease proved to be milder than that of type A viral hepatitis. A 5 ml dose of non-specific French-prepared human immunoglobulins had no prophylactic effects on the disease.

[Changes in HBs antigen and anti-HBs antibody in 77 patients with acute B-virus hepatitis]. / Evolution de l'antigène HBs et de l'anticorps anti-HBs chez 77 patients ayant une hépatite aiguë due au virus B.

Serum HBs antigen (HBs Ag) and anti-HBs antibody (anti-HBs), as determined by radioimmuno-assay or ELISA methods, were studied in a group of 77 patients with acute icterogenic viral hepatitis over a period of at least three months and correlated to the evolution of the disease either to return to good health or to a chronic state. The cumulative rate of patients in whom HBs Ag had disappeared (n = 53) was a linear function of time during the first sixteen weeks. Correlation seemed even stronger in the subgroup of patients restored to good health before the third month. Time of HBs Ag disappearance ranged from 5 days to 5 months in common forms of hepatitis. There was no evident correlation between the time of disappearance and the normalization of ALAT levels. Among the four cases of chronic persistent hepatitis, three had no detectable antigenemia six months later. Development of anti-HBs preceded the loss of HBs Ag in one case, was simultaneous or posterior to it in all other cases; the absence of any serologic HBV marker could last up to 4 months. No chronological link was found between seroconversion and normalization of ALAT levels. The correlation between time and HBs Ag disappearance from the blood could be specific for a given group of patients placed under specific conditions; its determination might help in understanding the factors that influence the course of the disease.

[Hepatic amebiasis: study of 152 cases]. / L'amibiase hépatique: étude de 152 observations.

The purpose of this study was to describe and analyse retrospectively the clinical, serological, anatomical and evolutive features of 152 cases of hepatic amebiasis in young adults, treated and followed up in France from 1969 to 1983. The disease was revealed 3 times out of 4 by tender hepatomegaly with fever, but only in 6 cases by complications. Serological tests (immunofluorescence or hemagglutination) were always positive for amebiasis, whereas Entamoeba histolytica was absent from stools in 96.7 p. 100 of the cases. Hepatic amebiasis always caused a hepatic abscess: in these cases, the superiority of ultrasonography over all other diagnostic methods was confirmed, especially concerning the detection of multiple abscesses (47 p. 100). Complete recovery was obtained by medical treatment in 117 cases, either alone (98 cases), or combined with needle aspiration (19 cases). Nitro-imidazoles are the simplest treatment, but nevertheless in 5 cases they were not effective. These patients were then treated with dehydroemetine, associated in 2 cases with surgery. Four patients relapsed at mid or long-term after apparent recovery, in the absence of any obvious reinfection. A significant correlation between the course of the treated disease and the size and number of abscesses was demonstrated: it was possible to define a group characterized by a slow and/or complicated course (with single abscess of the right lobe whose diameter is equal to or greater than 10 cm, or multiple abscesses). The pathogenesis of hepatic amebiasis is not yet fully understood.

[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.

[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.

[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.

[Treatment of fulminant falciparum malaria with erythrapheresis]. / Traitement par érythrophérèse d'un accès pernicieux palustre.

Ten days after his return from Cameroon, a twenty-six year old Frenchman, serving on voluntary service overseas, presented with fulminant falciparum malaria: shock, altered consciousness, haemolytic anaemia, threatening disseminated coagulation (platelets less than 150 X 10(-6).l-1; prothrombin time and Stuart factor less than 50%; fibrinogen less than 1.5 g.l-1). In spite of quinine therapy, parasitaemia increased from 4 to 35% within 24 h. Using an Haemonetics V50, the exchange of one and a half red blood cell masses was carried out with 17 red blood cell packs. Calcium gluconate was used to prevent the hypocalcaemia induced by the anticoagulant solution. The patient's platelets and plasma were completely reinjected. The result was very satisfactory. This kind of exchange, well tolerated clinically and biologically, would seem better than the classical exchange transfusion. When 10% of the red blood cells are infected by Plasmodium falciparum, it is necessary to exchange from one and a half to two blood masses. Lesser exchanges are always associated with important relapses and quinine therapy must be carried on during and after the exchange. Restricting this exchange only to red blood cells enabled the patient to benefit from his own coagulation factors, antibodies and platelets, and consequently to reduce the number of blood donors involved. However, metabolites (especially bilirubin and circulating immune complexes) were not eliminated. Partial plasmapheresis may be associated with erythropheresis using human albumin as plasma substitute. This technique needs to be assessed, in order to optimize immediate efficiency and post-transfusion infectious risk.

[Severe infections caused by methicillin-resistant Staphylococcus aureus. 62 cases]. / Infections graves à staphylocoques dorés résistants à la méticilline. 62 observations. GEISS. Groupe d'étude des infections sévères à staphylocoques.

A French multicentre study was conducted in 15 Infectious Diseases departments; 347 cases of severe staphylococcal infections were collected during one year (October 1989 to October 1990): Two-hundred and fifty-eight strains were analysed with complementary bacteriological studies, including 62 strains of methicillin-resistant Staphylococcus aureus. Epidemiological, clinical and therapeutic aspects were investigated. Nosocomial infection was responsible for 90 percent of the cases, and previous antibiotic therapy was reported in 74 percent. An invasive procedure was incriminated in 43 patients (69 percent); intravenous catheter (38 percent), mechanical ventilation (31 percent), surgery (22 percent), prosthetic device (20 percent). Thirty-nine patients were treated with glycopeptides either alone or in combination with beta-lactams, aminoglycosides, fucidic acid, fosfomycin, rifampicin, quinolones or synergistines, showing the great diversity in the choice of antibiotics in methicillin-resistant S. aureus infections. More than 90 percent of these strains were resistant to gentamicin and quinolones, 80 percent of clindamycin and 70 percent to rifampicin. No resistance to glycopeptides (vancomycin or teicoplanin) was observed. Prognosis was severe, with a mortality rate of 35 percent, justifying educational and prophylactic measures in at risk medical departments.

[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.

[Hepatic amebiasis in France. Apropos of 152 case reports]. / L'amibiase hépatique en France. A propos de 152 observations.

The authors report upon 152 cases of hepatic amebiasis (H.A.) observed in France between 1969 and 1983, among young european men (average age 29,2) who were hospitalised in the initial phase of their illness. H.A. was clinically revealed through a painful and febrile hepatomegaly in 3/4 cases and in 6 cases through complications. No chronic form was observed. The amebic serology (I.F.I. and/or H.A.P.) was always positive. The research of an intestinal portage of the parasite was generally negative. The hepatic functions were impaired in the third of the cases. Whichever technique was employed, the anatomic diagnosis has always been made in a phase of intra hepatic collection. The superiority of echotomography over other methods is confirmed (especially for diagnosis of multiple abscess: 47% of success). All patients recovered, most frequently through medical treatment (117 cases). The nitro-imidazoles (1,5 to 2 g per day during 7 to 14 days) remain the prefered treatment, but they are responsible for 5 failures which were overcome by emetine. On the other hand, 4 patients had, after being cured, showed middle and long term relapses without patient recontamination. The evolution of the treated H.A. is significantly correlated to the importance and/or the multiplicity of the liver collection: the voluminous abscess of the right lobe being the most potentially dangerous. The pathogenesis of the H.A. remains imperfectly known. The different clinical aspects which have been found, depend upon the preexistant immunity of the patient and could also be equally associated with a pathology of complex immunity systems.

[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.

[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.