The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patientshas 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 F .05 and P F .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 F .0001). HIV seropositivity (P F .0001), alcohol consumption (G50 g/d, P ‫؍‬ .0002), age at HCV infection (F25 years old, P F .0001), and severe immunosuppression (CD4 count I200 cells/L, P F .0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (G50 g/d), CD4 count (I200 cells/L), and age at HCV infection (F25 years old) (P F .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. (HEPATOLOGY 1999;30:1054-1058.)

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Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

Hepatitis B virus (HBV) resistance to lamivudine has not been extensively documented in human immunodeficiency virus (HIV)-infected patients. We studied the long-term incidence of HBV resistance to lamivudine in HIV-positive patients. Sixty-six HIV-HBV-coinfected patients were studied while receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy. All these patients had a detectable serum HBV DNA at the beginning of lamivudine therapy. Serum HBV DNA was quantified by molecular hybridization. Sequence analysis of the HBV polymerase was performed in patients who became resistant to lamivudine. After 2 months of lamivudine, HBV DNA became undetectable in 57 patients (86.4%, 95% CI: 75.7%-93.6%). After 2 years of lamivudine, 47% ؎ 18.6% of the patients, had sustained HBV-DNA suppression. In deeply immunosupressed HIV-HBV-coinfected patients, histological and biological activities are lower than in HIVnegative patients. 2,5 However, the natural history of liver fibrosis of coinfected patients has not been studied. Furthermore, the underlying liver disease of HIV-HBV-coinfected patients with immune restoration related to potent antiretroviral therapy is currently unknown.In HIV-HBV-coinfected patients, inhibition of HBV replication had been obtained in less than 8% of the cases with interferon alfa. 6,7 Lamivudine, an oral nucleoside analogue, is effective against both HIV and HBV replication. Lamivudine has promptly inhibited HBV replication in more than 80% of cases in both HIV-and non-HIV-infected patients. 8-10 However, HBV resistance to lamivudine caused by HBV-DNA polymerase gene mutations has been reported in both liver transplanted and immunocompetent patients. 8,[11][12][13][14][15][16][17] Incidence of HBV resistance to lamivudine is of 14% to 27% after 1 year of treatment in non-HIV-infected patients. 8,11 HBV resistance to lamivudine in HIV-infected patients has not been studied. We retrospectively analyzed a cohort of HIV-HBV-coinfected patients receiving lamivudine as a part of their antiretroviral therapy to study the long-term incidence of HBV resistance to lamivudine and to assess risk factors associated with this resistance. PATIENTS AND METHODSPatients. Studied patients belong to a cohort of 226 consecutive HBsAg carriers HIV-infected patients followed-up at our infectious diseases department since 1986. Patients were included if they fulfilled all the following criteria: (1) were receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy; (2) had a detectable serum HBV DNA by molecular hybridization at the beginning of lamivudine therapy. HBV-precore mutant infected patients (positive serum anti-HBe antibodies [HBeAb], negative HBeAg, and detectable serum HBV DNA) were also included; and (3) had serum HBV DNA and HBV-serological markers determinations at the second month of lamivudine therapy and at least twice during lamivudine therapy. Patients with hepatitis C or delta virus coinfections and those who had received a potent anti-HBV drug (ganciclovir, fosca...

The full spectrum of skin diseases related to travel in tropical areas is unknown. We prospectively studied 269 consecutive patients with travel-associated dermatosis who presented to our tropical disease unit in Paris during a 2-year period. The median age of these patients was 30 years; 137 patients were male; 76% of the patients were tourists; 38% had visited sub-Saharan Africa; and 85% had been appropriately vaccinated against tetanus. Cutaneous lesions appeared while the patient was still abroad in 61% of cases and after the patient's return to France in 39%. The diagnosis was definite in 260 cases; 137 of these cases (53%) involved an imported tropical disease. The most common diagnoses were cutaneous larva migrans (25%); pyodermas (18%); pruritic arthropod-reactive dermatitis (10%); myiasis (9%); tungiasis (6%); urticaria (5%); fever and rash (4%); and cutaneous leishmaniasis (3%). Hospitalization was necessary in 27 cases (10%), with a median duration of 5 days (range, 2-21 days). Travelers should be advised on how to avoid exposure to the agents and vectors of infectious dermatoses. Travel first-aid kits should include insect repellents and antibiotics effective against bacterial skin infections.

Key Points After being killed by artesunate, malaria parasites are expelled from red cells and then these pitted red cells reenter the circulation. When many pitted red cells are produced during therapy, their delayed clearance a few weeks later triggers hemolytic episodes.

During Plasmodium falciparum infection leading to cerebral malaria, cytokine production and cytoadherence of parasitized erythrocytes (PRBCs) to postcapillary venules are involved. We demonstrate that PRBC adhesion induces apoptosis in human endothelial cells (HLECs). PRBC adhesion modulated HLEC gene expression in tumor necrosis factor-alpha superfamily genes (Fas, Fas L, and DR-6) and apoptosis-related genes (Bad, Bax, caspase-3,SARP 2, DFF45/ICAD, IFN-gamma receptor 2, Bcl-w, Bik, and iNOS). Apoptosis was confirmed by (1) morphological modifications by electron microscopy, (2) annexin V binding, (3) DNA degradation, by measuring intracytoplasmic nucleosomes, and (4) caspase activity. The apoptotic stimulus was physical contact between HLECs and PRBCs and not parasite-secreted molecules. In addition, it was found that cytoplasmic (caspase 8) and mitochondrial (caspase 9) pathways were involved in this process. These data not only describe the direct apoptotic effect of PRBC adhesion on endothelial cells but also provide new useful tools that allow an evaluation of potential pharmaceuticals.

Residual immunity to the smallpox virus raises key questions about the persistence of long-term immune memory in the absence of antigen, since vaccination ended in 1980. IFN-γ–producing effector–memory and proliferative memory T cells were compared in 79 vaccinees 13–25 yr after their last immunization and in unvaccinated individuals. Only 20% of the vaccinees displayed both immediate IFN-γ–producing effector–memory responses and proliferative memory responses at 6 d; 52.5% showed only proliferative responses; and 27.5% had no detectable vaccinia-specific responses at all. Both responses were mediated by CD4 and CD8 T cells. The vaccinia-specific IFN-γ–producing cells were composed mainly of CD4Pos CD45RANeg CD11aHi CD27Pos and CCR7Neg T cells. Their frequency was low but could be expanded in vitro within 7 d. Time since first immunization affected their persistence: they vanished 45 yr after priming, but proliferative responses remained detectable. The number of recalls did not affect the persistence of residual effector–memory T cells. Programmed revaccination boosted both IFN-γ and proliferative responses within 2 mo of recall, even in vaccinees with previously undetectable residual effector–memory cells. Such long-term maintenance of vaccinia-specific immune memory in the absence of smallpox virus modifies our understanding of the mechanism of persistence of long-term memory to poxviruses and challenges vaccination strategies.