Early quantification of HCV core antigen may help to determine the duration of therapy for chronic genotype 2 or 3 HCV infection.

The aim of the present study was to evaluate the utility of hepatitis C virus (HCV) core antigen (coreAg) assessment for the identification of candidates for short-term therapy. Plasma samples from HCV genotype 2 or 3-infected patients participating in the NORDynamIC trial (n=382) comparing 12 and 24 weeks of combination treatment with pegylated interferon-α2a and a fixed dose of 800 mg ribavirin daily were analyzed for coreAg. Among the 126 patients (33% of the intention-to-treat population) achieving HCV coreAg levels in plasma below 0.2 pg/mL when assayed on treatment day 3, sustained viral response (SVR) rates of 86% and 84% were achieved in the 12- and 24-week arms, respectively. Similarly, among patients having received at least 80% of the target dose of both pegylated interferon α-2a and of ribavirin for at least 80% of the target treatment duration (per-protocol analysis), the SVR rates were 89% and 95%, respectively. Twelve weeks of combination treatment may be sufficient for genotype 2 or 3-infected patients achieving HCV coreAg levels below 0.2 pg/mL by day 3, signaling a rapid clearance of HCV viremia.

Hepatitis C treatment response kinetics and impact of baseline predictors.

The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and treatment outcome. Patients treated with peginterferon alfa-2a and ribavirin in standard dosing were included: 49 with genotype 1 treated for 48weeks and 139 with genotype 2 or 3 treated for 24weeks. The reduced SVR rates in patients older than 45years, with severe liver fibrosis or pretreatment viraemia above 400,000IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24weeks.

Effects of subcutaneous IL-2 therapy on telomere lengths in PBMC in HIV-infected patients.

In this study we investigated the effect of interleukin-2 (IL-2) on mean terminal restriction fragment (TRF) lengths in peripheral blood mononuclear cells (PBMC). Ten human immunodeficiency virus (HIV)-infected individuals were included and IL-2 was administered subcutaneously with 3 x 106 IU three times a week for 24 weeks. Mean TRF length was decreased on average by 267 bp at week 4 (P = 0.03) and 286 bp at week 8 (P = 0.09). Individual TRF changes at weeks 12, 16, 20 and 24 were highly variable. However, in the 12 weeks following therapy, TRF lengths generally increased reaching baseline levels by the end of the study. At baseline, mean TRF lengths were positively correlated to the ratio of naïve and memory phenotype within both CD4+ and CD8+ cells. This study shows that IL-2 treatment induces transient shortened mean TRF lengths in PBMC from HIV-infected individuals, indicating that IL-2 enhances the lymphocyte count by peripheral proliferation or recruitment of memory T cells into the blood.

Subcutaneous interleukin-2 in combination with anti-retroviral therapy for treatment of HIV-1-infected subjects.

A total of 11 HIV-1 positive patients, with CD4+ cell counts between 200 and 500/microl, who were in stable anti-retroviral therapy, were treated with subcutaneous recombinant human IL-2 thrice weekly administered on an out-patient basis in a dose-escalating manner. Subcutaneous IL-2 was well tolerated and associated with only mild to moderate constitutional symptoms and local inflammation at the injection site. CD4+ cell count increased from 404 +/- 48/microl at baseline to 639 +/- 88/microl at week 6, with proportionate increases in naive cells and memory cells. Increased doses of IL-2 were then needed to sustain the number of CD4+ cells. After discontinuation of IL-2 treatment, CD4+ cell count returned to baseline levels. IL-2 induced a reduction in the percentage of CD8+ CD38+ and CD8+ HLA-DR+ cells, an increase in the fraction of CD8+ CD25+ and CD8+ CD122+, and an elevation in the number of NK-cells. IL-2 did not induce any clinically significant change in plasma HIV-RNA. In conclusion, IL-2 can safely be administered subcutaneously on an out-patient basis to HIV-infected individuals with CD4+ cell counts from 200/microl to 500/microl and with some improvement in immunological abnormalities. Continuous therapy, however, seems to result in the development of tachyphylaxia.

Effects of subcutaneous interleukin-2 therapy on phenotype and function of peripheral blood mononuclear cells in human immunodeficiency virus infected patients.

In the context of clinical therapy with recombinant human interleukin-2 (IL-2), we monitored immunological alteration in 10 human immunodeficiency virus type-I (HIV-1)-infected individuals, on stable antiretroviral therapy, who had a CD4+ cell count between 200 and 500 cells/mm3. Subcutaneous IL-2 was prescribed thrice weekly (at a dose of 3 x 10(6) IU) for 24 weeks and the patients were followed-up for 32 weeks. IL-2 treatment induced an increase in the CD4+ percentage (P<0.001) and CD4+ cell count (P<0.009). Furthermore. natural killer (NK) cell activity was increased (P<0.001) at week 8 of treatment, whereas lymphokine-activated killer (LAK) cell activity showed a transient, nonsignificant increase at week 8 and was reduced (P<0.001) at 32 weeks. However, the cytotoxic T-lymphocyte (CTL) activity decreased against HIV antigens, and the proliferative response to Candida, IL-2 and phytohaemagglutinin (PHA) declined during the first 8 weeks (P<0.05) and returned to baseline levels after 32 weeks. The HIV RNA level did not change during IL-2 therapy; however, after 8 weeks of follow-up a significant increase (P<0.001) in viral load was observed. In

Use of medical chemoprophylaxis and antimosquito precautions in Danish malaria patients and their traveling companions.

BACKGROUND: The number of malaria cases imported to Denmark has been increasing for some years. To analyze the background for this we assessed the use of protective measures in Danish travelers visiting malarious areas. METHOD: Post-travel questionnaires were given during hospitalization to malaria patients, and sent by mail to their traveling companions. RESULTS: In total, 142 persons participated. Only 32% of the travelers used chemoprophylaxis correctly, according to Danish recommendations. Twelve percent of the travelers did not use chemoprophylaxis. Average compliance was 52%. Insufficient drug dosage was reported by 13%, and use of nonrecommended drugs by 7% of the travelers. Thirty-seven percent used insufficient antimosquito precautions, a problem which often coincided with irregular use of chemoprophylaxis. Malaria patients, sole travelers, and travelers with other ethnical background than Danish, were subgroups using insufficient malaria prophylaxis more frequently than healthy traveling companions. CONCLUSION: Insufficient use of the available antimalaria precautions by Danish travelers contributes greatly to maintaining a high incidence of imported malaria. Increased attention from physicians in educating travelers is important for optimizing malaria prophylaxis.

Retrospective evaluation of exposure to P. falciparum using antibodies to circumsporozoite protein and to cultured P. falciparum antigens.

A Danish school class travelled under primitive circumstances in East Africa for 28 d. Four out of 18 persons had febrile illnesses interpreted as malaria during the journey. Retrospective serological testing for antibodies against the P. falciparum circumsporozoite protein indicated a transmission rate of more than 80% despite extensive protection against mosquito bites. The study demonstrates the use of serological evaluation of malaria transmission risk as well as retrospective immunodiagnosis of clinical malaria. Three of the travellers with febrile illnesses used self-medication with mefloquine, and in 2 of the cases a diagnosis of malaria was supported by a positive immunofluorescence assay for malaria antibodies.

[Kawasaki syndrome in an adult]. / Kawasaki-syndrom hos en voksen.

Kawasaki syndrome (KS) is an acute, febrile, exanthemous illness characterized by vasculitis of unknown origin mostly seen in children younger than four years of age. We describe a 24-year-old white male who fulfilled the diagnostic criteria for KS. In addition to the diagnostic symptoms of KS this patient had symptoms from the liver and lungs.

[Varicella zoster virus vaccine--a review]. / Varicella zoster virus-vaccine--en oversigt.

The available published data on the efficacy and safety of a live attenuated varicella vaccine is presented. The data indicate that immunosuppressed leukemic children at high risk for severe varicella can be vaccinated resulting in complete or partial immunity in most children. Vaccination of immunosuppressed children is often associated with fever and rash. There seems to be a decreased risk of herpes zoster in vaccinated leukemic children when compared with a group of naturally infected leukemic children. In order to diminish the risk of varicella zoster virus (VZV) transmission to these high-risk persons family members of these, if susceptible to varicella infection, should be immunized. Although vaccination of healthy children is highly effective and associated with a low frequency of adverse events, vaccination in this group may be questioned due to the benign course of varicella. Due to the more severe VZV-infection seen among non-immune healthy adults, it seems reasonable to offer vaccination to this group. It will, however, require extensive serological testing to identify seronegative individuals. From a theoretical point of view a booster-vaccination to the elderly population, resulting in detectable cell-mediated immunity to VZV, should reduce the risk of herpes zoster. Large placebo-controlled studies are needed to confirm if such an immunization can prevent herpes zoster in this age group.

[Contributing causes of malaria among Danish travellers]. / Medvirkende årsager til malaria blandt danske rejsende.

A retrospective evaluation of contributing causes of malaria among Danish travellers, based on patient files and telephone interviews, is presented. Four centres participated, and 33% of all malaria cases reported to the Danish authorities in 1993 and 1994 were included (in total 82 patients). Ten out of 52 patients with falciparum malaria had not taken any chemoprophylaxis at all. Among the 42 patients who had, only 14 were both correctly advised and fully compliant. Within the remaining 28 patients, lack of compliance concerning the chemoprophylaxis was reported in 16, inadequate chemoprophylaxis was prescribed to 12 patients, and a further eight (19%) were underdosed. Only four out of 30 patients with vivax, ovale or malariae malaria had not used chemoprophylaxis. The distribution of contributing causes of chemoprophylaxis failure was similar to that of falciparum malaria, although noncompliance was more predominant in patients developing vivax, ovale or malariae malaria (58% compared to 38% in falciparum malaria).

[Survival time after the diagnosis of AIDS in the county of Funen]. / Livslaengde efter diagnosen AIDS på Fyn.

Since the diagnosis of AIDS was first made, a lot of efforts have been made to improve survival. Different studies have found varied results, both geographically as well as over periods of time. During the period 1.1.1985 to 31.12.1993 142 patients that were HIV-positive were seen in the geographically well defined area of Funen. During the period 1.1.1985 to 31.12.1990 the median time elapsed between the patient being found to be HIV-positive and the patient presenting with an AIDS-defining disease was found to be 8.8 years. In the period 1.1.1991 to 31.12.1993 it was 2.6 years (95% CL 1,3-?). The AIDS defining diseases were Pneumocystis carinii pneumonia in 43% of the cases, and oesophageal candidiasis in 24%. The median survival time after being diagnosed with AIDS was 2.0 years (95% CL 1,7-2,4). Heterosexual infection seems more pronounced in our material than for the country as a whole.

Hepatitis B, delta and human immunodeficiency virus infections among Omani patients with renal diseases: A seroprevalence study.

The prevalence of hepatitis B virus (HBV), hepatitis delta virus (HDV), and human immunodeficiency virus (HIV) infections were determined in 102 patients on regular hemodialysis, 82 kidney recipients and 1030 nondialyzed, nontransplanted patients with various renal diseases. The prevalence rates of hepatitis B surface antigen (HBsAg) in dialysis and renal transplant patients (12.7% and 11.0% respectively) were significantly higher than the rate in a control group of patients who had never been dialyzed nor transplanted (2.9%, P<0.05). In patients who were HBsAg positive, evidence of HDV infection was found in one dialysis and two transplant patients only. HIV infection was confirmed in only two of 102 (2.0%) and three of 82 (3.7%) hemodialysis and kidney recipients respectively. These data indicate hepatitis B, delta and HIV infections are major health problems among hemodialysis and renal transplant patients in the Sultanate of Oman.

Prevalence of antibodies to hepatitis C virus among Omani patients with renal disease.

The prevalence of hepatitis C virus (HCV) infection in Omani patients with renal disease was determined using a second-generation enzyme immunoassay which detects antibodies to three HCV antigens. Based on the results of this assay, 27 of 102 (26.5%) sera from patients on haemodialysis, 11 of 82 (13.4%) sera from kidney transplant patients, and 1 of 103 (1%) sera from non-dialysed, non-transplanted patients with various renal diseases had antibodies to HCV. Among healthy subjects, none of 134 medical students and 5 of 564 (0.9%) blood donors were anti-HCV positive. Thus, the prevalence of HCV infection in dialysis and renal transplant patients was significantly higher than that found in patients with renal disease who had been neither dialysed nor transplanted (p < 0.05). In the latter group of patients, the frequency of anti-HCV was low, and comparable to that of healthy Omani subjects.

Prevalence of hepatitis B, hepatitis delta, and human immunodeficiency virus infections in Omani patients with renal diseases.

PIP: Patients treated at the Royal Hospital in Oman during January-June 1991 were divided in 3 groups. The 1st group included 103 patients (49 males, 54 females, with a mean of 39 years) who attended the Nephrology Clinic and none of whom were on dialysis. In the 2nd group there were 102 patients (46 males, 56 females, with a mean age of 42 years) on regular hemodialysis (with a mean duration of 35 months) because of end-stage renal failure. The 3rd group comprised 82 kidney transplant patients (44 males, 38 females, with a mean age of 33 years) with a mean duration of prior hemodialysis of 9 months in 80 patients. Blood serum samples from all patients as well as from 134 medical students and 564 blood donors were tested for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) by enzyme-linked immunosorbent assay. HBsAg-positive samples were tested for antigen and antibody to hepatitis delta virus (HDV). The prevalence of HBsAg was significantly higher in hemodialysis and renal transplant patients than in nephrology clinic patients (P .05). Previous exposure to HBV was found in 48 of 103 (46.6%) nephrology clinic patients, in 53 of 102 (52%) hemodialysis patients, and in 43 of 82 (52.4%) renal transplant patients. Anti-HBc prevalence rates were significantly lower in medical students (23.1%) and blood donors (27%) than in the patient groups (P .001). In HBsAg-positive subjects HDV infection was found in 1 of 13 (7.7%) patients on dialysis and 2 of 9 (22.2%) kidney transplant recipients who had been transfused in the past. A double infection of HBV and HCV was found only in 4 hemodialysis and 2 transplant patients among 287 patients and 698 healthy subjects tested. Among 5 HIV-infected patients 3 transplant patients seroconverted between 3 and 7 months after kidney transplantation abroad; and 2 hemodialysis patients seroconverted after repeated dialysis and multiple blood transfusions used for kidney transplantation abroad.^ieng

Temporofacial zygomycosis in a pregnant woman.

A 38-year-old Omani woman, seven months pregnant, developed extensive zygomycosis involving maxillary and temporal bones. No evidence of any underlying immune deficiency was detected except that which may be attributed to pregnancy. After delivery the patient was treated with repeated courses of amphotericin B, which resulted in a complete clinical resolution. Zygomycosis in uncomplicated pregnancy has not been previously described.

[Results of treatment of meningitis during a 10-year period]. / Resultatet af 10 års meningitisbehandling.

A review of 131 cases of purulent meningitis is presented. The patients are mainly non-pediatric and, because of that, meningitis caused by Streptococcus pneumoniae predominates. This is the main reason for the high overall mortality of 15.6%. The main etiological cause of lethal meningitis was Streptococcus pneumoniae, and it is discussed whether chloramphenicol, previously shown to exert an antagonistic effect on beta-lactam antibiotics, contributes to the relatively high mortality. It is suggested that chloramphenicol should be withdrawn from meningitis treatment and replaced by cefuroxime.