Kjell Block Hellum

Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: A pilot study

The aim of this study was to determine the efficacy of 14 weeks of treatment in patients infected with hepatitis C virus (HCV) genotype 2 or 3 who achieve early virological response (EVR). In a noncontrolled multicenter trial, 122 treatment‐naive patients received 1.5 μg/kg pegylated interferon alfa‐2b subcutaneously once weekly and 800 to 1,400 mg/d ribavirin based on body weight. Treatment was stopped at week 14 in patients with EVR, defined as undetectable HCV RNA at weeks 4 and 8. Patients without EVR were assigned to 24 weeks of treatment. The primary end point was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after end of treatment. Among the 122 patients, 95 (78%) had EVR and received 14 weeks of treatment. The remaining 27 (22%) were treated for 24 weeks. SVR was obtained in 85 (90%) of 95 patients in the 14‐week treatment group and 15 of (56%) 27 in the 24‐week treatment group. Altogether, SVR was obtained in 100 of 122 patients (82%; 95% CI, 75%‐89%). SVR after 14 weeks of treatment was achieved more frequently among genotype 3a patients with low viral load compared with high viral load (98% vs. 79%; P = .019). Logistic regression analysis showed that absence of bridging fibrosis/cirrhosis was the only independent predictor of SVR. In conclusion, patients with genotype 2 or 3 and EVR obtained a high SVR after 14 weeks of treatment. The results need to be confirmed in a randomized, controlled study before this treatment approach can be recommended, particularly for patients with genotype 3 and high viral load or severe fibrosis. (HEPATOLOGY 2004;40: 1260–1265.)

Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response

A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment‐naïve HCV RNA–positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon α‐2b (1.5 μg/kg) subcutaneously weekly and ribavirin (800‐1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one‐sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention‐to‐treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7‐17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, −0.1 to +13.9). Conclusion: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks. (HEPATOLOGY 2007.)

African Tick Bite Fever in Travelers to Rural Sub-Equatorial Africa

To estimate the incidence of, identify risk factors for, and describe the clinical presentation of travel-associated African tick bite fever (ATBF), a rapidly emerging disease in travel medicine, we prospectively studied a cohort of 940 travelers to rural sub-Equatorial Africa. Diagnosis was based on suicide polymerase chain reaction and the detection of specific antibodies to Rickettia africae in serum samples by multiple-antigen microimmunofluorescence assay, Western blotting, and cross-adsorption assays. Thirty-eight travelers, 4.0% of the cohort and 26.6% of those reporting flulike symptoms, had ATBF diagnosed. More than 80% of the patients had fever, headache, and/or myalgia, whereas specific clinical features such as inoculation eschars, lymphadenitis, cutaneous rash, and aphthous stomatitis were seen in < or = 50% of patients. Game hunting, travel to southern Africa, and travel during November through April were found to be independent risk factors. Our study suggests that ATBF is not uncommon in travelers to rural sub-Saharan Africa and that many cases have a nonspecific presentation.

Treatment of Chronic Hepatitis C in Injecting Drug Users: 5 Years’ Follow-Up

Aim of the Study: To assess the long-term hepatitis C (HCV) treatment outcome in former injecting drug users (IDUs). Materials and Methods: A long-term follow-up of 27 former IDUs who had been successfully treated for chronic hepatitis C was performed. These patients represented all IDUs who had obtained a sustained virological response in a Norwegian HCV treatment trial. The patients had been treated with interferon-α alone or in combination with ribavirin. At 5 years’ follow-up the 27 IDUs were retested for HCV RNA and risk behaviour for HCV transmission after treatment was assessed. In the control group all 18 non-IDUs who had obtained a sustained virological response in the same treatment trial were included. Results: At follow-up 13–82 months (median 64) after the end of treatment only one case of probable reinfection was seen among the 27 IUDs. No reoccurrence of HCV was observed in the control group. The IDU who was HCV RNA positive at follow-up had continued injecting drugs and reported frequent needle sharing. At follow-up HCV of genotype 1a was detected in contrast to genotype 1b before treatment indicating that this patient was reinfected with HCV. A return to injecting drug use occurred in 9 (33%) of 27 IDUs. Conclusion: The long-term outcome of HCV treatment in former IDUs was excellent. Despite frequent reinitiation of drug injection all but 1 remained HCV RNA negative.

Comparison of preference-based utilities of the 15D, EQ-5D and SF-6D in patients with HIV/AIDS.

Objective: This article compares preference-based utilities from the multiattribute utility instrument 15D with those derived from the EQ-5D and the Short Form 36 (SF-6D) in patients with HIV/AIDS. In particular, we wanted to examine if the finer descriptive system of the 15D would result in better discriminative capacity or responsiveness. Methods: In a prospective observational study of 60 Norwegian patients with HIV/AIDS from two hospitals, the authors compared scores, assessed associations with disease staging systems, and assessed test–retest reliability and responsiveness of the instruments. Results: On average, the 15D gave higher utility scores than the other two measures, the mean utility scores were: 15D – 0.86, SF-6D – 0.73, and EQ-5D Index – 0.77. Test-retest reliability was acceptable for all measures, with intraclass correlation coefficients between 0.78 and 0.94. The correlation between scores of the 3 scales was substantial (ρ=0.74–0.80). There was no major difference in responsiveness between the measures. Conclusions: The different measures gave different utility values in this sample of patients with HIV/AIDS, although many of the measurement properties were similar. There was no evidence for better discriminative capacity or responsiveness for the 15D, than for the two other multiattribute measures.

Sub-acute neuropathy in patients with African tick bite fever.

African tick bite fever (ATBF) caused by Rickettsia africae is an emerging health problem in travellers to sub-Saharan Africa. We here present 6 patients with evidence of long-lasting sub-acute neuropathy following ATBF contracted during safari trips to southern Africa. Three patients developed radiating pain, paresthaesia and/or motor weakness of extremities, 2 had hemi-facial pain and paresthaesia, and 1 developed unilateral sensorineural hearing loss. When evaluated 3–26 months after symptom onset, cerebrospinal fluid samples from 5 patients were negative for R. africae PCR and serology, but revealed elevated protein content in 3 and mild pleocytosis in 1 case. Despite extensive investigations, no plausible alternative causes of neuropathy could be identified. Treatment with doxycycline in 2 patients had no clinical effect. Given the current increase of international safari tourism to sub-Saharan Africa, more cases of sub-acute neuropathy following ATBF may well be encountered in Europe and elsewhere in the y to come.

Low Frequency of Complications in Imported Falciparum Malaria: A Review of 222 Cases in South-eastern Norway

We performed a retrospective study of 222 cases of falciparum malaria diagnosed in Oslo and Akerhus counties, Norway, from January 1988 to December 1997. Except for 12 cases, all had acquired the disease in sub-Saharan Africa. Sixty-four (28.8%) cases occurred in assumed non-immune individuals; of these, 41 (64.1%) were compliant to recommended antimalarial chemoprophylaxis. The mean time lag from first symptom to diagnosis (total diagnosis delay) was 4.6 d (median 3 d, range 0-30 d) and the mean time from presentation to diagnosis (doctors delay) was 1.3 d (median 0 d, range 0-25 d). There were no fatal cases, and only 8 (3.6%) had a complicated course. The following factors were significantly associated with development of complicated disease: higher age, non-immunity combined with chemoprophylaxis non-compliance, prolonged doctors delay and prolonged total diagnosis delay (p < or = 0.05). Our data suggest that complicated disease in imported falciparum malaria may largely be prevented by high chemoprophylaxis compliance rates in non-immune travellers and a high index of suspicion in physicians evaluating febrile travellers.

Ciprofloxacin versus a Tobramycin/Cefuroxime Combination in the Treatment of Serious Systemic Infections: A Prospective, Randomized and Controlled Study of Efficacy and Safety

Sequential intravenous and oral ciprofloxacin (CF) was compared with a combination of tobramycin and cefuroxime (T/C) in the treatment of serious systemic infections. Altogether 310 patients were randomized, 160 receiving CF and 150 T/C, the 2 groups being reasonably well balanced. 29 patients without infection were excluded from the analysis. Complete clinical resolution was obtained in 75% (107/143) patients receiving CF and in 78% (107/138) receiving T/C; the difference was not statistically significant. The rate of bacterial eradication in septicaemia was 72% (95% confidence interval (95% c.i.): 58-86%) for patients treated with CF and 87% (95% c.i.: 77-96%) when T/C was given, while the eradication rates in urinary tract infection were 72% (95% c.i.: 54-90%) and 45% (95% c.i.: 23-67%) for CF and T/C, respectively. Significant differences in bacteriological response for other diagnoses were not detected. Also for lower respiratory tract infections (LTRI) the clinical and bacteriological responses were quite similar, although relatively more failures occurred in CF treated patients with LRTI caused by pneumococci. The frequencies of adverse reactions were comparable, but the reactions were less serious following CF treatment. Our results indicate that CF may be used for empirical treatment of serious infections. However, if pneumococcal etiology is likely, alternative antibiotics should be used, and if necessary, coverage against anaerobic bacteria should be added.

Exflagellation of Microgametocytes in Plasmodium vivax Malaria: A Diagnostic Conundrum

Objective: To present a clinical diagnostic conundrum of unidentified structures in a blood smear from a patient with Plasmodium vivax malaria. Clinical Presentation and Intervention: A 37-year-old Ethiopian male presented with a 4-month history of chills, chronic diarrhea and weight loss. He was diagnosed with P. vivax malaria, advanced HIV infection and Isospora belli enteritis. Unidentified structures initially confusing to the diagnosticians were seen in blood smears taken on admission. The structures were initially considered to represent atypical spirochetes, but were later identified as microgametes and other exflagellation forms of P. vivax. The patient recovered after receiving adequate treatment for his infections. Conclusion: This case illustrates that exflagellation may be observed in blood smears from patients with P. vivax malaria. Size and morphological characteristics differentiate malaria microgametes and other exflagellation forms from microfilaria, spirochetes and trypanosomes.