Silvio Caligaris

Multiple-Dose Pharmacokinetics of Efavirenz with and without the Use of Rifampicin in HIV-Positive Patients

Rifampicin (RIF) decreases serum concentrations of several antiretroviral drugs. We carried out a prospective, comparative study to define efavirenz (EFV) pharmacokinetics in 16 cases and 13 controls. Cases were HIV and tuberculosis (TB) co-infected adults assuming RIF 600 mg once daily and EFV 800 mg once daily. Patients on EFV at standard 600 mg dose without RIF were taken as controls. EFV levels in plasma were assayed by high-performance liquid chromatography (HLPC) predose (C(trough)) and at 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 16, 18, 22 and 24 hours post-dose, and pharmacokinetic parameters were determined by non-compartmental methods. Among cases, 81% were males, mean age was 37 years, 50% were Caucasians, mean weight was 64 kg, mean CD4 cell counts and log HIV RNA copies were 160/microl and 5.2 /microl, respectively. Cases had a significantly higher Cl/F/kg if compared with controls (0.269 +/- 0.12 versus 0.167 + 0.05 L/h/kg, p<0.01). Otherwise, dose-dependent pharmacokinetic parameters of EFV were similar between cases and controls. Interindividual variability was consistently higher among TB cases compared to controls for all considered parameters. All cases completed combined treatment and no increased EFV toxicity was observed. These results suggest that a dose of 800 mg of EFV in association with rifampicin may be appropriate for patients of weight > 60 kg in Europe. Therapeutic drug monitoring may be beneficial for patients on combination therapy with RIF.

CD11b Expression Identifies CD8+CD28+ T Lymphocytes with Phenotype and Function of Both Naive/Memory and Effector Cells

A previously unreported CD8+CD28+CD11b+ T cell subset occurs in healthy individuals and expands in patients suffering from primary viral infections. In functional terms, these cells share the features of naive/memory CD8+CD28+CD11b− and terminally differentiated effector CD8+CD28−CD11b+ subpopulations. Like CD28− cells, CD28+CD11b+ lymphocytes have the ability to produce IFN-γ, to express perforin granules in vivo, and to exert a potent cytolytic activity. Moreover, these cells can respond to chemotactic stimuli and can efficiently cross the endothelial barrier. In contrast, like their CD11b− counterpart, they still produce IL-2 and retain the ability to proliferate following mitogenic stimuli. The same CD28+CD11b+ subpopulation detected in vivo could be generated by culturing naive CD28+CD11b− cells in the presence of mitogenic stimuli following the acquisition of a CD45RO+ memory phenotype. Considering both phenotypic and functional properties, we argue that this subset may therefore constitute an intermediate phenotype in the process of CD8+ T cell differentiation and that the CD11b marker expression can distinguish between memory- and effector-type T cells in the human CD8+CD28+ T cell subset.

Louse-borne relapsing fever in a refugee from Mali

IntroductionDue to the increasing number of refugees from East Africa, louse-borne relapsing fever (LBRF) has become an emergent disease in Europe. No single case of LBRF has been reported in Europe in refugees from other parts of Africa.Case reportWe report a case of LBRF in a refugee from Mali, likely acquired in Libya, where several migration routes into Europe meet. The disease must be considered in any febrile refugee regardless the country of origin.

A Case of Rickettsia felis Infection Imported From Nepal

Rickettsia felis is an emerging spotted fever group pathogen that may be responsible for potentially life-threatening infections. A cosmopolitan distribution has been postulated though most human cases were observed in Africa and the Americas. We report an imported case from Nepal that occurred in an Italian tourist who presented with a 1-week history of fever, headache, nausea, vomiting, and a mild maculopapular rash 14 days after return.

Nodular Lesion of the Skin as Primary Cutaneous Tuberculosis

Extrapulmonary tuberculosis is of secondary impor-tance from the public health perspective,because it is notcontagious; nevertheless, it constitutes up to 40% ofall cases. Cutaneous tuberculosis is a rare condition incountries with low endemicity of the disease,and thusrepresents a serious diagnostic challenge to clinicians.

Whipple's disease concomitant with candida esophagitis and subsequent Giardia lamblia coinfection.

Whipples disease is a rare systemic condition resulting from a chronic infection by Tropheryma whipplei. Clinical presentation can be widely heterogeneous, often leading to delayed diagnosis and treatment. Furthermore, little is known about the underlying pathogenic mechanisms, although several abnormalities in immune cell function have been observed. We describe the case of a 51-year-old woman presenting with dysphagia, odynophagia, long-lasting low-grade fever, and malabsorption syndrome who underwent an upper gastrointestinal endoscopy showing esophageal candidiasis. On the same occasion, duodenal biopsies were also performed, with evidence of mucosal infiltration of periodic acid-Schiff-positive and CD68+ foamy macrophages at microscopic examination. Such findings were suggestive of Whipples disease, as also confirmed by molecular analysis by PCR for T. whipplei. No specific risk factors were identified in our patient that could explain the occurrence of an opportunistic infection such as candida esophagitis, thus leading to the hypothesis of a direct correlation with Whipples disease. Interestingly, a Giardia lamblia coinfection was subsequently identified, which is consistent with an underlying immune deficit although still undefined.

Imported malaria in northern Italy: epidemiology and clinical features observed over 18 years in the Teaching Hospital of Brescia

Background Even though malaria incidence is decreasing worldwide, travel-related cases reported in Europe have remained stable in recent years. In Italy, incidence had increased in the 1990s, reaching a peak in 1999; a slow decline was then reported over the subsequent decade. To our knowledge, few published data are available on imported malaria in Italy since 2010. In this article we aimed to analyse trends in imported malaria in the teaching hospital of Brescia, northern Italy, over the last 18 years. Methods All malaria cases diagnosed from 1999 to 2016 in Spedali Civili Hospital, Brescia, were retrospectively identified. Demographic, clinical and travel-related data were described. Results A total of 1200 cases of imported malaria were diagnosed in Brescia during the study period. Among them, 225 were children. A trend of increasing paediatric cases was identified over the study period, while cases in adults were stable. Most cases were diagnosed between August and October. Patients were most likely exposed in sub-Saharan Africa (87.2%). The main reported travel reason was travelling to visit friends and relatives (66.0%). A significantly higher risk of severe malaria was observed in non-immune patients and children visiting friend and relatives (P < 0.001 and P = 0.006, respectively). Conclusions Our study reveals a relatively stable incidence in imported malaria cases with a peak during the summertime. A large and increasing paediatric burden of disease was identified. Imported malaria requires attention since in Italy a potential reappearance of autochthonous Plasmodium vivax malaria transmission cannot be excluded. Preventive action and physician awareness should be especially directed to children visiting friends and relatives in endemic countries and to non-immune patients since they both represent high-risk groups for severe malaria.

Xpert MTB/RIF as add-on test to microscopy in a low tuberculosis incidence setting

Tuberculosis (TB) is a major public health concern worldwide. Early diagnosis, universal access to drug susceptibility testing and prompt initiation of treatment are key elements of the End TB strategy, and should therefore be implemented in all settings [1–5]. In order to reach TB elimination goals, the World Health Organization (WHO) currently recommends the use of a rapid molecular test, Xpert MTB/Rif (Xpert; Cepheid, Sunnyvale, CA, USA), as initial diagnostic tool when TB is suspected [6–8]. Although the excellent performance of this test in high TB burden areas is already supported by strong scientific evidence, few studies have been conducted so far to assess its impact on the diagnostic work-up of TB in low burden settings, sometimes with contrasting findings [7, 9, 10–12]. For example, according to Sohn et al. [10], Xpert testing might have limited impact in the ambulatory setting in Canada, owing to lower sensitivity and limited potential to expedite diagnosis beyond what is achieved with the existing, well-performing diagnostic algorithm. Xpert MTB/Rif should be used as an alternative test for microscopy for TB diagnosis in low incidence settings http://ow.ly/JQCF30i8nO3

The relationship between anaemia and malaria: apparently simple, yet controversial

Among many other factors, malaria plays a major causative role of anaemia globally. The mechanisms leading to anaemia in the course of malaria are extremely diverse, involving immunological factors that act differently according to age and malaria epidemiology. The malaria-attributable fraction of anaemia may then differ in different settings. While tremendous efforts are being made to control malaria, the availability of a simple and reliable biomarker of impact is of the upmost importance. Promising data are accumulating that Hb levels could be used as a proxy of malaria even in hypo-endemic areas, even if many grey areas still deserve research efforts.