Detectable cerebrospinal fluid JCV DNA in late-presenting HIV-positive patients: beyond progressive multifocal leukoencephalopathy?

In the absence of effective prophylaxis and treatment, therapeutic options in HIV-positive patients with progressive multifocal leukoencephalopathy (PML) are limited to antiretroviral therapy: nevertheless, outcome is poor. We conducted a retrospective study (2009-2015) describing the outcome of 25 HIV-positive patients with detectable cerebrospinal fluid JC virus DNA: 14 had a probable PML while the others had evidence of other inflammatory central nervous system (CNS) affecting disorders. In the former group, 6-month mortality was 45.5% vs 21.4 in the latter one: survival was higher than previously described but no predictor of poor outcome was identified. Two patients treated with 5HT2-inhibitors survived. The contributing role of JCV replication in other CNS-affecting disorders needs to be assessed as well as the benefits of 5HT2-inhibitors in HIV-positive patients with proven PML.

Prevalence and predictors of blood-brain barrier damage in the HAART era.

Blood-brain barrier damage (BBBD) is prevalent in HIV-positive patients and may enhance cell trafficking to the central nervous system. A retrospective analysis in adult HIV-positive patients with no central nervous system disease was conducted in order to estimate the prevalence and risk factors of BBBD (according to cerebrospinal fluid to plasma albumin ratios). One hundred fifty-eight HIV-positive adult patients were included. BBBD impairment and intrathecal IgG synthesis were respectively observed in 45 (28.5 %) and 100 patients (63.3 %). Low CD4 nadir and high CSF HIV RNA were independently associated with both abnormalities. BBBD is common in HIV-positive patients, and its main determinants are advanced immune depression and compartmental viral replication.

Tuberculosis, COVID-19 and migrants: Preliminary analysis of deaths occurring in 69 patients from two cohorts.

Little is known about the relationship between the COVID-19 and tuberculosis (TB). The aim of this study is to describe a group of patients who died with TB (active disease or sequelae) and COVID-19 in two cohorts. Data from 49 consecutive cases in 8 countries (cohort A) and 20 hospitalised patients with TB and COVID-19 (cohort B) were analysed and patients who died were described. Demographic and clinical variables were retrospectively collected, including co-morbidities and risk factors for TB and COVID-19 mortality. Overall, 8 out of 69 (11.6%) patients died, 7 from cohort A (14.3%) and one from cohort B (5%). Out of 69 patients 43 were migrants, 26/49 (53.1%) in cohort A and 17/20 (85.0%) in cohort B. Migrants: (1) were younger than natives; in cohort A the median (IQR) age was 40 (27-49) VS. 66 (46-70) years, whereas in cohort B 37 (27-46) VS. 48 (47-60) years; (2) had a lower mortality rate than natives (1/43, 2.3% versus 7/26, 26.9%; p-value: 0.002); (3) had fewer co-morbidities than natives (23/43, 53.5% versus 5/26-19.2%) natives; p-value: 0.005). The study findings show that: (1) mortality is likely to occur in elderly patients with co-morbidities; (2) TB might not be a major determinant of mortality and (3) migrants had lower mortality, probably because of their younger age and lower number of co-morbidities. However, in settings where advanced forms of TB frequently occur and are caused by drug-resistant strains of M. tuberculosis, higher mortality rates can be expected in young individuals.

[Imported dengue in two tertiary Italian hospitals: Use of rapid diagnostic tests]. / Dengue importée dans deux hôpitaux tertiaires en Italie : utilisation des tests de diagnostic rapides.

Dengue fever is growing at a global level both as number of cases and as geographic area of endemicity. Italy is not in endemic area, but the competent vector Aedes albopictus is widespread in this country, so that the possibility of introduction of the infection cannot be ruled out. We retrospectively collected demographic, clinical, and laboratory data about consecutive cases diagnosed in Torino and Negrar-Verona in the period 2010-2015. One hundred thirteen cases of dengue were observed, with an increasing trend during years. The infection was imported mostly from south-east Asia, but the risk appears to be higher in Latin America. More than half of the patients were admitted to the hospital but only one case of severe dengue was observed. Many patients presented after the resolution of symptoms. Rapid diagnostic tests were done in the majority of patients and allowed a diagnosis both in the acute (NS1 antigen) and convalescent (IgMantibodies) phases of the disease. An early diagnosis is paramount to avoid the spreading of the infection.

Blood Brain Barrier Impairment in HIV-Positive Naïve and Effectively Treated Patients: Immune Activation Versus Astrocytosis.

Blood brain barrier (BBB) damage is a common feature in central nervous system infections by HIV and it may persist despite effective antiretroviral therapy. Astrocyte involvement has not been studied in this setting. Patients were enrolled in an ongoing prospective study and subjects with central nervous system-affecting disorders were excluded. Patients were divided into two groups: treated subjects with cerebrospinal fluid (CSF) HIV RNA <50 copies/mL (CSF-controllers) and in late-presenters CD4+ T lymphocytes <100/uL. CSF biomarkers of neuronal or astrocyte damage were measured and compared to CSF serum-to-albumin ratio. 134 patients were included; 67 subjects in each group (50 %) with similar demographic characteristics (with the exception of older age in CSF controllers). CD4 (cells/uL), plasma and CSF HIV RNA (Log10 copies/mL) were 43 (20-96), 5.6 (5.2-6) and 3.9 (3.2-4.7) in LPs and 439 (245-615), <1.69 (9 patients <2.6) and <1.69 in CSFc. BBB impairment was observed in 17 late-presenters (25.4 %) and in 9 CSF-controllers (13.4 %). CSF biomarkers were similar but for higher CSF neopterin values in late-presenters (2.3 vs. 0.6 ng/mL, p < 0.001). CSARs were associated with CSF neopterin (rho = 0.31, p = 0.03) and HIV RNA (rho = 0.24, p = 0.05) in late-presenters and with CSF tau (rho = 0.51, p < 0.001), p-tau (rho = 0.47, p < 0.001) and S100beta (rho = 0.33, p = 0.009) in CSF-controllers. In HAART-treated subjects with suppressed CSF HIV RNA, BBB altered permeability was associated with markers of neuronal damage and astrocytosis. Additional treatment targeting astrocytosis and/or viral protein production might be needed in order to reduce HIV effects in the central nervous system.

Intestinal localization of anisakiasis manifested as acute abdomen.

Anisakis pathology is due mainly to two mechanisms: allergic reactions (from isolated urticaria and angioedema to life-threatening anaphylactic shock associated with gastrointestinal symptoms or 'gastroallergic anisakiasis'), and direct tissue damage, due to invasion of the gut wall, development of eosinophilic granuloma, or perforation (gastric or intestinal anisakiasis). Anisakiasis is a misdiagnosed and underestimated cause of acute abdomen: most patients undergo laparotomy, and virtually no cases are diagnosed before surgery. In some cases, diagnosis is obtained accidentally during other pathologic investigations. We report a case of acute abdomen due to terminal ileum involvement. Microscopic examination of the resected segment showed the presence of helminthic sections consistent with larvae of Anisakis spp. A history of raw fish ingestion was recorded. Histopathologic features are illustrated. A short but up-to-date review of the literature on diagnostic devices (particularly imaging and serology), clinical aspects and therapy is presented.

Severe and complicated Falciparum malaria in Italian travelers.

Imported malaria has been an important public health problem in Western countries in the last 20 years, since international travel has become an increasing habit for nonimmune populations and since chemoresistance to most antimalarial drugs has been spreading throughout the world. Moreover, immigration from African and Asian countries has been rapidly increasing, especially in Italy in the last few years. Malaria had been widespread in Italy in the past, but no new autochthonous cases have been reported since 1961. Nonetheless the number of reported cases throughout the country has been steadily growing because of imported malaria1-3 in nonimmune travelers as well as in immigrants from tropical countries. In our experience as well as according to other statistics, the vast majority of patients have Plasmodium falciparum malaria acquired in Africa.4,5 The clinical spectrum of this disease is wide, and severe cases are frequently observed, including a few fatal cases, which, although rare, are highlighted by mass media and impress the public opinion.5-8 The purpose of this study was to examine the clinical spectrum of malaria, with particular interest in severe falciparum malaria, and to define the frequency of this phenomenon and epidemiologic characteristics of patients who experience it as a life-threatening disease.

[Multiple cutaneous leishmaniasis after a stay in Central America]. / Leishmaniosi cutanea a lesioni multiple dopo un soggiorno in America Centrale.

Leishmaniasis is a protozoal disease affecting at least 12 millions persons, with 400,000 new cases per year. It is transmitted by a small insect, the phlebotomine sand fly. Clinical syndromes include visceral leishmaniasis and various cutaneous affections. We describe here the case of a patient affected by a multiple lesions New World cutaneous leishmaniasis, after staying in Costa Rica for tourism; we discuss the differential diagnosis and make a short summary of the principles of treatment.

Spontaneous release of interferon as a predictor of clinical evolution in HIV-positive subjects.

In order to establish a correlation with disease progression we prospectively evaluated ten clinical and immunologic parameters in 102 consecutive HIV-positive subjects. The eight immunologic variables were: in vitro spontaneous interferon release by peripheral blood monocytic cells, alpha- and gamma-interferon production induced by Newcastle Disease Virus and PHA, Multitest Mérieux score, PHA- and CON-A-induced lymphocyte transformation, absolute number of CD4+ cells and CD4/CD8 ratio, respectively. The two baseline clinical variables were risk factor and disease presentation. Generalized Wilcoxon analysis indicated a significant correlation of one clinical (disease presentation at entry) and three immunologic variables (spontaneous interferon release, CD4+ cell number, Multitest Mérieux) with disease progression. Baseline spontaneous release of alpha, acid-labile interferon showed the best correlation with disease progression, and appeared to be significantly associated with CD4+ cell loss. Spontaneous release of acid-labile alpha interferon by mononuclear cells in vitro could be highly predictive of disease evolution in HIV-Ab positive, AIDS-free subjects.

[Cardiac complications in HIV infections]. / Complicazioni cardiache nella infezione HIV.

UNLABELLED: Cardiological involvement in HIV infection is relatively rare but it presents important clinical aspects that are still open questions. We report our experience with HIV patients who underwent cardiological evaluation, Doppler echocardiography and follow-up. MATERIAL AND METHOD: We selected 127 patients (9%) on the basis of clinical suspicion of heart disease, taking them from the 1398 admitted for HIV infection between 1992 and 1995. Ninety-six patients had AIDS (group A) and 31 were in pre-AIDS phase (group B). The age was 21-52 years: 83 were males, 44 were females and 91% of the patients had been drug addicts. Echocardiography was executed with Hp Sonos 1000 and Sonos 2500 devices. Follow-up was 6-36 months. RESULTS: Ninety-two patients (6.5% on total admitted patients) had heart disease. Thirty-five patients were normal on echocardiography. Other diseases were: pericardial effusion in 38 cases (30%), with CD4+ number significantly lower (p < 0.005); dilated cardiomyopathy in 20 patients (16%), with a low CD4+ number (p < 0.005); reversible segmental or diffuse hypokinesia compatible with clinical myocarditis was seen in 11 patients (9%), especially in group A (p < 0.005); infective endocarditis in 17 patients (13%), especially group B (p < 0.005); right ventricular dilatation in 7; discrete right ventricular mass in 3 patients. Sixty-five patients (51%) died during follow-up (group A only). There were 19 cardiac deaths (15%), which represents 1.3% of the total number of patients. Nine of these (47%) were in patients with cardiomyopathy. Total mortality was 85% in patients with dilated cardiomyopathy, 73% in myocarditis cases, 71% in pericarditis cases (especially extracardiac), 66% in right ventricular dilatation cases, 18% in endocarditis cases, 34% in normal cases. CONCLUSIONS: Cardiac complications assume clinical importance, especially in the AIDS phase of HIV infection, but early diagnosis in the pre-AIDS phase is important for treatment. Clinical evaluation and echocardiography are corner-stones of the diagnosis. Prognosis depends especially on the clinical stage of HIV infection and myocardial involvement.