Filippo Lipani

Louseborne Relapsing Fever among East African Refugees, Italy, 2015

During June 9–September 30, 2015, five cases of louseborne relapsing fever were identified in Turin, Italy. All 5 cases were in young refugees from Somalia, 2 of whom had lived in Italy since 2011. Our report seems to confirm the possibility of local transmission of louse-borne relapsing fever.

Diagnosis of dengue fever in North West Italy in travelers from endemic areas: A retrospective study

BACKGROUND Domestic outbreaks of Dengue (DENV) fever from imported cases have to be considered a possible risk in non-endemic countries where Dengue vectors are present, such as in Italy. OBJECTIVE To review imported acute/recent DENV infections in a one-year survey in a North West Italy region where the presence of Aedes albopictus is documented. STUDY DESIGN We retrospectively reviewed laboratory and clinical records of Italian febrile travelers from Dengue endemic areas referring to the local reference Centre for Infectious Disease, covering a population of about 4 million people. RESULTS Acute/recent DENV infection was identified in 15 out of 91 travelers from endemic areas (16.5%) including 12 primary and 3 secondary infections; in 6 patients the virus was detectable in blood according to molecular real-time Polymerase Chain Reaction-based assays: in 9 patients the diagnosis of DENV infection was accomplished by the combination of specific IgM reactivity, high IgG titers, IgG seroconversion from negative to positive and increasing (four-fold) IgG titers in paired serum samples. Two cases of DENV infections were imported from South Egypt in patients travelling together, confirming the importance of returning travelers as sentinels of a rapidly changing epidemiology in specific geographic areas. CONCLUSIONS Our findings outline the high rate of imported Dengue infection in North West Italy and emphasize the need for a continued Dengue surveillance in non-endemic countries as well as a careful evaluation and follow-up of febrile patients returning from Dengue endemic countries.

Puumala virus pulmonary syndrome in a Romanian immigrant

Hantaviruses belong to the Bunyaviridae family, which is comprised of Bunyavirus, Phlebovirus, Nairovirus, and Hantavirus. Euroasiatic Hantaviruses belong to two distinct subfamilies: Murinae (comprising Hantaan, Dobrava, and Seoul viruses), which are responsible for hemorrhagic fever with renal syndrome (HFRS), and Arvicolinae (comprising Puumala virus), responsible for nephropathia epidemica (NE) and HFRS. On the contrary, the New World Hantavirus belongs to the Sigmodontinae subfamily and includes the North American viruses: Sin Nombre, Monongahela; New York, Bayou, Black Creek Canal, and the South American, which comprise the Andes, Oran, Lechiguanas, Laguna Negra, Juquitiba; both groups are responsible for the hantavirus pulmonary syndrome (HPS).

Echovirus-4 Meningitis Outbreak Imported from India

We describe seven cases of meningitis in a group of young Italian travelers coming back from India. Virologic studies identified echovirus-4 as the cause of this cluster of cases, the first imported echovirus outbreak in Italy. Enteroviruses may play an important role in undiagnosed fevers in travelers.

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.

Pharmacodynamic Analysis of Antimalarials Used in Plasmodium falciparum Imported Malaria in Northern Italy

BACKGROUND Conventional treatment of imported malaria in Italy consists of quinine or mefloquine. Since beta-arthemeter is now available, an open-label pharmacodynamic analysis was performed in 73 adults with uncomplicated Plasmodium falciparum malaria. In vitro susceptibility to mefloquine and quinine was evaluated at admission. METHODS According to clinical status, baseline parasitemia (P(0)), and premunition, the patients received intravenous quinine, oral mefloquine, or beta-arthemeter. The following parameters were measured: parasitemia at 0, 6, 12, and 24 hours and then every 24 hours until negative; time to 50%, 90%, and 100% reduction in parasite density (PC(50), PC(90), and PCT); parasite reduction ratio at 24 and 48 hours (PRR(24) and PRR(48)); percentage of patients with undetectable parasitemia at 48 hours (PPUP(48)); time required to eradication; in vitro susceptibility to mefloquine and quinine by World Health Organization Microtest Mark III. RESULTS Of the study patients, 54.8% were immigrants from malaria-endemic countries. All the infections were acquired in Africa. All the patients were treated successfully. According to the pharmacodynamic parameters measured, no significant differences were recorded among patients with or without prior exposure to malaria. Pharmacodynamic comparison was performed between quinine and beta-arthemeter. Significantly higher clearance times were recorded for beta-arthemeter vs quinine (PC(50), PC(90), and PCT: 16.8, 42.6, and 72 h for quinine vs 7.9, 12.2, and 48 h for beta-arthemeter; p values: .02, < .0001, and .008, respectively). The number of patients who obtained a PPUP(48) with beta-arthemeter was higher than with quinine (66.7 vs 9.1%, p < .003), and PRR(24) was significantly higher in beta-arthemeter-treated patients (617 vs 3.15, p = .0001). PRR(48) and time to eradication were not measurable in the beta-arthemeter group (negative P at 48 h in most cases). Two recrudescences occurred after 5 and 7 days of beta-arthemeter monotherapy. All strains were fully susceptible to quinine and mefloquine. CONCLUSIONS Pharmacodynamic properties of mefloquine and quinine are in the range reported in literature. The better PCT and pharmacodynamics of beta-arthemeter suggest that it could be used as a first-line agent, coadministered with mefloquine.

Epstein-Barr Virus May Contribute to Central Nervous System Involvement in HIV-positive Individuals

Epstein-Barr virus (EBV) often accesses the central nervous system (CNS) where it may lead to blood brain barrier (BBB) integrity disruption, facilitating the migration of immune cells into brain parenchyma. Our aim was to study the association between cerebrospinal fluid (CSF) EBV DNA and HIV-1 compartmental replication. 281 HIV-positive adults undergoing lumbar punctures for clinical reasons (excluding those with lymphoproliferative disorders) and CSF samples were examined. CSF virological, neurodamage (tau, p-tau, 1-42 beta amyloid) and immune activation (neopterin and S100beta) markers were measured by immune-enzymatic, ELISA and PCR validated methods. Two hundred eighty one patients were included; 111 (40.5 %) were naïve for antiretroviral treatment. CSF EBV DNA was detectable in 25 (21.9%) naïve and 26 (16%) treated patients at low levels (<100 and 146 copies/mL). Naïve EBV+ subjects presented higher CSF HIV RNA, biomarkers (t-tau, p-tau, neopterin) and higher rates of pleocytosis. Treated EBV+ individuals showed pleocytosis, higher CSF HIV RNA, CSF to serum albumin ratio, IgG index and neopterin. No association was observed between detectable CSF EBV DNA and the rate of CSF escape. In patients with plasma HIV RNA <20 copies/mL (n=97) CSF EBV DNA was detectable in 13 subjects (13.4%) and it was associated with pleocytosis, higher CSF HIV RNA and neopterin levels. EBV DNA was detectable in a considerable proportion of HIV-positive patients and it was associated with higher levels of CSF HIV RNA and neuronal damage/inflammation biomarkers. The role of EBV reactivation in HIV-associated CNS disorders warrant further studies. Importance EBV is a human gamma-herpesvirus with a seroprevalence in adults approaches 95% and the pattern of clinical manifestations is very heterogeneous and varies from asymptomatic or mild viral infection to a tightly linked with several malignancies as nasopharyngeal carcinoma, Hodgkin’s lymphoma and Burkitt’s lymphoma. HIV-infected and immunocompetent patients were both at risk of primary infection and complications linked to EBV. Primary tropism of EBV is for lymphocytes (type B, T and NK), epithelial, endothelial and smooth muscle cells and establishes lifelong latent infection. Central nervous system could be affected by this herpesvirus in primary infection and reactivation and EBV-DNA is not an uncommon finding in CSF in HIV-infected population. The significance of our research is in identifying the presence of a link between HIV and EBV CNS replication.

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.RésuméLa dengue se développe au niveau mondial, en nombre de cas et en zones géographiques d’endémicité. L’Italie n’est pas une zone d’endémicité mais le vecteur compétent, Aedes albopictus, y est largement répandu. La possibilité d’introduction de l’infection ne peut donc pas être écartée. Nous avons collecté de manière rétrospective des données démographiques, cliniques et de laboratoire sur plusieurs cas consécutifs diagnostiqués à Turin et à Negrar (province de Vérone) entre 2010 et 2015. Cent treize cas de dengue ont été rapportés avec une tendance à l’augmentation au cours des années. L’infection a été majoritairement importée d’Asie du Sud-Est, mais le risque semble être plus élevé en Amérique latine. Plus de la moitié des patients ont été admis à l’hôpital, mais un seul cas grave de dengue a été observé. De nombreux patients se sont présentés après la résolution des symptômes. Les techniques de diagnostic rapide ont été utilisées sur la majorité des patients et ont permis de diagnostiquer la maladie à la phase aiguë (antigène NS1) et à la phase de convalescence (anticorps IgM). Il est particulièrement important de parvenir à un diagnostic précoce pour éviter la propagation de l’infection.

High Incidence of Infections in HIV-positive Patients Treated for Lymphoproliferative Disorders

BACKGROUND Lymphoproliferative disorders are frequently diagnosed in HIV-positive patients and severe infections may occur during antineoplastic treatments: the incidence and impact of such events are not well-characterized. OBJECTIVE To describe the occurrence and mortality of incident infections in HIV-positive individuals treated for lymphoproliferative disorders. METHODS A retrospective study in HIV-positive adults with lymphoproliferative disorders (2000- 2012) who were hospitalised to receive antineoplastic chemotherapy; antimicrobial prophylaxis with alternate day co-trimoxazole (800/160 mg) was administered to all individuals. RESULTS 103 patients were included: mostly males (81, 78.6%), Caucasians (101, 98.1%), with a median age of 43 years (39-51). Fifty-eight (56.3%) patients had non-Hodgkins lymphoma (NHL), thirty-two (29.1%) had Hodgkins lymphoma (HL) and ten patients (9.7%) had Burkitts lymphoma (BL). Five year survival was 63.1%: the best survival rates were reported in HL (78.1%), followed by NHL (58.6%) and BL (50%). Forty-four patients (42.7%) developed 82 infections during follow up: identified causative agents were bacteria (35, 42.7%), viruses (28, 34.1%), mycobacteria (7, 8.5%), protozoa (7, 8.5%) and fungi (5, 6.1%). Cytomegalovirus infections (n=17, including 5 endorgan diseases) emerged 53 days after the diagnosis: multivariate analysis showed CD4+ cell count <100/uL as the only independently associated factor (p<0.001, aOR=23.5). Two factors were associated with mortality risk: an IPI/IPS-score of >2 (p=0.004, aOR=6.55) and the presence of CMV disease (p=0.032, aOR=2.73). CONCLUSION HIV positive patients receiving treatment for lymphoproliferative disorders suffer from a high incidence of infections and associated mortality risk. Tailored prophylactic strategies need to be considered in this setting.

Imported dengue in two tertiary Italian hospitals: Use of rapid diagnostic tests

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.RésuméLa dengue se développe au niveau mondial, en nombre de cas et en zones géographiques d’endémicité. L’Italie n’est pas une zone d’endémicité mais le vecteur compétent, Aedes albopictus, y est largement répandu. La possibilité d’introduction de l’infection ne peut donc pas être écartée. Nous avons collecté de manière rétrospective des données démographiques, cliniques et de laboratoire sur plusieurs cas consécutifs diagnostiqués à Turin et à Negrar (province de Vérone) entre 2010 et 2015. Cent treize cas de dengue ont été rapportés avec une tendance à l’augmentation au cours des années. L’infection a été majoritairement importée d’Asie du Sud-Est, mais le risque semble être plus élevé en Amérique latine. Plus de la moitié des patients ont été admis à l’hôpital, mais un seul cas grave de dengue a été observé. De nombreux patients se sont présentés après la résolution des symptômes. Les techniques de diagnostic rapide ont été utilisées sur la majorité des patients et ont permis de diagnostiquer la maladie à la phase aiguë (antigène NS1) et à la phase de convalescence (anticorps IgM). Il est particulièrement important de parvenir à un diagnostic précoce pour éviter la propagation de l’infection.