Sandfly fevers. by author. Prof. Anna Papa MD, PhD National Reference Centre for Arboviruses Aristotle University of Thessaloniki, Greece

Transcription

1 Sandfly fevers Prof. Anna Papa MD, PhD National Reference Centre for Arboviruses Aristotle University of Thessaloniki, Greece Caused by phleboviruses Genus Phlebovirus, Bunyaviridae family Sandfly fever Sicilian virus Sandfly fever Naples virus Toscana virus Novel phleboviruses Sandfly fevers PHLEBOVIRUSES DISEASE Asymptomatic infections Mild disease with flu-like symptoms CNS infections (meningitis, encephalitis) SFSV and SFNV cause a transient febrile illness. TOSV is neurovirulent, leading to aseptic meningitis and meningoencephalitis. 1

2 Main vectors of phleboviruses: phlebotomine sandflies Etymologia. Phlebotomus: from the Greek words phlebo + tomi=intersect a vein The sandfly becomes infected when biting an infected human in the period between 48 h before the onset of fever and 24 h after the end of the fever, and remains infected for its lifetime. Military importance of phleboviruses: Large number of invading non-immune persons may be incapacitated at the time when they are mostly needed. 1944, First use of DDT for the control of malaria vectors, decrease of SF cases. 2

3 The exact epidemiology of each species is not well understood because: - asymptomatic or mild febrile cases are significantly more prevalent than previously suspected. - the identification of the virus cannot be assessed with certainty (cross-reactions). Although sandflies are widely distributed, most sandfly fever cases occur around the Meditteranean Basin. Meditteranean Sea The incidence of SF in the Americas is relatively low. The sandflies there, are sylvan and do not enter houses to bite people. 3

4 Phlebotomus fever, papataci fever, 3-day fever A few days (2-5) after the infective bite, patients develop high fever, chills, severe frontal headaches, muscle and joint pains, flushing of the face, conjunctiva injection, and tachycardia. After 2 days the fever begins to subside and the temperature returns to normal. Fatigue, depression, bradycardia and subnormal blood pressure may persist from few days to several weeks. Recovery is usually complete. DD. Dengue, CHIK Sandfly fever Toscana virus infections - Asymptomatic - Influenza-like syndrome - Meningitis or meningoencephalitis in summer May to October, with peak in August. Central Italy: 80% of acute CNS viral infections in children and 50% of cases in adults during summer. Central Anatolia, Turkey: 15% of aseptic meningitis. Portugal: 5.6% of meningitis cases. Greece: 7-17% of CNS infections Significant public health issue in Europe 4

5 Phlebovirus infections in Greece, Time: April to October Tested: 494 patients with febrile syndrome (50% with CNS infection) Results: 43 (8.7%) patients had a phlebovirus infection. Phleboviruses account for % of CNS infections Phlebovirus infections Year LABORATORY DIAGNOSIS Total Phlebo pos CNS phlebo pos Virus isolation and RT-PCR in blood or cerebrospinal fluid is only possible in early stages of infection i.e. the first 1-2 days after symptom onset and before the IgM detection. In most cases the diagnosis is based on serological testing (ELISA, IFA) of acute and early convalescent sera. Serological cross reactions exist within the antigenic complex. Neutralization assays using early convalescent sera are the reference method to identify the viruses or to assess the antibody response specificity. * The patient has lifelong immunity to the infecting phlebovirus but not to heterologous serotypes. 5

6 Corfu virus Phleboviruses in Greece Lefkas virus SFSV* TOSV* Adria virus* Cyprus: Outbreak of phlebovirus infections, Cyprus virus Chios virus* Cyprus virus* May-September 2002, Nicosia 256/581 (44%) Greek soldiers years old. Fever (39-41 o C), headache, rigors, arthralgia, myalgia h. Malaise for 2 weeks. Leucopenia, monocytosis, 2X elevation of transaminases (mainly ALAT) Laboratory diagnosis Genetic detection of a SFS-like virus (Cyprus virus) Isolation in Vero E6 cells Detection of IgM and IgG antibodies 6

7 Turkey Summer of 2007 and 2008 Turkey in Kozan and Izmir in Med Turkey, and Ankara in central Turkey. A SFSV-like strain was isolated (SFTV) highly homologous to Cyprus virus. 23 Sept y boy admitted to a hospital in Thessaloniki, Greece, because of a first episode of febrile seizures. No underlying disease. Fever (38.2 C) and vomit while in the nursery school. Sudden adherence of eye gaze, peroral cyanosis, masseter muscle spasm, tonic convulsions of the body and extremities and involuntary loss of urine. The episode lasted 3 minutes. He presented irritability and felt sleepy. By the time he entered the hospital, he was apyretic. Clinical examination normal. leukocytosis (22.600/μl) % neutrophils. Full recovery, discharge 2 days later. Adria virus is pathogenic to humans D10759, UUKV AY293623, Chios virus, Greece GQ165521, Corfou virus, Greece 93 GU233649, Utique virus, Tunesia GU233647, Utique virus, Tunesia AY962268, SFSV, Cyprus EF095551, SFSV, Italy DQ375430, RVFV X56464, RVFV DQ862467, ARBV, Italy 99 Adria-1, Albania Adria-5, Albania Adria-15, Greece DQ656072, Massilia virus, France 87 DQ975233, TOSV, Italy 97 FJ153281, TOSV, France FJ153280, TOSV, Spain 69 FJ153279, TOSV, Spain GQ165522, Tehran virus, Iran GU183868, SFNV, Italy EF095548, SFNV, France Salehabad serocomplex 7

8 Female patient 49 years old, admission to a hospital with severe encephalitis. The woman had confusion and delirium. ICU, intubation. Total hospitalization time: 12 days. Serum and CSF samples sent for WNV testing: WNV negative, phlebovirus positive. Computed tomography scan image of the brain. The scan shows dilated lateral ventricles and increased attenuation of the subarachnoid spaces due to edema. CSF of 2 nd day of illness: detection of Toscana virus lineage C. FJ153280, EsPhGR40, Spain FJ153281, H/IMTSSA, France TOSV lineage B EF656363, AR, France 80 JX867534, T152, Tunesia NC_006319, ISS.Phl.3, Italy TOSV lineage A Genesi-2012-GR* Sandfly Fever Naples Serocomplex TOSV lineage C GQ403627, T8-09, Croatia JF939846, I-47, Tehran virus 95 15% nt difference 73 EF095548, Poona, Naples virus 85 JF939843, Sabin, Naples virus JF920139, Yu 8/76, Naples virus from Croatian strain 96 GU233649, P6_B1_2008, Utique virus GQ165521, Pa Ar814, Corfou virus* AY962268, Sandfly Sicilian Cyprus virus Sandfly Fever Sicilian Serocomplex GQ847513, Izmir 19, Sandfly Sicilian Turkey virus EF095551, Sabin, Sicilian virus JX472400, ISS Phl18, Arbia virus JX472403, I-81, Salehabad virus HM043725, Adria/ALB1/ Salehabad Serocomplex Thes-2009-GR, Adria virus*

9 In July 2013, a 45-year-old Greek male, was admitted to a hospital in northwestern Greece with 2-day history of fever, myalgia, arthralgia, mild headache, and hemorrhagic exanthema. A serum sample obtained from the patient on the 6 th day of illness was tested negative for West Nile virus infection. Instead, high titers of IgM and IgG antibodies against Toscana virus (TOSV) were detected, with low titers against sandfly fever Naples virus and no reactivity against sandfly fever Sicilian and Cyprus viruses, suggesting that the causative agent was TOSV or other phlebovirus with antigenic similarity to TOSV. IgM antibodies against A: Toscana virus B: Sandfly fever Sicilian virus. 9