Sandfly virus seroconversion associated with neurologic presentation.

OBJECTIVE: To describe the clinical presentation and unique neurologic manifestations of sandfly viruses (SFVs) in the Jerusalem area. METHODS: We identified all patients with acute seroconversion to SFV at the Hadassah-Hebrew University Medical Centers during the years 2008-2013 and retrospectively collected and analyzed the clinical and imaging data. RESULTS: Nine patients (ranging from 1.5 to 85 years old) were identified. Presentation included acute neurologic disease, mostly with fever, change in consciousness and behavior, seizures, headache, meningitis, limb paresis, or myelitis. Eight patients had clinical signs of meningitis, meningoencephalitis, or encephalitis alone. Four patients had myelitis. MRI identified pathologic symmetrical changes in the basal ganglia, thalami, and other deep structures in 5 patients, and additional myelitis of the spine was noted on imaging in 3 patients. Seven patients had long-term follow-up: 4 completely recovered and 3 had remaining neurologic sequelae, among them 1 with permanent severe brain damage. CONCLUSION: Neurologic involvement associated with acute SFV infections is considered to be benign. However, in this series, all 9 patients presented with significant neurologic pathology associated with a unique finding of myelitis and symmetrical basal ganglia, thalami, or white matter involvement. Thus, acute SFV infection should be included in the differential diagnosis in febrile onset of neurologic manifestations and neuroradiologic changes.

Primary Versus Nonprimary West Nile Virus Infection: A Cohort Study.

BACKGROUND: Since 2001, we have observed patients with a clinical picture consistent with West Nile virus (WNV) infection, which was defined as nonprimary infection (NPI) owing to the presence of highly elevated serum immunoglobulin G antibody titers with a high avidity index (≥ 55%), absent or low titers of serum and cerebrospinal fluid (CSF) immunoglobulin M, and occasionally positive results of WNV-specific real-time reverse-transcription polymerase chain reaction analysis of CSF and/or blood specimens. METHODS: We investigated 124 patients with a diagnosis of primary WNV infection (PI) or NPI during 2005-2007 at Sheba Medical Center (Tel-Hashomer, Israel). Logistic regression was used to evaluate the association of variables with PI and NPI and with in-hospital mortality. RESULTS: A total of 68 and 50 patients with PI and NPI, respectively were included; 6 patients had incomplete data. In multivariate models, NPI was significantly associated with underlying psychiatric disorders (adjusted odds ratio [aOR], 13.73; 95% confidence interval [CI], 2.28-82.56; P = .004), hospitalization during winter and spring (aOR, 8.82; 95% CI, 1.59-48.87; P = .013), and fever (aOR, 0.61; 95% CI, .39-.95; P = .031). In-hospital mortality was significantly associated with NPI (aOR, 3.86; 95% CI, 1.12-13.28; P = .032) and a higher Charlson comorbidity index (aOR, 1.37; 95% CI, 1.03-1.83; P = .032). CONCLUSIONS: The possibility that NPI may be an emerging clinical entity with a high mortality rate must be considered seriously.

West Nile fever in Israel: the reemergence of an endemic disease.

BACKGROUND: As a crossroads for bird migration between Africa and Eurasia and with its long history of human infection, Israel has been a major focus of attention during the continuing global spread of West Nile fever (WNF). This article reviews the background and reemergence of WNF in Israel; the recent epidemiology of WNF among Israelis; and the disease-control strategies being used to combat the disease. METHODS: Employing the comprehensive base of case data that are reported to the Ministry of Health, an epidemiological record was constructed that details the incidence and distribution of WNF cases in Israel in recent years. RESULTS: After decades of small, intermittent outbreaks, nearly 1400 cases of WNF were reported in Israel between 2000 and 2012. Incidence was consistently highest in the coastal cities, among elderly patients, and in the late summer months and early autumn. A broad range of control measures to prevent human infection has been implemented, and attention has been given to issues such as the protection of the national blood bank and the occurrence of long-term sequelae. CONCLUSIONS: The reemergence of WNF in Israel is likely the result of a combination of factors including past immunity to the virus among the human population, a marked increase in awareness of WNF among physicians, and more frequent requests for the laboratory testing of suspected cases. In the absence of effective vaccine to protect humans from WNF, the best disease-control strategies include intensive vector-control measures, the continued development of techniques to forecast outbreaks, and effective public education programs that are targeted toward the high-risk elderly population.

Barkedji virus, a novel mosquito-borne flavivirus identified in Culex perexiguus mosquitoes, Israel, 2011.

Barkedji virus, named after the area of its first identification in Senegal, is a newly discovered flavivirus (FV), for which we propose the abbreviation BJV. In the present study, we report the first-time detection of BJV in Culex perexiguus mosquitoes in Israel in 2011 and determination of its almost complete polyprotein gene sequence. We characterized the BJV genome and defined putative mature proteins, conserved structural elements and potential enzyme motifs along the polyprotein precursor. By comparing polyproteins and individual proteins of BJV with several other FVs, a distant relationship of BJV to Nounane virus (NOUV), a recently described African FV, is demonstrated. Phylogenetic analysis of 55 selected flaviviral polyprotein gene sequences exhibits two major clusters, one made up of the classical three clades of FVs: mosquito-borne, tick-borne and those without known vectors. The other cluster exclusively contains so-called 'insect-specific' FVs, which do not replicate in vertebrate cells. Based on our phylogenetic analysis, BJV is related to other members of the mosquito-borne clade with yet unknown vertebrate hosts, such as NOUV, Donggang virus, Chaoyang virus and Lammi virus. However, with a maximum identity of only 54 % to NOUV, BJV represents a distinct new virus species.

Capillary leakage in travelers with dengue infection: implications for pathogenesis.

Dengue hemorrhagic fever is characterized by the presence of a capillary leak syndrome. Its pathogenesis is presumed to differ from that of classical dengue fever (DF) and to be associated with secondary dengue infection. Returning travelers given a diagnosis of DF were evaluated for capillary leakage with abdominal sonography. Data were compared between travelers with primary/secondary infection defined by epidemiologic and serologic parameters. A total of 12 (34.3%) of 35 patients had sonographic signs of capillary leakage. Most (85%) patients with capillary leakage had classical DF. Capillary leak was diagnosed in 32% of primary dengue cases and in 40% of secondary dengue cases (P = 0.69). The two patients given a diagnosis of dengue hemorrhagic fever had primary infections. The high prevalence of capillary leakage among travelers, most of them with primary exposure to dengue, calls into question the importance of secondary infection in causing capillary leakage in dengue infection.

The clinical response of West Nile virus neuroinvasive disease to intravenous immunoglobulin therapy.

The aim of the study was to determine whether intravenous gamma globulin (IVIG) treatment is effective in patients with West Nile Virus (WNV) neuroinvasive disease. We contacted hospital based infectious disease experts in Israeli hospitals to identify patients with WNV neuroinvasive disease who were treated with IVIG. The main outcome measure was neurological response after treatment. There were 12 patients who received IVIG and four improved within 48 h. Three patients died, 6 had partial recovery, and 3 recovered completely. Eleven of the 12 patients were infected with Israeli genotypes that are highly homologous to Europe/Africa viruses. The rapid response in some patients suggests that IVIG is effective, and might be used to treat patients with WNV neuroinvasive disease with IVIG.

Protracted rheumatic manifestations in travelers.

BACKGROUND: Travel returnees may complain of protracted rheumatic symptoms, but there are sparse data regarding their causes. We aimed to describe travelers returning with new rheumatic symptoms. METHODS: We conducted a retrospective analysis of Israeli travelers who were referred to the Sheba Medical Center from January 2005 to January 2010 with prolonged (>4 weeks) nontraumatic arthralgia or arthritis. RESULTS: During 5 years, 14 patients (7 men and 7 women) with posttravel arthritis/arthralgia were seen. A total of 5 patients were diagnosed with reactive arthritis, and 9 were diagnosed with rheumatic symptoms related to infection with Alphaviruses: Chikungunya virus or Ross River virus. Some disability remained for several months in most cases, but only 1 case of reactive arthritis eventually evolved to a chronic spondyloarthropathy. CONCLUSIONS: Travel-related arthritis may persist even several months after the exposure. Assessing patients' travel history may help in the evaluation of some cases with rheumatic manifestations. Their prognosis may be better than that of autoimmune arthritides.

Chikungunya fever in Israeli travelers returning from northwestern India.

Chikungunya fever has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular touristic sites. We describe the case of three Israeli travelers who developed fever, maculopapular rash, and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic.

West Nile virus-induced pancreatitis.

West Nile Virus (WNV) infection is a fairly common infection in Israel, especially during the summer season. Common manifestations are fever, headaches, malaise and myalgia. Pancreatitis had been described only twice previously as a complication of WNV infection in the medical literature. In this report, an 88-year-old patient is described, who was admitted to hospital with fever, confusion and general deterioration in her condition, accompanied by severe abdominal pain. WNV infection was diagnosed by a lumbar puncture and serological tests. The laboratory results demonstrated elevated amylase and lipase levels. The patient was treated conservatively and the symptoms regressed slowly until full recovery. WNV infection and its complications are described, along with descriptions of previous reports of pancreatitis associated with WNV infection.

Long-term Death Rates, West Nile virus epidemic, Israel, 2000.

We studied the 2-year death rate of 246 adults discharged from hospital after experiencing acute West Nile Virus infection in Israel during 2000. The age- and sex-adjusted death rates were significantly higher than in the general population. This excess was greater for men. Significant adverse prognostic factors were age, male sex, diabetes mellitus, and dementia.

Stiff-person syndrome following West Nile fever.

BACKGROUND: Stiff-person syndrome is a rare autoimmune disorder associated with antibodies against glutamic acid decarboxylase (GAD), the key enzyme in gamma-aminobutyric acid synthesis. In most cases, a trigger cannot be identified. OBJECTIVE: To describe a 41-year-old man who developed stiff-person syndrome and antibodies to GAD following acute West Nile virus infection. DESIGN: A case report and a search in GenBank for common epitopes. RESULT: The search revealed a stretch of 12 amino acids in the NS1 protein of West Nile virus with a high degree of homology to the GAD65 region (an isoform of GAD) containing the PEVKEK motif. CONCLUSION: Cross-reactivity between antibodies directed against West Nile virus and GAD may have contributed to the development of stiff-person syndrome in this patient.