METHODS AND RESULTS: Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1.
CONCLUSIONS: These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.
METHODS: A sandwich ELISA using B. malayi soluble antigen was employed to detect antifilarial IgG4 antibodies in serum samples of 330 individuals who comprised 88 healthy individuals from nonendemic areas, 15 B. malayi microfilaraemic cases, 22 individuals with soil-transmitted helminthiases, 9 elephantiasis cases and 196 residents from a B. malayi-endemic area. An O.D. value of > 0.420 at serum dilution of 1:400 was used as the cut-off point. This cut-off point was obtained by taking the mean optical density (0.252 + 4 S.E.) of 36 negative sera which had O.D. values greater than 0.1 at serum dilution of 1:400.
RESULTS: All 15 microfilaraemic persons were positive for antifilarial IgG4 antibody. Non-endemic normals, soil-transmitted helminth infected persons and chronic elephantiasis cases were negative for antifilarial IgG4 antibody. Of the 196 individuals from the filaria endemic area, 37 (18.8%) demonstrated presence of antifilarial IgG4 antibodies; and only eight individuals (4.1%) were positive for microfilariae. All eight microfilaraemic individuals were also positive for antifilarial IgG4 antibodies.
CONCLUSION: Antifilarial IgG4-ELISA could detect 4.6 times more positive cases than the microfilaria detection method. With appropriate cut-off values that eliminate cross-reactivities, this serological tool is very useful for Brugia malayi prevalence surveys and diagnosis.
OBJECTIVE: to describe a case of Nipah virus encephalitis in a pig farm worker from Malaysia.
STUDY DESIGN: the clinical, laboratory and radiological findings of this patient were scrutinized. Special emphasis was placed on the electron microscopic analysis of the cerebrospinal fluid (CSF) specimen from this patient.
RESULTS: the neurological deficits indicative of cerebellar involvement were supported by the magnetic resonance imaging that showed prominent cerebellar and brainstem lesions. CSF examination provided further evidence of viral encephalitis. Complement fixation and/or RT-PCR assays were negative for Japanese encephalitis, herpes simplex, measles and mumps viruses. ELISA for detecting IgM and IgG antibodies against Hendra viral antigens were equivocal for the CSF specimen, and tested initially negative for the first serum sample but subsequently positive for the repeat serum sample. Transmission electron microscopy of negatively-stained preparations of CSF revealed enveloped virus-like structures fringed with surface projections as well as nucleocapsids with distinctive helical and herringbone patterns, features consistent with those of other paramyxoviruses, including Hendra virus.
CONCLUSION: this case report reiterates the relevant and feasible role of diagnostic electron microscopy for identifying and/or classifying novel or emerging viral pathogens for which sufficiently specific and sensitive tests are lacking.
METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression.
RESULTS: Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses.
CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.