Induction of Distinct Neurologic Disease Manifestations during Relapsing Fever Requires T Lymphocytes.

Relapsing fever borreliosis is a multisystemic infection characterized primarily by bacteremia but can extend to the CNS. The incidence of CNS disease manifestations in humans depends on the infecting relapsing fever Borrelia species. In the murine model of Borrelia hermsii infection we found high incidence of distinct signs of CNS disease that ranged from a flaccid tail to complete paralysis of hind limbs. Infiltration of large number of T cells into the spinal cord of B. hermsii-infected mice and the upregulation of MHC class II and CD80 on infiltrating macrophages and on microglial cells suggested a role for T cell and Ag-presenting cell interactions in this pathogenesis. Indeed, B. hermsii infection did not induce CNS disease manifestations in T cell-deficient mice (TCR-ß × d-/-), although it resulted in bacteremia comparable to wild-type (Wt) level. Moreover, the infiltration of immune cells into the spinal cord of TCR-ß × d-/- mice was reduced and the resident microglial cells were not activated. Histopathological analysis of lumbar sections of the spinal cord confirmed severe inflammation in Wt but not in TCR-ß × d-/- mice. Induction of CNS disease was dependent on the B. hermsii strain as well as on the ability of the host to control bacteremia. Mice that are impaired in controlling B. hermsii, such as CD14-/- mice, exhibited more severe CNS disease than Wt mice. This study demonstrates that distinct neurologic disease manifestations develop during relapsing fever and that T cells play a critical role in the induction of neuropathogenesis.

Rift Valley Fever Epidemiology, Surveillance, and Control: What Have Models Contributed?

Background: Rift Valley fever (RVF) is an emerging vector-borne zoonotic disease that represents a threat to human health, animal health, and livestock production, particularly in Africa. The epidemiology of RVF is not well understood, so that forecasting RVF outbreaks and carrying out efficient and timely control measures remains a challenge. Various epidemiological modeling tools have been used to increase knowledge on RVF epidemiology and to inform disease management policies.

Interlaboratory comparison of real-time polymerase chain reaction methods to detect Coxiella burnetii, the causative agent of Q fever

The bacterium Coxiella burnetii, which has a wide host range, causes Q fever. Infection with C burnetii can cause abortions, stillbirth, and the delivery of weak offspring in ruminants. Coxiella burnetii infection is zoonotic, and in human beings it can cause chronic, potentially fatal disease. Real-time polymerase chain reaction (PCR) is increasingly being used to detect the organism and to aid in diagnosis both in human and animal cases. Many different real-time PCR methods, which target different genes, have been described. To assess the comparability of the C. burnetii real-time PCR assays in use in different European laboratories, a panel of nucleic acid extracts was dispatched to 7 separate testing centers. The testing centers included laboratories from both human and animal health agencies. Each laboratory tested the samples using their in-house real-time PCR methods. The results of this comparison show that the most common target gene for real-time PCR assays is the IS1111 repeat element that is present in multiple copies in the C. burnetii genome. Many laboratories also use additional real-time PCR tests that target single-copy genes. The results of the current study demonstrate that the assays in use in the different laboratories are comparable, with general agreement of results for the panel of samples.

Coxiella burnetii (Q fever) seroprevalence in cattle

Human cases of Q fever appear to be common in Northern Ireland compared to the rest of the British Isles. The purpose of this study was to describe the seroepidemiology of Coxiella burnetii infection in cattle in Northern Ireland in terms of seroprevalence and determinants of infection. A total of 5182 animals (from a stratified systematic random sample of 273 herds) were tested with a commercial C. burnetii phase 2 IgG ELISA. A total of 6.2% of animals and 48.4% of herds tested positively. Results from a multilevel logistic regression model indicated that the odds of cattle being infected with Q fever increased with age, Friesian breed, being from large herds and from dairy herds. Large dairy herd animal prevalence was 12.5% compared to 2.1% for small beef herds. Preliminary seroprevalence in sheep (12.3%), goats (9.3%), pigs (0%) rats (9.7%) and mice (3.2%) using indirect immunofluorescence is reported.

Human seroprevalence to Coxiella bumetii (Q fever) in Northern Ireland

Despite the widespread prevalence of infection with Coxiella burnetii, there have been few large population-based studies examining the epidemiology of this infection. The aim of this study was to examine the distribution and determinants of C. burnetii past infection in Northern Ireland (NI). Coxiella burnetii phase II specific IgG antibodies were measured by enzyme-linked immunosorbent assay in stored serum from 2394 randomly selected subjects, aged 12-64, who had participated in population-based surveys of cardiovascular risk factors performed in 1986 and 1987. The overall prevalence of C. burnetii antibody positivity was 12.8%. The prevalence of sero-positivity was slightly higher in males than that in females (14.3% versus 11.2%, P = 0.02). Sero-positivity was low in children (

Sensitive detection of African swine fever virus using real-time PCR with a 5 ' conjugated minor groove binder probe

The design of a 5' conjugated minor groove binder (MGB) probe real-time PCR assay is described for the rapid, sensitive and specific detection of African swine fever virus (ASFV) DNA. The assay is designed against the 9GL region and is capable of detecting 20 copies of a DNA standard. It does not detect any of the other common swine DNA viruses tested in this study. The assay can detect ASFV DNA in a range of clinical samples. Sensitivity was equivalent to the Office International des Epizooties (OIE) recommended TaqMan assay. In addition the assay was found to have a detection limit 10-fold more sensitive than the conventional PCR recommended by the OIE. Linear range was ten logs from 2 x 10(1) to 2 x 10(10). The assay is rapid with an amplification time just over 2 h. The development of this assay provides a useful tool for the specific diagnosis of ASF in statutory or emergency testing programs or for the detection of ASFV DNA in research applications. (C) 2010 Elsevier B.V. All rights reserved.

Exploratory Space-Time Analyses of Rift Valley Fever in South Africa in 2008-2011

Background: Rift Valley fever (RVF) is a zoonotic arbovirosis for which the primary hosts are domestic livestock (cattle, sheep and goats). RVF was first described in South Africa in 1950-1951. Mechanisms for short and long distance transmission have been hypothesised, but there is little supporting evidence. Here we describe RVF occurrence and spatial distribution in South Africa in 2008-11, and investigate the presence of a contagious process in order to generate hypotheses on the different mechanisms of transmission. Methodology/Principal Findings: A total of 658 cases were extracted from World Animal Health Information Database. Descriptive statistics, epidemic curves and maps were produced. The space-time K-function was used to test for evidence of space-time interaction. Five RVF outbreak waves (one in 2008, two in 2009, one in 2010 and one in 2011) of varying duration, location and size were reported. About 70% of cases (n = 471) occurred in 2010, when the epidemic was almost country-wide. No strong evidence of space-time interaction was found for 2008 or the second wave in 2009. In the first wave of 2009, a significant space-time interaction was detected for up to one month and over 40 km. In 2010 and 2011 a significant intense, short and localised space-time interaction (up to 3 days and 15 km) was detected, followed by one of lower intensity (up to 2 weeks and 35 to 90 km). Conclusions/Significance: The description of the spatiotemporal patterns of RVF in South Africa between 2008 and 2011 supports the hypothesis that during an epidemic, disease spread may be supported by factors other than active vector dispersal. Limitations of under-reporting and space-time K-function properties are discussed. Further spatial analyses and data are required to explain factors and mechanisms driving RVF spread. © 2012 Métras et al.

Study of aflatoxin exposure in a Brazilian population using an aflatoxin - albumin biomarker

The evaluation of exposure to aflatoxins (AF) by measurement of the level of contamination in food is hampered due to the heterogeneous distribution of AF in food. Therefore, an alternative is to estimate the exposure using specific biological markers (biomarkers) based on an understanding of the metabolism of the compound. For AF, these include aflatoxin-N-7-guanine in the urine, or AFB(1)-albumin (AF-alb) in the blood. This study assessed the level of exposure to AF in Brazilian individuals using a biomarker approach, i.e. the AF-alb adducts. Blood samples were collected from urban residents (n=50; aged 18-52) in June 1999, at the Blood Center of Antonio Carlos de Camargo Hospital, Sao Paulo, Brazil. AF-alb adduct levels were determined, by ELISA following serum albumin extraction and digestion. AF-alb adducts were detected in 31/50 (62%) samples [range 0-57.3 pg AFB(1)-lys adducts/mg of blood albumin (pg/mg)]. The mean level of positives was 14.9 pg/mg and males had the two highest levels measured (57.1 and 57.3 pg/mg). There was no correlation with age or profession. This is the first study of Brazilian, or indeed South American, individuals that has determined exposure to AF at the individual level using a biomarker approach. These levels are similar to those observed in the Philippines. These data warrant further investigation of both the sources and consequences of exposure to this potent toxin in Brazil.

Two peptides, TsAP-1 and TsAP-2, from the venom of the Brazilian yellow scorpion, Tityus serrulatus: evaluation of their antimicrobial and anticancer activities

Here we report two novel 17-mer amidated linear peptides (TsAP-1 and TsAP-2) whose structures were deduced from cDNAs cloned from a venom-derived cDNA library of the Brazilian yellow scorpion, Tityus serrulatus. Both mature peptides were structurally-characterised following their location in chromatographic fractions of venom and synthetic replicates of each were subjected to a range of biological assays. The peptides were each active against model test micro-organisms but with different potencies. TsAP-1 was of low potency against all three test organisms (MICs 120-160µM), whereas TsAP-2 was of high potency against the Gram-positive bacterium, Staphylococcus aureus (MIC 5µM) and the yeast, Candida albicans (10µM). Haemolytic activity of TsAP-1 was low (4% at 160µM) and in contrast, that of TsAP-2 was considerably higher (18% at 20µM). Substitution of four neutral amino acid residues with Lys residues in each peptide had dramatic effects on their antimicrobial potencies and haemolytic activities, particularly those of TsAP-1. The MICs of the enhanced cationic analogue (TsAP-S1) were 2.5µM for S.aureus/C.albicans and 5µM for E.coli but with an associated large increase in haemolytic activity (30% at 5µM). The same Lys residue substitutions in TsAP-2 produced a dramatic effect on its MIC for E.coli lowering this from >320µM to 5µM. TsAP-1 was ineffective against three of the five human cancer cell lines tested while TsAP-2 inhibited the growth of all five. Lys residue substitution of both peptides enhanced their potency against all five cell lines with TsAp-S2 being the most potent with IC50 values ranging between 0.83 and 2.0 µM. TsAP-1 and TsAP-2 are novel scorpion venom peptides with broad spectrum antimicrobial and anticancer cell activities the potencies of which can be significantly enhanced by increasing their cationicity.