Modelling the spread of foot-and-mouth disease virus

Foot-and-mouth disease is an economically important viral disease in animals. It is shown that airborne diffusion is one of the main sources of contamination between animals and between herds. Epidemiological data linked to viral particle excretion can thus be used in a predictive model, added to meteorological data related to the few days before the slaughter of animals. The model computes, on a 10 km radius around the outbreak and in every space direction, the quantity of viral particles that a sensitive animal could have breathed. The aim is to define a risk area, and, according to the number and size of farms in the surrounding, to give arguments for the best sanitary decision within the emergency plan.     

Genetic characterization of canine distemper virus in Serengeti carnivores

The lion (Panthera leo) population in the Serengeti ecosystem was recently afflicted by a fatal epidemic involving neurological disease, encephalitis and pneumonia. The cause was identified as canine distemper virus (CDV). Several other species in the Serengeti were also affected. This report presents CDV H and P gene sequences isolated from Serengeti lions (Panthera leo), spotted hyenas (Crocuta crocuta), bat-eared fox (Otocyon megalotis) and domestic dog (Canis familiaris). Sequence analyses demonstrated that the four Serengeti species carry closely related CDV isolates which are genetically distinct from other CDV isolates from various species and locations. The results are consistent with the conclusions that: (1) a particularly virulent strain of CDV emerged among Serengeti carnivores within the last few years; (2) that strain has recognizable shared-derived (synapomorphic) genetic differences in both H and P genes when compared to CDV from other parts of the world; and (3) that the CDV strain has frequently crossed host species among Serengeti carnivores.     

Modelling the spread of HIV in social networks of injecting drug users

OBJECTIVE: To explore the risk of a future rise of HIV prevalence in populations of injecting drug users (IDU) with low HIV prevalence but continuing risk behaviour, and to study the potential influence of prevention measures on HIV incidence. METHODS: A stochastic simulation model was used to describe a network of long-term buddy relationships in a population of IDU. HIV transmission took place when borrowing injecting equipment from an infected buddy or stranger. The probability of transmission depended on the duration of infection. Individuals remained in the population on average for 10 years. Two surveys amongst IDU in The Netherlands containing information about risk behaviour were used to estimate model parameters. We investigated the effect of different prevention strategies. RESULTS: Below a threshold sharing frequency the epidemic never takes off; above the threshold there is a large stochastic variation in prevalence. After reduction of risk behaviour, HIV prevalence decreases very slowly. Reducing sharing with strangers is more effective than reducing the overall sharing frequency. Prevention focused on new IDU greatly reduces HIV incidence. Reduction of sharing frequency in HIV-positive IDU has no significant influence on HIV incidence at HIV testing rates of 10 and 50% per year, if infectivity is highest during primary infection. CONCLUSIONS: A stabilization of HIV prevalence does not exclude the possibility of a future rise. Predictions about the future course of an epidemic are inherently uncertain. The effect of prevention programmes on HIV prevalence only becomes visible on a long time-scale. Social networks of IDU play an important role in transmission dynamics and success of prevention.     

Screening for IgE mediated allergy among people working in the Marseilles harbour

Clinical application of colony-stimulating factors (CSFs) such as recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) are advancing rapidly now that these factors are approved as indicated therapy in patients with chemotherapy-induced neutropenia, patients undergoing autologous bone marrow transplantation (BMT) and patients who develop graft failure after BMT. Novel CSFs are also being explored for potential clinical application in situations not as significantly affected by rhG-CSF or rhGM-CSF. Studies determining unique effects of novel factors, combinations of factors and combinations with peripheral blood progenitor cell fusions which may lead to future clinical applications of CSFs will be reviewed.     

Immune responses to canine distemper virus in joint diseases of dogs

Wearing-off phenomenon that complicates levodopa therapy of Parkinson's disease has been attributed to a reduction in striatal dopamine storage due to the progressive degeneration of presynaptic dopaminergic terminals. To determine whether postsynaptic mechanisms also contribute to these response fluctuations, the duration of the antiparkinsonian response in parkinsonian patients grouped by disease severity was compared following discontinuation of a steady-state optimal-dose infusion of apomorphine. Although the plasma half-life of this dopamine receptor agonist remained constant, its mean efficacy half-time declined from 66 minutes in early, levodopa-naive patients to 33 minutes in advanced, complicated parkinsonians (p < 0.005). Since the motor effects of apomorphine do not depend on the presence of dopaminergic terminals, changes at the postsynaptic level undoubtedly contribute to the diminished response duration. The only slightly greater attenuation of levodopa's motor effects observed previously under similar conditions suggests these postjunctional alterations, possibly involving relatively plastic striatal dopaminoceptive systems, account for most of the shortening in the duration of levodopa action that underlie wearing-off fluctuations.     

Cytochromes P450, P420 & mixed-function oxidases as biomarkers of polychlorinated biphenyl (PCB) exposure in harbour seals (Phoca vitulina)

Hepatic microsomal cytochrome P450, EROD and ECOD activity were investigated as biomarkers of PCB exposure in harbour seals (Phoca vitulina). Due to the difficulty of obtaining undegraded seal liver samples, standard spectrophotometric methodology was adapted to investigate P420 (degraded P450) as a PCB biomarker with partially degraded samples. Total PCB burdens in both blubber and liver had positive correlations with P450, P420 and MFO activity levels. The use of P420 biomarkers in this study supports the inclusion of samples from by-caught marine mammals for future biomonitoring studies. P450 isozymes CYP1A (P4501A) and CYP2B (P4502B) in conjunction with MFO activity were investigated as "specific" biomarkers of PCB exposure. They were found to reliably reflect levels of [MC] and [PB]-type PCB exposure in harbour seal liver.     

Expression of a murine leukemia virus Gag-Escherichia coli RNase HI fusion polyprotein significantly inhibits virus spread

The antiviral strategy of capsid-targeted viral inactivation (CTVI) was designed to disable newly produced virions by fusing a Gag or Gag-Pol polyprotein to a degradative enzyme (e.g., a nuclease or protease) that would cause the degradative enzyme to be inserted into virions during assembly. Several new experimental approaches have been developed that increase the antiviral effect of the CTVI strategy on retroviral replication in vitro. A Moloney murine leukemia virus (Mo-MLV) Gag-Escherichia coli RNase HI fusion has a strong antiviral effect when used prophylactically, inhibiting the spread of Mo-MLV and reducing virus titers 1,500- to 2,500-fold. A significant (approximately 100-fold) overall improvement of the CTVI prophylactic antiviral effect was produced by a modification in the culture conditions which presumably increases the efficiency of delivery and expression of the Mo-MLV Gag fusion polyproteins. The therapeutic effect of Mo-MLV Gag-RNase HI polyproteins is to reduce the production of infectious Mo-MLV up to 18-fold. An Mo-MLV Gag-degradative enzyme fusion junction was designed that can be cleaved by the Mo-MLV protease to release the degradative enzyme.     

Rate of seasonal spread of respiratory syncytial virus in a pediatric hospital

The rate of nosocomial respiratory syncytial virus (RSV) infection was measured in a large pediatric hospital using an incidence density method. The at-risk days for nosocomial RSV were summed during a defined winter period in which there were 54 admissions with community-acquired RSV infection giving a rate of 2.9 cases per 1,000 at-risk days (95% confidence interval, 0.3-5.4 per 1,000).     

Sequence analysis and expression of the attachment and fusion proteins of canine distemper virus wild-type strain A75/17

The biological properties of wild-type A75/17 and cell culture-adapted Onderstepoort canine distemper virus differ markedly. To learn more about the molecular basis for these differences, we have isolated and sequenced the protein-coding regions of the attachment and fusion proteins of wild-type canine distemper virus strain A75/17. In the attachment protein, a total of 57 amino acid differences were observed between the Onderstepoort strain and strain A75/17, and these were distributed evenly over the entire protein. Interestingly, the attachment protein of strain A75/17 contained an extension of three amino acids at the C terminus. Expression studies showed that the attachment protein of strain A75/17 had a higher apparent molecular mass than the attachment protein of the Onderstepoort strain, in both the presence and absence of tunicamycin. In the fusion protein, 60 amino acid differences were observed between the two strains, of which 44 were clustered in the much smaller F2 portion of the molecule. Significantly, the AUG that has been proposed as a translation initiation codon in the Onderstepoort strain is an AUA codon in strain A75/17. Detailed mutation analyses showed that both the first and second AUGs of strain A75/17 are the major translation initiation sites of the fusion protein. Similar analyses demonstrated that, also in the Onderstepoort strain, the first two AUGs are the translation initiation codons which contribute most to the generation of precursor molecules yielding the mature form of the fusion protein.     

Rapid spread of HIV among injecting drug users in north-eastern states of India

Manipur, a north-eastern state of India bordering Myanmar, has experienced very rapid transmission of the human immunodeficiency virus (HIV) among its vast drug-injecting population. Seroprevalence among intravenous drug users increased from 0 per cent in September 1989 to 50 per cent within six months. With a minimum injecting population of 15,000 and seropositivity of over 50 per cent, the infection quickly spread to the population at large. One per cent of antenatal mothers tested seropositive by 1991. Forming part of the area of South-East Asia known as the Golden Triangle, and producing opium and its derivatives, Myanmar shares a long international border with four States of the region, and populations with a common language and culture move freely across borders. Two other north-eastern states of India bordering Myanmar have faced a similar epidemic within a short period of time. As a result of serosurveillance for HIV since 1986, the epidemic could be detected at an early stage. The present paper provides an account of the results of ongoing comprehensive studies conducted in the north-eastern states of India on drug-related HIV infection, already a serious problem, but possibly still restricted to that region of the country. The prevalence of intravenous drug users, their HIV serological status, the demographic profile, risk behaviour, the spread of the infection to other groups and the problems of harm minimization are also covered.     

Up-regulation of major histocompatibility complex class II antigen expression in the central nervous system of dogs with spontaneous canine distemper virus encephalitis

Major histocompatibility complex class II (MHC II) and canine distemper virus (CDV) antigen expression were compared by immunohistochemistry in the cerebellar white matter of ten dogs with naturally occurring canine distemper encephalitis. In addition, infiltrating mononuclear cells were characterized by employing poly- and monoclonal antibodies directed against human CD3, canine MHC II, CD5, B cell antigen and CDV-specific nucleoprotein. Positive antigen-antibody reaction was visualized by the avidin-biotin-peroxidase complex method on frozen sections. Histologically, neuropathological changes were categorized into acute, subacute, and chronic. In control brains, MHC II expression was weak and predominantly detected on resident microglia of the white matter and on endothelial, perivascular and intravascular cells. In CDV antigen-positive brains, MHC II was mainly found on microglia and to a lesser extent on endothelial, meningeal, choroid plexus epithelial, ependymal and intravascular cells. In addition, virtually all of the perivascular cells expressed MHC II antigen. CDV antigen was demonstrated most frequently in astrocytes. Of the perivascular lymphocytes, the majority were CD3-positive cells, followed by B cells. Only a small proportion of perivascular cells expressed the CD5 antigen. In addition, B cells and CD3 and CD5 antigen-positive cells were found occasionally in subacute and frequently in chronic demyelinating plaques. In acute encephalitis, CDV antigen exhibited a multifocal or diffuse distribution, and MHC II was moderately up-regulated throughout the white matter and accentuated in CDV antigen-positive plaques. In subacute encephalitis, moderate multifocal CDV antigen and moderate to strong diffuse MHC II-specific staining, especially prominent in CDV antigen-positive lesions, were observed. In chronic encephalitis, CDV antigen expression was restricted to single astrocytes at the edge of the lesions or was absent, while MHC II expression, especially prominent on microglia, was strongly up-regulated throughout the white matter, most pronounced in demyelinated plaques. In summary, in acute and subacute lesions without perivascular cuffs, MHC II expression correlated with the presence of CDV antigen. In contrast, in chronic lesions, MHC II expression on microglial cells was the most prominent despite a few CDV antigen-positive astrocytes, indicating that nonviral antigens may play an important role as triggering molecules for the process of demyelination.     

Immunohistochemical demonstration of spread of Aujeszky''s disease virus to the porcine central nervous system after intestinal inoculation

The effects of the non-mammalian tachykinin physalaemin were studied on the short circuit current (SCC) and on both influx (Ji) and outflux (Jo) of 36Cl- and 22Na+ across the isolated skin of Rana esculenta. Physalaemin, added to the internal bathing fluid, increased SCC in a dose-dependent manner with a maximal effect at 1 microM. This increase was due to a stimulation of both Na+ absorption and Cl- secretion. Bumetanide (20 microM in the internal fluid), an inhibitor of the Na+/K+/2Cl- cotransporter, reduced the action of physalaemin on SCC by 46%. Furthermore diphenylamine-2-carboxylic acid (DPC, 0.1 mM in the external fluid), an inhibitor of Cl- channels, decreased the effect of the peptide on SCC by 48%. It is concluded that physalaemin activates the Na+/K+/2Cl- cotransporter at the basolateral membrane, accumulating Cl- in the cells and favouring its exit through Cl- channels at the outermost membrane of the epithelium. An inhibitor of cyclooxygenases, i.e. naproxen, strongly inhibited the physalaemin effect on SCC, whereas 5,8,11-eicosatriynoic acid (ETI), an inhibitor of lipooxygenases was without effect. Therefore, it is proposed that prostaglandins (probably PGE2) are the cellular mediators of this action. An antagonist of NK1 receptors for tachykinins, CP 99,994, inhibited the physalaemin action on SCC, whereas challenge with SR 48,968, an antagonist of NK2 receptors, had no effect on physalaemin action. It is concluded that physalaemin effect on SCC in frog skin is mediated by its interaction with NK1 receptors.     

B and T cells are required for mouse mammary tumor virus spread within the mammary gland

Mouse mammary tumor virus (MMTV) is an infectious retrovirus transmitted through milk from mother to newborns. MMTV encodes a superantigen (SAg) whose activity is indispensable for the virus life cycle, since a genetically engineered virus with a mutation in the sag gene neither amplified in cells of the immune system of suckling pups nor infected their mammary glands. When wild-type MMTV was injected directly into the mammary glands of uninfected pubescent mice, their lymphoid as well as mammary gland cells became virus infected. To test whether this infection of lymphoid cells was dependent on SAg activity and required for virus spread within the mammary gland, we performed mammary gland injections of wild-type MMTV(C3H) into two strains of transgenic mice that lacked SAg-cognate, V beta 14+ T cells. Neither the MTV-ORF or LEL strains showed infection of their mammary glands. Moreover, no MMTV infection of their peripheral lymphocytes was detected. Similar experiments with mice lacking B cells (mu-chain knockouts) showed no detectable virus spread in the mammary glands or lymphoid tissues. These data suggest that SAg activity and MMTV-infected lymphocytes are required, not only for initial steps of viral infection, but also for virus spread within the mammary gland. Virus spread at late times in infection determines whether MMTV induces mammary tumors.     

Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users

To assess the effect of human immunodeficiency virus (HIV) immunosuppression on ongoing hepatitis C virus (HCV) infection, CD4 lymphocyte counts and serum concentrations of HCV RNA, HIV RNA, and alanine aminotransferase (ALT) were evaluated among members of a cohort of injecting drug users (IDUs). With 100 participants randomly selected at various stages of HIV-related immunosuppression, serum HCV RNA concentrations increased with age (P = .007) and were higher in HIV-positive IDUs with 201-500 (P = .026) and 51-200 (P = .004) CD4 cells/mL than in HIV-negative participants. Among 27 HCV-infected IDUs who acquired HIV infection, serum HCV RNA concentrations varied between semiannual visits by a mean of 0.45 logs, increasing by 0.60 logs after HIV seroconversion (P < .0001), by 0.12 logs each subsequent year (P = .006), and by 0.36 logs per log increase in CD4 cells (P = .01). Serum ALT levels were similar between HIV-positive (40.1 IU/mL) and HIV-negative (45.4 IU/mL) patients (P > .10). While HIV infection and possibly HIV progression are associated with increased HCV RNA levels, other factors appear to affect biochemical and virologic markers of HCV infection in some dually infected persons.     

Prevalence of infection with dengue virus among international travelers

BACKGROUND: Dengue has been recognized as a potential hazard to tourists. A prospective, controlled study in the outpatient clinic of a German infectious disease clinic was conducted to assess the prevalence of dengue virus infection among international travelers. METHODS: Serum samples from 130 patients with signs or recent history clinically compatible with dengue (fever, headache, muscle and joint pain, or rash), 95 matched controls with diarrhea, and 26 patients who never visited a country endemic for dengue were investigated. RESULTS: Nine (6.9%) of the 130 patients with compatible symptoms and 1 (1%) of the 95 controls with diarrhea developed rising antibody titers against dengue virus. Of these 10 patients with probable dengue infection, 6 had been to Thailand, 2 to Malaysia, and 1 each to Indonesia and Brazil. CONCLUSIONS: Infection with dengue virus appears to be a realistic threat to travelers to Southeast Asia. Symptoms commonly associated with dengue, such as fever, myalgia, arthralgia, and vomiting, can be helpful for diagnosis when present, but the absence of typical symptoms does not exclude infection.     

Suppression and the upward spread of masking

The purpose of this study is to clarify the role of suppression in the growth of masking when a signal is well above the masker in frequency (upward spread of masking). Classical psychophysical models assume that masking is primarily due to the spread of masker excitation, and that the nonlinear upward spread of masking reflects a differential growth in excitation between the masker and the signal at the signal frequency. In contrast, recent physiological studies have indicated that upward spread of masking in the auditory nerve is due to the increasing effect of suppression with increasing masker level. This study compares thresholds for signals between 2.4 and 5.6 kHz in simultaneous and nonsimultaneous masking for conditions in which the masker is either at or well below the signal frequency. Maximum differences between simultaneous and nonsimultaneous masking were small (< 6 dB) for the on-frequency conditions but larger for the off-frequency conditions (15-32 dB). The results suggest that suppression plays a major role in determining thresholds at high masker levels, when the masker is well below the signal in frequency. This is consistent with the conclusions of physiological studies. However, for signal levels higher than about 40 dB SPL, the growth of masking for signals above the masker frequency is nonlinear even in the nonsimultaneous-masking conditions, where suppression is not expected. This is consistent with an explanation based on the compressive response of the basilar membrane, and confirms that suppression is not necessary for nonlinear upward spread of masking.     

The significance of measles virus antigen and genome distribution in the CNS in SSPE for mechanisms of viral spread and demyelination

Two timolol preparations, a gel and an eyedrop with a thickening agent, and one commercial eyedrop without a thickening agent, were studied in rabbits. After topical administration of these three preparations in rabbits, aqueous humor was withdrawn and the proteins removed from the samples by precipitation with acetonitrile. Timolol concentrations were determined directly by an HPLC method. The HPLC mobile phase was composed of methanol and 5 mM d-camphorsulfonic acid (in 1% acetic acid) with a ratio of 49:51 (v/v). A reversed phase C18 column was used to separate samples with a flow rate of 0.8 mL/min and a UV detector set at 284 nm. A two-compartment pharmacokinetic model was used to fit the aqueous humor level for determining the drainage (kd) and absorption rate constants (ka) in the precorneal area as well as the elimination rate constant (ke) of timolol in aqueous humor. For ka +kd, the eyedrop without a thickening agent had the highest value (0.160 min-1), followed by the eyedrop with a thickening agent (0.030 min-1), and the gel had the lowest value (0.009 min-1). It suggests that the gel has a longer retention time in eyes to improve ocular bioavailability and decrease side effects. The AUC0 approximately infinity for the aqueous humor profile with time coordinates were 4142, 2974, and 1604 micrograms min/mL, for the gel, the eyedrop with a thickening agent, and the eyedrop without a thickening agent, respectively. In another study, timolol preparations were also topically administered in alpha-chymotrypsin-induced glaucoma rabbits for determining the lowering effect on intraocular pressure (IOP). The durations of depressing IOP for the gel, the eyedrop with a thickening agent, and the eyedrop without a thickening agent were 24, 14 and 10 hrs, respectively. Thus, the gel preparation has a longer duration and a higher ocular bioavailability which might be further developed in the treatment of open-angle glaucoma.