Rodent-borne hemorrhagic fevers: under-recognized, widely spread and preventable - epidemiology, diagnostics and treatment.

This review presents an overview of the most important rodent-borne hemorrhagic fever pathogens directly transmitted from rodents to humans, namely Leptospira and hantaviruses, together with the New- and Old-World arenaviruses. These zoonotic diseases frequently share clinical symptoms, transmission routes and other epidemiological features and often have an emerging pattern. Differential diagnostics could benefit from a syndrome-based approach grouping these pathogens. In this review extensive descriptions of the epidemiology, clinical symptoms, diagnostics and treatment are provided including a practical overview, listing clinical features, diagnostics and risk factors for each selected rodent-borne hemorrhagic fever pathogen.

Histopathology and immunohistochemistry in the diagnosis of bioterrorism agents.

From October to November 2001, the inhalational and cutaneous anthrax cases that occurred in the U.S. underscored the importance of recognizing the clinical and pathological features of infectious agents that can be used in acts of terrorism. Early confirmation of bio-terrorist acts can only be performed by making organism-specific diagnosis of cases with clinical and pathologic syndromes that could be caused by possible bioterrorism weapons. Recognition and diagnosis of these cases is central to establish adequate responses. This review will examine the events that occurred during the anthrax bio-terrorist attack with specific emphasis on the role of pathology and immunohistochemistry and will describe the histopathologic features of category A bioterrorism agents (anthrax, plague, tularemia, botulism, smallpox, and viral hemorrhagic fevers).

Molecular approaches for the treatment of hemorrhagic fever virus infections.

Viruses causing hemorrhagic fevers in man belong to the following virus groups: togavirus (Chikungunya), flavivirus (dengue, yellow fever, Kyasanur Forest disease, Omsk hemorrhagic fever), arenavirus (Argentinian hemorrhagic fever, Bolivian hemorrhagic fever, Lassa fever), filovirus (Ebola, Marburg), phlebovirus (Rift Valley fever), nairovirus (Crimian-Congo hemorrhagic fever) and hantavirus (hemorrhagic fever with renal syndrome, nephropathic epidemia). Hemorrhagic fever virus infections can be approached by different therapeutic strategies: (i) vaccination; (ii) administration of high-titered antibodies; and (iii) treatment with antiviral drugs. Depending on the molecular target of their interaction, antiviral agents could be classified as follows: IMP dehydrogenase inhibitors (i.e., ribavirin and its derivatives); OMP decarboxylase inhibitors (i.e., pyrazofurin); CTP synthetase inhibitors (i.e., cyclopentylcytosine and cyclopentenylcytosine); SAH hydrolase inhibitors (i.e., neplanocin A); polyanionic substances (i.e., sulfated polymers); interferon and immunomodulators.

[The morphological changes in Ebola infection in guinea pigs]. / Morfologicheskie izmeneniia pri Ebola-infektsii u morskikh svinok.

Ebola virus reproduction and morphological lesions were investigated in infected guinea pigs by electron microscopy. The liver was found to be the main target organ, whereas in other internal organs the pathological changes were insignificant. Ebola virus reproduction was demonstrated only in cells of the mononuclear phagocyte system.

[The ultrastructural changes in guinea pig organs during the serial passage of the Ebola virus]. / Ul'trastrukturnye izmeneniia v organakh morskikh svinok pri posledovatel'nom passirovanii virusa Ebola.

Morphological study of internal organs of guinea pigs inoculated with Ebola virus at 2-8 passages was carried out. In the course of these passages the number of infected cells and virus particles in the organs was shown to increase, and the destructive changes in organs became more pronounced. In the 1st-3rd passages Ebola virus replication was observed in macrophagal cells only but beginning from the 4th passage of virus reproduction was found also in hepatocytes, spongiocytes, and fibroblasts.

Association of Ebola-related Reston virus particles and antigen with tissue lesions of monkeys imported to the United States.

During 1989-1990, an epizootic involving a filovirus closely related to Ebola virus occurred in a Reston, Virginia, primate-holding facility. Tissues were collected from cynomolgus monkeys and examined by electron microscopy and immunohistochemistry for Ebola-related viral antigen. Viral replication was extensive in fixed tissue macrophages, interstitial fibroblasts of many organs, circulating macrophages and monocytes, and was observed less frequently in vascular endothelial cells, hepatocytes, adrenal cortical cells and renal tubular epithelium. Viral replication was observed infrequently in epithelial cells lining ducts or mucous membranes, intestinal epithelial cells, eosinophils and plasma cells. Replication of Reston virus in lymphocytes was never observed, in contrast to reports of lymphocytes of monkeys experimentally infected with the Ebola-Zaire virus. Free filoviral particles were seen in pulmonary alveoli and renal tubular lumina, which correlates with epidemiological evidence of droplet and fomite transmission. Viral infection of interstitial fibroblasts and macrophages caused multisystemic disruptive lesions involving connective tissue. Focal necrosis in organs where viral replication was minimal may have been secondary to ischaemia caused by fibrin deposition and occasional platelet-fibrin thrombi. Immunoelectron microscopy on sections of liver, differentiated viral tubular inclusion masses and precursor material from non-viral tubuloreticular inclusions. Immunohistochemistry showed that the distribution of viral antigen in affected tissue correlated well with ultrastructural localization of virions.

Use of immunoelectron microscopy to show Ebola virus during the 1989 United States epizootic.

A filovirus, serologically related to Ebola virus, was detected by "post-embedment" immunoelectron microscopical examination of MA-104 cells. These had been infected by inoculation with serum samples obtained during the 1989 epizootic in cynomolgus monkeys (Macaca fascicularis), imported from the Philippines and maintained at Reston, Virginia, USA, a primate holding facility. The immunoelectron microscopy method, when used in conjunction with standard transmission electron microscopy (TEM) of infected cells, provided consistent results and was simple to perform in this epizootic. It is concluded that immunoelectron microscopy is potentially useful in the direct immunological diagnosis of Ebola and related filoviral infections (such as Marburg) in clinical samples obtained from those with acute infection.

Preliminary report: isolation of Ebola virus from monkeys imported to USA.

An epizootic caused by an Ebola-related filovirus and by simian haemorrhagic fever virus began among cynomolgus monkeys in a US quarantine facility after introduction of monkeys from the Philippines. This incident, the first in which a filovirus has been isolated from non-human primates without deliberate infection, raises the possibility that cynomolgus monkeys could be a reservoir of Ebola virus infection.

Primate viral diseases in perspective.

The recent occurrence of fatal Herpesvirus simiae (B virus) infection in human subjects has again focused the attention of primatologists on this virus. B virus, however, is only one of a number of viral diseases that plays a role in primate colony management. This report is to emphasize to the primatologist a number of viruses other than H. simiae, with high morbidity and mortality rates, of importance for health management of nonhuman primate animal colonies. This concept is supported by the recent occurrence in colonies of nonhuman primates of simian hemorrhagic fever virus, SA8, herpesvirus, respiratory syncytial virus, encephalomyocarditis virus, Ebola virus, and simian immunodeficiency viruses.

Molecular cloning of serogroup- and serotype-specific genome segments from bluetongue virus serotype 11.

Genome segments 2, 6, 8, and 9 of bluetongue virus (BTV) serotype 11, coding for P2, NS1, NS2, and P6, respectively, were cloned into pUC 8. Sizes of segment-2 and segment-6 clones indicated partial copies (55% and 80% of full length, respectively), whereas segment 8 and 9 clones represented full-length copies. Northern blot hybridizations of the clones to the 5 United States BTV prototypic serotypes (2, 10, 11, 13, and 17) revealed segment-2 clone to be serotype-specific to BTV-11, whereas segment 6, 8, and 9 clones were able to detect all serotypes to varying degrees. All clones failed to detect the related orbivirus, epizootic hemorrhagic disease virus.