Exotic emerging diseases

Emerging infectious diseases is a term for new infectious diseases in humans that have either newly appeared in a population or have already existed but are rapidly increasing in incidence or geographic range. The term also covers diseases that are caused by novel pathogens. These have developed from bacteria or viruses that were previously harmless for humans but have continuously genetically changed and evolved in such a way that they suddenly pose a threat to humans. Some of them originate in the animal kingdom and have become able to infect humans due to genetic changes, while other pathogens can turn from initially harmless to humans to life-threatening.

Among the rather unusual emerging infectious diseases are bornavirus encephalitis and Crimean-Congo haemorrhagic fever.

In 2018, bornavirus (Borna disease virus 1, BoDV-1) was identified as the cause of severe inflammations of the brain (encephalitides) in humans that occurred in three recipients of donor organs from the same post-mortem donor [1, 2]. After initially flu-like symptoms, severe neurological manifestations such as behavioural disorders, subsultus as well as speech and gait impairments (paresis) occur. In most of the known cases the disease led to death within a few weeks after onset of the first symptoms [3].

BoDV-1 is known as the causative agent of Borna disease in horses, sheep and other mammals in central Europe and naturally occurs in the bicoloured shrew (Crocidura leucodon), which is particularly common in southern regions of Germany as well as in parts of Austria, Liechtenstein and Switzerland.  However, BoDV-1 should not be confused with the variegated-squirrel bornavirus 1 (VSBV-1), which was discovered in 2015 after three variegated-squirrel (Sciurus variegatoides) breeders from Saxony-Anhalt, Germany, died from encephalitides [1, 4, 5].

Most likely, humans get infected with BoDV-1 through contact with excretions of infected shrews, e.g. by consuming contaminated food or water, by inhaling contaminated dust or through direct contact with shrews or through shrew bites. It is also conceivable that, for instance, pets that hunt shrews play a role in human infections. To date, human-to-human transmission is considered unlikely. Infected animals other than shrews, such as horses, sheep and other domestic animals, also do not seem to be infectious to humans. [3]

Another novel pathogen is Crimean-Congo hemorrhagic fever virus (CCHFV), which is most common in Africa, Eastern Europe, parts of Asia and the Middle East (countries below latitude 50 degrees north) [6]. The virus was first isolated in 1965 in former Belgian Congo, but the first cases of human infection already occurred in Crimea in the 1940s. After unspecific initial symptoms (e.g. fever, shivering, headache), approximately one in eight infected persons develop severe symptoms such as multiple bleedings of mucous membranes and skin, cardiac arrhythmia and a reduced leukocyte and thrombocyte count in the blood. Up to 30% of severe cases are fatal [7].

Ticks of the genus Hyalomma are the main CCHFV reservoir and transmit the virus through their bites. Humans can also get infected through contact with blood or tissue of an infected animal, for instance, during slaughter. Human-to-human transmission is also possible through contact with blood or other bodily fluids of an infected person.

Although almost everything is focused on SARS-CoV-2, EUROIMMUN has also continued to pursue other areas of development. As a result, we are now able to offer new test systems for detection of antibodies against bornavirus (Anti-Bornavirus IIFT, IgG, order no. FI 2620 G) and against CCHFV (Anti-Crimean-Congo fever virus (CCHFV) ELISA (IgG or IgM; order no. EI 279a-9601 G or M). The company is thus adding two more assays for novel pathogens to its already very extensive product portfolio for infection diagnostics.

Because of the close relationship between bornaviruses the Anti-Bornavirus IIFT, which is suitable for both serum and CSF samples, can also detect antibodies against other human-pathogenic bornaviruses such as VSBV-1. However, the immunofluorescence test can currently only be used for research and not for in vitro diagnostics.

The Anti-Crimean-Congo Fever Virus (CCHFV) ELISA (IgG or IgM; order no. EI 279a-9601 G or M) is based on a recombinant nucleocapsid protein of Crimean-Congo fever virus and provides detection of human antibodies of immunoglobulin classes IgM or IgG against Crimean-Congo fever virus in human serum. The test is CE marked and can therefore be used to support the diagnosis of a CCHFV infection. It is a useful supplement to direct pathogen detection. Preliminary study data on the ELISAs was recently published in PLOS Neglected Tropical Diseases [8].

[1] Tappe, D., et al. Sci Rep 9, 20154 doi:10.1038/s41598-019-56839-4 (2019). [2] Schlottau, K., et al. N Engl J Med 379:1377-1379 (2018). [3] RKI-Merkblatt – Informationen zur Vermeidung von Infektionen mit den Borna Disease Virus 1. Robert Koch-Institut, Berlin, (2019) [4] Pörtner, K., et al. Dtsch Arztebl 116(50) (2019). [5] Hoffmann, B., Tet al. N Engl J Med 373.  (2015). [6] Introduction to Crimean-Congo Haemorrhagic Fever. World Health Organization (2019). [7] Nasirian H. Comp Immunol Microbiol Infect Dis 69:101429 (2020). [8] Emmerich P., et al.  PLOS Neg Trop Dis https://doi.org/10.1371/journal.pntd.0009280 (2021).

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