Throughout the world, humans have been affected by various types of diseases with different origins. Zoonotic diseases, or diseases which have the capability to jump species, animals to humans or vice versa, have been particularly troublesome and deadly. Zoonotic diseases are unique in that they are mainly caused by pathogens such as fungi, bacteria, parasites, or viruses. These pathogens typically survive in a reservoir host, which have immunity to the pathogen. The list of possible reservoir hosts capable of transmitting disease to humans is expansive. However the most common are apes, insects, rodents, and bats. The diseases are then passed to humans who come in contact with an infected animal through bites or scratches, an infected animal’s environment, or animal secretions such as saliva, feces, or mucus. Often these diseases have a higher virulence because of the lack of any immunity within the human population and the ease of transmission. Some more infamous zoonotic diseases are West Nile, Rabies, Ebola, and Dengue fever.
As of recent, more and more zoonotic diseases are emerging because of an increase in human and wildlife interaction. An increase in farming and or deforestation has resulted in humans and wildlife into the same habitat. A prime example of this is the emergence of the Nipah virus (NiV). Nipah virus, prototypical species of the genus Henipavirus, are emerging highly pathogenic Paramyxoviruses (family-Paramyxoviridae) which cause severe encephalitic and respiratory disease in a wide range of mammalian species, including humans.
NiV infection has been found in 5 of 14 fruit bat species, with the highest being Pteropus hypomelanus with a 31% infection rate. Despite having a relatively high infection rate, the species of Pteropus fruit bats are not susceptible to the virus. The virus is primarily transmitted via body secretions or partially eaten fruit. Pigs have been found to be particularly susceptible to NiV as well as highly contagious to each other. Pigs have been identified as an intermediate and an amplifying host. An amplifying host is defined as a host in which the pathogen can become so prevalent a vector, such as a mosquito, can become infectious.
Pigs transmit NiV differently than bats in that they shed the virus primarily by coughing and the expulsion of respiratory secretions and saliva. NiV has not been isolated in pig urine. Pigs are primarily infected directly from Pteropus fruit bats or other pigs. Humans have been found to be infected by three different pathways, Pteropus fruit bat to human, pig to human, and or human to human. Most recent transmission of NiV has been a result of human to human transmission through close contact through respiratory secretions or urine.
Nipah Virus (NiV)
Structure and Virulence
The Henipavirus family is pleomorphic, meaning their shape is varied, and traditionally 40-600 nm in diameter. The core of a virion contains a linear ribonucleprotein (RNP) comprising of negative sense single stranded RNA. Also present in the RNP are three critically important proteins. Nucelocapsid proteins (N) are tighly bound to the various nucleotides of the RNA strand. N protein is the most abundant protein present and necessary for capsid structure. Phosphoproteins (P) and large polymerase proteins (L) are also bound to the RNA and aid RNA polymerase in transcribing RNA to mRNA to antigenomic RNA. The virion is enveloped by a traditional lipid bilayer but “spiked” with fusion (F) and receptor-binding glycoproteins (G). The fusion proteins are responsible for fusing the viral membrane to the host membrane triggering the release of the contents of the virion. The receptor-binding glycoporteins are extremely specific and bind only to Ephrin B2 (EFNB2) surface proteins. Specifically, NiV has been found to alternatively bind to EFB3 as well. The EFNB2 surface proteins are highly conserved across the mammalian lineage. On the underside of the lipid bilayer matrix proteins (M) are present for structural support and regulating the budding process. Other proteins, C, V, and W, are also present in the cytoplasm and involved in regulation of transcription and replication. In regards to the Nipah virus genome, the exact structure is not completely understood. However because of the strong homology between Hendra virus and Nipah virus, a nearly identical structure is hypothesized. The negative sense single stranded RNA is of traditional 3’ to 5’ orientation. All the previously mentioned proteins are encoded by the RNA in the order of 3’-N-P-M-F-G-L- 5’. Similar to all paramyxoviruses NiV RNA replication occurs in the cyptoplasm. All but the P gene are monocystronic, in that they code for a single protein. The P gene also encoded for the C, V, and W proteins which play a role in the virulence of NiV.
The Nipah virus primarily attacks the respiratory system, which is supported by the finding of high concentrations of viral antigens are found in the respiratory tract and lung epithelium. NiV infection also produces signs of nervousness, twitching and trembling, hemorrhaging, and lesions in both the brain and lungs. Nipah virus infection in human infection is particularly encephalitic. The onset of a fever after and incubation period as short as two days or as long as a month is the first sign of infection. Common signs of a viral infection such as headache and drowsiness occurred along with the fever. Doctors are able to distinguish a Nipah viral infection by the distinctive symptoms of encephalitis, vasculities, neurological deficits due to necrosis, thrombosis, and ischemia. The cerebrospinal fluid is also heavily impacted with an increase of proteins and dead cells present.
The First Outbreak of Nipah Virus
It was first noted in September 1998 in the north-western part of peninsular Malaysia. By March 1999, the outbreak had spread to other pig-farming areas of the country, inclusive of the neighbouring country, Singapore. A total of 283 human cases of viral encephalitis with 109 deaths were recorded in Malaysia from 29 September 1998 to December 1999. During the outbreak period, a number of surveillances under three broad groups; Surveillance in Human Health Sector, Surveillance in Animal Health Sector, and Surveillance for the Reservoir Hosts, were carried out to determine the prevalence, risk of virus infections and transmission in human and swine populations as well as the source and reservoir hosts of Nipah virus. Surveillance data showed that the virus spread rapidly among pigs within infected farms and transmission was attributed to direct contact with infective excretions and secretions. The spread of the virus among pig farms within and between states of peninsular Malaysia was due to movement of pigs. The transmission of the virus to humans was through close contact with infected pigs. Human to human transmission was considered a rare event though the Nipah virus could be isolated from saliva, urine, nasal and pharyngeal secretions of patients. Field investigations identified fruitbats of the Pteropid species as the natural reservoir hosts of the viruses.
Nipah Virus Scare in South India
Current situation in Calicut Medical College due to #NipahVirus (24 April, 2018).
The death toll due to outbreak of Nipah virus raised to 12 in the southern state of India (Kerala), with one more person succumbing to the deadly virus in Kozhikode this morning, said a Health ministry official (24 April, 2018).
Meanwhile, there are reports of dead bats being found on the premises of a government school in Himachal Pradesh, samples of which have been sent for testing to NIV, Pune, to ascertain the reason behind their deaths.
According to the health ministry officials, of the 12 deaths in Kerala so far due to the virus, nine people died in Kozhikode district and three in Mallappuram. Besides, about 160 samples have been sent for testing at the virology institute.
While 18 people with specific symptoms are admitted at hospitals in Kozhikode, 22 patients with suspected Nipah cases, all from Malappuram district, are admitted at Kozhikode Medical College for observation.
“They are all contacts of the confirmed cases and their lab results are awaited. Also, 95 families are under surveillance,” a health ministry official said.
Despite the severe pathogenicity of these viruses and their pandemic potential, no therapeutics or vaccines are currently approved for use in humans.
According to National Vector Borne Disease Control Programme, the drug ribavirin has been shown to be effective against the viruses in vitro, but human investigations to date have been inconclusive and the clinical usefulness of the drug remains uncertain.
Favipiravir (T-705) is a purine analogue antiviral approved for use in Japan against emerging influenza strains; and several phase 2 and 3 clinical trials are ongoing in the United States and Europe. Favipiravir has demonstrated efficacy against a broad spectrum of RNA viruses, including members of the Paramyxoviridae, Filoviridae, Arenaviridae families, and the Bunyavirales order. In vitro, favipiravir inhibited Nipah and Hendra virus replication and transcription at micromolar concentrations. In the Syrian hamster model, either twice daily oral or once daily subcutaneous administration of favipiravir for 14 days fully protected animals challenged with a lethal dose of Nipah virus.
This first successful treatment of henipavirus infection in vivo with a small molecule drug suggests that favipiravir should be further evaluated as an antiviral treatment option for henipavirus infections.
In the wake of Nipah virus cases in Kerala, the Indian Council for Medical Research (ICMR) has written to the Queensland government in Australia asking it to provide an antibody developed there to test if it can “neutralise” the virus in humans.
Knowledge and awareness on the disease should be improved and disseminated to health services, veterinarians, farmers and consumers. It is important to enhance our preparedness to counter potential future introduction of exotic pathogens as henipaviruses in non-endemic areas by conducting active pre-emergence research. Of utmost importance, monitoring the evolving epidemiology of a dangerous pathogen like the Nipah virus is an essential element to be able to promptly adapt control plans in the case that it might become a new public health priority.
©BforBiotech by Bedadyuti Mohanty, Assistant Managing Editor by Profession and Bio-technologist by heart.