Is the Zoonotic Nipah Virus an example of things to come as human beings continue to encroach on the ecosystems of earth?

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Is the Zoonotic Nipah Virus an example of things to come as human beings continue to encroach on the ecosystems of earth?

An Important Emerging Infectious Disease: The Zoonotic Nipah Virus

Introduction



The Zoonotic Nipah Virus, a relatively recent emerging infection, seems to be evolving to become fatally infectious to humans, and serves as an example of human environmental encroachment and manipulation that disturbs ecosystems causing infections, that would normally only cycle through animal populations, to jump the fence into humans.



The most concerning factor about Nipah the increase in its mortality rate in humans (40% in 1999 to 74% in 2004) and its shortened its transmission path (first bats to pigs to humans, and then only bats to human and, maybe, human to human).

Nipah originally occurred in the pig industry. This occurrence serves as an example of a human activity causing environmental encroachment (creating a false high population density for pigs near a bat habitat). And it caused an initial economic impact on human beings (the slaughter of at least 800,000 pigs in the Malaysian pig industry).

One wonders if it did not have such an economic impact would it have been so closely studied as only 105 initial human cases were discovered (but then that is rather pessimistic of me). One would like to think that the 105 human fatalities caused the intensive scientific search, not the economic loss. Which, as the last known fatalities did not result in massive economic loss, shows that the search for a remedy is an altruistic one.

Name of the Disease and its Etymology

The Nipah Virus Encephalitis is named after the village Sungai Nipah, in Negeri Sembilan, Malaysia, where the victim that the virus was isolated from died.

Symptoms of the disease

The symptoms of a Nipah virus infection are similar to Japanese Encephalitis and first can appear as a common flu. It has an incubation period of 4 to 18 days. In many cases the infection is minimal or almost unnoticeable; but in serious cases the symptoms manifest as “influenza-like,” with high fever, headache, and myalgia (muscle pain). If the disease progresses, inflammation of the brain occurs along with drowsiness, seizures, disorientation, behavioral abnormalities, coma, and difficulty breathing. Patients entering a coma did not survive. One noticeable symptom that is noticeably different from other encephalitis type diseases is a jerking of the neck and stomach muscles.

History of the Disease

The Nipah virus was first isolated in April 10,1999, from a worker who had died in the village of Sungai Nipah in Negeri Simbilan in the country of Malaysia. Prior to its isolation, there had been reports of illness amongst pig farmers in 1997; one of whom died. In 1998 another outbreak of viral encephalitis occurred amongst two neighboring villages. At the end of 1998, ten workers died after being in comas from four days to several weeks. 15% of these cases were identified as Japanese Encephalitis while 85% were of an unknown origin. From March 1 to May 10, 1999, 224 cases of viral encephalitis were reported in Negeri Sembilan; and out of these 224, 100 cases were fatal.

The origin of the infections was traced back to pigs that were also affected by the virus, and between February 28 to April 26, 1999, the Malaysian government instigated a pig extermination program to eradicate the virus. 901,918 pigs were culled in the infected areas of the State of Perak, Selangor and Negeri Sembilan.

In May, 1999 the World Health Organization declared the outbreak to be over. Two years later, the Office International des Epizooties (OIE) announced that the Nipah virus was no longer in the Malaysian pig population as of the middle of 2001.

In January and February 2001, an outbreak of a febrile illness similar to a Nipah virus infection occurred in Siliguri, West Bengal, India. A follow-up study in 2006 indicated that the Siliguri outbreak is a variety of Nipah virus.

In April and May 2001, nine patient deaths from a febrile neurologic illness occurred and some villagers in Meherpur District, Bangladesh showed reactive antibodies to the Nipah virus antigen. Then in January 2003, more illnesses of a febrile neurologic disorder ending with eight deaths occurred in some villages in the Naogaon District of Bangladesh, 150 km from the Meherpur District in Bangladesh. The worrisome condition of these outbreaks was that there was no obvious zoonotic point of origin as with the pigs in Malaysia. Antigens for the Nipah virus were found in local Pteropus bats, but the more serious fact was that it appeared that family members of the patients may have contracted the Nipah virus from infected family members. This indicated that the virus was possibly able to be transmitted by human-to-human contact.

Another Bangladeshi outbreak occurred from January to April 2004 where 35 of 47 people infected died. The virus had changed from a 40% mortality rate in Malaysia in 1999 (105 people out of 245 died), to a mortality rate of 74% (35 out of 47) in 2004 in Bangladesh.

By 2005, scientists determined that the Nipah virus occurs naturally in the native fruit bats P (Pteropus). hypomelanus, P. vampyrus, P. lylei of Thailand and Cambodia, local Pteropus bats (P. giganteus ) of Bangladesh, and in two types of Malaysian fruit bats (Cynopterus brachyotis and Eonycteris spelaea) and one type of Malaysian insect eating bat (S. kuhlii). Also in 2005, Scientists determined that the specific cell surface receptor, Ephrin-B2, is used by Nipah and Hendra viruses to get inside cells. This receptor is found on cells in the central nervous system and those lining blood vessels, which helps explain the neurologic symptoms of the disease. By identifying the cell receptors, scientists hope to be able to create vaccines and treatments for the disease.

The Pathogen that Causes the Disease

The pathogen that causes the febrile encephalitis is called Nipah Virus. It is of the family: Paramyxovirus and the genus: Heniparvirus. Not much is known about its life cycle but according to CIDRAP (Center for Infectious Disease Research & Policy) in the Academic Health Center at the University of Minnesota, its morphology is “Helical.” It is “enveloped with distinct surface projections” and is “150 to 200 nm in diameter; 10,000 to 10,040 nm long, spherical or filamentous, but pleomorphic forms occur.” Its “Genetic composition” “is that of an” RNA virus. Single stranded. Mostly negative-sense, but positive-sense template strands exist,” and it is “15,200 to 15,900 nucleotides long.” Although no standard method for the detection of the Nipah Virus, listed below are the current procedures used to detect the virus:

     “History/clinical signs

     Virus isolation (kidney, liver, cerebrospinal fluid)

     IgG-, IgM-capture enzyme linked immunosorbent assay (ELISA)

     Virus neutralization

     Immunohistochemistry (lung, kidney, spleen, heart)

     Reverse transcriptase polymerase chain reaction (RT-PCR)”

Ecology of the Disease:

Reservoir: The virus's natural reservoir includes seven species of fruit bat; P (Pteropus). hypomelanus, P. vampyrus, P. lylei of Thailand and Cambodia, local Pteropus bats (P. giganteus ) of Bangladesh, two types of Malaysian fruit bats (Cynopterus brachyotis and Eonycteris spelaea), and one type of Malaysian insect eating bat (S. kuhlii]

Hosts: Pigs, humans, and possibly one dog. A Nipah viral infection in pigs began the initial infection in humans. Later in Bangladesh and Siliguri, India, human infections occurred without exposure to pigs.

Potential seropositive animals: “Rats, cats, dogs, goats, horses. It is unknown at this time whether seropositive animals could be a source of disease transmission.”

So far what is known about the pathogen’s cycle in swine after inoculation is 14 to 16 days when inoculated orally with mild symptoms and gross pathology. With a parenteral inoculation resembling a natural infection the incubation period was 7 to 10 days. And with an in-contact exposure there was a rapid infection response with neutralizing antibodies noted within 14 days (see table 1 below)

Table 1.

Clinical Presentation of Nipah Virus by Route of Exposure

Route of exposure      Characteristics

Oral inoculation      —Incubation period 14-16 days

—Mild clinical signs and gross pathology

Parenteral inoculation      —Narrow study of two pigs revealed a more severe disease, closer resembling natural exposure

—Incubation period about 7-10 days

In-contact pigs      —Rapid infection

—Neutralizing antibodies detected at day 14

The symptoms in pigs have similar manifestations, respiratory and neurologic, that lead to death. Also the incubation periods are similar (4 to 18 days in humans and 7 to 14 days in pigs). The mortality rate in pigs was not available as euthanasia was practiced when a pig became infected. See table 2 for the Nipah virus’ symptoms in pigs. Not much is known about the virus’cycle in fruit bats or in the one dog that tested seropositive for the virus.

Table 2.

Clinical Features of Nipah Virus in Swine*†

Developmental stage      Characteristics

All age-groups      Clinical signs that vary with stage of development:

—Nervous signs

—Twitching/trembling

—Muscle fasciculation

—Tetanic spasm

—Hind limb weakness

—Death 1-2 days after onset of respiratory distress

—Coagulopathy leading to petechial and ecchymotic hemorrhage

—Some affected pigs may be asymptomatic

—Virus tends to be vasotropic and neurotropic

Suckling pigs      Disease has not been reported in this group

Young pigs      —Coughing

—Open-mouth breathing

—Abnormal posturing

—Convulsions

Weaners and growers      General flu-like ailments common

—Fever

—Anorexia

—Dyspnea

—Coughing

Adults      —Neuropathy

~Head bobbing/banging

~Spasms

~Agitation/biting

—Flatulence

—Early abortion

—Stillbirths

—Sudden death

—Fever

—Anorexia

—Dyspnea

—Pneumonia

—Coughing

—Mucoid nasal secretions, may be yellow-green in color and/or blood-tinged

—Sudden death

Necropsy      —Lung consolidation, especially diaphragmatic lobes

—Thickened interlobular septae

—Bronchi saturated with frothy exudates, may be bloody

—Renal congestion and hemorrhage

—Visceral organs appear normal

*Concurrent death of cats, dogs, and rats may occur on an affected farm.

†Case-fatality rate is unknown, since euthanasia is often mandated.

Approaches to Managing the Disease

So far no treatments are known for the infection though the antiviral drug, Ribavirin, may be effective in reducing the mortality rate amongst patients that incur encephalitis. Intensive care for patients infected with the Nipah virus is necessary with intubation for respiratory infection and fever management. Biosafety measures need to be taken by care providers as the infection can spread through exposure to bodily fluids such as mucus. Also pig workers need to wear protective clothing to prevent exposure from the body fluids from pigs.

The most immediate and extreme approach to managing the disease at its onset was the testing of pig farms for infection resulting in the culling of 900,000 pigs from infected farms in Malaysia, placing a temporary ban on the transportation of pigs, educating the populace about contact with pigs, and the use of protective clothing for the people working with the pigs (farmers, researchers, military personnel in charge of pig culling). Also the evacuation of people from the farming communities during the outbreak was practiced by the Malaysian government. In Singapore abattoirs were closed when workers became ill with Nipah-like symptoms. As part of a global response, tissue samples were brought to the CDC in America. Also a screening tool, ELISA (enzyme-linked immunosorbent assay), was developed and screening at abattoirs commenced. Any samples testing positive for a Nipah antibody were sent to CSIRO [Commonwealth Scientific and Industrial Research Organisation (Australia)] for a Viral Neutralization Test to determine the existence of the virus. The Malaysian government also set up two funds, the Humanitarian Fund and the Nipah Trust fund to help individual families cope with the hardship of losing a loved one to the disease (Humanitarian Fund) and to provide financial assistance for those who had pigs culled (Nipah Trust Fund).

Subsequent management practices include further clinical study of the virus, setting safe pig farming practice standards, creating detection protocols, creating trade agreements regarding the movement of pigs due to purchasing and selling, and the encouragement of universities to create stringent courses in epidemiology.

Suggestions for a “Community Approach” to managing the disease:

As with the increase of Sleeping Sickness in Africa caused by the introduction of European cattle, the deforestation and habitat reduction required to raise the introduced cattle, and the parasite moving from its wild host to the domesticated cattle host and then to the ranchers who raised the cattle; so is the Nipah virus similar in its mutation from wild animals (fruit bats) to domesticated animals (pigs) to humans. Our “industrialized” methods of animal farming, with its cost-cutting practice of creating falsely high population densities of the animal product, create scenarios for zoonosis. I wish to propose two levels of “Community Approaches” to managing the Nipah Virus disease. One, local and practical, and one more global and ideological.

Local “Community Approach”

A local community approach would be to educate communities regarding the risk of disease transmission from their domesticated animals and to disseminate, in layman’s terms, the etiology of the disease so that practical approaches, such as encouraging pig farmers to construct their farms far from fruit bearing trees and other habitats where fruit bats and pigs can intermingle, wearing protective clothing while working in close contact with their livestock, and washing their hands after handing pigs and pig products. And in Bangladesh and Sigiluri, educate the populace regarding the danger of fruit bat droppings and other excretions as well as the importance of washing fruit and ones hands after handing fruit or cleaning up fruit bat excretions. Also I would create local farming councils where the farmers would be empowered to create their own methods of combating zoonotic diseases such as figuring out ways to maintain large livestock herds without having to have them living in population dense settings where outbreaks can cause mass die-offs and increased risks of infection.

Global “Community Approach”

It seems to me that one of the main causes of zoonotic diseases is humanity’s model of mono-cropping food plants and mono-raising food animals to increase individual profit and maximize production per land area. A pig farm not only produces many pigs for food, it produces tons of pig excrement waste which, because of its concentrated volume, overwhelms the capacity of the local environment to dispose of it in a natural manner. Current organic research is showing effective pest management practices using crop rotation and planting crops in a symbiotic manner (marigolds with food crops to utilize the marigold’s natural resistance to certain pests to help protect the food crop). Perhaps decreasing herd sizes by organizing ranges and food crop farms in conjunction with each other can reduce the risk of diseases brought about by population density. Or maybe raising smaller amounts of compatible domestic animals with others (goat, pig, sheep herds) instead of just one large pig or sheep or goat herd so a disease that infects one animal type might not spread as it cannot infect another animal type. This would reduce the economic impact on individual farms if one animal type had to be culled due to an outbreak. The individual farmer would still have two of his/her type of animal if one type had to be culled.

Why I think this is more of a Global Community Approach is due to the increase in the Global economy where conventional agricultural practices are dominant as they generate the highest short-term profit. Developing countries look to the wealthier developed countries as models for commercial success, but, as with the Sleeping Sickness example in Africa, transplanting one commercially successful method in one environment to another may not be the best and most profitable technique in the long run.

Currently there is a strong global scientific community response to disease where a disease can be isolated in one region, as with the Nipah virus in Malaysia, and those researchers have the world’s epidemiologic resources to call on for aid. Malaysia was able to send its samples to labs in Australia, America, and France for help in isolating and genetically blueprinting the virus. But, due to the nature of competition in the world market, proactive agricultural practices that might help reduce the risks of infection may be up against the desire for short-term profitability.

References:

Mandeep S. Chadha, James A. Comer, Luis Lowe, et al. Nipah Virus-associated Encephalitis Outbreak, Siliguri, India. Emerging Infectious Diseases Vol. 12, No. 2, February 2006 235. National Institute of Virology, Pune, India; and Centers for

Disease Control and Prevention, Atlanta, Georgia, USA . Available from: www.cdc.gov/eid

CDC, Hendra Virus Disease & Nipah Virus Encephalitis Fact Sheet. Available from:

www.cdc.gov/eid

Food and Agriculture Organization of the United Nations Regional Office for Asia and the Pacific Animal Production and Health Commission for Asia and the Pacific (APHCA), MANUAL ON THE DIAGNOSIS OF NIPAH VIRUS INFECTION IN ANIMALS, January 2002. RAP publication no. 2002/01 ISBN 974-680-208-9

Center for Infectious Disease Research & Policy Academic Health Center, University of Minnesota, Nipah Virus Copyright © 2006 Regents of the University of Minnesota. Available from: http://www.cidrap.umn.edu/cidrap/content/biosecurity/ag-biosec/anim-disease/nipah.html

DISEASE INFORMATION. "Emergency report" by the Director General of the Malaysian Veterinary Services, Dr Mohd Nordin Mohd Nor, to the OIE, May 28 1999, Vol. 12 - No. 20.

DISEASE INFORMATION. NIPAH DISEASE IN PENINSULAR MALAYSIA Continuation of the surveillance programme by the Director General of the Malaysian Veterinary Services, Dr Mohd Nordin Mohd Nor, to the OIE, March 31 2000, Vol. 13 - No. 12.

Epstein JH, Rahman SA, Zambriski JA, Halpin K, Meehan G, Jamaluddin AA, et al. Feral cats and risk for Nipah virus transmission. Emerg Infect Dis. 2006 Jul. Available from: http://www.cdc.gov/ncidod/EID/vol12no07/05-0799.htm

See Yee Ai. Living with the unknown. Star Publications (Malaysia) Bhd. April 10, 2000. Available from: http//www.thestar.com.my/

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Mary Kugler. Nipah Virus. Your Guide to Rare Diseases. September 19, 2004. Available from: http://rarediseases.about.com/od/rarediseasesn/a/091104.htm

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The National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services Scientists Discover How Nipah Virus Enters Cells. July 6, 2005 Available from http://www3.niaid.nih.gov/news/newsreleases/2005/nipah.htm

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