The legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (> 50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families-Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In the light of recent reports of coronaviruses including a SARS-CoV-2-related virus in Sunda pangolins in China, the lack of any coronavirus detection in our 'upstream' market chain samples suggests that these detections in 'downstream' animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally.
Nipah encephalitis is a particular dangerous disease that affects animals and man. Fatal cases of the disease have been identified in the persons looking after pigs in the villages of Malaysia. The causative agent is presumably referred to as morbilliviruses of the Paramixoviridae family. Two hundred persons died among the ill patients with the signs of encephalitis. The principal hosts of the virus were fox-bats (Megaschiroptera) inhabiting in the surrounding forests. The present paper descries the epidemiological features of the disease, its clinical manifestations, abnormal anatomic changes, diagnosis, and implemented controlling measures.
Two related, novel, zoonotic paramyxoviruses have been described recently. Hendra virus was first reported in horses and thence humans in Australia in 1994; Nipah virus was first reported in pigs and thence humans in Malaysia in 1998. Human cases of Nipah virus infection, apparently unassociated with infection in livestock, have been reported in Bangladesh since 2001. Species of fruit bats (genus Pteropus) have been identified as natural hosts of both agents. Anthropogenic changes (habitat loss, hunting) that have impacted the population dynamics of Pteropus species across much of their range are hypothesised to have facilitated emergence. Current strategies for the management of henipaviruses are directed at minimising contact with the natural hosts, monitoring identified intermediate hosts, improving biosecurity on farms, and better disease recognition and diagnosis. Investigation of the emergence and ecology of henipaviruses warrants a broad, cross-disciplinary ecosystem health approach that recognises the critical linkages between human activity, ecological change, and livestock and human health.
The authors review common themes in the ecology of emerging viruses that cause neurological disease. Three issues emerge. First, 49% of emerging viruses are characterized by encephalitis or serious neurological clinical symptoms. Second, all of these viruses are driven to emerge by ecological, environmental, or human demographic changes, some of which are poorly understood. Finally, the control of these viruses would be enhanced by collaborative multidisciplinary research into these drivers of emergence. The authors highlight this review with a case study of Nipah virus, which emerged in Malaysia due largely to shifts in livestock production and alterations to reservoir host habitat. Collaboration between virologists, ecologists, disease modelers and wildlife biologists has been instrumental in retracing the factors involved in this virus's emergence.
Bats are slowly gaining recognition as a potential reservoir for viruses harmful to human (Smith and Wang, 2013). Bats are reservoir to viruses causing Ebola virus diseases (EBV) (Leroy et al., 2005), Nipah Encephalitis (NiV) (Chua et al., 2002), SARS(Li et al., 2005) and MERS-CoV (Yang et al., 2015) being the latest one making headlines. About 18 years ago, a major outbreak of Nipah virus encephalitis occurred in Peninsular Malaysia resulted in the deaths of 105 persons and the slaughter of approximately 1.1 million pigs. In 2006, a novel bat orthoreovirus was found to be associated with acute respiratory syndrome in Malaysia. Following that incidents, many studies have been done on bats, particularly to determine their species, behaviour, and antibody level and there were also studies in human on antibody prevalence to batsrelated viruses e.g. Nipah and Hendra and PRV. Humans may become infected with viruses from bats through intermediate host (swine, horse) or through aerosol or direct contact with bats. Communities living adjacent to bat roosts should aware of possible risk of infection transmission from bats. An earlier study in Guatemala demonstrated that risk of exposure to bats in communities near bats roosts was common, but recognition of the potential for disease transmission from bats was low (Moran et al., 2015). Surprisingly, there is no local published data on public awareness towards bats-related infection despite potential risk of getting the infection. This study aimed to determine knowledge and awareness on bat-related infections, attitudes towards bats and practices related to health-seeking behaviours following exposure to bats.
Several sites, Z-7L, Z-5 and Z-14, in Sibu district, Sarawak, Malaysia, experienced intense dengue transmission in 2014 that continued into 2015. A pilot study with Bacillus thuringiensis israelensis (Bti) to control Aedes aegypti (L.) and Ae. albopictus (Skuse) was evaluated in Z-7L, a densely populated site of 12 ha. Bti treatments were conducted weekly from epidemiology week (EW) 24/2015 for 4 weeks, followed by fortnight treatments for 2 months, in addition to the routine control activities. Bti was directly introduced into potable containers and the outdoor artificial and natural containers were treated via a wide area spray application method using a backpack mister. Aedes indices significantly reduced during the treatment and post treatment phases, compared to the control site, Z-5 (p<0.05). A 51 fold reduction in the incidence rate per 100,000 population (IR) was observed, with one case in 25 weeks (EW 29-52). In Z-5 and Z-14, control sites, a 6 fold reduction in the IR was observed from EW 29-52. However, almost every week there were dengue cases in Z-14 and until EW 44 in Z-5. In 2016, dengue cases resurfaced in Z-7L from EW 4. Intensive routine control activities were conducted, but the IR continued to escalate. The wide area Bti spray misting of the outdoor containers was then included from EW 27 on fortnight intervals. A 6 fold reduction in IR was observed in the Bti treatment phase (EW 32-52) with no successive weekly cases after EW 37. However, in the control sites, there were dengue cases throughout the year from EW 1-52, particularly in Z-14. We feel that the wide area Bti spray application method is an integral component in the control program, in conjunction with other control measures carried out, to suppress the vector population in outdoor cryptic containers and to interrupt the disease transmission.
Bat-borne viruses carry undeniable risks to the health of human beings and animals, and there is growing recognition of the need for a 'One Health' approach to understand their frequently complex spill-over routes. While domesticated animals can play central roles in major spill-over events of zoonotic bat-borne viruses, for example during the pig-amplified Malaysian Nipah virus outbreak of 1998-1999, the extent of their potential to act as bridging or amplifying species for these viruses has not been characterised systematically. This review aims to compile current knowledge on the role of domesticated animals as hosts of two types of bat-borne viruses, henipaviruses and filoviruses. A systematic literature search of these virus-host interactions in domesticated animals identified 72 relevant studies, which were categorised by year, location, design and type of evidence generated. The review then focusses on Africa as a case study, comparing research efforts in domesticated animals and bats with the distributions of documented human cases. Major gaps remain in our knowledge of the potential ability of domesticated animals to contract or spread these zoonoses. Closing these gaps will be necessary to fully evaluate and mitigate spill-over risks of these viruses, especially with global agricultural intensification.
An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in the city of Wuhan in China and has widely spread worldwide. Currently, it is vital to explore potential intermediate hosts of SARS-CoV-2 to control COVID-19 spread. Therefore, we reinvestigated published data from pangolin lung samples from which SARS-CoV-like CoVs were detected by Liu et al. [1]. We found genomic and evolutionary evidence of the occurrence of a SARS-CoV-2-like CoV (named Pangolin-CoV) in dead Malayan pangolins. Pangolin-CoV is 91.02% and 90.55% identical to SARS-CoV-2 and BatCoV RaTG13, respectively, at the whole-genome level. Aside from RaTG13, Pangolin-CoV is the most closely related CoV to SARS-CoV-2. The S1 protein of Pangolin-CoV is much more closely related to SARS-CoV-2 than to RaTG13. Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13. Both Pangolin-CoV and RaTG13 lost the putative furin recognition sequence motif at S1/S2 cleavage site that can be observed in the SARS-CoV-2. Conclusively, this study suggests that pangolin species are a natural reservoir of SARS-CoV-2-like CoVs.
Numerous human diseases, including those caused by viruses like Nipah virus and SARS-CoV, can be traced back to bats as their origin. Malaysia, notably Sabah and Sarawak in Borneo Island, is home to a rich diversity of bats that serve as hosts for various viruses. This comprehensive review represents the inaugural exploration of viruses found in Malaysian bats, as documented in scientific journals. It also encompasses documented instances of bat virus-related disease outbreaks in Malaysia up to the present day, along with an analysis of the risk factors associated with virus spillover events. Furthermore, this review offers insights into prospective research areas of significance and suggests potential mitigation strategies.
This study evaluated rabies epidemiology in Far EastAsia. Questionnaires were sent by the OIE to Far East Asian countries and eight questionnaires were returned. Data were collected from these returns, as well as from recent publications, to gather information regarding rabies epidemiology in these countries. More than 29,000 human deaths were reported in 2006 in Far East Asia, representing more than 50% of all human rabies cases around the globe. There are only a few countries or regions from which no human rabies was reported in 2006 such as Japan, Singapore, South Korea, Malaysia, Hong Kong, and Taiwan. In many of these rabies endemic countries, the number of human rabies cases has not changed much during the past decade. The only country with a steady decline is Thailand, where the number of cases has decreased from around 200 to about 20 cases per year. The most dramatic changes were observed in China. Human rabies cases declined from around 5,000 cases per year in the 1980s to about 160 in the mid-1990s. However, these trends have since been reversed. A steady increase has been reported over the past 10 years with more than 3,200 cases reported in 2006. Although there are many factors that contribute to the epidemic or endemic nature of rabies in these countries, the single most important factor is the failure to immunize domestic dogs, which transmit rabies to humans. Dog vaccination is at or below 5% in many of these countries, and cannot stop the transmission of rabies from dogs to dogs, thus to humans. It is thus most importantforthese countries to initiate mass vaccination campaigns in dog populations in order to stop the occurrence of human rabies in Far East Asia.
Dengue fever is a recurring public health problem afflicting thousands of Malaysians annually. In this paper, the risk map for dengue fever in the peninsular Malaysian states of Selangor and Kuala Lumpur was modelled based on co-kriging and geographical information systems. Using population density and rainfall as the model's only input factors, the area with the highest risk for dengue infection was given as Gombak and Petaling, two districts located on opposite sides of Kuala Lumpur city that was also included in the risk assessment. Comparison of the modelled risk map with the dengue case dataset of 2010, obtained from the Ministry of Health of Malaysia, confirmed that the highest number of cases had been found in an area centred on Kuala Lumpur as predicted our risk profiling.
The objectives of this review were to understand the epidemiology and outbreak of NiV infection and to discuss the preventive and control measures across different regions. We searched PubMed and Scopus for relevant articles from January 1999 to July 2018 and identified 927 articles which were screened for titles, abstracts and full texts by two review authors independently. The screening process resulted in 44 articles which were used to extract relevant information. Information on epidemiology of NiV, outbreaks in Malaysia, Singapore, Bangladesh, India and Philippines, including diagnosis, prevention, treatment, vaccines, control, surveillance and economic burden due to NiV were discussed. Interdisciplinary and multi sectoral approach is vital in preventing the emergence of NiV. It is necessary to undertake rigorous research for developing vaccines and medicines to prevent and treat NiV.
The ongoing outbreak of viral pneumonia in China and across the world is associated with a new coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are probable reservoir hosts for SARS-CoV-2, the identity of any intermediate host that may have facilitated transfer to humans is unknown. Here we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity in the receptor-binding domain to SARS-CoV-2. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of new coronaviruses and should be removed from wet markets to prevent zoonotic transmission.
Nipah virus is a recently emergent paramyxovirus that is capable of causing severe disease in both humans and animals. The first outbreak of Nipah virus occurred in Malaysia and Singapore in 1999 and, more recently, outbreaks were detected in Bangladesh. In humans, Nipah virus causes febrile encephalitis with respiratory syndrome that has a high mortality rate. The reservoir for Nipah virus is believed to be fruit bats, and humans are infected by contact with infected bats or by contact with an intermediate animal host such as pigs. Person to person spread of the virus has also been described. Nipah virus retains many of the genetic and biologic properties found in other paramyxoviruses, though it also has several unique characteristics. However, the virologic characteristics that allow the virus to cause severe disease over a broad host range, and the epidemiologic, environmental and virologic features that favor transmission to humans are unknown. This review summarizes what is known about the virology, epidemiology, pathology, diagnosis and control of this novel pathogen.
Nipah virus, a paramyxovirus related to Hendra virus, first emerged in Malaysia in 1998. Clinical presentation ranges from asymptomatic infection to fatal encephalitis. Malaysia has had no more cases since 1999, but outbreaks continue to occur in Bangladesh and India. In the Malaysia-Singapore outbreak, transmission occurred primarily through contact with pigs, whereas in Bangladesh and India, it is associated with ingestion of contaminated date palm sap and human-to-human transmission. Bats are the main reservoir for this virus, which can cause disease in humans and animals. There are currently no effective therapeutics, and supportive care and prevention are the mainstays of management.
We isolated and characterized Nipah virus (NiV) from Pteropus vampyrus bats, the putative reservoir for the 1998 outbreak in Malaysia, and provide evidence of viral recrudescence. This isolate is monophyletic with previous NiVs in combined analysis, and the nucleocapsid gene phylogeny species.
The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health1. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG132. Although bats may be the reservoir host for a variety of coronaviruses3,4, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.
Bats are special in their ability to host emerging viruses. As the only flying mammal, bats endure high metabolic rates yet exhibit elongated lifespans. It is currently unclear whether these unique features are interlinked. The important inflammasome sensor, NLR family pyrin domain containing 3 (NLRP3), has been linked to both viral-induced and age-related inflammation. Here, we report significantly dampened activation of the NLRP3 inflammasome in bat primary immune cells compared to human or mouse counterparts. Lower induction of apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and secretion of interleukin-1β in response to both 'sterile' stimuli and infection with multiple zoonotic viruses including influenza A virus (-single-stranded (ss) RNA), Melaka virus (PRV3M, double-stranded RNA) and Middle East respiratory syndrome coronavirus (+ssRNA) was observed. Importantly, this reduction of inflammation had no impact on the overall viral loads. We identified dampened transcriptional priming, a novel splice variant and an altered leucine-rich repeat domain of bat NLRP3 as the cause. Our results elucidate an important mechanism through which bats dampen inflammation with implications for longevity and unique viral reservoir status.