International Journal of Pharmaceutical and Phytopharmacological Research
ISSN (Print): 2250-1029
ISSN (Online): 2249-6084
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A Comprehensive Review of Nipah Virus Infection: Origin, Transmission, and Pathogenesis |
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Ramdas Bhat1*, Preeti Shanbhag1, Ramakrishna Shabaraya2 |
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1Department of Pharmacology, Srinivas College of Pharmacy, Mangalore, Karnataka, India. 2Srinivas College of Pharmacy, Mangalore, Karnataka, India. |
ABSTRACT
This comprehensive review provides a deep exploration of Nipah virus (NiV) infection, encompassing its virology, epidemiology, pathogenesis, clinical manifestations, treatment, prognosis, and prevention strategies. NiV is an enveloped virus with crucial glycoproteins for host cell entry, and it poses an ongoing threat with unpredictable outbreaks occurring in Southeast Asia. The pathogenesis involves both respiratory and neurological manifestations, often resulting in severe outcomes, highlighting the importance of early diagnosis and supportive care. While treatment options are limited, experimental therapies such as ribavirin and monoclonal antibodies show potential efficacy. The prognosis varies widely, underscoring the importance of swift medical intervention. Prevention strategies, including stringent infection control measures in healthcare settings and public health interventions, are pivotal in curtailing NiV outbreaks. The future outlook involves intensive efforts in vaccine development and antiviral research to enhance preparedness. Epidemiological studies, robust surveillance, and community education are essential components of a comprehensive approach to NiV management. This review serves as a valuable resource, emphasizing the urgent need for ongoing research and global collaboration in our continued battle against the Nipah virus. With a concise summary of key aspects, this review provides a comprehensive understanding of NiV, serving as a valuable reference for researchers, healthcare professionals, and policymakers, ultimately contributing to our collective efforts to combat this challenging zoonotic pathogen.
Key Words: Nipah virus (NiV), Zoonotic pathogen, Ribavirin, Monoclonal antibodies, Favipiravir
INTRODUCTION
Nipah virus (NiV) emerged on the global stage in the late 1990s, originating in the serene Malaysian village of Kampung Sungai Nipah. This formidable zoonotic pathogen is exceptionally lethal and capable of causing severe respiratory distress, encephalitis, and death in humans [1]. Its primary natural reservoir comprises fruit bats, particularly those of the Pteropus genus. However, it has demonstrated the ability to infect a diverse range of animals, including pigs, horses, and others. Transmission from animals to humans can occur through direct contact with infected bodily fluids or indirectly via contact with contaminated food or water sources [2].
The discovery of the Nipah virus traces back to early March 1999 when virologists from the University of Malaya isolated the virus from the cerebrospinal fluid of an encephalitis patient. When Vero cells were exposed to this cerebrospinal fluid, the development of syncytia, multinucleated cells indicative of viral infection, was observed. Electron microscopic studies confirmed its classification within the Paramyxoviridae family. The name "Nipah virus" was proposed due to the initial isolate obtained from a tragic human case in Kampung Sungai Nipah, a village in Negeri Sembilan, Malaysia [1, 3].
Further investigations revealed that Nipah virus-infected cells strongly reacted with Hendra virus antiserum, indicating a close relationship between these two viruses. However, these cells did not exhibit reactivity with antisera against other paramyxoviruses or unrelated viruses like measles virus, respiratory syncytial virus, parainfluenza viruses, herpesvirus, enteroviruses, or Japanese encephalitis virus [4]. In-depth studies disclosed that while the Nipah virus and the Hendra virus shared a relationship, they were not identical. Cross-neutralization studies demonstrated an 8- to 16-fold difference in neutralizing antibodies between the two viruses. Initially classified as a potential new member of the genus Morbillivirus and tentatively named equine morbillivirus (EMV), whole-genome analysis ultimately revealed significant molecular distinctions setting Nipah virus apart from known morbilliviruses. Subsequent scrutiny of the Nipah virus genome solidified its status as a novel paramyxovirus, necessitating the creation of the new genus Henipavirus [5]. In 2002, the International Committee for Virus Taxonomy (ICTV) approved the establishment of the new genus Henipa virus to accommodate these distinct and potent viruses. It's essential to note that the Malaysian strain of Nipah virus (NiV-MY) exhibits slight variations from the strain found in Bangladesh (NiV-BD). The outbreak in the Philippines was most likely caused by the NiV-MY strain, emphasizing the genetic diversity and complexity of this formidable viral pathogen [6].
The initial documented outbreak of NiV in humans occurred in Malaysia during 1998-1999, and since then, it has spread to other countries and regions, encompassing Bangladesh, India, Indonesia, and the Philippines [3]. Notably, the most recent NiV outbreak unfolded in India in 2022, marking it as the deadliest encounter with the virus to date. This current outbreak of NiV in India commenced in May 2022 within the state of Kerala, gradually extending its grip into other states, including Karnataka, Tamil Nadu, and Telangana [7, 8]. A chilling aspect of this outbreak is the predominant affliction of young adults, with a staggering case fatality rate exceeding 70%, serving as a dire testament to the gravity of the situation [6].
This comprehensive review article endeavors to provide an in-depth understanding of the Nipah virus, covering its origin, transmission, pathogenesis, and the measures implemented to control and prevent its spread. It serves as an invaluable resource for researchers, healthcare professionals, and policymakers grappling with the daunting challenge posed by this infectious disease threat.
Structure of Nıpah vırus
The Nipah virus, an enveloped pathogen, possesses a distinctive viral structure that plays pivotal roles in its lifecycle and pathogenicity. Encased within a lipid envelope derived from host cell membranes, the virus harbors essential glycoproteins crucial for its infectious prowess. Two major glycoproteins, Fusion (F) and Attachment (G), adorn the viral envelope. The F glycoprotein orchestrates the fusion of the viral envelope with the host cell membrane, facilitating viral entry. Meanwhile, the G glycoprotein acts as a key liaison, binding to specific cellular receptors and initiating the viral entry process. Beneath the envelope lies the Matrix (M) protein, providing structural integrity to the virion and participating in viral assembly and budding. Deep within the viral particle, the genetic material is encapsulated in ribonucleoprotein (RNP) complexes. These RNPs consist of the viral RNA genome intricately wrapped with nucleocapsid (N) proteins, serving as the core machinery for viral replication and transcription once inside the host cell. Understanding this intricate viral structure, particularly the role of glycoproteins in attachment and fusion, is fundamental for developing antiviral therapies and vaccines, as it offers potential targets to inhibit viral entry and infection. Furthermore, the structural insights aid in comprehending the virus's interaction with host cells and immune responses, paving the way for strategies to control and treat Nipah virus infections [9-11].
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Figure 1. Structure of Nipah virus [12]. |
Epıdemıology
The first known occurrence of the Nipah virus in Malaysia-Singapore during 1998-1999 initially puzzled health authorities, as it was initially mistaken for Japanese encephalitis. However, after a thorough investigation, it was correctly identified as the Nipah virus. Subsequent outbreaks in different regions, like the Meherpur district of Bangladesh and Siliguri city in West Bengal, India, in 2001, showed significant differences compared to the Malaysian outbreak. These Indo-Bangladesh outbreaks had unique characteristics, including a higher likelihood of human-to-human transmission and infections within healthcare settings, often through droplets or contaminated surfaces. Moreover, the disease seemed more severe and progressed rapidly in these outbreaks, possibly leading to complications like acute respiratory distress syndrome (ARDS) and respiratory failure, resulting in multiple organ dysfunction syndrome (MODS) [1, 3, 6, 13].
A common factor in these Indo-Bangladesh outbreaks, including the 2018 outbreak in Kerala, India, was the link to the consumption of raw date palm sap contaminated by fruit bats. This mode of transmission gained attention due to the virus's remarkable stability in date palm sap, remaining viable for up to seven days at 22°C, and its resilience across a wide pH range from 3 to 11. Additionally, human-to-human transmission became evident in these outbreaks, highlighting the complex nature of Nipah virus transmission dynamics. For instance, in the Siliguri outbreak in 2001, a single patient admitted to a private hospital infected 23 hospital staff and 8 visitors, largely due to inadequate adherence to standard precautions. Furthermore, variations in viral strains (BD vs. MY) contributed to differences in transmission rates, with studies indicating that the BD strain resulted in higher levels of viral RNA in the blood and increased viral shedding in oral secretions, potentially explaining the higher secondary infection rates and more severe illnesses [14, 15].
Nipah virus research is also marked by the existence of various strains, such as s, NiV-C, and NiV-I, each having differences in their genetic makeup and disease severity. For instance, NiV-M caused the initial Malaysian outbreak, while NiV-B was associated with outbreaks in Bangladesh and India. These strains exhibit variations in how they spread, with NiV-M being considered more readily transmitted from animals to humans [16].
India has been grappling with a particularly deadly Nipah virus outbreak, marked by a daunting case fatality rate exceeding 60%. Fruit bats are believed to be the primary source of this outbreak, which has spread across multiple states. Despite government efforts to control the outbreak, the risk of further transmission remains alarmingly high [17]. It's essential to remember that the Nipah virus situation is continually evolving, and the most recent statistics may not be fully reflected in this response.
Mode of transmission
The mode of transmission of the Nipah virus (NiV) primarily involves direct or indirect contact with infected animals or their bodily fluids, as well as human-to-human transmission. Here are the key modes of transmission:
Direct contact with infected animals
The primary natural reservoir of the Nipah virus is fruit bats, particularly those of the Pteropus genus. People can become infected when they come into direct contact with infected bats or their excretions, such as saliva, urine, or feces. Handling or consuming products from these bats, like raw date palm sap contaminated with bat excreta, can lead to transmission [18].
Indirect contact with contaminated surfaces
NiV can survive on surfaces and in the environment for a certain period. Contact with surfaces, equipment, or objects contaminated with infected bat excreta or bodily fluids can result in transmission if individuals touch their eyes, nose, or mouth after such contact without proper hand hygiene [17].
Consumption of contaminated food or water
In some outbreaks, Nipah virus transmission has occurred through the consumption of raw date palm sap that has been contaminated with the saliva or urine of infected fruit bats. The virus can remain viable in date palm sap for a certain period, making it a potential source of infection [18].
Human-to-human transmission
The Nipah virus has the capacity for human-to-human transmission, primarily through close contact with an infected person's bodily fluids, including respiratory secretions, blood, urine, and saliva. This type of transmission is a significant concern during outbreaks, particularly in healthcare settings where there may be exposure to infected patients or their contaminated medical equipment [15].
Nosocomial transmission
Nipah virus outbreaks in healthcare settings have occurred due to lapses in infection control measures. Healthcare workers and caregivers are at risk of infection if they do not take appropriate precautions when caring for patients with Nipah virus infection, including the use of personal protective equipment (PPE) [16].
Airborne transmission (Rare)
Although not the primary mode of transmission, there have been rare instances of airborne transmission of the Nipah virus in healthcare settings, particularly when aerosol-generating procedures are performed on infected patients. This emphasizes the importance of strict infection control measures, including the use of N95 respirators in such situations [7].
Pathogenesis
The pathogenesis of Nipah Virus (NiV) infection is a multifaceted and highly intricate process, encompassing a series of interconnected stages that collectively contribute to the severity and complexity of the disease. This journey begins with NiV's primary target: the epithelial cells that line the respiratory tract, with a notable predilection for the bronchioles. Upon breaching this initial defense, NiV establishes a foothold within the bronchial and alveolar tissues, setting the stage for a robust immune response [11].
This immune response is characterized by the release of an array of cytokines and chemokines, signaling molecules that orchestrate the body's defense mechanisms. However, in the context of NiV infection, this immune activation often leads to a cascade of events akin to acute respiratory distress syndrome (ARDS). Patients may experience respiratory distress, compromised lung function, and a host of respiratory symptoms as the immune system fights to contain the virus. As the infection progresses, the airway epithelium responds by releasing inflammatory mediators, including interleukins and granulocyte-colony stimulating factors. These compounds further fuel the inflammatory response, intensifying the overall pathology of the infection and exacerbating respiratory symptoms. The heightened inflammation within the respiratory tract can have a profound impact on the patient's well-being, making respiratory management a critical aspect of care [11, 19].
However, the consequences of NiV infection extend far beyond the respiratory system. The virus possesses the ability to disseminate systematically, infiltrating the endothelial cells that line blood vessels. This facilitates NiV's entry into the bloodstream, enabling it to infiltrate and affect various organ systems throughout the body. The outcome is often multi-organ failure, a dire condition where several vital organs malfunction simultaneously. It's noteworthy that in animal models, NiV has demonstrated its capacity to infect leukocytes, a subset of white blood cells, further complicating the immune response and contributing to the lethal nature of the infection.
Moreover, NiV displays a pronounced neurotropism, a characteristic that allows it to target neural tissues effectively. This neurotropic inclination has profound implications as it enables the virus to infiltrate the Central Nervous System (CNS) through multiple routes. One such pathway involves NiV entering the CNS via blood vessels, particularly those within the cerebrum. This mode of entry can potentially disrupt the protective Blood-Brain Barrier (BBB), which typically serves as a formidable defense against pathogens gaining access to the brain. Consequently, this breach can result in severe neurological complications, further complicating the clinical picture.
Recent research has uncovered an alternative route of CNS invasion. In this scenario, NiV gains access to the CNS via the olfactory nerve, responsible for the sense of smell. Once inside the olfactory nerve, the virus can disperse throughout the ventral cortex of the brain, exacerbating neurological dysfunction and potentially leading to life-threatening outcomes [11, 19].
Clinical manifestations and symptoms
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Figure 2. Clinical manifestation of Nipah virus in humans. |
Clinical manifestation in humans
Nipah virus infection, known primarily for its impact on the nervous system, has shown that it can affect various parts of the body, including the respiratory system. In the Malaysian outbreak, reports suggested that respiratory issues were seen in about 14% to 29% of cases. However, it wasn't clear whether these respiratory problems were part of the initial symptoms or developed later, possibly due to aspiration or ventilator-related pneumonia. In contrast, the Singapore outbreak had a unique pattern. Two out of eleven patients primarily had respiratory symptoms without accompanying brain inflammation, while the rest had brain inflammation. On the other hand, cases in Bangladesh and India had a higher occurrence of respiratory issues, accounting for up to two-thirds of cases, and some even developed acute respiratory distress syndrome (ARDS). The differences in these respiratory involvement rates could be linked to variations in the virus strains, which we'll delve into further [20, 21].
Besides the clinical symptoms, findings from brain scans have been crucial in understanding Nipah virus infection. In the Malaysian outbreak, MRI scans showed extensive damage in specific brain regions like the cortex, temporal lobe, and pons. Notably, patients who had relapsed or developed brain inflammation later showed multiple areas with patchy and connected cortical damage. In contrast, patients in the Singapore outbreak had a different pattern on their MRI scans. They had small lesions, each less than 1 cm in size, distributed on both sides of the deep white matter and subcortical regions. Some of these lesions became more visible after contrast material was given. These affected areas included the cerebral cortex, brainstem, and corpus callosum. Interestingly, these abnormalities were mainly detected through diffusion-weighted (DW) MRI, a technique commonly used to identify conditions like stroke. This pattern, characterized by tiny DW abnormalities followed by T1 hyperintensities, was distinct from what's typically seen in herpesvirus and Japanese encephalitis. Instead, it seemed more aligned with virus-related microangiopathy and resulting small-scale brain tissue damage [18, 21].
Clinical manifestation in animals
Nipah virus infection in animals, with a particular focus on species such as pigs and certain bat species, presents a multifaceted spectrum of clinical manifestations that play a pivotal role in comprehending the intricacies of viral dynamics within both natural reservoirs and intermediate hosts. This comprehensive understanding, rooted in a scientific perspective, forms the cornerstone for the development of targeted strategies aimed at disease control and prevention [15, 17].
In pigs, which serve as recognized intermediate hosts for Nipah virus transmission to humans, a wide array of clinical signs may manifest. These encompass a range of respiratory issues, including persistent coughing and conspicuous dyspnea, reflecting the virus's propensity to target the respiratory system. Neurological symptoms also come into play, with observable tremors, muscle weakness, and impaired coordination providing further insight into the virus-host interaction. Notably, Nipah virus infections in pigs have been linked to reproductive complications, with instances of abortion and stillbirths in pregnant sows. Most alarmingly, sudden and unanticipated deaths can occur among infected pigs, frequently in the absence of overt preceding clinical signs, underscoring the elusive nature of this virus [18, 19].
Fruit bats, notably, the species classified as flying foxes, serve as the natural reservoir hosts for the Nipah virus. Remarkably, these bats tend to exhibit a lack of discernible clinical signs when infected, serving as asymptomatic carriers of the virus. Instead, they harbor and excrete the virus within their bodily fluids and excreta, highlighting their pivotal role as a source of transmission. This unique characteristic underscores the significance of bat-to-animal or bat-to-human transmission via contaminated excretions or saliva [22, 23].
Prognosis of nipah virus infection
The prognosis of Nipah virus infection varies based on factors like illness severity, timely medical care, and individual characteristics. Nipah virus (NiV) infection varies widely, with case fatality rates ranging from 40% to 100%. Several poor prognostic factors have been identified, including older age, severe brain-stem involvement characterized by reduced consciousness, vomiting, abnormal Doll's-eye reflex, abnormal pupils, hypertension, and tachycardia during the illness. These factors signal the potential for severe neurological and systemic complications. However, it's important to recognize that individual outcomes can differ, and early diagnosis, prompt supportive care, and experimental treatments when available are critical in improving the chances of a better prognosis. Public health measures also play a vital role in containing NiV outbreaks and preventing further transmission. Severe cases, especially encephalitis, have higher mortality rates. Early medical intervention, maintaining hydration, and managing symptoms can improve outcomes. Case fatality rates differ between outbreaks and regions, influenced by virus strains and healthcare resources. Survivors may experience long-term neurological issues. Effective transmission control measures and ongoing research into treatments and vaccines offer hope for improved outcomes in the future [11, 23].
Diagnosis of nipah virus infection
Diagnosing Nipah virus infection involves a comprehensive approach combining clinical evaluation, laboratory tests, and epidemiological investigation:
Clinical evaluation
Healthcare professionals begin by conducting a meticulous assessment of the patient's symptoms and medical history. They inquire about potential exposure to the Nipah virus, which can cause symptoms ranging from mild respiratory illness to severe encephalitis. Neurological symptoms, including disorientation and coma, are particularly concerning.
Laboratory tests
Various laboratory methods play a critical role in confirming Nipah virus infection:
Enzyme-linked immunosorbent assay (ELISA)
ELISA is a widely used serological test that detects viral antigens and evaluates the antibody response. Different techniques of ELISA are employed, including ELISA capture, recombinant protein-based ELISA, and indirect ELISAs for IgG and IgM. These tests are valuable for specific virus detection and assessing the immune response [24].
Virus neutralization test (VNT)
VNT measures the ability of serum to neutralize the virus and prevent its cytopathic effect. It is considered the reference serological test and can be performed using Vero cells or a pseudo-type vesicular stomatitis virus (VSV) containing viral envelope proteins. Plate-based VNT tests are also available [25].
Molecular biology methods
Polymerase chain reaction (PCR) techniques, including reverse transcription PCR (RT-PCR) and nested PCR, are highly sensitive and specific for detecting viral genetic material. These methods target specific viral sequences, such as the N, M, and P genes. Quantitative real-time PCR (qRT-PCR) allows for quantifying viral RNA accurately [26].
Viral isolation
Viral isolation involves culturing samples suspected of containing the virus in suitable cell lines, such as Vero cells. Cytopathic effects, like syncytia formation and plaques, indicate viral growth. Additional tests, including immunostaining, seroneutralization (SN), and PCR, are performed on culture supernatants [27].
Immunohistochemistry (IHC)
IHC uses specific antibodies to stain formalin-fixed tissues, helping detect viral antigens and associated lesions in various organs. This technique is valuable for understanding the virus's impact on different tissues [28].
Epidemiological ınvestigation
Public health authorities conduct epidemiological investigations to understand virus transmission and implement control measures:
Epidemiological investigations provide crucial insights into virus transmission dynamics and guide public health interventions to prevent further spread. This multifaceted approach is essential for diagnosing Nipah virus infection and responding effectively to outbreaks.
Treatment of nipah virus infection
Nipah virus is a zoonotic virus that can cause severe respiratory and neurological symptoms in humans. Given the absence of a specific antiviral medication approved for the Nipah virus, medical management primarily focuses on supportive care.
Isolation and infection control
Patients suspected or confirmed to have Nipah virus infection should be isolated in dedicated healthcare facilities to prevent the spread of the virus to healthcare workers and other patients. Strict infection control measures are crucial. Healthcare personnel must wear appropriate personal protective equipment (PPE), including gloves, gowns, masks, and goggles, to minimize the risk of transmission [30].
Supportive care
Hydration is a critical aspect of care. Intravenous fluids are often administered to maintain hydration levels, as severe cases of Nipah virus infection can lead to dehydration. Pain relief medications may be provided to alleviate discomfort and pain experienced by the patient. Fever management is essential. Antipyretic medications, such as acetaminophen, can be administered to reduce fever. In severe cases, patients may experience respiratory distress, and mechanical ventilation may be necessary to assist with breathing [31].
Experimental treatments
Several experimental treatments have been explored for Nipah virus infection.
Ribavirin
Ribavirin, an antiviral medication, has been under investigation for its potential to treat Nipah virus (NiV) infection. Studies conducted in a laboratory setting (in vitro) and on animals have shown mixed results regarding the effectiveness of ribavirin against NiV and the related Hendra virus. Some laboratory studies have suggested that ribavirin can effectively inhibit the replication of the virus in cell cultures. However, when tested in animal models, ribavirin treatment has yielded varying outcomes, with some studies indicating that it only delayed the progression of the disease but didn't prevent death from NiV or Hendra virus infection. During the NiV outbreak in Malaysia in 1998-1999, there was a notable human study involving patients who either received ribavirin treatment or did not due to unavailability or refusal. This study indicated a 36% reduction in mortality among the treated group. However, it's important to note that the allocation of treatment was not done through randomization, which could introduce bias into the results. The precise dosage of ribavirin for NiV treatment has not been firmly established, but it may follow guidelines similar to those recommended by the World Health Organization (WHO) for Lassa fever. This could include an initial dose of 30 mg/kg for children and 2,000 mg/kg for adults, followed by a 10-day treatment with specific dosing schedules. Ribavirin's oral bioavailability varies (between 32.6% and 52%), and it undergoes first-pass metabolism. It can partially cross the blood-brain barrier. Ribavirin is associated with significant adverse drug reactions, including neutropenia (8% to 40%), anemia (11% to 35%, with higher rates in children and adolescents), and lymphocytopenia (12% to 14%). There have even been reports of suicidal thoughts associated with its use, primarily observed with long-term administration. Animal studies have shown that ribavirin can cause birth defects, but there is a lack of human studies on its teratogenic effects. Due to its long elimination half-life, it's recommended to wait at least seven months after ribavirin treatment before attempting pregnancy. In 2008, the Infectious Diseases Society of America recommended the use of ribavirin for NiV infections. However, further research is necessary to establish its effectiveness definitively, particularly through controlled trials [32-35].
Monoclonal antibody m102.4
The experimental monoclonal antibody m102.4 targets specific parts of the Henipavirus G envelope glycoprotein. In vitro studies have shown that m102.4 is a potent cross-reactive neutralizing antibody against NiV. In animal experiments, including studies on ferrets and African green monkeys, m102.4 has demonstrated effectiveness in preventing infection and death following NiV exposure. In a real-world case in Queensland, Australia, m102.4 was offered on compassionate grounds to individuals exposed to Hendra virus, and they did not develop Hendra virus infection. However, it remains uncertain whether the treatment was effective or if these patients were not infected [36, 37].
Favipiravir
The viral RNA-dependent RNA polymerase inhibitor favipiravir was developed by Toyama Chemical Company as an antiviral for use against influenza. In a Syrian hamster model for Nipah virus infection, favipiravir was successfully used in lethally challenged hamsters [38].
4'azidocytidine and 4'-chloromethyl-2'-deoxy-2'-fluorocytidine
These compounds, which are similar to cytidine, have demonstrated potent antiviral effects against Nipah virus (NiV) when tested in a laboratory setting (in vitro). However, the prodrug version of 4'azidocytidine, known as Balapiravir, did not yield promising outcomes in clinical trials aimed at treating infections caused by flaviviruses. Consequently, it was discontinued due to its poor performance as a prodrug and the presence of undesirable side effects. Nevertheless, modified versions of 4'azidocytidine showed more promising results when compared to the original compound [39-41].
Peptide fusion ınhibitors
Peptide fusion inhibitors have a specific purpose to hinder the fusion of the virus with the host cell's membrane. In animal studies, finely tuned lipopeptide fusion inhibitors have demonstrated their ability to shield against fatal Nipah virus (NiV) infections. Interestingly, Enfuvirtide (marketed as Fuzeon™), an FDA-approved therapeutic for HIV-1, also falls into the category of lipopeptide fusion inhibitors. This suggests that Enfuvirtide may hold promise as a treatment against NiV due to its mechanism of action [42, 43].
Defective ınterfering particles (DIPs)
Defective Interfering Particles (DIPs) harbor defective genetic material capable of modifying the behavior of a viral population, effectively impeding the replication of the Nipah virus (NiV). Laboratory tests conducted in controlled environments have demonstrated that DIPs can significantly lower the viral concentration and mitigate damage to host cells. Although their application as a NiV treatment is in the early exploratory stages, further investigations involving animal studies are warranted. It's worth noting that DIPs have also exhibited potential in combating the influenza A virus, showcasing their broader antiviral potential [44, 45].
Table 1. Nipah virus vaccine in Clinical trial [46].
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Candidate Name /Identifier |
Development Stage |
Developers |
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Subunit Vaccine |
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HeV sG |
Preclinical |
Zoetis, Inc./USU |
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Vectored Vaccines |
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VSV-NiVB F and/or G |
Preclinical |
UTMB |
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VSV-NiVM G |
Preclinical |
CDC |
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VSV-NiVM G |
Preclinical |
RML |
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VSV-NiVM F and/or G |
Preclinical |
Yale University |
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VSV-HeV G |
Preclinical |
TJU/RML |
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RABV-HeV G |
Preclinical |
TJU/RML |
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ALVAC-F/G |
Preclinical |
CFIA-NCFAD |
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AAV-NiVM G |
Preclinical |
INSERM |
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rMV-Ed-G |
Preclinical |
UoT |
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V-NiVG |
Preclinical |
USU |
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rLa-NiVG and/or rLa-NiVF |
Preclinical |
CAAS-SKLVB |
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Passive Antibody Transfer |
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Polyclonal serum NiV F or G |
Preclinical |
INSERM |
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Mouse mAbs NiV F or G |
Preclinical |
INSERM |
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Human mAb m102.4 Henipah G |
Preclinical |
USU |
Disease prevention
Preventing Nipah virus (NiV) infection, especially among healthcare workers (HCWs), is of utmost importance due to the potential severity of this pathogen. Lessons learned from previous outbreaks like Ebola and severe acute respiratory syndrome (SARS) have led to the establishment of robust guidelines for HCW protection. The core elements of an effective infection prevention and control strategy include standard precautions, rigorous hand hygiene, and the use of personal protective equipment (PPE). These measures are critical for all patient-care activities, including procedures that generate aerosols. In the event of a NiV infection within a healthcare setting, swift implementation of additional precautions such as droplet, contact, and airborne precautions is essential. This may involve isolating infected patients in single-patient rooms or cohorting them to minimize contact with susceptible individuals. Immediate isolation and strict adherence to infection control protocols are imperative at the first suspicion of a NiV case [11, 14, 47].
In regions at risk for NiV outbreaks, healthcare facilities should be well-prepared to handle NiV cases. This readiness includes comprehensive screening, admission procedures, and efficient triage systems. Management of visitor access and movement should also be established to minimize potential exposure risks. Adherence to standard precautions should be unwavering across all aspects of patient care, encompassing patient handling, specimen collection, cleaning, and waste disposal. Hand hygiene plays a pivotal role in preventing NiV transmission, with consistent and thorough handwashing using soap and water or alcohol-based hand rubs before and after any patient contact being paramount. The persistence of NiV on surfaces, as observed in previous outbreaks, underscores the importance of rigorous hand hygiene practices. When conducting procedures that generate aerosols or patient examinations, proper PPE usage is imperative. For NiV, the highest level of protection (Level B/A OSHA) is recommended. HCWs should receive thorough training on the correct use and, importantly, the safe removal or doffing of PPE to minimize contamination risks [16, 30, 47, 48].
Preventative measures extend to avoiding contact with infected animals, particularly fruit bats, and their secretions, as NiV is transmitted from animals to humans. Public health measures, such as contact tracing to identify potential exposures and isolating confirmed cases, are crucial to prevent further spread [49-51]. Additionally, quarantine measures may be implemented for individuals with close contact with confirmed cases, allowing for symptom monitoring and reducing transmission risks [22, 30].
Future prospects
Prospects for Nipah virus research are promising and encompass a wide range of critical areas. Currently, there is no vaccine available for Nipah virus infection, Vaccine development will continue to be a top priority, with researchers working towards safe and effective vaccines for both humans and potential intermediate hosts like pigs. Various vaccine candidates, including subunit vaccines, virus-like particles, and live attenuated vaccines, will undergo rigorous testing to assess their efficacy and safety, aiming for emergency use authorization and widespread deployment during outbreaks.
Concurrently, research into antiviral therapies will intensify, exploring both existing antiviral drugs for repurposing and the development of novel therapeutic agents. The goal is to identify treatments that can effectively inhibit Nipah virus replication and improve patient outcomes. Additionally, diagnostics will be refined to include rapid point-of-care tests, improved molecular assays, and serological tests, enhancing early and accurate detection of the virus.
Epidemiological studies will provide valuable insights into Nipah virus transmission dynamics, reservoirs, and risk factors. Longitudinal studies in endemic regions will help uncover seasonal patterns and potential hotspots for virus spillover. The One Health approach, involving collaboration among experts in virology, epidemiology, veterinary medicine, and environmental science, will be crucial in understanding the complex interplay between human, animal, and environmental factors in Nipah virus transmission.
Enhanced surveillance systems will be established to monitor bat populations and detect potential outbreaks early, enabling rapid response and containment efforts. Research into the behavior and ecology of natural reservoir hosts, particularly fruit bats, will contribute to targeted prevention measures. International collaboration, data sharing, and the exchange of best practices will facilitate a coordinated global response to Nipah virus threats. Community education initiatives will be vital in at-risk regions, raising awareness about the risks associated with the Nipah virus and promoting preventive behaviors. Finally, global preparedness efforts will focus on stockpiling medical supplies, establishing rapid response teams, and conducting simulation exercises to ensure effective responses to future Nipah virus outbreaks.
CONCLUSION
The Nipah virus remains a formidable global health concern, demanding continued research and preparedness efforts. While treatment options and prognosis vary, early diagnosis and supportive care are pivotal in improving outcomes. Prevention, through stringent infection control and future vaccine deployment, is paramount. Collaborative research, surveillance, and public awareness initiatives offer hope in our ongoing battle against this deadly pathogen.
Acknowledgments: I would like to thank the staff of the Department of Pharmacology, Srinivas College of Pharmacy for their support.
Conflict of interest: None
Financial support: None
Ethics statement: None
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