How do humans get Nipah virus? NiV can be transmitted to people by: Direct contact with infected wild or domesticated animals, or their excretions and secretions (such as urine, saliva, blood, pharyngeal and respiratory secretions). Transmission to humans via virus-containing aerosols should also be considered [44] Consumption of unprocessed meat from infected animals, or unheated/raw food products that have been contaminated by body fluids of infected animals (such as palm sap or fruit contaminated by an infected fruit bat). Contact with the body fluids of an infected person (such as nasal or respiratory droplets, urine, blood). The main mode of transmission varied between the affected countries [18]. In Malaysia and Singapore, the outbreaks were linked to pigs as intermediate hosts, while in the Philippines horses were the intermediate hosts [6,7,18,45]. In all instances, the consumption of fruits contaminated with bat droppings is believed to have caused the initial infections in domestic animals. In India and in Bangladesh, outbreaks were linked to the consumption of date palm sap [18]. Human-to-human transmissions in the community and/or hospital settings were reported in several countries including Bangladesh, India and the Philippines [6,35,46-49]. The initial signs and symptoms of NiV infection are nonspecific, which is why it is often misdiagnosed at first. A syndromic testing approach for pathogens causing symptoms such as febrile, respiratory or encephalitic disease could be considered for more accurate diagnosis [19]. Moreover, HeV and NiV are closely related, and diagnostic assays can cross-react depending on the RNA or antigen targeted. In the early stages of disease, NiV infection can be confirmed by RT-PCR testing of RNA extracted from throat and nasal swabs, cerebrospinal fluid, urine, and blood. Animal experiments demonstrated shedding in faeces, but stools are not listed in humans amongst the standard diagnostic samples. Exact virus kinetics are not known as well. Several narrow- and broad-range RT-PCR assays exist for strain detection, including a few commercial ones [19]. Later (10–14 days after the onset of symptoms) in the course of illness and after recovery, the diagnosis relies on antibody testing, using immunoassays (e.g. enzyme-linked immunosorbent assay (ELISA), and Luminex) or virus neutralisation. This also depends on the post-symptoms timing, the kinetics of antibodies and available laboratory facilities. Virus isolation and virus neutralisation tests need to be performed at BSL-4 [3]. Neutralisation tests can also be performed at BSL-2 if pseudoviruses are used [3]. BSL-2 facilities can be used for RNA isolation on inactivated samples from suspected clinical materials, but proper risk assessments need to be observed for any work. Currently there are no points of care/rapid tests available for NiV [19]. Various diagnostic tests are available for animals. Immunohistochemistry can be performed on infected animal or human tissues using specific anti-henipavirus antibodies. This is sometimes useful to confirm the diagnosis, although detection of viral RNA by RT-PCR and confirmation by sequencing are preferred methods. Case management and treatment Guidelines for the clinical management of patients with NiV infection have been made available in various countries, including affected countries such as Bangladesh, India and Malaysia. NiV clinical management is based on general, supportive treatment (ensuring fluid and electrolyte balance, oxygen inhalation if required), symptomatic treatment (treating fever, convulsions, shock), and adopting procedures to prevent further spread of the disease (implementing isolation measures, barrier nursing, safe handling of deceased bodies). NiV-specific immunotherapeutic treatments (such as m102.4 monoclonal antibody against the G protein) are under development and evaluation. This treatment showed effectiveness in animal models [50]. Based on a completed phase 1 clinical trial, it can also be used in patients on a compassionate use basis. As for treatment, several antiviral medications have been employed/tested for NiV infection. Remdesivir was found effective against NiV-B in non-human primates as a post-exposure prophylaxis when given 24 hours after intranasal and intratracheal lethal challenge and treatment pursued for 12 days [51]. It may be complementary to immunotherapeutic treatments. In Malaysia, ribavirin was used to treat a small proportion of patients, but its efficacy in people remained unclear [52]. After this, it was also used in India with supposed positive outcomes [53]. However, governing conditions and the true efficacy of this treatment remain unclear [54]. Other drugs tested and showing inhibition either in vitro or in animal models are favipiravir (T-705) [55] and 4ʹ-chloromethyl-2ʹ-deoxy-2ʹ-fluorocytidine (ALS-8112) [56].