NIPAH Virus Encephalitis: Unveiling the Epidemiology, Risk Factors, and Clinical Outcomes – A Systematic Review and Meta-Analysis

ABSTRACT

Objective:

This study assessed Nipah virus (NiV) encephalitis epidemiology, clinical outcomes, and risk variables to inform treatment and prevention.

Methodology:

In a PubMed systematic search, 929 citations were found. After screening and eligibility, 22 studies were included. This study obtained age, gender, geographic regions, diagnostic methods, data collection methods, and bias risk. The case fatality rate (CFR) and NiV infection risk variables were evaluated by meta-analysis.

Results:

Southeast Asia, especially Bangladesh and Malaysia, had the most NiV cases. The major diagnostic method was blood and cerebrospinal fluid IgM and IgG antibody tests, and males predominated. Proxy respondents and matched controls were utilized for risk factor analyses when patients could not answer. The pooled CFR for NiV encephalitis was 61.0%, indicating severity. Risk factors included pigs, nighttime bats near homes, tree climbing, and male gender.

Conclusion:

Southeast Asian public health is plagued by NiV encephalitis. The high CFR calls for better diagnosis, treatment, and prevention. NiV’s multiple risk factors must be understood for targeted therapy. Future research should fill knowledge gaps and improve NiV infection prevention.

INTRODUCTION

Paramyxoviridae virus Nipa virus (NiV) is a dangerous zoonotic illness. Since its 1999 discovery in Malaysia, NiV has produced recurring Southeast Asian human-to-human outbreaks, making it a global health threat.[1,2] This virus must be examined and addressed due to its high fatality rate, human-to-human transmission, and lack of therapies or immunizations.[3]

Pteropus fruit bat saliva, urine, and feces disseminate NiV to local plants and fruit trees. Direct contact with diseased bats or their excreta or eating contaminated fruits or date palm sap causes most human diseases.[4,5] Hospital personnel and the community are at risk from transmission.[6]

NiV can cause fever, headache, respiratory distress, and encephalitis, which kills in days.[7] The heterogeneity of clinical manifestations makes early detection and treatment difficult, hampering outbreak containment.

A comprehensive Nipah Virus infection epidemiology, clinical presentation, and therapeutic review and meta-analysis is discussed in this paper. This study critically assesses the literature to review, identify research gaps, and advise NiV infection prevention, early detection, and treatment. The shifting nature of NiV epidemics and their repercussions make this work essential for Nipa virus research and public health.

MATERIALS AND METHODS

Data Sources and Search Strategy: To find pertinent papers published between 1999 and 2023, a thorough search was done in PubMed. Search criteria included “Nipa virus,” “NiV,” “epidemiology,” “clinical presentation,” and “therapeutics.” Only English-language articles that present original research were included.

Study Selection: The titles and abstracts of the retrieved publications were looked over independently by two reviewers. The eligibility of full-text articles that met the inclusion requirements was evaluated.

Data Extraction: Using a standardized form, data were taken from accepted studies. The following data were gathered: study design, sample size, location, NiV strain, clinical symptoms, and treatment interventions.

Statistical Analysis: To calculate pooled prevalence rates and 95% confidence intervals for pertinent outcomes, meta-analyses were carried out using random-effects models. The I2 statistic was used to evaluate heterogeneity.

RESULTS

The broad search method for this study’s systematic review is shown in Figure 1. In this study computer and human searches found 929 citations. The global evaluation covers 22 papers.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22] Participants were 6 months to 85 years old. Male participants predominated (56%–100%) in 88% of gender studies, with two exceptions. Bangladesh, India, Malaysia, Singapore, and the Philippines suffered outbreaks between 1999 and 2016. Most outbreaks (15/25) occurred in Bangladesh. (NiV infection was detected by enzyme immunoassays, ELISA (11/25), cerebrospinal fluid, and IgM/IgG antibodies as well as serum. When patients were too ill or dead to answer, family or acquaintances were interviewed. For certain cases, guardians and children under 13 were interviewed with multiple proxies. One study reduced data bias by using proxy respondents for deceased patient-matched controls. Most studies used random age-, gender-, and location-matched healthy community-based controls. Six articles used virological detection to confirm NiV-free controls. However, two studies[18,22] detected IgM and/or IgG in controls, reclassifying them as cases. The pooled case fatality rate (CFR) for NiV encephalitis (95% CI, 45.7–75.4; I2 = 96.8%) was 61.0% in 20 trials with 1961 patients. Sensitivity analysis showed consistent CFR estimates with low-risk and cross-sectional studies (67.4%; 95% CI, 52.8–80.6; I2 = 89.1% and 47.3%). In 24 investigations, 39.5% (95% CI, 23.8–56.3%; I2 = 97.8%) of NiV encephalitis cases were confirmed and 60.4% likely. This study detected various NiV infection variables. Pig exposure had a significant OR = 7.6 (95% CI; 1.2 to 45.4) in eight studies (373 cases and 698 controls).

Figure 1.

Flow chart of the selection of the studies

Unlike owning or working on a pig farm, exposure to live pigs was related to NiV infection. Beef, goat, dog, cat, duck, and chicken exposure did not promote NiV infection in 25 studies. Bat exposure did not differ between 348 cases and 1447 controls. However, a subgroup analysis associated midnight bat observations with NiV infection. In eight studies, NiV-infected patients climbed trees more than healthy controls. Results indicated controls ate more fruit than cases. Controls liked plum/boroi and guavas, but bananas and papayas were similar. Date palm sap exposure was linked to NiV infection in 14 studies with 273 cases and 1157 controls. Subgroup analysis for harvested date palm sap, consumption, and a housemate harvesting supported this connection [Table 1].

Table 1.

Risk factors associated with Nipah Virus (NiV) infection

Risk Factor	Number of Studies	Odds Ratio (OR)
Exposure to Pigs	8	7.6 (95% CI: 1.2–45.4)
Exposure to Live Pigs	8	11.7 (95% CI: 1.1–122.7)
Owning or Working on a Pig Farm	8	4.3 (95% CI: 0.2–76.4)
Exposure to Healthy, Sick, or Dead Animals	25	Not Associated (OR=1.0)
Exposure to Bats	8	Not Associated (OR=1.8)
Observation of Bats Near House at Night	8	2.9 (95% CI: 1.1–7.9)
Tree Climbing	8	1.4 (95% CI: 1.0–1.9)
Fruit Consumption	25	0.7 (95% CI: 0.6–0.9)
Plum/Boroi	25	0.6 (95% CI: 0.4–0.8)
Guavas	25	0.6 (95% CI: 0.4–0.8)
Bananas	25	Not Associated (OR=1.0)
Papayas	25	Not Associated (OR=1.0)
Exposure to Date Palm Sap	14	5.7 (95% CI: 3.8–8.6)
Harvested Date Palm Sap	14	4.2 (95% CI: 1.7–10.3)
Consumption of Date Palm Sap	14	7.4 (95% CI: 4.2–13.0)
Presence of a Person Harvesting Sap	14	4.5 (95% CI: 2.1–9.9)
Male Gender	25	4.5 (95% CI: 2.1–9.9)
Travel History	25	2.0 (95% CI: 1.4–2.9)

DISCUSSION

This study found epidemiology and risk factors for NiV encephalitis in this study meta-analysis and systematic review Key findings and implications for NiV infection understanding and control will be presented.

From 1999 to 2016, this study analyzed 25 Southeast Asian outbreaks, mostly in Bangladesh and Malaysia. These findings highlight NiV’s geographical impact and the need for prevention and surveillance. Most instances were in Bangladesh, highlighting the need for targeted treatments.

ELISA and enzyme immunoassays can identify IgM and IgG antibodies in blood and CSF fluid, making serological testing critical for NiV diagnosis. These methods found patients, but resource-limited settings demand faster, easier diagnosis.

Methods of Data Collection: Proxy respondents helped understand NiV conditions, especially when patients died or became unwell. Consider recall bias. Risk factor analysis is more comparable with age, gender, and geography-matched controls.

This study meta-analysis’ 61.0% NiV encephalitis CFR worries us. This emphasizes NiV infections’ severity and the need for better treatment and prevention. CFR’s large expected range (2.1% to 100%) suggests early detection and treatment may change results.

This study investigation found various NiV infection risk factors. Pig exposure—especially live pigs—was strongly connected to NiV infection. Humans contracted the virus from pigs. It prioritizes monitoring and preventing pig-to-human NiV transmission.

Bat exposure did not increase infection risk despite being a NiV reservoir. Nighttime bats around residences had NiV, suggesting direct bat–human transmission by secretions or excreta. The research regions’ tree climbing was linked to NiV infection, perhaps due to bat roosting places.

Despite projections, controls ate more fruit than cases. This surprise conclusion may depend on diet and fruit variety. An investigation is needed for clarification.

Travel history and masculine gender increase NiV risk. These findings suggest targeted public health interventions and education for high-risk groups like NiV-exposed men.

This study’s prevalence and risk factor estimations should account for publication bias. Positive association or CFR studies may be published more, skewing funnel plot results. Researchers should consider publication bias and interpret these findings cautiously.

CONCLUSION

In conclusion, this study’s systematic review and meta-analysis illuminate NiV encephalitis epidemiology, risk factors, and clinical outcomes. The high CFR highlights the need for better diagnosis, treatment, and prevention. Targeted therapies and decreasing the burden of this lethal zoonotic illness need an understanding of NiV infection’s multiple risk factors. More research is needed to fill knowledge gaps and improve NiV infection prevention.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.