In recent years, we’ve seen that major outbreaks are caused by zoonotic infections. Including HIV-1 and HIV-2, the 1918 influenza virus, the Middle East respiratory syndrome coronavirus, and SARS-CoV-2. These outbursts have a devastating effect on the global population. We are still struggling to find solutions for these animal-borne diseases, and Lassa fever is one of them.
Every year, there are between 1, 00,000 and 3, 00,000 cases of Lassa fever (LF) worldwide. Lassa fever has a particularly serious effect on Sierra Leone, and Liberia, where it is thought to be responsible for 5,000 annual deaths and 10-16 percent of hospital admissions.
As of now, there is no vaccine for Lassa fever yet. After the major outbreak in 2018, many global organizations including the world health organization are working toward developing an effective vaccine.
But, there are many promising vaccines in the pipeline one of which is a chimpanzee adenovirus-vectored vaccination called ChAdOx1-Lassa-GPC contains the Josiah strain Lassa virus (LASV) glycoprotein precursor (GPC) gene.
A study demonstrates the immunogenicity of ChAdOx1-Lassa-GPC by showing that it causes strong T-cell and antibody responses in mice. Additionally, a single dosage of ChAdOx1-Lassa-GPC completely prevents Hartley guinea pigs from morbidity and mortality after being challenged lethally with a LASV modified for guinea pigs (strain Josiah). However, more research needs to be done before this can be considered a vaccination.2
Despite steps to prevent and limit LASV propagation, the fight against Lassa fever is impeded by a lack of vaccinations, well-documented treatments, and suitable diagnostics. There are presently no commercially accessible diagnostics that can capture viral strain diversity and provide a diagnosis at any moment during the clinical course of the disease. Since there are a limited number of diagnostic options present, a few rapid diagnostic kits for LASV diagnosis are available.
The purpose of this blog is to explore the effectiveness of the rapid diagnostic kits for Lassa and the challenges with conventional diagnostic methods.
Early detection and identification are crucial since antiviral Ribavirin treatment must be given within six days of infection for maximum effectiveness.
Lassa fever is prevalent in Nigeria, with cases discovered and reported approximately every year. During a significant outbreak in 2018, almost 600 persons were reported to be infected, including 171 deaths. This demonstrates that existing LASV diagnostic procedures are problematic to use in low-resource health centers and may be less sensitive to detecting new or emerging LASV strains. Thus, advancement in diagnostic techniques is the best way to prevent and manage this epidemic at an early stage.3
During the 2018 LF epidemic in Nigeria, researchers compared the performance of the Pan-LASV RDT (Rapid Diagnostic test) to current quantitative PCR (qPCR) techniques. When compared to the composite findings of two qPCR tests for patients with acute LF (RDT positive, IgG/IgM negative) during the first screening, RDT performance was 83.3 percent sensitivity and 92.8 percent specificity. The Pan-Lassa RDT detected 100% of samples with Ct values less than 22 on both qPCR tests. There were significantly higher case fatality rates and liver transaminase values in RDT-positive participants compared to RDT-negative subjects. The table below represents the comparison between these two. 4
The Pan-Lassa RDT may be useful in settings where nosocomial infections from LF patients pose an immediate threat to health care workers, such as in outbreaks. The Pan-Lassa RDT has high sensitivity and specificity in detecting patients with a high viral load.
Researchers collected samples from suspected LF patients reported to the Institute of Lassa Fever Research and Control at Irrua Specialist Teaching Hospital (ISTH) for testing in 2018. The current study comprised patient samples (N=434) with sufficient volume to conduct various diagnostic tests.5
Acute LF was diagnosed in patients who tested positive for the Pan-Lassa RDT (n=118). When RDT was negative but anti-LASV IgM antibodies were positive, patients were classified as having Post-acute LF (n=115). Patients in the Non-LF disease group were negative on all ReLASV immunoassays and had only anti-LASV IgG antibodies (n =197).
There was no statistically significant relationship between the day of onset and either the RDT score or the level of IgM production.
The clinical symptoms of LF are non-specific, allowing for a wide range of differential diagnoses, especially in the early phase of the disease. As a result, early diagnosis is essential for accurate intervention.
The diagnosis that is commonly used is magnetic bead-based immunodiagnostics for both Lassa virus antigens and antibodies, molecular probe-based quantitative real-time PCR but the major challenge in PCR-based assay is the high specificity of PCR-based tests might be challenging due to significant gene mutations in LASV strains throughout a large geographic area, which raises the possibility of primer and/or probe failures.
These diagnostic tests might take up to 3 to 5 days, which is a critical time following disease onset. Proper healthcare facilities are required but in the endemic areas, it is not practical.
In a nation like Africa, where health services are underfunded, such situations are highly dangerous, especially during an outbreak. The healthcare system is underdeveloped and has faced several challenges, particularly at the local government level. There is no provision for competent and functioning surveillance systems, and thus no monitoring system to monitor infectious disease outbreaks, bioterrorism, chemical poisoning, and so on. To achieve success in health care, rapid kits might be really beneficial.6
For epidemic investigation and patient care, there is still an urgent need for field-friendly, low-cost, accurate, and speedy diagnostic tests. In Nigeria, a fast immunoassay for the LASV subtypes present in Sierra Leone, as well as a comparable test designed to identify all strains, are being evaluated. Emerging technologies, such as CRISPR-based specialized high-sensitivity enzymatic reporter unlocking, may provide a multiplexed and portable nucleic acid detection platform for assessing novel LASV strains in the near future.6
Although the results discussed here are promising and performed well but more data are needed from other countries as well to observe the performance in different geographical regions. More research is needed to produce a clinical reference standard for the diagnosing of Lassa fever. In addition, well-conducted field and laboratory experiments with a clear description of the patient/sample flow and time will be required in the future.7
Reviewer: Priyanka
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