Clinical Diagnosis of Monkeypox Virus: Current and Upcoming Tests

Just as the world was reeling from the effects of the COVID-19 pandemic, an unexpected monkeypox outbreak occurred. By July 2022, 16,016 monkeypox cases had been confirmed globally in 75 countries. This prompted the World Health Organization (WHO) to declare the monkeypox outbreak a Public Health Emergency of International Concern (PHEIC). Public health officials are in the process of identifying positive cases and tracing their contacts so that they can contain the spread of the virus. 

Most of the confirmed monkeypox cases are in Europe and America which are non-endemic areas. The virus has spread to South Korea and Singapore, indicating a spread across the continents. 

The re-emergence of the viral infection may be attributed to the cessation of the smallpox vaccination which happened in the early 1980s as a result of the consequent decline in herd immunity. 

What is Monkeypox?

Monkeypox virus is a type of virus belonging to the orthopoxvirus class and it causes a zoonotic disease known as monkeypox. The symptoms of monkeypox are similar to those of smallpox but they are less severe. Monkeypox is endemic to west and central Africa. Two strains aka clades of monkeypox have been identified: the West African clade and the central African (Congo Basin) clade.

How is Monkeypox Transmitted?

Monkeypox is a zoonotic disease and hence is mostly spread from animals to humans. However, a recent outbreak suggests transmission of monkeypox through sexual contact. The virus could also be transmitted from contact with contaminated surfaces.

How is Monkeypox Tested?

A specimen is obtained by swabbing the suspected monkeypox rash and it is sent to a lab for testing. Specimens collected for monkeypox testing need to be handled with a risk-based approach in mind. Nucleic Acid Amplification Test (NAAT), such as quantitative Polymerase Chain Reaction (qPCR) test, is then conducted. The PCR can be conventional or real-time PCR. Antigen and antibody tests are not effective because they cannot differentiate between orthopoxviruses. Real-time quantitative PCR (RT-qPCR) has several advantages, including high sensitivity and the ability to detect early infection. It also has potential applications in molecular epidemiology. However, its use may be limited in rural or third-world countries with poor supporting infrastructure. 

WHO recommends combining PCR tests with gene sequencing. Sequencing helps identify the clade and give a better understanding of the epidemiology of the monkeypox virus. Nested-multiplex PCR is useful in detecting the presence of orthopoxviruses. However, the test may not meet the sensitivity requirements for monkeypox testing. 

All the testing reagents should be stored according to the manufacturer’s specifications. PCR tests are usually very sensitive, and every effort needs to be made to prevent contamination. 

Reporting of Monkeypox Test Results

All labs that test for monkeypox are required to report both negative and positive tests according to the national reporting standards. It is important for testing labs in WHO member countries to make the monkeypox genetic sequencing data available in publicly accessible databases. 

Biosafety Measures in the Lab

Monkeypox specimens should be refrigerated at a temperature of 2-8 degrees Celsius as soon as it has been collected. If the test is conducted more than seven days after the sample collection, the specimen should be frozen at a temperature of -20 degrees Celsius or lower. In addition, the specimens should be transported according to national and international standards. 

Challenges in Monkeypox Testing

The Poxviridae family, which includes the monkeypox virus, has very large genomes. This creates a wide potential target for PCR testing. For example, varicella-zoster which causes chickenpox can cause a false positive if the PCR test is not optimized and therefore has reduced analytical sensitivity. Contamination in the laboratory is another potential cause for false positive results. Genetic changes in the monkeypox virus have been observed in the current outbreak. This automatically reduces the sensitivity of PCR tests. Lastly, highly specific genetic tests present specimen and data management challenges that testing laboratories must contend with.

How a Diagnostics LIMS Supports Monkeypox Testing 

A Laboratory Information Management System (LIMS) is an indispensable tool in managing lab workflows. It offers end-to-end tracking of samples throughout the entire lifecycle. A diagnostics LIMS also helps manage tests, test results, and supports reporting of test results. A cloud-hosted diagnostics LIMS ensures remote access to lab data and promotes data sharing while, at the same time, provides maximum data protection and security. A cloud-based diagnostics LIMS also enables delivery of test reports to patients and physicians via a patient portal and a physician portal respectively. Furthermore, it can be integrated with the reporting system of the state, tribal, local, or territorial (STLT) health departments for automated reporting of test results.   

A Concerted Effort Needed to Beat Monkeypox 

The world came together to beat the deadly coronavirus. A similar effort must be put together if monkeypox is to be subdued. Countries must put in place measures for information sharing to keep track of the spread of the virus and to be able to respond accordingly. Nations must also be willing to share resources with those in poorer settings or far-flung, rural areas to prevent uncontrollable breakouts in such areas. And just like with the COVID-19 pandemic, technology must be leveraged to ensure speed and accuracy in testing and instituting early and effective treatment of monkeypox.