Mpox Outbreaks and Latest Concerns of the New Strain
Mpox, formerly called monkeypox, is a rare viral disease caused by an orthopoxvirus- monkeypox virus (MPXV). It has recently caused outbreaks in a number of countries, raising global health concerns. In this article, we delve into the current situation, the strains involved, and tools for detection.
There are 2 major genetic groups (clades) of MPXV; Clade I (formerly known as Central African or Congo basin clade) and Clade II (formerly known as West African clade). Clade II is split into Clade IIb and Clade IIa, with subgroup clusters (lineages).
Current Mpox Outbreaks and Concerns
In 2022, the World Health Organisation (WHO) declared a public health emergency of international concern. This was in response to an outbreak of nonendemic mpox in multiple countries. Human-to-human transmission largely fueled the spread of this virus; consequently, from January 2022 to August 2023, around 89,000 cases of mpox were confirmed by the WHO in 113 countries.
The majority of the cases seen in the outbreak in 2022 were from Clade IIb, lineage B.1.
More recently, the Republic of South Africa notified WHO of 20 confirmed mpox (monkeypox) cases between 8 May and 2 July 2024, including three deaths (Case Fatality Rate (CFR) 15%).
Currently, there is also a major outbreak of mpox in the Democratic Republic of the Congo (DRC), where cases have increased over a number of years. According to the WHO, in 2024, (as of 26 May), a total of 7851 mpox cases were reported there, with 384 deaths (CFR 4.9%). around 50% of these are among children under the age of 15 years. An outbreak in South Kivu province, near the border with Rwanda, Burundi and Uganda, is causing particular concern.
Of particular interest is that sequencing of samples from this most recent outbreak determined that this is a new mpox strain. There are mutations present that appear to enable greater human circulation.
"The new strain of clade I MPXV linked to human-to-human transmission represents a renewed risk of cross-border and international spread which may potentially lead to an increased risk of severe illness."
WHO, Mpox - Democratic Republic of the Congo 14 June 2024
Detection Challenges
It is evident that scientists need to develop effective and rapid techniques to diagnose, monitor and treat mpox. Currently, the preferred diagnosis method is a polymerase chain reaction (PCR) method to detect viral DNA, while antibody detection methods are of no benefit due to their inability to distinguish between different orthopoxviruses. Read on to find out more about why this is the case, and more about the disease, or jump straight to the bottom of the page for our solution: Critical reagents and a protocol for serology assays with specificity to mpox - which could revolutionize our approach to this disease, including the latest variant that has just been reported.
What is Monkeypox (Mpox)?
As suggested by its name, monkeypox is a zoonotic disease first identified in 1959 in monkeys. However, the first human case was not confirmed until 1970 in the DRC. Monkeypox disease is caused by a virus belonging to the orthopoxvirus genus of the poxviridae family and is endemic mainly in western and central Africa. It is grouped under the same genus as variola virus (smallpox), vaccinia (smallpox vaccine), and cowpox, all of which share high genetic homology. Our current understanding of the disease, its origins, and its transmission methods provides a solid foundation for further research and development of effective diagnostic and treatment strategies. Transmission of monkeypox occurs through close contact with an infected person's skin lesions, respiratory secretions, and contaminated surfaces. The disease is generally self-limiting, and treatment for most people focuses on symptom relief. It is characterized by a fever, swollen lymph nodes, fatigue, headache, and a painful rash often mistaken for chickenpox, making diagnosis based on clinical symptoms alone challenging.
Mpox Virus Structure
As a poxvirus, mpox is a highly complex, ‘brick-shaped’ virus. It is relatively large, extending to a length of 220-450nm and a width of 140-260nm. Mpox is composed of four components: the core, outer membrane, lateral bodies, and outer lipoprotein envelope. At the centre of the virus is the core, which holds the linear double-stranded DNA genome surrounded by core fibrils. The palisade layer then encompasses this. All these components, including the lateral bodies, are then contained within the outer membrane, which is decorated with surface tubules. It is important to note that the proteins on the outer and inner envelopes are different. Despite needing host ribosomes to translate mRNA, the genome of poxviruses encodes for their own replication, transcription, and assembly proteins. The Monkeypox virus exists in two infectious forms: Intracellular mature virions (MV) are single membrane-bound and are released during host cell lysis. MVs are very stable and are believed to be involved in the transmission between hosts. When translocating to Golgi bodies, extracellular enveloped virions (EVs) gain a double membrane to form an antigenically distinct triple membrane. As this outer membrane is fragile, EVs are thought to be designed to spread within the host.
Why is Mpox Diagnosis so Difficult?
Orthopoxviruses have highly conserved genomes, which can lead to significant antibody cross-reactivity among its members. Hence, developing a standard antibody test for the mpox virus is complicated by cross reactive immune responses induced by vaccinia, the virus used in smallpox vaccines. Therefore, there is no approved serology assay that can differentiate between antibodies produced due to mpox infection and those made after vaccination.
B21R-BSA Conjugate Peptides for Diagnostic Testing
Biosynth has developed new conjugate peptides for Monkeypox virus: (MPV) B21R-A and B21R-B. These have been used as critical reagents to develop a high-throughput multiplex microsphere immunoassay using a combination our mpox-specific peptides alongside cross-reactive OPV proteins that resulted in the specific serologic detection of mpox infection with 93% sensitivity and 98% specificity,
Read the paper here: ‘Development of a novel serological assay for the detection of mpox infection in vaccinated populations, '
These unique mpox peptides contain the surface glycoprotein B21R, with regions that contain important antibody targets as well as several key immunodominant epitopes. When conjugated to a carrier protein like BSA, this has greatly improved the assay's sensitivity compared to unconjugated peptides and enhanced stability.
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Reagents for the Latest Outbreak Variants
At Biosynth we pride ourselves on staying with the science. We have already aligned and evaluated the sequences of the newest strain of this ongoing outbreak and have determined that DL7025 B21R-A is a 100% match for the new variant, and DL7031 B21R-B is a 97% match with only conservative substitution. Based on these data, we are confident that these peptides are suitable tools for detection the emerging clade I MPXV strain.
Contact us now to discuss working with Biosynth to ensure long term and bulk supply for critical reagents for mpox detection.
References and Resources
Development of a novel serological assay for the detection of mpox infection in vaccinated populations
Jennifer L. Yates, Danielle T. Hunt, [...], Philip Noone, Christina Egan, Mark K. Slifka and William T. Lee
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