Monkeypox (Mpox) is a viral zoonotic disease that has gained much attention lately due to increased spreading and severity beyond its endemic regions in Central and West Africa. The possibility of human-to-human transmission of the Monkeypox viral disease is, therefore, considered a very important public health concern. Since the discovery of the virus in 1970, there have been thousands of reported cases and the recent outbreaks extend beyond Africa into previously non-endemic regions. The virus caused mortality rates of as high as 10-11% due to the Central African clade and has raised significant alarm amongst world health authorities.
With the recent outbreak, the WHO declared it a Public Health Emergency of International Concern in 2022, having reported over 80,000 cases from more than 100 countries. Understanding monkeypox is important, especially in severely hit areas with limited access to health care, as it requires awareness and early detection with proper public health interventions.
Origin of Disease
Monkeypox is a viral zoonotic infection manifesting due to the monkeypox virus. It belongs to the Orthopoxvirus genus, which also comprises the variola virus-smallpox and vaccinia virus-applied in smallpox vaccines. The first human case of Mpox virus was discovered in 1970 in the Democratic Republic of the Congo. Since the discovery, the disease has been reported primarily within Central and West African nations. With worldwide sporadic cases emerging through international travel and the exotic pet trade, the ability of the virus to infect such a wide range of hosts from rodents to non-human primates raises significant control challenges.
Mortality Rate
The mortality rate associated with Mpox varies significantly depending on the viral clade. The Central African Congo Basin clade is more virulent, with mortalities running at 10-11%, whereas the West African clade has a much less severe course, with mortalities of about 1% to 3%. These figures, although much lower than the figures for smallpox, Monkeypox viral disease do bring out the gravity of the disease amidst susceptible populations such as young, pregnant women, and immunocompromised individuals.
How Did Humans Get Affected by Monkeypox?
Human infections are generally transmitted through direct contact with an infected animal’s blood, bodily fluids, and skin/mucosal lesions. Human-to-human transmission happens by way of respiratory droplets during prolonged face-to-face contact, as well as from contact with contaminated materials from an infected person, including their bedding or clothing. Complicating the containment efforts, the virus remains infectious for a considerable amount of time on environmental surfaces in which it has landed.
Aspects of Disease
Causative Agent
The Mpox virus is an enveloped double-stranded DNA virus and has a genetic relationship to the variola virus, which causes smallpox. It has significant implications for cross-protection provided by the vaccine against smallpox. The high environmental stability of the virus contributes much to its persistence and potential for the spread of Monkeypox viral disease. Its genetic makeup can easily allow this virus to infect many hosts, and mutations may have some influence on transmissibility and virulence. Hence, there is a need for continued genetic surveillance.
Affected People
Historically, infections were limited to rural, forested areas of Central and West Africa, where contact with animal reservoirs was more frequent. Recent outbreaks in non-endemic regions involved urban populations as well. This shift in paradigm indicates that global awareness and preparedness are needed. Children, pregnant women, and people with immune suppression who belong to vulnerable groups are at higher risk of severe diseases and complications.
Highest Recorded case
The Centers for Disease Control and Prevention (CDC) reports that several thousand cases have been reported throughout the world since the discovery of the virus. The greatest number of total cases and deaths each year is reported from the Democratic Republic of the Congo. Because of significant underreporting, especially from the regions with no efficient surveillance systems, precise global statistics for Monkeypox viral disease are challenging to obtain. Nevertheless, the outbreaks in recent times outside Africa have prompted strict reporting and increased international cooperation.
Differential Diagnosis
Presentation of the Disease
Clinical manifestations of monkeypox are similar to smallpox, hence its characteristics of fever, headache, muscle aches, and a characteristic rash that progresses through stages of development, namely macules, papules, vesicles, pustules, and scabs. Many of these symptoms could be confused with other diseases. Hence, clinical diagnosis without confirmation from a laboratory is almost impossible. It is necessary for the health-care provider to recognize the characteristic clinical progression so that early identification and isolation of the case can take place to avoid further spread.
Diagnosis
Being similar in appearance to other diseases calls for Monkeypox viral disease diagnosis to be confirmed in the laboratory. The methods used for diagnosis include:
- Polymerase Chain Reaction (PCR): PCR is a gold standard test for diagnosing Mpox. Testing for PCR detects the presence of viral DNA in the clinical specimen, such as skin lesions, throat swabs, or blood, helping the physician arrive at a final diagnosis of the disease. The technique of PCR also differentiates between Central African and West African clades, making it an important component in ascertaining the epidemiology and potential severity of an outbreak.
- Serological Testing: Serological tests detect antibodies against the Mpox virus, indicating past or recent infection. This is very useful in epidemiological investigations but not in the diagnosis of an acute infection.
- Virus Isolation: The virus can be isolated in cell culture, though this method is less commonly employed due to its complexity in performing and requiring high-containment laboratory facilities.
Disease Mistaken for Other Diseases
Clinical manifestations of Monkeypox viral disease can be mistaken with quite a number of other diseases. The most common differential diagnosis includes the following:
- Smallpox: Monkeypox is a disease characterized by symptoms similar to those seen in smallpox patients. It is less severe in symptom presentation than smallpox. Although eradicated, the similar clinical features with monkeypox, particularly the rash, make it a necessity for differential diagnosis especially in regions that have limited access to modern diagnostic tools.
- Chickenpox (Varicella): The rash of chickenpox is of a vesicular nature and could easily present similarly to that of monkeypox. However, the lesions in chickenpox are more superficial and the appearance of rash appears in successive crops rather than simultaneously.
- Measles: Initial presentation of fever and rash may be easily confused with monkeypox. The measles rash, however, usually starts from the hairline progressing downwards, which has a different rash distribution compared to the monkeypox.
- Bacterial Skin Infections: Conditions like impetigo can present with pustular lesions which can easily be mistaken for those of monkeypox, especially in resource-poor regions where sophisticated diagnostic facilities are lacking.
- Syphilis: The rash from secondary syphilis can be widespread and easily mistaken for a monkeypox infection, especially from areas that are known to be endemic for syphilis.
Prevention
The prevention of the spread of Monkeypox viral disease includes not only public health measures but also involves regulatory oversight of the key strategies noted below:
- Reducing Zoonotic Transmission: The regulatory guidelines should focus on educating the communities regarding the risks associated with contact with wild animals, in particular rodents and primates. Handling, trade, consumption, and putting in place regulations over bushmeat consumption in averting the risk of zoonotic spillover.
- Human-to-Human Transmission: Requires strict infection control policies like the use of personal protective equipment (PPE) by healthcare workers and adherence to isolation protocols for suspected cases. This must be complemented by the responsibility of regulatory bodies to ensure health facilities are equipped with the necessary resources to manage and handle outbreaks.
- Vaccination: The smallpox vaccine is being considered for re-vaccination for people at risk, particularly in endemic areas. This requires assessment by the regulatory managers about the need for vaccination campaigns in light of available epidemiological data and risk assessments. More recently, newer vaccines like MVA-BN, sold under brand names such as Imvamune or Imvanex, offer safer vaccines with much fewer side effects, which could be crucial if large-scale vaccinations are required.
- Surveillance and Reporting: The surveillance and reporting system needs strengthening for quick identification and reporting of cases. The regulatory frameworks should obligate the reporting of cases of monkeypox to national and international health authorities for timely coordination.
Why is Smallpox Vaccine Effective Against Monkeypox Virus?
The smallpox vaccine provides protection against Monkeypox viral disease because of the significant molecular similarities between the vaccinia virus, used in the vaccine, and the monkeypox virus. These viruses share high sequence homology, particularly in the proteins found in their envelope and membrane structures. These shared antigens are targeted by neutralizing antibodies and cytotoxic T cells as part of the immune response of the smallpox vaccine. Therefore, such immune elements can be effective in their action by cross-reactivity with the presented elements of the monkeypox virus. This molecular mimicry explains the protective effectiveness of the smallpox vaccine against monkeypox.
Treatment
Currently, there is no specific antiviral treatment for monkeypox that is approved for widespread use. However, several therapeutic options are under investigation or have been used off-label:
- Tecovirimat (ST-246): The US FDA has approved this for the treatment of smallpox. Animal models showed efficacy of tecovirimat against monkeypox. The recommendation includes its use in severe cases to be considered especially for immunocompromised patients.
- Cidofovir and Brincidofovir: Both antivirals have activity against orthopoxviruses and may be used in severe or complicated cases. The use of these drugs should be guided by clinical trials and regulatory approvals specific to monkeypox.
- Supportive Care: Management for monkeypox includes symptomatic pain management, hydration, and treatment of secondary bacterial infections. Regulatory guidelines should implement supportive care protocols in healthcare facilities for recovery.
Follow-Up
Follow-up care for Monkeypox viral disease patients is important. It will enable the observation of complications and ensure the complete recovery of the patient. The healthcare person has to ensure follow-up protocols for the discharged patients through regular health checks and monitoring of the long-term effects. Thorough investigations by public health authorities are needed to trace the source of infection to prevent further outbreaks. Continuous surveillance and updated guidelines are considered crucial in managing the ever-evolving threat of monkeypox.
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REFERENCE
1.Tan, C., Zhu, F., Pan, P., Wu, A., & Li, C. (2023). Development of multi-epitope vaccines against the monkeypox virus based on envelope proteins using immunoinformatics approaches. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1112816
2.Mpox. (2024, August 26). https://www.who.int/news-room/fact-sheets/detail/mpox
3.Ciccarese G, Di Biagio A, Drago F, Mastrolonardo M, Pipoli A, Lo Caputo S, Serviddio G, Santantonio T, Parodi A. Monkeypox virus infection mimicking primary syphilis. Infez Med. 2023 Mar 1;31(1):113-115. doi: 10.53854/liim-3101-16. PMID: 36908381; PMCID: PMC9994820.
4.Kumar A, Borkar SK, Choudhari SG, Mendhe HG, Bankar NJ. Recent Outbreak of Monkeypox: Implications for Public Health Recommendations and Crisis Management in India. Cureus. 2023 Sep 21;15(9):e45671. doi: 10.7759/cureus.45671. PMID: 37868437; PMCID: PMC10589906.
