Monkeypox Vs Smallpox: Key Differences

Introduction

Monkeypox - now known as mpox - and smallpox stand as significant chapters in the history of infectious diseases, each with its distinctive characteristics and impact on global health. While mpox continues to be endemic in certain parts of the world - specifically Central and West Africa - smallpox was declared eradicated by the World Health Organisation (WHO) in 1980, with the last known natural case occurring in 1977. This eradication followed approximately 3000 years of devastation caused by smallpox - making it one of the deadliest diseases known to humanity. 

The recent outbreak of mpox, which began in early May 2022, saw cases reported across countries where the disease is not endemic - including those in Europe and North America. The WHO declared this outbreak a Public Health Emergency of International Concern (PHEIC) in July 2022, subsequently causing widespread anxiety. In particular, people feared that it could lead to another deadly pandemic, like that caused by COVID-19, or devastation similar to smallpox. Consequently, it is imperative that we better understand mpox - especially its distinction from smallpox regarding factors like transmission, clinical presentation, and global impact.

Causative agents

Understanding the differences between mpox and smallpox requires consideration of their different causative agents. The table below provides a comparison of these agents, including their characteristics and modes of transmission.

Clinical presentation

The symptoms of mpox and smallpox are similar. In the early stages, both infections cause the following:

• Fever
• Back pain
• Muscle aches
• Headaches
• Fatigue/lack of energy

Crucially, mpox also causes swollen lymph nodes - a symptom not seen in cases of smallpox. In the recent outbreak of mpox, rectal symptoms such as bloody stools and rectal pain were also frequently reported. Smallpox can cause abdominal pain and vomiting, but this is less common. The main distinguishing factor between the clinical presentations of the two diseases is the presence or absence of swollen lymph nodes. 

As the infection progresses, both cause a rash with distinctive skin lesions. These lesions progress to vesicles (small blisters filled with clear fluid) and eventually pustules (small blisters filled with pus). With both mpox and smallpox, the lesions can appear anywhere on the body, but generally begin in different areas:

• Mpox lesions often begin on the face or in the genital area, before spreading to other parts of the body such as the hands and feet
• Smallpox lesions typically begin in the mouth and on the tongue, before spreading to the skin of the face, arms, legs, hands, and feet

Notably, patients with mpox may experience a rash as their first symptom; however, in most cases, the rash will develop later on. 

Of the two viral infections, smallpox is associated with more severe symptoms and a higher mortality rate - with mpox rarely being fatal. 

Diagnosis and detection

It is imperative to understand the methods used for diagnosing patients and detecting signs of infection. This relates critically to mpox, which remains an issue today. Smallpox, on the other hand, has been eradicated - hence only a brief overview of its past diagnostic techniques is provided. 

Diagnostic methods for mpox

Mpox are diagnosed using a laboratory test known as polymerase chain reaction (PCR). Typically, healthcare professionals use a variation of this test termed real-time PCR. This test uses swabs from skin lesions; viral DNA in the swabs is then analysed using real-time PCR to confirm whether MPXV is present. If it is, the mpox diagnosis is confirmed. 

Despite the genetic similarity between mpox and other poxviruses - such as smallpox - real-time PCR is accurate in specifically detecting mpox. This is because the test identifies unique viral DNA sequences (targets) in the MPXV virus.² 

Historical diagnosis of smallpox

Smallpox was eradicated before the invention of PCR in 1983. Therefore, diagnosing this infection relied heavily on clinical examination. Physicians would examine the distribution, morphology, and progression of skin lesions. This often led to an accurate diagnosis, but misdiagnosis could occur when other conditions presented with similar symptoms. 

Vaccination and prevention

Eradication of smallpox

Smallpox is the only human disease to be eradicated through vaccination efforts. Eradication was achieved through a coordinated global campaign led by the WHO, which included two key strategies:

• Mass vaccination programmes: vaccinations were carefully monitored and designed to reach 80% of the population to ensure herd immunity. Some countries also carried out childhood immunisation programmes
• Surveillance programmes: cases of smallpox were reported, and morbidity and mortality data were collected. Health units provided weekly reports of these data so that special teams could investigate cases and outbreaks to contain the disease

Vaccination for mpox and current preventative measures

There are three vaccines against mpox. All of these were developed against smallpox, but due to the genetic similarity of the two causative viruses (variola virus and MPXV), they are also effective against mpox.³ Because mpox is not as deadly or widespread as smallpox was historically, there are currently no mass vaccination programmes. Instead, vaccination is recommended for people at risk of infection - for example, someone who has been in close contact with someone who has mpox. However, vaccine availability is limited in regions where the disease is endemic.⁴

Besides vaccinating people at risk, there are several strategies to prevent the spread of mpox. These focus on awareness, surveillance, early detection and diagnosis, isolation of infected people, and infection control measures - including hand hygiene, respiratory hygiene, and management of exposure to mpox. These efforts aim to reduce the spread of the disease and prevent outbreaks, but success varies depending on local healthcare infrastructure and resources. As with vaccination efforts, prevention is less successful in regions where mpox is endemic. 

Global impact

Current status of mpox outbreaks

While still endemic in regions of Central and West Africa, the outbreak seen across non-endemic countries had its PHEIC status lifted in May 2023. The people primarily affected by this outbreak were men who have sex with men - highlighting that the principal mode of transmission was sexual contact. This represented a change in the epidemiology of mpox, which, beforehand, was thought to spread primarily via zoonotic transmission. The implications of this shift are paramount - especially regarding future surveillance, response, and raising awareness among the most at-risk groups. 

Reflection on the impact of smallpox eradication

The eradication of smallpox is one of the most significant achievements in the history of public health: a testament to the power of vaccination and international collaboration in combating infectious diseases. Its eradication has had far-reaching implications, with millions of lives saved and resources repurposed. On top of this, the economic effects were huge; the total benefit equates to an estimated $350 million per year for industrialised countries and $1070 million per year for developing countries.⁵

FAQs

What can be mistaken for mpox?

Other conditions can cause rashes that resemble the skin lesions seen in mpox patients. Examples include molluscum contagiosum, syphilis, varicella zoster (chickenpox), measles, rickettsialpox, and scabies.⁶

Are mpox lesions itchy?

Yes, the skin lesions caused by mpox are often itchy. Typically, the itchiness occurs at the healing phase, once the lesions are no longer painful. 

Can you pop mpox lesions?

Mpox lesions aren’t poppable initially, but they are at later stages. However, they should not be popped as this doesn’t speed up recovery. Also, popping mpox lesions can create further risks: spreading the virus to other parts of the body, spreading the virus to others, and developing bacterial infections in the open lesions. 

Who is at risk for mpox?

The most at-risk groups are men who have sex with men, people who have multiple or new sexual partners, and people in close contact with others infected with mpox.

Will mpox go away on its own?

Yes, most people recover from mpox without treatment. Recovery usually takes a few weeks and can be supported by getting plenty of rest, consuming plenty of fluids, eating healthy foods, and taking medication for pain and fever. 

What is the death rate of mpox?

The Clade I type of MPXV has a fatality rate of approximately 10%. The recent mpox outbreak was caused by Clade II, specifically Clade IIb, MPXV - which has a fatality rate of less than 1%. 

Summary

Mpox and smallpox, although caused by genetically similar viruses, are distinct diseases with some vital differences. These relate specifically to their modes of transmission, severity, and impact in today’s world. While smallpox - a devastating disease that caused millions of deaths over thousands of years - has been eradicated and thus no longer poses a threat to society, mpox continues to be relevant. In particular, mpox remains endemic in regions across Central and West Africa and recently generated global concern after an outbreak in non-endemic countries. This outbreak highlighted the need for continued vigilance in disease surveillance and response and sustained investment in global health initiatives; this way, we can safeguard public health for future generations.