Monkeypox 101, unanswered questions, and the bigger picture

This month we’ve witnessed the global Avian flu outbreak, chocolates laced with salmonella, severe hepatitis of unknown cause among children, Ebola outbreak in Central Africa, the first Polio case in Mozambique in 30 years, and . . . a global outbreak of monkeypox. I partnered with Dr. Anne Rimoin, a global health expert in monkeypox and emerging diseases and Professor at UCLA, to explain monkeypox, the burning, unanswered questions, and why the bigger picture matters. 

Monkeypox 101

Monkeypox joins its old cousin, smallpox, in the viral family of orthopoxviruses (or poxviruses for short). The first animal case was a monkey (hence the name) in 1958. The first human case of monkeypox was discovered in 1970 in Democratic Republic of Congo. Since then, it’s become endemic in West and Central Africa. It’s not unusual to have a case randomly pop up outside of this area. In 2021, for example, Texas and Maryland each reported a case among travelers from Nigeria. Since the 1970s, we’ve seen a major increase in monkeypox cases overall (see figure below). We expect this trend will continue due to the eradication of smallpox (and, thus, end of smallpox vaccination and waning immunity) combined with growing populations exposed to monkeypox. It’s a predictable stage for large outbreaks.

Monkeypox is a viral zoonotic disease, which means for an outbreak to start, the virus needs to jump from an animal to a human. We don’t know the natural reservoir animal (i.e., where the virus calls “home”), but we do know rodents and small mammals can harbor the virus and infect humans through scratches, bites, or wild game. After a human is infected, they can infect other humans through several avenues:

1. Respiratory droplets and aerosols from prolonged face-to-face contact;

2. Contact with bodily fluids or monkeypox lesions;

3. Indirect contact with items that have been contaminated with fluids or sores, like clothing or bedding.

Monkeypox has a long incubation period, which means the interval from infection to onset of symptoms ranges from 5 to 21 days. In general, poxviruses rarely transmit prior to disease onset, which means there is little asymptomatic spread. The distinctive symptoms of human monkeypox greatly aid in its containment.

Once someone is infected they can be sick for 2-4 weeks. The infection period is categorized into two periods:

1. Invasion period (0-5 days): People typically present flu-like symptoms (fever and body aches) and swollen lymph nodes.

2. Rash period (1-3 days of fever): A distinctive rash typically starts in the face, which then moves to extremities. A distinct sign of monkeypox is vesicles that can form, as seen below.

Typical clinical presentation of human monkeypox in a 7-y-old female child, Sankuru District, Democratic Republic of Congo. Source here.

In Africa, mortality estimates range from 1-10%. The range is attributed to different “clades” or families of monkeypox: the Congo Basin clade (10.6% case fatality rate) and the West African clade (3.6% case fatality rate). In the current outbreak, the U.K. confirmed a case with the West African clade—the less severe kind. The high mortality rate is also attributed to low access to care and limited resources. During a 2003 outbreak in the U.S., for example, 26% of cases were hospitalized and 15% had severe disease, but none died. Interestingly, during this outbreak, scientists found previous smallpox vaccination was not associated with severity. Also, children were more likely to be hospitalized in an ICU than adults.

Current global outbreak

Earlier this month, the U.K. reported an index case that was infected while traveling to Nigeria. Quickly thereafter, eight more cases were identified within the U.K. The outbreak became worrisome, not only because of the unusually large number of cases, but also because some cases did not have a travel history, and two outbreaks were hundreds of miles away from each other. This meant there was undetected community transmission and a high likelihood of more cases, possibly on a global level. 

Suspicions were confirmed later this week when more countries reported monkeypox. The count changes quickly, but we have at least 110 suspected cases, spanning 11 countries. The majority are male, younger, and presenting with classic skin lesions. Of the information we do have, 36% of cases are hospitalized. The U.S. confirmed the first case on Wednesday in Massachusetts, and yesterday a suspected, hospitalized case was reported in NYC. 

Unanswered questions and good news

This is a very rare virus, and, as with any new outbreak, there are a lot of unanswered questions. The WHO plans to convene an emergency meeting with experts in monkeypox and the larger orthopoxvirus family. We anticipate interesting discussion around the following key questions:

1. How large and expansive will this outbreak be? How long has it been spreading?

2. How has it been spreading? Monkeypox is not typically transmissible human-to-human because it requires a very large dose of virus, so it’s not clear whether this outbreak is driven by mutations, human behavior, the environment, and/or new hosts. The 2003 U.S. monkeypox outbreak showed us that the virus is capable of spreading to new animal reservoirs outside central Africa. In that case, American prairie dogs were infected by rodents and served as amplification vectors. American ground squirrels are also highly susceptible to the virus. If monkeypox were to become established in a wildlife reservoir outside Africa, the public health setback would be difficult to reverse.

3. Has monkeypox mutated to be more like smallpox? We are all keeping a close eye on where new cases land on the genomic tree below. A few hours ago, a Portuguese science team posted the first genomic sequence. This case doesn’t look much different from previous cases, which means the virus didn’t substantially mutate. This is one clue that the outbreak is likely being driven by environmental conditions, but we need more genomic sequences and “real world” epidemiological data to confirm. 

4. Is the North America outbreak linked to the European outbreak? We suspect they are, but need confirmation through genomic sequencing.

5. Is there some connection to the COVID19 pandemic, or is it just bad luck?

Although we have a lot of questions, the virus is not novel like SARS-CoV-2, and scientific teams in Africa can provide important insights on response, containment, and treatment. Also, we already have a lot of tools that work:

• Vaccines: We have a full stock of smallpox vaccines, thanks to bioterrorism preparation. Smallpox vaccines work on monkeypox, especially if the vaccine was recent. In fact, the CDC reports that smallpox vaccination within 3 years is 85% effective at preventing monkeypox disease. The sooner the person received the vaccine, the more effective it will be. In the same vein, post-exposure vaccination is helpful with confirmed cases and contacts (like healthcare workers). This is called a “ring” vaccination strategy. If someone has a confirmed exposure, the smallpox vaccine can (and should) be given within four days after exposure to prevent disease. If the vaccine is given between 4 and 14 days it can reduce, but not entirely prevent, symptoms.

• Treatment: Effective therapeutics have already been developed but not widely available. The antiviral ST-246 (tercovirimat), for example, was developed specifically for smallpox but works for all orthopoxviruses including monkeypox. 

• Other mitigation measures: COVID-19 mitigation measures, like masks and improved ventilation and filtration, will help with reducing spread. In fact, in 2021, a monkeypox case landed in Dallas from Nigeria. It’s largely hypothesized that the mask mandate helped contain the virus.

Bigger context

With the plethora of viral outbreaks, it may feel like Jumanji. While there’s increased public awareness of infectious diseases overall (due to the pandemic), more outbreaks are also truly happening. Since the 1918 flu, we’ve seen the emergence of diseases come faster and faster. 

Global number of human infectious disease outbreaks and richness of causal diseases 1980–2010. Outbreak records are plotted with respect to (a) total global outbreaks (left axis, bars) and total number of diseases causing outbreaks in each year (right axis, dots), (b) host type, (c) pathogen taxonomy and (d) transmission mode. Journal of Royal Society Source Here

This is mainly due to three things:

1. Climate change: People are moving into areas that have never been inhabited before; animals, like mosquitos, are also shifting. A recent Nature report found the potential for spillover events (animal-to-human) is increasing dramatically as Earth's climate heats up, introducing humans to thousands of new viruses.

2. Technological change. Humans and goods are traveling more than ever due to globalization and increased travel. Viruses can be easily introduced in places that they’ve never been. 

3. Demographic change. Population growth, change in land use, urbanization, and aging populations also increase contacts, transmissibility, and immunosuppressive risks of spillover events. 

To stop this, we need global teamwork. Low-hanging fruit includes supporting scientific teams studying emerging diseases on the ground and reducing spillover events. This also highlights the importance of public health preparedness. If we invest in and implement a robust public health infrastructure, it will help with COVID-19, monkeypox, and beyond.

Bottom line

It’s too early to tell if we should be worried, but we are confident the current outbreak will be nothing close to the COVID-19 pandemic. We live in the harsh reality where the next epidemic is just around the corner. We need to learn from the lessons of the past and present and prepare for the future. As one virologist said, “[The monkeypox outbreak] is a good dress rehearsal to see whether we have learned anything.”

Love, YLE and Dr. Anne Rimoin

Dr. Rimoin is a global leader in monkeypox and emerging diseases and Professor and Endowed Chair in Infectious Diseases and Public Health at UCLA. She is also the founder of the UCLA-DRC Health Research Training Program investigating emerging infections.

“Your Local Epidemiologist (YLE)” is written by Dr. Katelyn Jetelina, MPH PhD—an epidemiologist, biostatistician, wife, and mom of two little girls. During the day she works at a nonpartisan health policy think tank, and at night she writes this newsletter. Her main goal is to “translate” the ever-evolving public health science so that people will be well equipped to make evidence-based decisions. This newsletter is free thanks to the generous support of fellow YLE community members. To support the effort, please subscribe here: