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Ending An Epidemic Without a Vaccine

Effective strategies for combating the pandemic have been deployed around the world – from lockdowns to surveillance and containment. As the curve flattens, the next challenge ahead of us – beyond managing caseloads in countries that are still awaiting the surge - like India, sub-Saharan Africa, and parts of Europe – is to develop strategies that will allow society to move forward.

In this article, we’ll first examine how some other epidemics – Ebola and SARS developed over time, and what insights these epidemics can provide for the world moving forward in the shadow of SARS-CoV-2. Overall, it’s important to realize that zoonotic viruses, those that come from a known or unknown animal reservoir, cannot be eradicated. It’s also worth keeping in mind that such widespread appearance of a virus The most effective approach in the future will be to develop monitoring systems that are able to detect new transmission early, and to have public health strategies that are able to spool up quickly to deal with the threat.

 

Ebola


The first Ebola case appeared in 1976, at the Yambuku mission hospital. Staff first ruled out malaria, typhoid, or yellow fever, then appealed to international aid organizations to help determine the cause of the illness. They sent samples to international laboratories that specialized in unusual virus identification. Within five weeks it became clear that the infection agent was a filamentous virus, related to the previously characterized Marburg virus. Upon realization of the severity of the outbreak – Marburg viruses were known to cause highly transmissible, highly lethal infections – the entire area from Yambuku to Kinshasa was put under strict isolation.

By the end of the epidemic, 318 people had been infected with the virus, and 280 people had died. In the years since, 19 outbreaks of Ebola have occurred in the region – and all have been less deadly since the very first one. In each instance, the international response to the outbreak has instituted isolation programs, public health campaigns, and changes to social rituals such as burials that have been highly successful at keeping death rates low.

In the years following the initial outbreak, scientists identified the zoonotic reservoir of the virus, Wahlberg’s epauletted fruitbat. Their work allowed public health officials to inform local residents about best practices for avoiding the infection in the first place.

However, this all changed in 2014, when a new Ebola outbreak began in the West African country of Guinea. This area of the continent had never seen an Ebola outbreak, which may have contributed to the slow response – the same process that took five weeks in 1976 took almost three months in 2014, ensuring high levels of community spread. The long time between the appearance of the first case and official diagnosis allowed the virus to cross into two neighboring countries, Sierra Leone and Liberia. In all three countries, rural and urban populations alike were unwilling to cooperate with public health officials.  

According to West African Scholar Dr. Mariane Ferme, the lack of cooperation with non-governmental organizations like Medecins Sans Frontiers was due to the lack of trust “between the population and government public health infrastructures in those countries.” Any attempts by aid organizations to change social practice were  “perceived by people as being part and parcel of the same public heath intervention” that was so mistrusted.  

According to a paper by Dr. Joel Breman, the principal investigator who led the 1979 search for the zoonotic reservoir of Ebola Zaire virus, reported that “hospital closure, isolation of patients, culturally sensitive rapid burial, and community cooperation and quarantine…were not in implemented initially in West Africa,” as a result of this mistrust. The slow identification and subsequent community transmission led to the most fatal Ebola outbreak in recorded history. 25,000 people were infected, and more than 10,000 died.

How it stopped

The end of the epidemic came in March of 2016, when the WHO announced that two full quarantine periods, 42 days, had passed without any new infections being reported. However, this announcement was preemptive, as several more clusters of infections appeared in the next year.

Part of the reason for recurrence was the fact that the virus, even after being cleared from the body, survives in compartments that aren’t monitored by the immune system. Ocular fluids, like tears, may contain active viruses, and culturable virus was discovered in the seminal fluid of a man almost nine months after the date of his recovery from the virus.

In the aftermath of the disaster, an uncontrolled outbreak of a deadly disease that had heretofore seemed manageable, the public health community awakened to the imperative that better measures needed to be taken in advance of the next outbreak. Medcins Sans Frontiers (MSF), a key aid organization, published a report identifying the potential fallout of not responding quickly enough to a new epidemic.

The torturously slow initial response resulted in a sufficiently high caseload that hospitals like the MSF’s ELWA3 centre in Monrovia “ were forced to turn away visibly ill people from the front gate, in the full knowledge that they would likely return to their communities and infect others,” said Dr. Joanne Liu, MSF international President.

Infected individuals returning to their communities further complicates returning to normal after the initial outbreak, as there is no way to declare an end to the epidemic until every single case has been contact traced, diagnosed, and treated or quarantined. A single case that slips through the cracks is sufficient to reignite the epidemic. An overwhelmed medical system that is forced to turn away symptomatic patients ensures that the epidemic continues for much longer than it would otherwise.

 The final recommendations on what the world could learn from Ebola come from a joint report by Harvard and the London School of Health and Tropical Medicine.

In the thick of the COVID-19 pandemic, their recommendations readr like a laundry list of the failures of many western countries faced with an outbreak they did not expect to see: adequate healthcare, solid monitoring, and fast response times.

Fundamentally, though, there needs to be trust. West African Epidemic was significantly worse than any other Ebola outbreak in history because it happened in a place that had never seen Ebola in the first place, and also at a time with, overall, decreased trust in the government.

 SARS and MERS 

Examining the course of SARS and MERS, two coronaviruses that are closely related to SARS-CoV-2, is also helpful for understanding different trajectories of recovery. SARS, Severe acute respiratory syndrome, has not been seen since 2004. However, MERS, Middle East Respiratory Syndrome, has never been fully controlled, and new cases have appeared as recently as March 2020.

The infection caused by SARS-CoV was first identified in November of 2002 in Guangdong Province in southern China. The outbreak ended in 2004, and has not resurfaced since. There were just over 8000 cases globally, spread through 29 countries by similar mechanisms as those seen with SARS-CoV-2 – slow response times to early infections, infected individuals traveling to immunologically naïve countries, and officials obscuring full case numbers. At the end of the outbreak, the final death toll from SARS was 774 individuals from 11 countries, for a case fatality rate of 9.6%. 

What is clear from the data above, is that there was no clear correlation between the case fatality rate and the number of cases in a country. South Africa, which saw only one case – had a 100% CFR – while China, which registered more than 5000 cases, had a 7% fatality rate.

 The last two cases of SARS were identified on April 22nd of 2004, and were linked to the Beijing Institute of Virology where live SARS virus was being studied. The infected individuals were not known to have worked with the virus itself, creating some ambiguity about how they got to be exposed in the first place. Once these individuals were cleared, SARS disappeared from the world.

But it didn’t disappear from the minds of virologists and epidemiologists interesting in tracking down the actual origin point of the virus. Some believed the virus had come from bats, reasserted in civet cats, and then jumped to humans at the wet markets widespread through the country. Eventually, the outbreak was tied directly to horseshoe bats living in a remote cave outside of Kunming, in Yunnan Province. The team that identified the bat reservoir, led by students Ben Hu, Lei-Ping Zeng, Xing-Lou Yang, at the Wuhan Institute of Virology, spent five years collecting fecal swabs and dropping samples from bats living in the cave. At the end of five years, they demonstrated that, while the bats in the cave were not infected directly with the human virus, the population contained all of the viral fragments necessary to recombine into the virus that eventually jumped into humans.

What was interesting, was that the bat reservoir was located in Yunnan Province, some distance away from Guangdong Province, the presumed origin point of the virus itself. The mechanism by which a diverse viral population in bats reassembled into a single viral genome able to infect humans 1400km away is still mysterious.

In the end, there was no vaccine was developed for SARS. In part, this is due to the fact that the outbreak ended and other diseases were given priority. The difficulties were similar to those encountered by researchers attempting to develop an Ebola vaccine – it’s a sporadic illness that doesn’t appear to have a truly global impact. It’s limited scope results in limited funding and a very narrow window for human trials. human trials. Trials for the first effective Ebola vaccine were finally approved during the 2014 epidemic, amid global fears that the West African outbreak might grow to a level of pandemic.

With SARS, officials took more straightforward approaches – they closed animal markets, and established a health surveillance network that would accelerate the identification of a new virus. These approaches were effective until recently – with no new coronaviruses circulating in the population, the defense mechanisms against them worked strikingly well. 

With the emergence of SARS-CoV-2 came the realization that not all countries had taken the lessons to heart – specifically, those that hadn’t had very high case loads in the previous epidemic. Perhaps the best lesson that can be drawn from this fiasco is that next time will be better, and that all of us will have a better sense of how to react, how to prepare.