Uganda Discovered the Zika Virus. And the Solution for It.

KAMPALA, Uganda — The Uganda Virus Research Institute (UVRI) is nestled in a series of rolling hills outside of Entebbe, the town on the banks of Lake Victoria that served as the seat of government during Uganda’s time as a British protectorate. At the institute’s main entrance hang maps from old studies and magnified images of some of the viruses that have been isolated or discovered here, including West Nile virus.

But it’s the Zika virus — which has infected tens, if not hundreds, of thousands of people in the Americas in recent months and may be linked to a spate of children born with underdeveloped brains in Brazil — that’s now bringing Ugandan epidemiologists unexpected attention. UVRI scientists first discovered Zika in the blood of a rhesus monkey back in 1947. And while Uganda has never had an outbreak of the virus, the country’s unique approach to monitoring the spread of similar diseases could hold the key to stopping future epidemics in their tracks.

Consider how Uganda dealt with the Ebola virus. Long before Ebola made its recent rampage across West Africa infecting more than 28,000 people, Uganda, in eastern Africa, had its own Ebola outbreak — two in fact, in 2012. Led by scientists at UVRI, however, the outbreaks were quickly identified and contained. Only 21 people died as a result — in contrast to more than 11,300 in West Africa in the past two years.

“They were prepared for the outbreak,” said Michel Van Herp, an epidemiologist with the emergency medical group Doctors Without Borders. “They had had that kind of training before. They were not naive to those pathogens.”

Uganda’s success in containing outbreaks is no accident. It is the product of a long history of cutting-edge infectious disease research, dating back to the founding of UVRI, then under a different name, by the U.S.-based Rockefeller Foundation in 1936 to stem the spread of yellow fever in East Africa. The institute passed into the hands of the East African Community in 1950 and then over to the Ugandan Ministry of Health in 1977, but it has continued to do groundbreaking work. Scientists here have discovered dozens of diseases and pioneered a viral surveillance system that has played a critical role in curbing potential epidemics.

The Ugandan system contrasts sharply with the short-term thinking of the World Health Organization. On Feb. 1, the WHO declared Zika a “public health emergency of international concern,” triggering a flood of money and attention directed at those South American countries hardest hit by the crisis. But UVRI has shown that crisis management of this sort is a poor replacement for vigilantly monitoring for potential public health crises in the first place and aggressively containing them once they arise.

“Ebola came; they react. When Zika came, there was a reaction,” said Ernest Tambo, a lecturer at the Université des Montagnes in Cameroon and epidemiological specialist who has worked throughout Africa. “When should the global community become proactive?”

Another way of posing that question is: When will the world catch up with Uganda?

The landlocked East African nation has always had an unenviable combination of scarce health care resources and a multiplicity of deadly diseases. “Uganda is a biodiversity hotspot,” said Julius Lutwama, UVRI’s senior principal research officer. “We have wide flora, wide fauna, and, of course, the good temperature, the good climate. And what is good for humans, what is good for animals, of course, is also good for viruses.”

Uganda’s record of controlling diseases is far from perfect (a malaria outbreak continues to plague the country’s north). But the presence in the country of so many of the world’s most virulent pathogens has compelled it to become a world leader in virus surveillance. “They’re always monitoring the conditions, so that there’s no outbreak that they’re not aware of,” said Martha Kaddumukasa, an entomologist at Uganda’s Makerere University who did part of her doctoral research at UVRI.

The institute has paid special attention to arboviruses — the family of viruses to which Zika belongs, along with dengue and yellow fever — as well as viral hemorrhagic fevers, including Ebola and Marburg. For decades, UVRI has been collecting and monitoring patient blood samples and parasites from around the country, looking for unusual viral activity. They also map disease patterns — both among people and animals — to alert health workers where to look for unusual illnesses and what to do if one appears. Local medical workers were credited with being the first to call attention to recent hemorrhagic fever cases.

Kaddumukasa, who has conducted research in other regional laboratories, called UVRI’s virus surveillance capacity “one of a kind” for East Africa. In part, this reflects a commitment from the Ugandan government, but also the institute’s unique collaborations with the U.S. Centers for Disease Control and other international institutions.

Uganda’s dealings with Zika showcase both the depth and longevity of the country’s surveillance system. The story of the virus’s discovery is relatively banal: As part of the institute’s yellow fever research, scientists were monitoring a monkey deep in the Zika forest, on the outskirts of Entebbe. One day in 1947, it developed a fever and a blood sample was taken. The scientists isolated a previously unknown virus and, ultimately, gave it the name of the forest where it was discovered.

In the papers heralding their finding, the scientists took care to acknowledge how little they had actually learned about the virus — where it originated, how it was transmitted, or what its impact on humans would be. That didn’t stop one of its discoverers from cautioning: “The absence of the recognition of a disease in humans caused by Zika virus does not necessarily mean that the disease is either rare or unimportant.”

It took another five years for the virus to be isolated in humans, in Nigeria. Over the course of the next 50 years, Uganda would only have two confirmed cases. There would be less than 20 globally. As a result, international researchers gradually lost interest in the virus. But in Uganda, scientists and public health officials never entirely let up on their surveillance efforts. The country continued to look out for Zika with its routine monitoring system — a system thorough enough that, though it has never been a priority, a rash of Zika cases would probably be noticed quickly enough to weigh public health concerns and deploy treatment or containment options before it was too late, according to Kaddumukasa.

In 2012, UVRI’s overall surveillance and detection capacity got an upgrade when the CDC opened a laboratory to rapidly diagnose viral hemorrhagic fevers, like Ebola. The timing was prescient. Uganda sustained three hemorrhagic fever outbreaks that year — first Ebola, then Marburg, then Ebola again. In each case, doctors with the CDC and UVRI identified the virus within a matter of days and led efforts to contain its spread.

The Ugandan experience stands in stark contrast to the Ebola outbreak in West Africa, where it took the Guinean health system more than three months to recognize the disease, by which point it had already spread dangerously across the region. The lesson was clear: There was a need for more robust, comprehensive surveillance systems at both local and national levels to detect possible outbreaks and prompt quicker responses.

“Essentially, every country has to have sufficient infrastructure to be able to monitor the health situation and detect any abnormalities,” said Michael Edelstein, an epidemiologist with Chatham House’s Centre on Global Health Security in London. “They have to train the workforce at different levels, have a basic laboratory system.”

Not every country needs something on the scale of UVRI, according to Edelstein, but they do need “the core capacity to detect pathogens in a timely manner.”

A minimum national surveillance system is spelled out in the WHO’s International Health Regulations (IHR), which came into force in 2007 and are binding on 196 countries — though there is no real enforcement mechanism. As of 2014, they were fully implemented in only 64 countries. With the latest implementation extension set to come to an end in June of this year, it will soon be clear whether the recent outbreaks have convinced the lagging nations to fully implement the IHR where the WHO’s cajoling did not.

But improved surveillance is not a panacea, especially if it doesn’t then trigger an appropriate response. For instance, by March 2014, Van Herp says that everyone knew what was happening with Ebola in West Africa, “but the will to intervene was very weak.” He sees parallels with Angola, where a yellow fever outbreak has infected nearly 40 people and left 10 dead in recent weeks, but drawn little international attention.

That’s why it’s important that UVRI does more than merely conduct disease surveillance. As an active participant in the East African Integrated Disease Surveillance Network (EAIDSNet), it is also helping devise cross-border strategies for disease surveillance and control so that it’s possible to organize an effective regional response and, if necessary, to attract international attention in a timely fashion, rather than when it’s too late to make a difference

It’s here that parts of sub-Saharan Africa — including Uganda — are out in front of the rest of the developing world: With budgets tight in most individual countries, the region is making the most of pooled resources. In addition to EAIDSNet, there is another network operating in southern Africa called the Southern African Centre for Infectious Disease Surveillance. And, in the wake of Ebola, the France-based NGO Connecting Organizations for Regional Disease Surveillance has been working with West African institutions to set up another. There is currently no comparable network anywhere in South America.

If one existed, would it have halted Zika’s spread? Almost certainly not. But more regional — and international — discussion might have helped doctors in South America hit upon the virus much sooner as the reason a growing number of patients are suffering from the same symptoms, and it might have accelerated their response.

Although UVRI has been able to offer little help in stemming the Zika outbreak, there is a recognition on the Entebbe campus that the institute has an increasingly important role to play, not just in combating future outbreaks, but serving as an example for other disease hotspots to replicate. In addition to modeling country surveillance strategies and promoting regional collaboration, that means continuing to lead the hunt for new viruses and working to better understand the ones that have already been found. According to Lutwama, UVRI scientists have already discovered four new viruses in the last five years.

That same impulse sent Kaddumukasa back to the Zika forest. Even before the current outbreak, the Ugandan entomologist suspected the forest’s inhabitants might still hold the answers to some of the world’s greatest medical mysteries. So, since 1997, she has been collecting and cataloguing mosquitoes — 163,790, so far — and then passing them along to a technician at UVRI to test for any viruses they may contain.

“Just like Zika virus was isolated from monkeys in Zika forest, there’s need to monitor the mosquitoes of Zika forest,” she said. “To stop the spread of infections in Uganda, to the world at large, you need to monitor. Continually monitor.”

Photo credit: ISAAC KASAMANI/AFP/Getty Images