WHO moves rapidly on DRC Ebola outbreak but sceptics warn against complacency

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Although the rapid World Health Organisation response to the outbreak of Ebola in the Democratic Republic of the Congo (DRC) is a far cry from the tragically slow reaction to the West African outbreak in 2014, experts warn there is no room for complacency.

In the week since the Democratic Republic of the Congo (DRC) declared a new Ebola outbreak, health officials have set in motion a plan to distribute an experimental vaccine, logistics experts have established an air-bridge to ferry responders and equipment into the epicenter, and the director-general of the World Health Organisation (WHO) has flown in from Geneva to take stock.

Stat News reports that it has been an extraordinarily rapid response – and a far cry from the tragically slow reaction by the global community following the West African Ebola outbreak that began in 2014. “I think the response so far has been impressive,” said Tom Inglesby, director of the Centre for Health Security at Johns Hopkins Bloomberg School of Health. Inglesby said the early engagement of many partners – the Wellcome Trust has already committed funds; Doctors Without Borders is setting up treatment facilities; GAVI the Vaccine Alliance has agreed to finance the vaccination efforts – suggests health experts across different organisations are coordinating well. “The speed with which they’re doing it and the apparent coordination on a rapid pace seems to be different than in the past,” he said.

The report says at the centre of the response is the WHO and many long-time observers say it is too soon to conclude that the beleaguered agency has ironed out all its emergency response problems – even if the initial steps it has taken are encouraging.

Ron Klain, who served as President Obama’s Ebola czar during the West African outbreak and who has been critical of the WHO, is among those urging a wait-and-see approach. He cautioned that the early days after an Ebola outbreak is declared are plagued by misinformation and too little information. Figuring out what is happening takes some time. “In every kind of incident like this, there’s just a lot of confusion at first. What the facts really are. Where is this disease? How long has it been there?” Klain warned. “Until that sorts out a bit, it’s also premature to make conclusions about how well we’re doing.”

In the meantime, Klain suggested there’s no room for complacency. “I just think vigilance is the most important thing – and a little humility,” he is quoted in the report as saying. “And not too much ‘Hey, it’s all great!’ Because we don’t know if it’s all great or not.”

The outbreak is in the western part of DRC, in Equateur province. As of Tuesday, the WHO estimated there have been 41 cases, three of them health care workers. Of the confirmed, probable, and suspected cases, at least 19 have died, including one of the health workers.

Cases have been identified in three locations that are miles apart – in a region of the world where roads are poor and traveling 100 miles can take half a day or longer. On Monday the WHO reported there are two probable cases in a village called Wangata. It borders on the Equateur capital, Mbandaka, which is home to 1.2m people. Both are situated on the Congo River.

The report says the epicentre of the outbreak is Bikoro, a town about 175 miles south of Mbandaka. Bikoro, too, is a port, on a lake that feeds into the Congo and Ubangi rivers. Those two major water highways link the outbreak zone to the capitals of DRC and the Republic of the Congo to the south and the capital of the Central African Republic to the north. The combined population of those capitals – Kinshasa, Brazzaville, and Bangui respectively – exceeds 14m people.

The report says that sobering geography has ignited fears that this outbreak could again see Ebola racing through crowded African cities, as it did during the West African outbreak. The WHO warned of the potential for urban spread almost immediately after DRC sounded its alarm, and that concern is clearly fuelling the urgency behind this response.

That is headway, Klain conceded. “No one’s being complacent, no one’s just assuming that it will go away on its own, no one’s assuming it’s going to be small. That by itself is progress. No question about that,” he said.

Ashish Jha, a global health expert who served as co-chair of an independent panel that analysed the WHO’s response to the West African Ebola crisis, shares Klain’s view that it is too soon to know if the early and positive optics are indications that the WHO has fundamentally changed its approach to disease events like this. His question: Is this a one-time fix or evidence of systematic change at the WHO?

So far, he sees developments like the weekend visit to Bikoro by WHO director-general Tedros Adhanom Ghebreyesus and Peter Salama, who runs the WHO’s emergency response operations, as symbolic rather than substantive. “I believe in symbolism, so I think the symbolism was good. But I’m not sure it tells me a lot about how much better prepared we are, and how much more effective WHO’s response is going to be,” said Jha, the director of the Harvard Global Health Institute.

“As long as we’re doing the work of actually building up an effective response system, then I think this is fine, this is good. I just want to make sure that we don’t confuse this for that,” he said.

David Fidler, an adjunct senior fellow on cybersecurity and global health at the Council on Foreign Relations, said he, too, is holding off on drawing too many conclusions. “We have seen in the past accolades for WHO appearing to learn the lessons from past outbreaks and mistakes. And then things fall apart again,” said Fidler, who is also a professor of global health law at Indiana University. “That’s the story of the 2014 Ebola disaster – all the lessons WHO and countries supposedly learned were not in fact learned. This one in the DRC just doesn’t feel enough to pat the WHO on the back yet,” he said.

Klain worries about what he calls “the execution gap.” “I do think there is always, always a gap between public statements and declarations that things are going to be done and then actually those things happening,” he said.

The report says how big that gap will be in this outbreak remains to be seen. But for now, there are at least some reasons to take heart, said Lawrence Gostin, faculty director of the O’Neill Institute for National and Global Health Law at Georgetown University. “Tedros seems to be right on top of it. He’s been responding publicly almost daily on his Twitter feed and elsewhere,” Gostin said. “The tone is right. He’s partnered right away with the ministry of health and with other international organizations and has been responsive.”

The timing of the outbreak may be added motivation for the WHO to move quickly. The report says next Monday is the start of the World Health Assembly, the WHO’s annual general meeting. It will be Tedros’ first as director-general, and he and the agency are being closely watched.

In an interview from Kinshasa on Sunday, the director-general noted he and his team had planned to use the past weekend to prepare for the World Health Assembly. Instead, he flew to DRC on Friday night, flying back to Geneva on Sunday night.

Inglesby said in the report that delegations to the assembly will be looking for assurances that the WHO is on top of this outbreak. “I think everyone will be watching. I’m sure it will be very important for WHO to report on exactly what their risk assessment is, what they’ve been able to do in the last 10 days since this all was uncovered, and to report to WHA,” he said.

 

The DRC and UN agencies began deploying emergency teams of specialists over the weekend to try to prevent the spread of the epidemic, reports The Times. The DRC Health Minister Oly Ilunga Kalenga said: “We have to pool our efforts quickly and align ourselves with the government response plan to fight this new epidemic effectively,” Kalenga was quoted as saying in a joint statement following their visit to the state capita.

The report says Congo first reported the outbreak, centred around the village of Ikoko Impenge, near the town of Bikoro, on Tuesday, with 32 suspected, probable or confirmed cases of the disease, including 18 deaths since 4 April. Some deaths occurring as early as January have not yet been linked to the epidemic.

Congo had suffered eight Ebola epidemics previous but owing to remote geography and poor transport links they have tended to fizzle out rather than spread to become a national crisis. But, the report says, this epidemic’s proximity to the Congo River, a major transport route and lifeline both to Congo’s capital Kinshasa and to neighbouring Congo Republic’s capital Brazzaville, makes it more likely the virus could break out into a wider area.

“The WHO is strengthening its presence, positioning a dozen epidemiologists who will be divided on the axes of Mbandaka, Bikoro and Iboko to investigate alerts,” its Congo representative Allarangar Yokouide said.

 

In the latest Ebola outbreak developments in the DRC, two more probable cases were reported, and the WHO fleshed out more details about the response’s vaccination component. Also, initial talks are under way about possibly using experimental antivirals for treating sick patients, and new information about the initial outbreak cluster and the tough conditions responders face were revealed in a situation report from the International Federation of Red Cross and Red Crescent Societies (IFRC).

A Centre for Infectious Disease Research and Policy (CIDRAP), University of Minnesota report says that on Twitter, Dr Peter Salama, WHO deputy director-general for emergency preparedness and response, said two more probable cases have been reported in the outbreak, raising the overall total to 41, which includes 2 confirmed cases, along with 22 probable and 17 suspected infections.

And now that regulatory and ethics groups in the DRC government have given the green light to use of the VSV-EBOV vaccine, the WHO has spelled out some of the details of the upcoming immunisation campaign, which will also involve a clinical trial. VSV-EBOV was developed the Public Health Agency of Canada and is licensed by NewLink Genetics and Merck. A phase 3 ring vaccination trial at the tail end of Guinea’s Ebola outbreak showed that it was highly effective.

The report says before DRC government officials approved its use in the country’s latest outbreak, the WHO had already been laying the groundwork to use it, which includes establishing cold chain storage conditions – a challenge in a remote outbreak setting where electrical service is in short supply. GAVI the Vaccine Alliance, had already agreed to pay for the vaccine, and in 2017, WHO vaccine advisors recommended compassionate use of the not-yet-licensed VSV-EBOV in an outbreak setting.

Getting the vaccine – drawn from a small stockpile in Geneva with more available from Merck – to the outbreak area will be a challenge, and the WHO said the DRC health ministry, Doctors Without Borders (MSF), and the WHO and its partners are working out the logistical issues. Last week, Wellcome Trust and the UK Department for International Development pledged $4m to help the WHO conduct critical research during the DRC’s outbreak.

The report says a ring vaccination strategy, similar to the one in Guinea, will include vaccinating contacts, contacts of contacts, international and local healthcare and frontline response workers in the hot spots, and healthcare and frontline responders in areas at risk for Ebola spread. Participation in the campaign is voluntary, and for those who are vaccinated, immunisation teams will make six follow-up visits, at 3, 14, 21, 42, 63, and 84 days after vaccination.

When WHO vaccine advisors last year recommended use of VSV-EBOV to help tamp down outbreaks, it said deployment should be used as an opportunity to gather more data on safety, efficacy, and effectiveness. It said it didn’t have enough information, especially regarding duration of protection, to recommend mass vaccination outside of outbreak settings in populations at risk or for healthcare workers in those areas.

The report says VSV-EBOV has been shown to provide rapid protection after a single dose, and, in an encouraging development, a study published April reported antibody response in vaccine trial participants up to 2 years after one dose.

The DRC cleared the vaccine for use in an Ebola outbreak last year in the remote northern Bas-Uele province, but it was never used given that officials quickly contained the outbreak, which was limited to four deaths and another four illnesses.

The report says moving forward with using a vaccine to treat Ebola and Marburg virus – which causes a similar viral haemorrhagic fever disease – is still a key global health goal. Last week the WHO posted a draft research and development roadmap for countermeasures against the two diseases, which is open for comments through 8 June. The report says CIDRAP led the writing of the draft with support from Wellcome Trust and in collaboration with the WHO. The WHO’s emergency response team is already using the guide for deploying the vaccine in the DRC’s outbreak.

The WHO is in preliminary talks with DRC government officials and MSF, which supports patient treatment, to see if experimental Ebola treatments should be used, Tarik Jasarevic, a WHO spokesperson, is quoted in the report as saying. If there’s a role for new treatments, the next step would be to work through getting the needed regulatory and ethical approvals to use experimental antivirals on a compassionate basis to treat patients infected with Ebola, he said.

During West Africa’s outbreak, some treatments were studied in clinical trials, which got a late start and were limited by declining case numbers. Some of the experimental or repurposed treatments studied in West Africa’s outbreak included favipiravir, an antiviral drug made in Japan. An early study done during Guinea’s outbreak suggested the drug may have activity against the virus at early infection stages. The drug was approved in Japan in 2014 for pandemic flu stockpiling.

Another repurposed treatment studied during West Africa’s outbreak, also in Guinea, was interferons. Treatments developed specifically for Ebola that were studied in West Africa’s outbreak included two monoclonal antibody cocktails: (1) ZMapp, developed in the US and tested in Sierra Leone, and (2) MIL 77, a closely related product made by China that was used to treat a British nurse infected in Sierra Leone. Also, a few trials of convalescent whole blood and plasma took place in Guinea, Liberia, and Sierra Leone.

In a situation update, the IFRC said the outbreak location around Bikoro is typically accessible by four-wheel drive vehicles, but the rainy season is still under way, making the area accessible only by motorbikes and helicopters. The IFRC report was posted on ReliefWeb, a humanitarian information portal. It said the Ikoko Impenge outbreak epicenter is a very remote village and that its health area doesn’t have mobile phone coverage.

Bikoro’s main economic activity is fishing from Lake Tumba, with fish transported to Brazzaville and Kinshasa via Mbandaka, the province’s capital, the IFRC said, adding that people from two neighboring health zones pass through Bikoro to access the lake for fishing, posing a risk of further Ebola spread. Health officials have already warned that waterway transport along the border with the Republic of Congo and the Central African Republic poses a risk of virus spread, as well.

Though the epidemiologic investigation is still under way, the IFRC said the first case-patient in the recent cluster was a policeman who arrived from Igende, and then died in a health center in the village of Ikoki Impenge in Bikoro health district. After the man’s funeral, 11 family members got sick, and 7 died. All 7 had attended the man’s funeral or cared for him while he was sick. Funeral rituals and caring for sick patients are known risk factors for contracting Ebola.

 

The international response to health emergencies in sub-Saharan Africa is often maddeningly slow. But, says a Science Mag report, this time around, international agencies and the DRC government sprang into action, hoping to quickly extinguish the outbreak.

“Everything is organised,” says virologist Yap Boum, who works with Doctors Without Borders (MSF) and is helping launch the vaccine effort. Boum, who lives in Yaoundé, Cameroon, began planning his trip to the DRC as soon as it confirmed on 8 May that two Ebola cases had occurred in the remote Bikoro health district in the Équateur province.

By tracing contacts between the infected people and others who had Ebola symptoms, such as high fevers and diarrhoea, the DRC’s Ministry of Public Health (MOPH) determined that the virus has likely been spreading since early April.

Boum says the most alarming news from the DRC so far is that two of the probable cases are in Mbandaka, a port city of 1.2m people. “The possibility of the virus spreading is huge,” adds Boum, noting that while Ebola is incubating undetected – which can take several weeks – the victim is already infectious. DRC President Joseph Kabila has authorised MOPH to use every tool at its disposal, including the experimental vaccine against Ebola, which worked spectacularly well in a clinical trial that Boum helped run in Guinea in 2015 at the tail end of the recent West African epidemic.

The WHO also acted quickly, immediately sending a team to the DRC to coordinate the response, which includes improved surveillance, introduction of safe medical and burial techniques, and the establishment of quarantine units operated by MSF and others.

The report says the DRC considered using the vaccine for an Ebola outbreak last year, but it met with hurdles including importing the vaccine and uncertainty about whether the virus had moved beyond remote villages. “This time they’re much better prepared,” says Seth Berkley, who heads GAVI the Vaccine Alliance, a non-profit based in Geneva, Switzerland, that purchased a stockpile of the experimental vaccine and is providing financial assistance to the DRC.

The vaccine consists of a harmless livestock virus genetically engineered to display Ebola surface proteins. It is made by Merck and not yet licensed for use by any country but can be given as part of a trial under what are known as compassionate use regulations. The trial protocol, approved by DRC last year, relies on a “ring” strategy in which only people who have come in contact with cases, their contacts, health care workers, and other front-line responders are vaccinated. The report says surveillance teams had identified 393 contacts. Some 8,000 doses are being shipped to the DRC from WHO’s Geneva headquarters and Merck’s US storage site. Special Arktek containers have already arrived that can maintain the vaccine at below freezing temperatures for travel to remote locations.

The report sayas MSF will sponsor the trial in collaboration with investigators from the DRC’s health ministry. The team will follow vaccinated people for 84 days to assess whether any develop Ebola and to evaluate side effects.

The vaccine is but one of many tools being wielded to stop the outbreak as quickly as possible. All told, GAVI, WHO, the UN, and the Wellcome Trust have committed about $8m to the DRC response, which includes sending mobile laboratories and equipment to the affected region, parts of which cannot be reached by car. “It’s absolutely a dire scene in terms of infrastructure,” said Peter Salama, who heads WHO’s Health Emergencies Programme. “This is going to be tough and it’s going to be costly to stamp out this outbreak.”

 

Amanda Glassman, Liesl Schnabel and Rebecca Forman at the Centre for Global Development write, meanwhile, on the Reliefweb site that while new tools are in place, it’s past time to recognise the need to adequately finance preparedness at home and abroad, and to act on existing opportunities to deploy funding and link tightly to progress on preparedness metrics.

They write: “An infectious disease outbreak in the DRC – or anywhere in the world for that matter – poses a threat everywhere. Pathogens don’t respect borders and can travel quickly from even the most remote places to major cities around the globe. Population growth and urbanisation in the last several decades have forced people and animals into tighter living quarters, increasing opportunities for zoonotic disease transmission. Meanwhile, synthetic disease creation raises risks of bioterrorism or accidental pathogen release from a laboratory.

“A widespread pandemic could lead to a devastating loss of lives and have damaging economic consequences. Conservative estimates suggest the 2003 SARS outbreak cost the global economy between $30bn and $40bn in a six-month timespan. And experts project a moderately severe to severe pandemic could cause a global economic loss of $570bn, or roughly 0.7% of the world’s income.

“The Global Health Security Agenda’s Joint External Evaluation (JEE), launched in 2016, is used as an evaluation tool to help countries systematically evaluate their preparedness capacity for pandemic – helping to identify gaps and target areas for improvement. As of today, only 27 of 199 countries have completed their JEEs. Of the 27 countries with completed JEEs, only 2 have used the results generated to develop costed plans. One immediate priority is to estimate the cost of filling the highest-priority gaps.

“Though all agree that domestic resources should be deployed to fill gaps once they are identified, allocating these monies has proven extremely difficult. The challenge is particularly great in low- and middle-income countries with limited budgets and many competing health priorities.

“There are at least three new funding mechanisms that might be deployed for preparedness, but they require adjustments – their total amounts, their incentives, and their allocation and focus on results need further attention:

“A US emergency reserve fund exists, but it is small and only for use at home: The very same day the new outbreak was declared, the White House submitted a rescission package to Congress that proposed returning to the Treasury $252m in unspent funding previously appropriated for Ebola response in FY 2015, draining the remainder of that emergency account. This is exactly the wrong approach. In fact, the US should be reinvesting this money into bilateral or multilateral preparedness efforts or setting it aside for the next disease threat. During the 2014 Ebola outbreak, precious time was wasted waiting for Congress to allocate appropriate funding to the outbreak, and we can’t afford to repeat this mistake. Congress deserves credit for creating an ‘Emergency Reserve Fund’ for contagious infectious disease outbreaks with a domestic focus, but the account only has $105m – which could be rapidly exhausted in the face of a pandemic. The fund should be at least $500m, a small share of the likely economic costs of faster spread in the absence of response.

“The poorest countries have insurance, but there is still weak incentive to prepare: For IDA-eligible countries, the World Bank’s Pandemic Emergency Financing Facility (PEF) has created an incentive to invest in preparedness. The financing facility is a form of indemnity insurance that disburses a set amount when activation criteria associated with an outbreak are met, creating a modest incentive for countries to minimise expenses associated with an outbreak by being prepared ahead of time. However, there is still work to be done: as is, the incentive is not universally understood, the activation criteria are not well defined, and the fund is not complete. IDA countries insured by the facility still need to be persuaded that the potential of outbreak-related “savings” is an adequate incentive to invest domestically in preparedness.

“There’s new money for global public goods, but will it go towards preparedness? The World Bank’s recent announcement of a general capital increase includes up to $100m of IBRD annual income for programmes addressing global public goods (GPG). There’s an indication that the bank’s board of governors could increase the amount in the future. GPG includes pandemic preparedness and antimicrobial resistance. This funding could be used to buy down the cost of IBRD lending in low- and middle-income countries for this use or could be provided as a straight grant. This opportunity may require some demand creation efforts from the World Bank’s HNP practice and has the potential to be co-funded with philanthropic monies.

“In addition to resources and incentives, leadership itself is a critical component of pandemic preparedness. The recent news that Tim Ziemer, the head of global health security on the White House’s National Security Council, has left the administration—and that he will not be replaced—is incredibly worrisome. The current administration has a real opportunity to lead on the global health security agenda, but it won’t be able to without smart people in critical positions leading the way.

“As news of the most recent Ebola outbreak in the DRC develops, it will be important for us to not only stop the spread of infection, but also for the US and other key development actors to invest directly in preparedness—watch for more on this issue from CGD soon.”

 

The WHO has released a manual that provides concise and up-to-date knowledge on 15 infectious diseases that have the potential to become international threats, and tips on how to respond to each of them.

The WHO said that the 21st century has already been marked by major epidemics. Old diseases – cholera, plague and yellow fever – have returned, and new ones have emerged – SARS, pandemic influenza, MERS, Ebola and Zika. These epidemics and their impact on global public health have convinced the world’s governments of the need for a collective and coordinated defence against emerging public health threats and accelerated the revision of the International Health Regulations (2005), entered into force in 2007.

Another Ebola epidemic, another plague epidemic or a new influenza pandemic are not mere probabilities, the threat is real. Whether transmitted by mosquitoes, other insects, via contact with animals or person-to-person, the only major uncertainty is when and where they, or a new, but equally lethal epidemic, will emerge. These diseases all have the potential to spread internationally highlighting the importance of immediate and coordinated response.

The diseases covered are: Ebola virus disease, lassa fever, Crimean-Congo haemorrhagic fever, yellow fever, Zika, chikungunya, avian and other zoonotic influenza, seasonal influenza, pandemic influenza, Middle-East respiratory syndrome (MERS), cholera, monkeypox, plague, leptospirosis and meningococcal meningitis.

Although originally developed as guidance for WHO officials, this publication is available to a wide readership including all frontline responders – communities, government officials, non-State actors and public health professionals – who need to respond rapidly and effectively when an outbreak is detected.

Stat News report
The Times report
Centre for Infectious Disease Research and Policy, University of Minnesota material
Science Mag report
Reliefweb material
WHO material


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