Virus World

A second Ebola patient has died in northwestern Democratic Republic of Congo, the World Health Organization (WHO) said on Tuesday, days into a fresh outbreak of the deadly disease. Genetic testing showed an infection confirmed last week in the city of Mbandaka was a new "spillover event", a transmission from an infected animal, and not linked to any previous outbreaks, said the country's National Institute of Biomedical Research.  The second fatality was a 25-year-old woman who was the sister-in-law of the first case, the WHO said on Twitter. She began experiencing symptoms 12 days earlier, it said. The first patient began showing symptoms on April 5, but did not seek treatment for more than a week. He died in an Ebola treatment centre on April 21. The lag time has health workers rushing to identify contacts who may have been infected, the WHO said.

At least 145 people came into contact with the confirmed cases and their health is being closely monitored, the WHO said, noting later that one of the first cases was a health worker.  Mbandaka, a trading hub on the banks of the Congo River, is a city of over one million where people live in close proximity with road, water and air links to the capital Kinshasa. WHO emergencies director for Africa, Ibrahima Soce Fall, said there was a risk the disease could spread to neighbouring Central African Republic and Congo Brazzaville.  "This is concerning but taking into account the capacity build up and experience in Congo we believe it can be contained," Fall said at a press conference in Geneva. Congo has seen 13 previous outbreaks of Ebola, including one in 2018-2020 in the east that killed nearly 2,300 people, the second highest toll recorded in the history of the hemorrhagic fever. The most recent outbreak ended in December in the east after six deaths. Mbandaka, the capital of Equateur province, has also contended with two previous outbreaks - in 2018 and in 2020. The country's equatorial forests are a natural reservoir for the Ebola virus, which was discovered near the Ebola River in northern Congo in 1976.

Today marks the end of the 12th Ebola outbreak in the Democratic Republic of the Congo, just three months after the first case was reported in North Kivu. The Ebola outbreak that re-emerged in February came nine months after another outbreak in the same province was declared over.  The World Health Organization (WHO) congratulates the Democratic Republic of the Congo’s health authorities and the heath workers on the ground for their swift response which built on the country’s previous experience in tackling Ebola outbreaks. This outbreak is the country’s  fourth in less than three years. Eleven confirmed cases and one probable case, six deaths and six recoveries were recorded in four health zones in North Kivu since 7 February when the Ministry of Health announced the resurgence of Ebola in Butembo, a city in North Kivu Province and one of the hotspots of the 2018–2020 outbreak. Results from genome sequencing conducted by the country’s National Institute of Biomedical Research found that the first Ebola case detected in the outbreak was linked to the previous outbreak, but the source of infection is yet to be determined.

“Huge credit must be given to the local health workers and the national authorities for their prompt response, tenacity, experience and hard work that brought this outbreak under control,” said Dr Matshidiso Moeti, WHO Regional Direct for Africa. “Although the outbreak has ended, we must stay alert for possible resurgence and at the same time use the growing expertise on emergency response to address other health threats the country faces.” The response was coordinated by the Provincial Department of Health in collaboration with WHO and partners. WHO had nearly 60 experts on the ground and as soon as the outbreak was declared helped local workers to trace contacts, provide treatment, engage communities and vaccinate nearly 2000 people at high risk, including over 500 frontline workers.  The response was often hampered by insecurity caused by armed groups and social disturbances which at times limited the movement of responders. The area where the outbreak took place is one where the population is highly mobile as people move to conduct business or visit family and friends. Butembo city is about 150 km from the Uganda border and there were concerns over the potential cross-border spread of the outbreak. However, due to the effective response the outbreak stayed limited to North Kivu province.

While the 12th outbreak is over, there is a need for continued vigilance and maintaining a strong surveillance system as potential flare-ups are possible in the months to come. It is important to continue with sustained disease surveillance, monitoring of alerts and working with communities to detect and respond rapidly to any new cases and WHO will continue to assist health authorities with their efforts to contain quickly a sudden re-emergence of Ebola. WHO continues to work with the Democratic Republic of the Congo to fight other public health problems such as outbreaks of measles and cholera, the COVID-19 pandemic and a weak health system. The 2018–2020 outbreak was the 10th in the Democratic Republic of the Congo and the country’s deadliest, with 3481 cases, 2299 deaths and 1162 survivors. The country also experienced its 11th outbreak which took place in Equateur Province last year. Currently there is an ongoing Ebola outbreak in Guinea, which began in February of this year.

The wife of a survivor of a large Ebola outbreak in the Democratic Republic of the Congo has died from the disease nearly 8 months after the outbreak was declared over, WHO said, raising concerns about a resurgence of the virus.According to WHO, the DRC Ministry of Health reported the new case in Butembo, a city in North Kivu, the eastern province where the 2018-2020 outbreak took place.  The woman, whose samples tested positive for Ebola, sought medical attention for Ebola-like symptoms and later died. So far, more than 70 contacts have been identified, WHO said. “The expertise and capacity of local health teams has been critical in detecting this new Ebola case and paving the way for a timely response,” WHO Regional Director for Africa Matshidiso Moeti, MBBS, MSc, said in a press release. “WHO is providing support to local and national health authorities to quickly trace, identify and treat the contacts to curtail the further spread of the virus.”

The North Kivu outbreak lasted nearly 2 years and was declared over in June 2020. There were 3,481 cases and 2,299 deaths attributed to the outbreak, and more than 1,160 people recovered. It was the second largest Ebola outbreak on record after the West African epidemic, which lasted from 2014-2016 and killed more than 11,000 people. WHO reported that genome sequencing is currently underway to identify the strain of Ebola the woman had and to determine if it is linked to the previous outbreak. It is unclear if the woman had been vaccinated against Ebola or how she was infected. WHO warned last year that the region could see flare-ups of Ebola, which occurred frequently following the West African epidemic. Ebola survivors who no longer have symptoms can still carry the virus — in semen, for example — allowing for its reintroduction.

The mortality rate among patients in the Democratic Republic of the Congo with severe or critical cases of COVID-19 is nearly 50%, according to a study in The American Journal of Tropical Medicine and Hygiene. The study was the first to explore the clinical characteristics and outcome management of COVID-19 patients in an African country. Jean Nachega, MD, PhD, MPH, FRCP, FAAS, associate professor of epidemiology, infectious diseases and microbiology at University of Pittsburgh and adjunct professor of medicine at Stellenbosch University in Cape Town, and colleagues conducted a retrospective cohort study using data from the Democratic Republic of the Congo (DRC) health ministry’s COVID-19 database that was collected between March 10, 2020, and July 31, 2020. The study included data from 766 patients with COVID-19 admitted to the seven largest health facilities in Kinshasa.

“Whilst it is generally thought that COVID-19 in Africa causes lower mortality rates than in Western countries, COVID-19 is an important disease and does cause mortality in elderly adults with comorbidities,” Sir Alimuddin Zumla, KBE, FRCP, FRCPath, FRSB, senior co-author and professor of infectious diseases and international health at University College London, told Healio. “Physicians should not become complacent.” Among the patients in the study, overall hospital mortality was 13.2% (95% CI, 10.9-15.8), with a higher rate of mortality among patients with severe and critical disease than those with mild or moderate disease (45% vs. 2.6%; P < .001). According to the study, 34.6% of patients had at least one comorbidity and 48.5% had more than one. The most common comorbidities were hypertension (25.4%) and diabetes (14%). Of the patients who died, four were children. “One surprising finding was the high COVID-19 death rate among young patients”— 11.8% among patients aged 20 years or younger — “when compared to the United States, where hospitalization rates and death rates in children and adolescents with COVID-19 are lower than those in adults,” Nachega, told Healio.

Published in American J. Topical Medicine and Hygiene (Oct. 2, 2020):

https://doi.org/10.4269/ajtmh.20-1240

The country is now battling two Ebola outbreaks, the coronavirus and the world's largest measles epidemic. A second Ebola outbreak has been confirmed in the Democratic Republic of Congo, some 600 miles from an ongoing epidemic that has claimed more than 2,200 lives. According to the World Health Organization six cases of the highly contagious haemorrhagic fever have been identified and four people have so far died near Mbandaka, the regional capital of Équateur Province.

The outbreak was first announced on local radio by the region's governor, Bobo Boloko Bolumbu, on Monday morning. He said samples from the cases were sent to the INRB, the country’s national medical research organisation in Kinshasa, for secondary confirmation. “The laboratory has given us the information that all the deaths analysed since the 18th of May are a consequence of the Ebola virus,” the governor said. “However, for precision, the samples have been sent to the INRB for quality control. 

“I ask the population to be calm and to continue to respect hygiene measures. Regularly wash your hands with soap. Don’t, say, greet with your hands. Don’t touch ill or dead people who had a fever or bleeding,” he added. DRC's health minister, Eteni Longondo, and the WHO later confirmed the outbreak in Wangata, near Mbandaka. Of the initial six cases, three of  have been confirmed with laboratory testing. Four people have died and two are receiving critical care. ...

In past Ebola outbreaks, fatality rates have varied from 25% to 90% - but effective treatments are now available, and patients who receive care early see their chances of survival improve significantly.  An outbreak of Ebola has been declared in the Democratic Republic of the Congo - four months after the last one ended. A case was confirmed in a 31-year-old man on 5 April. He was admitted to an Ebola treatment centre on Thursday, but died hours later. The World Health Organisation's regional director for Africa, Dr Matshidiso Moeti, said: "Time is not on our side. The disease has had a two-week head start and we are now playing catch-up." Overall, this is the 14th Ebola outbreak that the Democratic Republic of the Congo has seen since 1976, which is when the virus was first discovered.

Efforts to stem the current outbreak have already begun, with officials confirming that the patient who died has received a safe and dignified burial.  More than 70 of his contacts are also being traced - and vaccinations in the city of Mbandaka are going to be stepped up. Ebola is transmitted by coming into contact with the bodily fluids of an infected person or contaminated materials.  Early symptoms include muscle aches and a fever, which resemble those seen in other common diseases such as malaria. In past Ebola outbreaks, fatality rates have varied from 25% to 90% - but effective treatments are now available, and patients who receive care early see their chances of survival improve significantly. Dr Moeti added: "The positive news is that health authorities in the Democratic Republic of the Congo have more experience than anyone else in the world at controlling Ebola outbreaks quickly."

During the 2018–2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus–based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)–specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. 

Published in NEJM (April 1, 2021):

https://doi.org/10.1056/NEJMoa2024670 

The disease killed at least 55 people in an outbreak that began June 1, the 11th bout of Ebola to strike the Democratic Republic of Congo. KINSHASA, Democratic Republic of Congo — The government on Wednesday declared the end of the latest Ebola epidemic in the Democratic Republic of Congo, closing the file on an outbreak in the northwestern province of Equateur that killed dozens over six months. “I am happy to solemnly declare the end of the 11th epidemic of the Ebola virus,” Health Minister Eteni Longondo told journalists. The World Health Organization said the latest outbreak had killed 55 people among 119 confirmed and 11 probable cases since June 1. Dr. Longondo’s announcement came after the Democratic Republic of Congo crossed a threshold of 42 days without a recorded case — double the period that the deadly virus takes to incubate. As during a preceding epidemic in the east of the country, the widespread use of vaccinations, which were administered to more than 40,000 people, helped curb the disease, the W.H.O. said.

The outbreak in Equateur began as health workers were still battling an Ebola epidemic in the east and amid tough measures, since eased, to combat the coronavirus. Despite the official end of the Equateur outbreak, Dr. Longondo expressed caution. “There remains a high risk of a resurgence, and this should be an alarm signal for strengthening the monitoring system,” the minister said.  The eastern outbreak, which ran from Aug. 1, 2018 to June 25 of this year, was the country’s worst ever, with 2,277 deaths. It was also the second highest toll in the 44-year history of the disease, surpassed only by a three-country outbreak in West Africa from 2013 to 2016 that killed 11,300 people. The Ebola virus spreads via contact with the blood, body fluids, secretions or organs of an infected or recently deceased person. The early symptoms are high fever, weakness, intense muscle and joint pain, headaches and sore throats, followed by internal and external bleeding and organ failure. The death rate ranges as high as 90 percent in some outbreaks, according to the W.H.O.

U.S. regulators Wednesday approved the first drug for the treatment of Ebola. The Food and Drug Administration OK'd the drug developed by Regeneron Pharmaceuticals for treating adults and children with the Zaire Ebola virus strain, the most deadly of six known types. It typically kills 60% to 90% of patients. The drug was one of four tested during an outbreak in Congo that killed nearly 2,300 people before it ended in June. Survival was significantly better in study participants given Regeneron’s Inmazeb or a second experimental drug. The study was ended ahead of schedule last year so all patients could get access to those drugs. Regeneron’s treatment is a combination of three antibodies that work by killing the virus. It’s given once by IV. “When you have three drugs that bind to the (virus), there’s a low probability that the virus can evade all of them,” said Leah Lipsich, who heads Regeneron’s global program for infectious diseases. She said that should help prevent the virus from becoming resistant to the drug.

Seeking U.S. approval first is a common strategy for drugmakers developing treatments for diseases mainly found in the tropics and in developing countries. The FDA’s action will make it easier for Regeneron to get approval or allow emergency use during outbreaks in African countries, where the approval process is not straightforward, Lipsich said. The study in Congo involved 681 people, who were give one of four treatments. After four weeks, about a third of those who got Regeneron’s drug had died. Results were about the same for a second drug. But about half had died among the groups given one of the other two drugs, ZMapp or remdesivir. Gilead Science’s remdesivir is now being used as a treatment for coronavirus. Ebola is very contagious and is spread mainly through contact with body fluids from infected people. Symptoms include fever, muscle pain, vomiting, kidney and liver damage, and sometimes internal and external bleeding. The FDA approved the first vaccine for Ebola last December. The U.S. government, which helped fund the approved drug’s development, will buy thousands of doses over the next six years to go into the Strategic National Stockpile. Ebola cases are rare in the U.S., but occasionally are diagnosed in travelers returning from areas with an outbreak.

FDA release (Oct. 14, 2020):

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-ebola-virus

A trial of four experimental Ebola treatments carried out in the Democratic Republic of the Congo (DRC) has been stopped early after two of them showed strong signs of being able to save patients’ lives. The preliminary results were reported this morning by Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, one of the partners in the study. The two treatments will now be made widely available and could help end the yearlong outbreak in the DRC, which has already killed more than 1800 people, scientists say.

The PALM trial (short for the Swahili expression pamoja tulinde maisha, which means “together save lives”) evaluated three Ebola antibody preparations and one antiviral drug in a randomized controlled trial conducted in the midst of the devastating outbreak, which has hit two provinces in the eastern DRC mired in violence. “Today, we have started a new chapter. From now on, we will no longer say that Ebola is not curable,” Jean-Jacques Muyembe-Tamfum, head of the DRC’s National Institute for Biomedical Research in Kinshasa, a partner in the trial, said at the press conference. “This advance will, in the future, help save thousands of lives.” (Muyembe, who was part of the team that discovered Ebola 43 years ago, took over command of the outbreak response in the DRC on 22 July.)

Still, the data on ZMapp were deemed good enough to use the drug as a control in future trials. In the PALM trial, three other trials were compared to ZMapp:

• The monoclonal antibody mAb114, which has its roots in the 1995 Ebola outbreak in Kikwit, DRC. During that episode, Muyembe attempted to treat patients with a mixture of antibodies from Ebola survivors. Years later, researchers at NIAID isolated antibodies from those survivors; mAb114, which is now being developed with Ridgeback Biotherapeutics in Miami, Florida, was the most promising one.
• REGN-EB3, a cocktail of three monoclonal antibodies developed by Regeneron Pharmaceuticals in Eastview, New York. The antibodies were generated by inoculating mice with “humanized” immune systems with the Ebola virus.
• The antiviral drug remdesivir, produced by Gilead Sciences in Foster City, California.

The trial started in November 2018 in four Ebola treatment units in the communities of Beni, Butembo, Katwa, and Mangina, with the aim of enrolling 725 patients. On 9 August, an independent data and safety monitoring board reviewed data for 499 patients and found that REGN-EB3 was much better than ZMapp. Overall, 49% of patients receiving ZMapp—and 53% of those who received remdesivir—died, compared with only 29% of those on REGN-EB3. That difference was big enough to meet the predetermined criterion for stopping the trial early. In the group that received mAb114, mortality was 34%, a rate deemed close enough to that of the Regeneron cocktail that its use should continue.  In the 41% of trial participants who sought treatment early after infection and had lower levels of Ebola virus in their blood, the two new treatments had astonishing success: Mortality plummeted to 6% in the Regeneron antibody group and to 11% with mAb114. (With ZMapp and remdesivir, mortality rates in people with low viral load were 24% and 33%, respectively.) There is far less hope for patients with a high viral load, however: Even with the best treatment, REGN-EB3, their death rate was 60%.