Emergencies

Ebola – DRC+
Public Health Emergency of International Concern (PHEIC)

Ebola Outbreak in DRC 69: 26 November 2019
Situation Update
In the week of 18 to 24 November 2019, seven new confirmed EVD cases were reported from four health zones in two affected provinces in Democratic Republic of the Congo. The majority of the confirmed cases in this week came from Mabalako Health Zone (57%; n=4).

Violence and civil unrest in the week have led to the suspension of Ebola response activities in some areas of Beni, Butembo, and Oicha health zones. On 26 November 2019, some response personnel were temporarily relocated from Beni, though most remain in place to continue responding. The immediate focus will be on maintaining the safety and welfare of response personnel while preserving essential response activities in these places.

The disruptions to the response and lack of access to Ebola-affected communities is threatening to reverse recent progress. As seen previously during this outbreak, such disruptions limit contact tracing, surveillance, and vaccination efforts, and they often result in increased transmission…

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Dead and injured following attacks on Ebola responders in the Democratic Republic of the Congo
Attacks in eastern Democratic Republic of the Congo
28 November 2019 News release
Two attacks in eastern Democratic Republic of the Congo (DRC) have killed 4 workers responding to the Ebola outbreak and injured 5 others.
The attacks occurred overnight on a shared living camp in Biakato Mines and an Ebola response coordination office in Mangina.
We are heartbroken that people have died in the line of duty as they worked to save others,” said Dr Tedros Adhanom Ghebreyesus, World Health Organization Director-General. “The world has lost brave professionals.”
The dead include a member of a vaccination team, two drivers and a police officer. No WHO staff are among those killed, one staff member was injured.
“My heart goes out to the family and friends of the first responders killed in these attacks,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “We are doing everything possible to bring the injured and front-line workers in the impacted areas to safety. These constant attacks must stop. We will continue to work with the DRC Government, partners and MONUSCO to ensure the security of our staff and other health workers.”…

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New England Journal of Medicine
Online November 27, 2019
DOI: 10.1056/NEJMoa1910993
Original Article
A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics
Sabue Mulangu, M.D., Lori E. Dodd, Ph.D., Richard T. Davey, Jr., M.D., Olivier Tshiani Mbaya, M.D., Michael Proschan, Ph.D., Daniel Mukadi, M.D., Mariano Lusakibanza Manzo, Ph.D., Didier Nzolo, M.D., Antoine Tshomba Oloma, M.D., Augustin Ibanda, B.S., Rosine Ali, M.S., Sinaré Coulibaly, M.D., Adam C. Levine, M.D., Rebecca Grais, Ph.D., Janet Diaz, M.D., H. Clifford Lane, M.D., Jean-Jacques Muyembe-Tamfum, M.D., and the PALM Writing Group for the PALM Consortium Study Team*
Abstract
Background
Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial.
Methods
We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase–polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days.
Results
A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P=0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P=0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs.
Conclusions
Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586. opens in new tab.)

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Investigational Drugs Reduce Risk of Death from Ebola Virus Disease – NIH
Study Leaders Publish Results from NIH-DRC-WHO Clinical Trial of Four Experimental Therapies.
November 27, 2019
The investigational therapeutics mAb114 and REGN-EB3 offer patients a greater chance of surviving Ebola virus disease (EVD) compared to the investigational treatment ZMapp, according to published results from a clinical trial conducted in the Democratic Republic of the Congo (DRC). The new report also shows that early diagnosis and treatment are associated with an increased likelihood of survival from EVD.
The results appear online this week in the New England Journal of Medicine. An announcement made on August 12, 2019, noted that the study leaders halted the trial early, on August 9, 2019, as recommended by an independent data and safety monitoring board based on its review of preliminary data from 499 study patients. The preliminary analysis found that both mAb114 and REGN-EB3 performed better than ZMapp. The fourth drug, remdesivir, performed similarly to ZMapp. Today’s publication provides a comprehensive analysis of the full dataset from nearly 200 additional patients enrolled in the clinical study.
The clinical trial known as PALM, short for “Pamoja Tulinde Maisha,” a Kiswahili phrase that translates to “together save lives,” was organized by an international research consortium coordinated by the World Health Organization (WHO). It is led and funded by the DRC’s National Institute for Biomedical Research (INRB) and Ministry of Health, and the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health. Professor Jean-Jacques Muyembe-Tamfum, M.D., Ph.D., director-general of the INRB and head of the DRC’s Ebola response, and Richard T. Davey, Jr., M.D., deputy director of NIAID’s Division of Clinical Research, are co-principal investigators for the study.
“Response teams have faced unprecedented challenges in ongoing efforts to save lives and control the outbreak of Ebola in a highly insecure region of the Democratic Republic of the Congo,” said NIAID Director Anthony S. Fauci, M.D. “Although effective treatments alone will not end this outbreak, the PALM study findings identify the first efficacious treatments for Ebola virus disease and therefore mark a significant step forward in improving care for Ebola patients. We thank the study team for their extraordinary efforts to conduct this landmark trial.”
The study enrolled 681 people with Ebola virus disease between November 2018 and August 2019 at four Ebola treatment centers (ETCs) in the cities of Beni, Butembo, Katwa and Mangina. Staff from The Alliance for International Medical Action (ALIMA), International Medical Corps (IMC), Médecins Sans Frontières/Doctors Without Borders (MSF) and the DRC Ministry of Health implemented the trial at the ETCs with support from Congolese staff, the World Health Organization, the Frederick National Laboratory for Cancer Research and The Mitchell Group.
The study was designed to compare mortality among patients who received one of three investigational Ebola drugs with that from a control group of patients who received the investigational monoclonal antibody cocktail ZMapp, developed by Mapp Biopharmaceutical, Inc. The other therapies were mAb114, a single monoclonal antibody product developed for clinical use by NIAID’s Vaccine Research Center and the INRB and licensed to Ridgeback Biotherapeutics and Mapp Biopharmaceutical; REGN-EB3, a monoclonal antibody cocktail developed by Regeneron Pharmaceuticals, Inc.; and remdesivir, an antiviral drug developed by Gilead Sciences, Inc. The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also has provided support for the development of REGN-EB3, ZMapp and mAb114.
The four therapies are administered as intravenous infusions. REGN-EB3 and mAb114 are administered as single infusions and ZMapp and remdesivir are administered as infusions over multiple days. Study participants also received optimized supportive care, including oral and/or intravenous fluids, electrolyte replacement, monitoring of oxygen levels and blood pressure (with supportive measures as needed), blood transfusions, pain management, and antibiotics and antimalarials as indicated….
All four study drugs were generally well tolerated. There were a total of four serious adverse events that were judged to be potentially related to the experimental drugs. Three of these were in two of the patients who received ZMapp. One was in a patient who received remdesivir.
The authors note that despite encouraging findings regarding mAb114 and REGN-EB3, approximately one-third of patients who received these therapeutics died, highlighting the potential to improve upon these results, whether through further optimization of supportive care, combination therapy using agents with complementary mechanisms of action or other strategies.
“Despite unprecedented challenges — including an unstable electrical power grid and evacuations of staff and patients from treatment centers due to violent attacks — the PALM trial demonstrates that scientifically rigorous and ethically sound clinical research can be conducted during disease outbreaks,” said H. Clifford Lane, M.D., NIAID deputy director for Clinical Research and Special Projects. “We thank the patients and the medical staff in the field and at the treatment sites for their participation and exceptional commitment to the trial.”

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POLIO
Public Health Emergency of International Concern (PHEIC)

Polio this week as of 20 November 2019
:: A four-day regional emergency preparedness workshop is currently underway in Lomé, Togo, for senior public health officials to strengthen the capabilities within West African countries to respond to polio outbreaks. Read more about the workshop.
:: “It was good to know that a country like India could eradicate polio. It gives us hope that Pakistan can do it too, and we will soon be polio free.” These are the words of Aziz Memon, a Rotarian who has dedicated his life to fight polio in Pakistan. Read about his journey.

Summary of new viruses this week (AFP cases and ES positives):
:: Pakistan— five WPV1 cases, two cVDPV2 cases and one cVDPV2 positive environmental sample;
:: Democratic Republic of the Congo (DR Congo)- five cVDPV2 cases;
:: Benin – four cVDPV2 cases;
:: Ghana— four cVDPV2 cases and two cVDPV2 positive environmental samples;
:: Philippines – three cVDPV2 cases and five cVDPV2 positive environmental samples;
:: Togo – two cVDPV2 cases.

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More than 3.1 million Iraqi children to be vaccinated against polio
Baghdad, 26 November 2019 – Health authorities in Iraq, in partnership with the World Health Organization (WHO) and UNICEF, have launched a campaign to reach more than 3.1 million children under-5 years of age with lifesaving polio vaccine.

The 5-day campaign aims to target children in 65 districts in the governorates of Baghdad, Babylon, Diwaniya, Diyala, Muthanna, Thi-Qar, Missan and Basra.

“Over the years, WHO, the Ministry of Health and UNICEF have worked hard to improve immunization coverage in the country. Therefore, it is important that we keep building on our work by making sure that children are vaccinated against childhood preventable diseases like polio and we keep Iraq polio free,” said Dr Adham Ismail, WHO Representative for Iraq. “During this second phase of the campaign, we want to reach all the children under 5 regardless of their previous vaccination status with oral polio vaccine leaving no one out no matter where they are,” added Dr Adham…

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Editor’s Note:
WHO has posted a refreshed emergencies page which presents an updated listing of Grade 3,2,1 emergencies as below.

WHO Grade 3 Emergencies [to 30 Nov 2019]

Democratic Republic of the Congo
:: Dead and injured following attacks on Ebola responders in the Democratic Republic of the Congo 28 November 2019
:: Ebola Outbreak in DRC 69: 26 November 2019

Mozambique floods – No new digest announcements identified
Nigeria – No new digest announcements identified
Somalia – No new digest announcements identified
South Sudan – No new digest announcements identified
Syrian Arab Republic – No new digest announcements identified
Yemen – No new digest announcements identified

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WHO Grade 2 Emergencies [to 30 Nov 2019]

Afghanistan – No new digest announcements identified
Angola – No new digest announcements identified
Burkina Faso [in French] – No new digest announcements identified
Burundi – No new digest announcements identified
Cameroon – No new digest announcements identified
Central African Republic – No new digest announcements identified
Ethiopia – No new digest announcements identified
HIV in Pakistan – No new digest announcements identified
Iran floods 2019 – No new digest announcements identified
Iraq – No new digest announcements identified
Libya – No new digest announcements identified
Malawi floods – No new digest announcements identified
Measles in Europe – No new digest announcements identified
MERS-CoV – No new digest announcements identified
Myanmar – No new digest announcements identified
Niger – No new digest announcements identified
occupied Palestinian territory – No new digest announcements identified
Sudan – No new digest announcements identified
Ukraine – No new digest announcements identified
Zimbabwe – No new digest announcements identified

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WHO Grade 1 Emergencies [to 30 Nov 2019]

Chad – No new digest announcements identified
Djibouti – No new digest announcements identified
Kenya – No new digest announcements identified
Mali – No new digest announcements identified
Namibia – viral hepatitis – No new digest announcements identified
Tanzania – No new digest announcements identified

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UN OCHA – L3 Emergencies
The UN and its humanitarian partners are currently responding to three ‘L3’ emergencies. This is the global humanitarian system’s classification for the response to the most severe, large-scale humanitarian crises. 
Syrian Arab Republic – No new digest announcements identified
Yemen – No new digest announcements identified

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UN OCHA – Corporate Emergencies
When the USG/ERC declares a Corporate Emergency Response, all OCHA offices, branches and sections provide their full support to response activities both at HQ and in the field.
Editor’s Note:
Ebola in the DRC has bene added as a OCHA “Corporate Emergency” this week:
CYCLONE IDAI and Kenneth – No new digest announcements identified
EBOLA OUTBREAK IN THE DRC – No new digest announcements identified

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