Saturday, September 1, 2018

PRO/AH/EDR> Ebola update (81): Congo DR (NK) case update, response, clinical trials

A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases

In this update:
[1] Case update
- Epidemiological situation report, 1 Sep 2018, DRC Ministry of
- WHO: Outbreak news
[2] Response
- WHO: Public health response
[3] Clinical trials
- Experimental Ebola drugs face tough test in war zone

[1] Case update
- Sat 1 Sep 2018. Epidemiological situation report, DRC Ministry of
Health [in French, machine trans., edited]

The Epidemiological Situation of Ebola Virus Disease on 31 Aug 2018:
- A total of 120 cases of haemorrhagic fever were reported in the
region: 90 confirmed and 30 probable.
- 11 suspected cases are under investigation.
- 2 new confirmed cases in Beni
- 1 confirmed case death in Mabalako

Distribution of cases by age and sex of the epidemic to Ebola Virus
Disease (EVD) in North Kivu Province
[Graph legend]
This graph reveals that
- Women have been more affected than men by this 10th outbreak of
- For men, the most affected age group is 35-44;
- Among women, the most affected age group is 25-34.

- Since the beginning of vaccination on 8 Aug 2018, 5462 people have
been vaccinated, including 2852 in Mabalako, 1433 in Beni, 1037 in
Mandima, 121 in Oicha, and 19 in Kinshasa.

Communicated by:
ProMED-mail Rapporteur Mary Marshall

- 31 Aug 2018. Ebola Virus Disease - Democratic Republic of the Congo
[WHO Disease outbreak news, part 1, edited]

The outbreak of EVD in the DRC is at a key juncture. Recent trends
(Fig. 1) suggest that control measures are working. Over the past
week, contact follow-up rates have substantially improved, most
patients recently admitted to Ebola treatment centres (ETC) received
therapeutics within hours of being confirmed, and ring vaccination
activities have scaled to reach contacts (and their contacts) of most
confirmed cases reported in the last 3 weeks. However, the outbreak
trend must be interpreted with caution. Since the last Disease
Outbreak News on 24 Aug 2018, 13 additional confirmed and probable
cases have been reported, the majority (n=8) were from the city of
Beni. Moreover, substantial risks remain, posed by potential
undocumented chains of transmission; 4 of the 13 new cases were not
known contacts. Likewise, sporadic instances of high-risk behaviours
in some communities (such as unsafe burials and reluctance towards
contact tracing, vaccination, and admission to ETCs if symptoms
developed), poor infection prevention and control (IPC) practices in
some community health centres, and delays in patients reaching ETCs
when symptoms develop all have the potential to further propagate the

As of 29 Aug 2018, a total of 116 EVD cases (86 confirmed and 30
probable), including 77 deaths (47 confirmed and 30 probable) have
been reported in 5 health zones in North Kivu (Beni, Butembo, Oicha,
Mabalako, Musienene) and one health zone in Ituri (Mandima). Eight
suspected cases from Mabalako (n=5) and Beni (n=3) are currently
pending laboratory testing to confirm or exclude EVD. The majority of
cases (65 confirmed and 21 probable) have been reported from Mabalako
Health Zone (Fig. 2). The median age of confirmed and probable cases
is 35 years (interquartile range 19-45.5 years), and 56 percent were
female (Fig. 3).

Fifteen cases have been reported among health workers, of which 14
were laboratory confirmed; one has died. All health-worker exposures
likely occurred in health facilities outside of the dedicated ETCs.
WHO and partners continue to work with health workers and communities
to increase awareness on IPC measures, as well as vaccinate those at
risk of infection.

In addition to the ongoing response activities within outbreak
affected areas, the MoH, WHO, and partners will be implementing a
30-day strategic plan to ensure operational readiness measures against
EVD are strengthened in all provinces of the DRC. The 1st phase of
implementation will prioritise 6 provinces at highest risk of case
importations: South Kivu, Maniema, Ituri, Tanganika, Haut Uele, and
Bas Uele. The main objective is to ensure that these provinces
implement essential operational readiness measures, including
enhancing surveillance, IPC, and social mobilization to mitigate,
rapidly detect, investigate, and effectively respond to a possible
outbreak of EVD.

Fig. 1: Confirmed and probable EVD cases by week of illness onset, 29
Aug 2018 (n=115)

Fig. 2: Confirmed and probable EVD cases by health zone in North Kivu
and Ituri provinces, DRC, 29 Aug 2018

Fig. 3: Confirmed and probable EVD cases by age and sex, as of 29 Aug
2018 (n=111)

Communicated by:
ProMED-mail Rapporteur Mary Marshall
Greg Folkers

[The graphs included in the above reports contain essential
information and should be viewed at the URLs provided above. The DRC
MOH webpage graph provides a current breakdown of total cases by sex,
age, and probable vs. confirmed. But to assess control efforts, the
cumulative number of cases is often less instructive than the trending
number of cases. That is why Fig. 1 in the WHO report, the number of
new EVD cases reported week-by-week, is meaningful.

The good news (albeit quite preliminary) is that the number of new
cases over the last 3 weeks has been trending downwards, which may be
a sign of real progress in outbreak control. Also encouraging is the
fact that no new cases of Ebola have developed in healthcare workers
since the establishment of Ebola treatment centers, a sign of more
effective quarantine and other infection prevention and control

The troubling news is there continues to be new Ebola cases in
individuals who were not known contacts of registered patients [4 out
of the 13 new cases 24-31 Aug). In addition, there have been several
"Ebola community deaths" as noted in the 30 Aug DRC MOH report (Ebola
update (80), which
presumably occurred outside of quarantined treatment centers. These
"de novo" cases of Ebola indicate that there continue to be unknown
disease foci and transmission chains, which could quickly reverse the
downward weekly trend in new cases. - Mod.LXL]

[2] Response
- 31 Aug 2018. Ebola virus disease - Democratic Republic of the Congo
WHO Disease outbreak news, part 2 [edited]

Public health response
The MoH continues to strengthen response measures, with support from
WHO and partners. Priorities include response coordination,
surveillance, contact tracing, laboratory capacity, IPC, clinical
management, vaccination, risk communication and community engagement,
safe and dignified burials, cross-border surveillance, and
preparedness activities in neighbouring provinces and countries.

As of 29 Aug 2018, 2444 contacts remain under surveillance, of which
79-97 percent were followed up with daily during the past 7 days.
During this period, contact tracing teams have faced, and are working
to overcome, many challenges, including community refusal in some
areas, insecurity, and the movement of contacts, making them hard to
follow. The Ministry of Health (MoH), WHO, and partners continue to
systematically monitor and rapidly investigate all alerts in all
provinces of the DRC and in neighbouring countries.

As of 29 Aug 2018, 26 vaccination rings have been defined, and 4
additional rings are being defined. Vaccination teams have been
vaccinating these rings, which include the contacts and the contacts
of contacts of 44 recently confirmed cases from the last 21 days. As
of 30 Aug 2018, over 5130 contacts and contacts of contacts have been
vaccinated, of which over 1040 healthcare or frontline workers and
over 1340 are children. More than 7000 additional doses of vaccine
have been transported to Beni to supplement doses currently in place,
and additional doses (2160) arrived on 29 Aug 2018 from the USA.

As of 30 Aug 2018, WHO has deployed over 180 multidisciplinary
specialists to support response activities, including logisticians,
epidemiologists, laboratory experts, communicators, clinical care
specialists, community engagement specialists, and emergency
coordinators. Global Outbreak Alert and Response Network (GOARN)
partner institutions continue to support the response as well as
ongoing readiness and preparedness activities in non-affected
provinces of the DRC and in neighbouring countries.

ETCs are fully operational in Beni and Mangina with support from The
Alliance for International Medical Action (ALIMA) and Medecins Sans
Frontieres (MSF), respectively. MSF opened a 7-bed transit center in
Makeke on 9 Aug 2018. International Medical Corps (IMC) is planning on
establishing an ETC in Makeke, which will then replace the transit
center. ETCs are providing therapeutics under the monitored emergency
use of unregistered and experimental interventions (MEURI) protocol in
collaboration with the MoH and the Institut National de Recherche
Biomedicale (INRB). WHO is providing technical clinical expertise
onsite and is assisting with the creation of a data safety management

For the 1st time, there is regulatory and ethical approval to provide
access to 5 investigational Ebola therapeutics under the MEURI
framework for people infected with EVD. Three are already in use
(mAb114, Remdesivir (GS5734), and ZMapp), and more may follow
(REGN3470-3471-3479 and Faviripir). To date, 20 patients have received
investigational therapeutics: 13 mAb 114, 5 remdisivir, and 2 zMAPP.

A team of IPC specialists are holding daily training with healthcare
and frontline workers, assessing and decontaminating facilities, and
providing essential hand hygiene solutions and personal protective
equipment. A team of experts deployed by WHO are supplementing local
capacity, working with dozens of healthcare centres to identify areas
requiring strengthening, and provide training and supplies as needed.
They are assisting the health centres to set up triage to ensure that
patients with suspected Ebola can be separated and treated away from
other patients to reduce the risk of the disease spreading.

The MOH, WHO, UNICEF, the Red Cross, and partners are intensifying
activities to engage with local communities in Beni and Mutembo. Local
leaders, religious leaders, opinion leaders, and community networks
such as youth groups and motorbike taxi drivers are engaged with to
support community outreach for Ebola prevention and early care-seeking
through active dialogues on radio and interpersonal communication.
Local frontline community outreach workers are working closely across
Ebola response teams to strengthen community engagement and
psychosocial support in contact tracing, patient care, and safe and
dignified burials.

>From 6-8 Aug 2018, Knowledge, Attitudes and Practices (KAP) surveys
were conducted on 335 individuals in Mabalako and Beni and found that
there was a high level of awareness on EVD (76 percent). However, it
was also found that there was a low level of knowledge on EVD
transmission and prevention (22 percent) and low level of knowledge of
the EVD vaccine (23 percent). The 2nd KAP survey is planned for the
week of 8 Sep 2018. A community feedback mechanism for collecting
feedback, questions, complaints, and rumours to inform localized
community engagement strategies is established to adapt risk
communication and community engagement strategies to community needs.

The Red Cross of the DRC, with the support of the International
Federation of Red Cross (IFRC) and International Committee of the Red
Cross (ICRC), is responding to the current EVD outbreak in North Kivu
with Safe and Dignified Burials (SDB). As of 29 Aug 2018, 10 SDB teams
are operational in Beni, Mangina, Butembo, Bunia, and Mambasa. As of
29 Aug 2018, 80 SDBs have been successfully conducted. As of 27 Aug
2018, 34 Points of Entry (PoE) in North Kivu are functional with
health-screening activities, and the total number of alerts from these
PoEs to this date is 36.

WHO risk assessment

This latest outbreak of EVD is affecting northeastern provinces of the
DRC, which border Uganda, Rwanda, and South Sudan. Potential risk
factors for transmission of EVD at the national and regional levels
include the transportation links between the affected areas, the rest
of the country, and neighbouring countries; the internal displacement
of populations; and displacement of Congolese refugees to neighbouring
countries. The country is concurrently experiencing several epidemics
and a long-term humanitarian crisis. Additionally, the security
situation in North Kivu and Ituri may hinder the implementation of
response activities. Based on this context, the public-health risk was
assessed to be high at the national and regional levels, and low

As the risk of national and regional spread remains high, it is
important for neighbouring provinces and countries to enhance
surveillance and preparedness activities. WHO will continue to work
with neighbouring countries and partners to ensure health authorities
are alerted and are operationally ready to respond.

Communicated by:
ProMED-mail Rapporteur Mary Marshall
Greg Folkers

[I have little to add to this comprehensive WHO summary and assessment
of current Ebola response. What I find encouraging is the systematic
effort to numerically track the ring vaccination campaign, despite the
very unstable and sometimes chaotic conditions under which the
vaccinators must operate. Also noteworthy is the comparatively rapid
introduction of not just one but multiple new investigational
therapeutics, only months after they were 1st contemplated for use
during the earlier Equateur outbreak. The numbers of patients
eventually treated with these different experimental medicines may be
too small to draw meaningful conclusions (although small numbers would
in fact be "a consummation devoutly to be wished"), but the regulatory
framework and implementation process used in the DRC may serve as a
model for conducting future drug trials in the midst of an
unpredictable outbreak. For our previous discussions of experimental
therapeutics for Ebola, see the following: Ebola update (59), Ebola update (39), and Ebola update (29) For a perspective on the
challenges of doing clinical trials during an active outbreak in a
poor and unstable country, see article below. - Mod.LXL]

[3] Clinical trials
- 31 Aug 2018. Experimental Ebola drugs face tough test in war zone
Source: Nature [edited]

Health workers fighting the ongoing Ebola outbreak in the DRC have
given nearly 20 people experimental drugs to treat the virus since
mid-August [2018]. But because the drugs have been dispensed on a
case-by-case, "compassionate use" basis, it is hard to know whether
any are effective. Now, desperate to determine which therapy works
best, researchers from the DRC and US governments, the World Health
Organization, and other groups are meeting this week to plan a
clinical trial that will compare multiple drugs as the outbreak

For ethical reasons, the trial scientists say they do not intend to
give any study participants a placebo. Instead, they hope to compare
the 2 experimental medicines now in use to ZMapp, an antibody therapy
that showed promise in limited tests 3 years ago during a major Ebola
epidemic in West Africa. Patients in the coming trial would receive
one of these 3 drugs at random. The study design draws on a flexible
clinical-trial framework that the WHO expects to unveil early next
week. The framework is intended for use in multiple Ebola outbreaks,
to produce data that can be pooled over time.

The scientists working on the DRC trial hope to launch the effort in
the coming weeks. "A clinical trial will give us the scientific
evidence we need," says Jean-Jacques Muyembe-Tamfum, director-general
of the National Institute for Biomedical Research in Kinshasa, which
will lead the study.

But planning for the trial is complicated by the realities of working
in a conflict zone: the DRC's North Kivu and Ituri provinces, where
fighting has killed more than 5 million people over the past 2
decades. Instability in the region could prevent clinicians from
giving patients repeated infusions of drugs and collecting the
biochemical data that a trial would require. "We can't control what
happens around a treatment centre," Muyembe-Tamfum says. "Armed groups
can do what they want."

The current outbreak began on [1 Aug 2018] and has grown to include
115 confirmed and probable cases of Ebola, including 77 people who
have died, the DRC health ministry said on [28 Aug 2018].
Public-health workers have vaccinated 4645 people, and doctors have
given 3 people the antiviral drug remdesivir, made by Gilead Sciences
of Foster City, California. Another 13 patients have received mAb114,
an experimental treatment derived from antibodies found in the blood
of a person who contracted Ebola in 1995 and survived.

That swift response is a major shift from the handling of the Ebola
epidemic that struck West Africa in 2014. Experimental drugs were not
used widely in West Africa then, because there was no proof of their
safety or efficacy: clinical trials did not begin until the outbreak
was near its end. That delay helped to drive the death rate among
Africans infected with Ebola to 63 percent. But several Westerners
infected with Ebola received the nascent therapies in top hospitals;
the fatality rate for this group of patients was just 18 perent. The
controversy over this disparity eventually prompted the WHO to develop
guidelines aimed at ensuring wider access to experimental treatments
during future Ebola outbreaks.

But the only way to determine how well a drug works -- and to rule out
confounding factors, such as overall quality of medical care -- is
through a randomized, controlled clinical trial. Thus far, researchers
have not managed to complete a trial of any experimental Ebola drug,
because outbreaks of the disease have ended before enough patients
enrolled in the studies. So the WHO has been working with
international experts to create a basic trial design that can be
adapted as data accumulate and logistical challenges change.

Muyembe-Tamfum says that the trial being planned now for the DRC will
make use of that framework. It is likely to test 3 drugs: mAb114,
remdesivir, and ZMapp, made by Mapp Biopharmaceutical in San Diego,

Although there are fewer data on mAb114 than on the other 2 drugs, it
has attracted researchers because it is relatively simple to
administer. Patients require just one dose, and the medicine is stable
when refrigerated, an advantage in hot countries such as the DRC that
lack steady electricity supplies.

But the inclusion of ZMapp complicates the trial plan, because the
drug must be kept frozen and is given as multiple hours-long
infusions, delivered under the watchful eyes of clinicians. "If you
have 50 patients, this would require a huge number of doctors," says
Augustin Augier, the secretary-general of Paris-based ALIMA, one of
the main medical organizations treating patients in the latest Ebola
outbreak. "But if ZMapp turns out to be 2 times more superior to the
other drugs, you will want to use it anyways."

Stationing a large number of medical professionals in an Ebola unit is
particularly fraught during the latest outbreak, because those people
could become targets for the more than 100 militias roving the eastern
DRC. If armed groups show up at a treatment centre, health workers
might leave rather than risk their lives, and any clinical trial could
come to a halt. "We are far better off than we were in West Africa,
but this outbreak has tough challenges with security," says Anthony
Fauci, head of the US National Institute of Allergy and Infectious
Diseases in Bethesda, Maryland.

But Ana Maria Henao Restrepo, who helps to lead the WHO's Ebola
Research and Development team, is unfazed. "Every trial has its own
challenges," she says. "That's why we are coming out with an approach
that's flexible."

1. The PREVAIL II Writing Group. N. Engl. J. Med. 2016; 375:
2. Davey, R. T. et al. J. Infect. Dis. 2018.

[HealthMap/ProMED-mail map:
DR Congo: <>]

[See Also:
Ebola update (80): Congo DR (NK) case update
Ebola update (79): Congo DR (NK) case update, response, vacc, support,
Ebola update (78): Congo DR (NK) case update, health protection of
medical teams
Ebola update (77): Congo DR (NK) case update, risk, control, research
Ebola update (76): Congo DR (NK) case update, response
Ebola update (75): Congo DR (NK) cases, WHO, response, perspectives
Ebola update (74): Congo DR (NK) cases, response, WHO, reflections
Ebola update (73): Congo DR (NK) cases, anti-viral, research
Ebola update (72): Congo DR (NK) cases, response, research
Ebola update (71): Congo DR (NK) cases, response, bats
Ebola update (70): Congo DR (NK) cases, recommendations, war, comment
Ebola update (69): Congo DR (NK,IT) cases, Uganda NOT, WHO response
Ebola update (68): Congo DR (NK) WHO, Uganda cases, concerns,
Ebola update (67): Congo DR (NK) cases, response, issues, research
Ebola update (66): Congo DR (NK) cases, response
Ebola update (65): Congo DR (NK) cases, vaccines
Ebola update (64): Congo DR (NK) cases, security, genome
Ebola update (63): Congo DR (NK) cases, vaccine, security, burial,
Ebola update (62): Congo DR (NK) WHO, response, genetics
Ebola update (61): Congo DR (NK) WHO, cases, response
Ebola update (60): DR Congo (NK) case update, response, risk
Ebola update (59): Congo DR (NK) case update, risk, response,
Ebola update (58): Congo DR (NK) outbreak, Ebola Zaire confirmed
Ebola update (57): Congo DR (NK):
Ebola update (56): northeast Congo DR, Ebola-like cases, US negative,
Ebola update (55): Sierra Leone Ebola virus variant, Congo DR cases,
Ebola update (54): Congo DR, cases, therapeutics
Ebola update (53): Congo DR, cases, surveillance, action
Ebola update (52): Congo DR, cases, health workers, W Africa survivor
Ebola update (51): Congo DR, cases, response
Ebola update (50): Congo DR, Japanese response, CIDRAP, WHO, survey
Ebola update (49): Congo DR, suspect deaths comment
Ebola update (48): Congo DR, MSF, susp. deaths, RFI
Ebola update (47): DR Congo, epidemiology, response, Libya RFI
Ebola update (46): Congo DR, cases
Ebola update (45): Congo DR, cases, outbreak, MSF
Ebola update (44): Congo DR, cases, research, course
Ebola update (43): Congo DR, cases, vaccine, persistence, lessons
Ebola update (42): Congo DR, cases, vaccine
Ebola update (41): Congo DR, cases, WHO, contacts
Ebola update (40): Congo DR, cases, WHO, vaccine, treatment,
Ebola update (39): Congo DR, cases, WHO, response, facilities,
treatment, research
Ebola update (38): DR Congo, cases, WHO, Oxfam
Ebola update (37): Congo DR, cases, response
Ebola update (36): Congo DR, cases, threat, assistance
Ebola update (35): Congo DR, cases, response, WHO
Ebola update (34): Congo DR, cases, response, WHO
Ebola update (33): Congo DR, cases, response, WHO, diagnosis
Ebola update (32): Congo DR, cases, preparation, research
Ebola update (31): Congo DR, cases, response, WHO
Ebola update (30): Congo DR, cases, WHO, action
Ebola update (29): Congo DR, cases, MSF, antivirals
Ebola update (28): Congo DR, cases, WHO, response, treatment, funding
Ebola update (27): Congo DR, cases, travel screening, children
Ebola update (26): Congo DR, border controls, bat reservoir
Ebola update (25): Congo DR, case update, intl. travel screening
Ebola update (24): Congo DR, case update, African aid response
Ebola update (23): Congo DR, cases, vacc. campaign targets, vaccine
Ebola update (22): Congo DR, cases, cures, domestic and international
Ebola update (21): Congo DR, update, WHO, vaccination, therapeutics
Ebola update (20): Congo DR, case update, lessons, logistics,
financing, flights
Ebola update (19): Congo DR, case update
Ebola update (18): cases, Uganda NOT, Congo DR vaccination campaign
Ebola update (17): case update, public fears, government responses
Ebola update (16): cases, Congo DR cultural factors, vaccine impl.,
case terminology
Ebola update (15): case update, quarantine breaches, border controls,
Ebola update (14): case update, response, prediction, maps
Ebola update (13): case update, prevention
Ebola update (12): update, USA, response
Ebola update (11): WHO, vaccination, response
Ebola update (10): urban case Congo DR, response, support
Ebola update (09): update, alerts, prevention
Ebola update (08): summary, emergency plan, vaccine, roads
Ebola update (07): Congo DR, nurse, Uganda susp, WHO, border, vaccine
Ebola update (06): Congo DR, susp, RFI, vulnerability, response,
Ebola update (05): Congo DR, outbreak update, vaccine, preparedness,
Ebola update (04): Nigeria, Kenya, Congo DR (ET), WHO
Ebola update (03): Congo DR (ET), WHO
Ebola update (02): Congo DR (ET)]
ProMED-mail makes every effort to verify the reports that
are posted, but the accuracy and completeness of the
information, and of any statements or opinions based
thereon, are not guaranteed. The reader assumes all risks in
using information posted or archived by ProMED-mail. ISID
and its associated service providers shall not be held
responsible for errors or omissions or held liable for any
damages incurred as a result of use or reliance upon posted
or archived material.
Donate to ProMED-mail. Details available at:
Visit ProMED-mail's web site at <>.
Send all items for posting to: (NOT to
an individual moderator). If you do not give your full name
name and affiliation, it may not be posted. You may unsub-
scribe at <>.
For assistance from a human being, send mail to:



Post a Comment