Posted on 10TH APR 2017
tagged Ebola, Worldwide

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

In this update:
- Sierra Leone nosocomial transmission
- Sierra Leone mental health
- Documentary on pandemics
- Therapeutic approach
- Mathematical models
- Liberia
- Vaccination strategies

- Sierra Leone nosocomial transmission
5 Apr 2017: Nosocomial Ebola transmission rate among children 'lower than feared"
[During the Ebola outbreak in Sierra Leone, nosocomial transmission of Ebola virus disease among pediatric patients was only 0.5 per cent, considerably less than originally expected given the varying adherence to quarantine measures among different health facilities. "In the western area of Sierra Leone, patients with suspected [Ebola virus disease (EVD)] were isolated in 'Red Zones' in Ebola holding units (EHUs) whilst awaiting results of EVD tests," Felicity Fitzgerald, MRCPCH, from the UCL Great Ormond Street Institute of Child Health, and colleagues wrote. "Turnaround times for results averaged 48 hours but were frequently longer due to overwhelming demand and system bottlenecks. Concerns were raised that EHUs could act as amplification sites for EVD owing to close proximity between patients and duration of exposure."
According to researchers, if a child was EVD-negative but required additional clinical care, they were required to remain at an EHU, further increasing their risk of exposure to nosocomial infection. To determine whether uninfected children were at heightened risk of acquiring EVD while in EHUs, Fitzgerald and colleagues described prognoses of EVD-negative children and nosocomial infection risk by estimating the rate of readmission with EVD.] ...
Citation. Fitzgerald F, et al. Nosocomial Ebola transmission rate among children 'lower than feared'. Clin Infect Dis. 2017, doi: 10.1093/cid/cix223.]

- Sierra Leone mental health
7 Apr 2017: Sierra Leone grapples with mental health impact of Ebola
[With the recent Ebola [Ebola virus disease (EVD)] crisis, officials in Sierra Leone have seen a rise in mental health concerns. [One individual's] problems are typical. He survived Ebola but lost many family members during the epidemic. He said he turned to alcohol to cope with his grief. He was still receiving care in the Ebola treatment unit when his parents died from the [viral disease]. He didn't get to say goodbye and doesn't even know where they are buried. Those who survived [EVD] have faced stigma. [This individual] was shunned by his community. It was only through support from the Sierra Leone Association of Ebola Survivors that he started to heal. Many of the [EVD] survivors in Sierra Leone are going through similar struggles, said Dr Stephen Sevalie, one of the country's only psychiatrists. According to Dr Stephen Savalie, "Our data have not been analyzed yet, but I can tell you that mental health symptoms are quite high among Ebola survivors."] ...
[According to this report, Ebola survivors are having to deal with loss of eyesight, joint pain and fatigue, and significant mental health issues like depression and anxiety. An estimated 240 000 people in Sierra Leone suffer from depression.]

- Documentary on pandemics
7 Apr 2017: CNN documentary, Unseen Enemy, is a terrifying look at human vulnerability in face of pandemics
[On CNN [on 7 Apr 2017], director Janet Tobias's chilling documentary Unseen Enemy is a sobering wake-up call -- as we learn about the looming potential crises of diseases like Ebola and Zika, as well as things that might seem common, like the flu. The documentary examines the insidious biological chatter of viruses, which can lead to them staying one step ahead of technology with their cunning.]
[It has already aired, but perhaps may be reshown at a future time. Another documentary, Facing Darkness, is described in ProMED-mail's Ebola update (13): news, treatment, research, funding 20170402.4943034 and will play again 10 Apr 2017 at selected theatres in the country. - Mod.LK]

- Therapeutic approach
4 Apr 2017: Topoisomerase II inhibitors induce DNA damage-dependent interferon responses circumventing Ebola virus immune evasion
[Citation. Luthra P, Aguirre S, Yen BC, et al. Topoisomerase II inhibitors induce DNA damage-dependent interferon responses circumventing Ebola virus immune evasion. mBio 2017; 8(2): e00368-17.
Abstract. Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified 5 DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs. These compounds were demonstrated to induce IFN responses in an ATM kinase-dependent manner and to also trigger the DNA-sensing cGAS-STING pathway of IFN induction. These compounds also suppress EBOV replication in vitro and induce IFN in the presence of IFN-antagonist proteins from multiple negative-sense RNA viruses. These findings provide new insights into signaling pathways activated by important chemotherapy drugs and identify a novel therapeutic approach for IFN induction that may be exploited to inhibit RNA virus replication.]

- Mathematical models
9 Apr 2017: Windows of opportunity for Ebola virus infection treatment and vaccination
[Citation. Nguyen VK, Hernandez-Vargas EA. Windows of opportunity for Ebola virus infection, treatment and vaccination. bioRxiv, 2017. http://dx.doi.org/10.1101/125336 (not peer reviewed)
Abstract. Ebola virus (EBOV) infection causes a high death toll, killing a high proportion of EBOV infected patients within 7 days. Comprehensive data on EBOV infection are very fragmented, hampering efforts in developing therapeutics and vaccines against EBOV. Under this circumstance, mathematical models become valuable resources to explore potential controlling strategies. In this paper, we employed experimental data of EBOV-infected nonhuman primates (NHPs) to construct a mathematical framework for determining windows of opportunity for treatment and vaccination. Considering a prophylactic vaccine based on recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (VSV-EBOV), we found that the time window can be subject-specific, but vaccination could be protective if a subject is vaccinated during a period from 1-4 weeks to 4 months before infection. For the case of a therapeutic vaccine based on monoclonal antibodies (mAbs), a single dose might resolve the invasive EBOV replication even it was administrated as late as 4 days after infection. Our mathematical models can be used as building blocks for developing therapeutic and vaccine modalities as well as for evaluating public health intervention strategies in outbreaks. Future laboratory experiments will help to validate and refine the estimates of the windows of opportunity proposed here.]

- Liberia
4 Apr 2017: Liberia expands large-scale Ebola vaccine study
[The Partnership for Research on Ebolavirus [EBOV] in Liberia (PREVAIL) has announced the expansion of the Ebola vaccine study at Redemption Hospital. The study will assess 3 different test vaccine strategies in an effort to find which shows the most promise to prevent or quickly control future Ebola outbreaks. It is a continuation of a previous vaccine effort that began in February 2015 in Liberia, according to a [press release issued Tue 4 Apr 2017].
The start of the expansion of the Ebola vaccine study in Liberia follows a similar effort of the multi-country study, which started in Guinea on 27 Mar 2017. An extension of the study to Sierra Leone is being planned.
Janssen Vaccines and Prevention BV, part of the Janssen Pharmaceutical Companies of Johnson & Johnson; Bavarian Nordic; and Merck, Sharpe & Dohme, Corp (MSD outside USA and Canada) are supplying the test vaccines for the study.]

- Vaccination strategies
6 Apr 2017 West Africa: Ebola: New trial launched in West Africa to evaluate 3 vaccination strategies
[The trial will compare 3 experimental Ebola vaccination strategies with placebo regimens. It will be conducted in 2 stages, the 1st stage to take place in Guinea and Liberia. In Guinea, the trial is being conducted under the sponsorship of Inserm with the support of NIH and in collaboration with the Guinean authorities, and involves a partnership with the non-governmental organization ALIMA (Alliance for International Medical Action). The NIH is sponsoring the trial based in Liberia, under its collaboration with the Liberia Ministry of Health in the Partnership for Research on Ebola virus in Liberia (PREVAIL). Pending confirmation of funding, LSHTM [London School of Hygiene & Tropical Medicine] will sponsor the planned site in Sierra Leone working with the University of Sierra Leone's College of Medicine and Allied Health Sciences, which would conduct the study.
In its 1st stage, the trial will evaluate one of the 3 strategies, a prime-boost vaccination combining 2 different vaccines (one made by Janssen and the other by Bavarian Nordic) compared with a similar placebo regimen. Enrolment into this stage in Guinea and Liberia began on 27 Mar and 3 Apr 2017, respectively. In a 2nd stage, which is expected to start in the 2nd half of 2017, the trial will evaluate all 3 vaccination strategies, including 2 additional strategies involving the Merck Sharp & Dohme, Corp vaccine.] ...


6 Apr 2017 West Africa: Large trial launches of different Ebola vaccine strategies
[An international consortium is launching a large trial in West Africa to test different Ebola vaccines and strategies, a step that could shed light on how quickly a strong immune response kicks in, how long the response lasts, and the safety profile of the vaccine candidates. According to a statement today [6 Apr 2017] from the National Institutes of Health (NIH), the group is called PREVAC (the Partnership for Research on Ebola Vaccination). It includes the NIH, the French National Institute of Health and Medical Research (Inserm), the London School of Hygiene and Tropical Medicine [LSHTM], and health officials in Guinea and Liberia.
The main goal of PREVAC phase 2 trials, which will enroll more than 5000 adults and children in Guinea and Liberia, is to identify the most promising regimens for preventing and controlling future outbreaks. An additional study site is planned for Sierra Leone. The groups will explore the safety of 3 vaccine strategies and if they trigger an immune response, how long the response lasts, and how the vaccines work in different groups, such as children, for whom there is only limited information.
Participants will be followed for at least 12 months, and an independent safety board will closely monitor safety and immune response throughout the trial. Children ages 12-17 will be immunized before younger children are, and the safety board will evaluate those data before determining if it is safe to immunize children ages 5-11. If no safety signals are seen with the 2nd group, then kids ages 1-4 will be vaccinated.] ...

[compiled by: Celeste Whitlow ]

communicated by:

[HealthMap/ProMED-mail maps:
Liberia http://healthmap.org/promed/p/54
Guinea http://healthmap.org/promed/p/45
Sierra Leone http://healthmap.org/promed/p/46
- Mod.LK]

See Also
Ebola update (13): news, treatment, research, funding 20170402.4943034
Ebola update (12): news, research, vaccine 20170326.4927435
Ebola update (11): news, vaccine, research 20170312.4896304
Ebola update (10): news, research 20170305.4881172
Ebola update (09): news, research, funding 20170226.4866142
Ebola update (08): news, research, vaccine 20170219.4850524
Ebola update (07): research, economy 20170213.4836546
Ebola update (06): research, treatment, funding 20170206.4819835
Ebola update (05): news, vaccine, funding, documentary films 20170129.4801064
Ebola update (04): research 20170123.4786222
Ebola update (03): news, research 20170115.4767977
Ebola update (02): news, research, vaccine, comment 20170108.4750411
Ebola update (01): News, research, vaccine 20170103.4738060
Ebola update (72): vaccine, research, NGO, media 20161226.4724859
Ebola update (71): research, economy 20161218.4706276
Ebola update (70): news, research, economy, funding 20161211.4690740
Ebola update (69): news, NGO, research, economy, funding, vaccine 20161204.4675615
Ebola update (68): news, economy 20161127.4657148
Ebola update (67): news, research, funding 20161120.4642402
Ebola update (66): news, research, funding, economy 20161115.4629793
Ebola update (65): news, research, commentary, economy, funding, vaccine 20161106.4609611
Ebola update (64): news, research 20161030.4595759
Ebola update (63): news, research 20161023.4579436
Ebola update (62): news, research, treatment, funding 20161017.4564066
Ebola update (61): news, funding, economy 20161009.4547627
Ebola update (60): news, research, economy 20161002.4531285
Ebola update (59): news, research, funding 20160925.4514591
Ebola update (58): news, research, funding, vaccine 20160918.4497393
Ebola update (57): news, research, funding 20160911.4481043
Ebola update (56): news, vaccine, research 20160904.4465145
Ebola update (55): research, funding 20160828.4446844
Ebola update (54): rapid test recall, nurse, research 20160821.4431433
Ebola update (53): Guinea, research 20160814.4415032
Ebola update (52): funding, research 20160808.4400521
Ebola update (51): funding, research, miscellaneous 20160731.4383179
Ebola update (50): Liberia, Sierra Leone, research 20160724.4366266
Ebola update (49): Sierra Leone, research, history 20160717.4350351
Ebola update (48): CDC, research, funding, economy 20160710.4336146
Ebola update (47): Liberia, US preparedness, funding, research 20160703.4323924