Global & Disaster Medicine

Archive for the ‘MERS-CoV’ Category

WHO: Prioritizing Emerging Infectious Diseases in Need of Research and Development

The World Health Organization R&D Blueprint aims to accelerate the availability of medical technologies during epidemics by focusing on a list of prioritized emerging diseases for which medical countermeasures are insufficient or nonexistent. The prioritization process has 3 components: a Delphi process to narrow down a list of potential priority diseases, a multicriteria decision analysis to rank the short list of diseases, and a final Delphi round to arrive at a final list of 10 diseases.

A group of international experts applied this process in January 2017, resulting in a list of 10 priority diseases. The robustness of the list was tested by performing a sensitivity analysis. The new process corrected major shortcomings in the pre–R&D Blueprint approach to disease prioritization and increased confidence in the results.

Multicriteria scores of diseases considered in the 2017 prioritization exercise for the development of the World Health Organization R&D Blueprint to prioritize emerging infectious diseases in need of research and development. A) Disease final ranking using the geometric average of the comparison matrices. B) Disease final ranking using the arithmetic average of the raw data. Error bars correspond to SD, indicating disagreement among experts. C) Disease final ranking using the SMART Vaccines

Multicriteria scores of diseases considered in the 2017 prioritization exercise for the development of the World Health Organization R&D Blueprint to prioritize emerging infectious diseases in need of research and development. A) Disease final ranking using the geometric average of the comparison matrices. B) Disease final ranking using the arithmetic average of the raw data. Error bars correspond to SD, indicating disagreement among experts. C) Disease final ranking using the SMART Vaccines prioritization tool (56). P1, Ebola virus infection; P2, Marburg virus infection; P3, Middle East Respiratory Syndrome coronavirus infection; P4, severe acute respiratory syndrome; P5, Lassa virus infection; P6, Nipah virus infection; P7, Rift Valley fever; P8, Zika virus infection; P9, Crimean-Congo hemorrhagic fever; P10, severe fever with thrombocytopenia syndrome; P11, South American hemorrhagic fever; P12, plague; P13, hantavirus infection.

Si Mehand M, Millett P, Al-Shorbaji F, Roth C, Kieny MP, Murgue B. World Health Organization methodology to prioritize emerging infectious diseases in need of research and development. Emerg Infect Dis. 2018 Sep [date cited]. https://doi.org/10.3201/eid2409.171427


WHO, August 2018: A snapshot of MERS-CoV cases over the past year and an assessment of the global risk

WHO

Between 2012 and 30 June 2018, 2229 laboratory confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection were reported to WHO, 83% of whom were reported by the Kingdom of Saudi Arabia (Figure 1). In total, cases have been reported from 27 countries in the Middle East, North Africa, Europe, the United States of America, and Asia (Table 1). Males above the age of 60 with an underlying medical conditions, such as diabetes, hypertension and renal failure, are at a higher risk of severe disease, including death. To date, 791 individuals have died (crude CFR 35.5%).

Image result for middle east respiratory syndrome coronavirus
Since the last global update published on 21 July 2017, 189 laboratory-confirmed cases of MERS-CoV from four countries were reported to WHO (182 from Saudi Arabia, three from Oman, three from the United Arab Emirates, and one from Malaysia), of whom 60 (31.7%) have died. Among these cases, 75.5% were male and the median age was 54 years old (IQR 40-65.5; range 10-93 years old). The median age is similar to the median age of all cases reported to WHO since 2012 (52 years old, IQR 37-65).
At the time of writing, 19 of 189 (10.0%) patients were reported as asymptomatic or having mild. At least one underlying condition was reported in 137 cases (72%) since the last update, including chronic renal failure, heart disease, diabetes mellitus, and hypertension.
Overall, the epidemiology, transmission patterns, clinical presentation of MERS patients and viral characteristics reported since the last update are consistent with past patterns described in previous WHO risk assessments: MERS-CoV is a zoonotic virus that has repeatedly entered the human population via direct or indirect contact with infected dromedary camels in the Arabian Peninsula. Limited, non-sustained human-to-human transmission mainly in health care settings continues to occur, primarily in Saudi Arabia. The risk of exported cases to areas outside of the Middle East due to travel remains significant.
While there have been significant improvements in surveillance for MERS, especially in the Middle East, and in reacting to suspect clusters, early identification in the community and in health care systems, compliance with the infection prevention and control measures and contact follow up remain major challenges for MERS outbreak prevention and control.

The continued importance of MERS-CoV in health care settings
Since the last global update of 21 July 2017, 17 of the 45 secondary cases reported to WHO were associated with transmission in a health care facility. These cases included health care workers (12 cases), patients sharing rooms/wards with MERS patients, or family visitors.
Though not unexpected, these transmission events continue to be deeply concerning, given that MERS-CoV is still a relatively rare disease about which medical personnel in health care facilities have low awareness. Globally, awareness for MERS is low and, because symptoms of MERS-CoV infection are non-specific, initial cases are sometimes easily missed. With improved compliance in infection prevention and control, namely adherence to the standard precautions at all times, human-to-human transmission in health care facilities can be reduced and possibly eliminated with additional use of transmissionbased precautions.
Since the last update of July 2017, several MERS clusters were reported, including the following:
 In July-August 2017, two clusters of MERS were reported from AL-Jawf Region, Saudi Arabia. These clusters were not epidemiologically linked.
 The first health care associated cluster included 13 cases, 2 who died. Among the 12 secondary cases, 10 were asymptomatic, including 8 health care workers.
 The second cluster included 7 cases, 6 of whom were household contacts. Of the 6 secondary cases, five were asymptomatic. None of the cases identified in this cluster were health care workers and there were no fatalities.
 In January-February 2018, a health care associated cluster was reported in Hafr Al Batin Region, Saudi Arabia. The cluster included 4 cases and 1 death, including 3 asymptomatic health care workers identified through contact tracing.
 In February-March 2018, a health care associated cluster of 6 cases occurred in a hospital in Riyadh, Saudi Arabia. Of the 6 cases, none were health care workers and three were fatal.
 In March 2018, there was a household cluster reported from Jeddah, Saudi Arabia. This cluster included 3 individuals, all of whom survived.

In May-June 2018, a household cluster was reported from the Najran Region, Saudi Arabia. The index case reported regular contact with dromedary camels. Ten family contacts and one health care worker were identified as secondary cases. Out of the 12 cases identified in this cluster, none were fatal.
Since 2015, the increase in the number of asymptomatic contacts identified in health care settings is due to a policy change by the Ministry of Health of the Kingdom of Saudi Arabia, in which all high-risk contacts are tested for MERSCoV regardless of the development of symptoms. This comprehensive contact identification, follow-up, testing and isolation of positive cases continues into 2018.
Drivers of transmission and the exact modes of transmission in health care settings still are unclear and are currently the focus of collaborative scientific research. From observational studies, transmission in health care settings is believed to have occurred before adequate infection prevention and control procedures were applied and cases were isolated. Investigations at the time of the outbreaks indicate that aerosolizing procedures conducted in crowded emergency departments or medical wards with sub-optimal infection prevention and control measures in place resulted in human-to-human transmission and environmental contamination.
Community-acquired cases and reported links to dromedary camels
Since the last update, 56 human cases are believed to have been infected in the community. Of these 56 reported cases, 37 (66.1%) reported direct or indirect contact with dromedaries in Saudi Arabia (33 cases), Oman (2 cases), the United Arab Emirates (one case) and Malaysia (one case; contact with dromedary was in Saudi Arabia).
Improvement in multi-sectoral investigation of community-acquired cases is evident, including testing of dromedary animals/herds in the vicinity of community-acquired laboratory-confirmed cases and follow-up of human contacts of laboratory-confirmed cases. The Ministries of Health in affected countries notify the Ministries of Agriculture when human cases report a link with animals. Investigations in animals are carried out by officials from the Ministries of Agriculture and results, if positive for MERS-CoV, are reported to OIE.
Exported cases identified outside the Middle East Since the last update, one case was reported outside of the Middle East. The case, a 55 year old, had recently returned from Jeddah to Malaysia in December 2017. The patient was treated and recovered, contacts were identified and followed and no further cases were identified by authorities in Malaysia.

Summary – information available from 2012 to date
Thus far, no sustained human-to-human transmission has occurred anywhere in the world, however limited non-sustained human-to-human transmission in health care facilities remains a prominent feature of this virus. WHO continues to work with health authorities in the affected countries to prevent and minimize health care-associated cases. WHO understands that health authorities in affected countries, especially those in the most affected countries, are aggressively investigating cases and contacts, including testing for MERS-CoV among asymptomatic contacts, and applying mitigation measures to stop human-to-human transmission in health care settings. These efforts are proving successful in mitigating the size of outbreaks.

Of all laboratory-confirmed cases reported to date (n=2228), the median age is 52 (IQR 37-65) and 67.2% are male.
At the time of reporting, 21% of the 2228 cases were reported to have no or mild symptoms, while 46% had severe disease or died. Overall, 18.6% of the cases reported to date are health care workers.

Since 2012, 27 countries have reported cases of MERS-CoV infection. In the Middle East: Bahrain, Egypt, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, the United Arab Emirates and Yemen; in Africa: Algeria and Tunisia; in Europe: Austria, France, Germany, Greece, Italy, the Netherlands, Turkey and the United Kingdom; in Asia: China, the Republic of Korea, Malaysia, the Philippines and Thailand; and in the Americas: the United States of America (Table 1).
The majority of cases (approximately 83%) have been reported from Saudi Arabia (Figure 1).
Populations in close contact with dromedaries (e.g. farmers, abattoir workers, shepherds, dromedary owners) and health care workers caring for MERS-CoV patients are believed to be at higher risk of infection. Healthy adults infected with MERS-CoV tend to have mild subclinical or asymptomatic infections. To date, limited human-to-human transmission has occurred between close contacts of confirmed cases in household settings. More efficient human-to-human transmission occurs in health care settings due to inadequate and/or incomplete compliance with the infection prevention and control measures and delay in triage or isolation of suspected MERS patients. Health care-associated transmission has been documented in several countries between 2012-2016, including Saudi Arabia, Jordan, the United Arab Emirates, France, the United Kingdom, and the Republic of Korea with varying outbreak sizes (2-180 reported cases per outbreak). The largest outbreak outside of the Middle East occurred in the Republic of Korea resulting in 186 cases (including one case who travelled to China) and 39 deaths. Overall, the reproduction number (R0) of MERS-CoV is <1 with significant heterogeneity in specific contexts. Specifically, outbreaks in health care settings can have R>1, but they can be brought under control (R<1) with proper application of infection prevention and control measures and early isolation of subsequent cases.


Saudi Arabian Ministry of Health (MOH): 30 new MERS-CoV cases

Saudi MOH

National Portal «Saudi»

(Epidemic Week)​ – Starting Date
Events​
​(32) – 05/08/2018 MERS-CoV: 1 case​
​​(31) – 29/07/2018 MERS-CoV: 2 case​​​s
​​​(30) – 22/07/2018 MERS-CoV: 1 case​​
​​(29) – 15/07/2018 MERS-CoV: 1 case​
(28) – 08/07/2018​ MERS-CoV: 4 cases​
(27)​ – 01/07/2018 MERS-CoV: 1 case​
(​26) – 24/06/2018​ MERS-CoV: 1 case​
​(25) – 17/06/2018 MERS-CoV: 1 case​​
(24) – 10/06/2018​ MERS-CoV: 2 cases​​
​(23) – 03/06/2018 MERS-CoV: 3 case​s
​(22) – 07/05/2018 MERS-CoV: 11 cases​
​(21) – 20/05/2018​ MERS-CoV: 2 case​​​s


At the end of June 2018, a total of 2229 laboratory-confirmed cases of Middle East respiratory syndrome (MERS), including 791 associated deaths (case–fatality rate: 35.5%) were reported globally

WHO

Update for June 2018

  • At the end of June 2018, a total of 2229 laboratory-confirmed cases of Middle East respiratory syndrome (MERS), including 791 associated deaths (case–fatality rate: 35.5%) were reported globally; the majority of these cases were reported from Saudi Arabia (1853 cases, including 717 related deaths with a case–fatality rate of 38.7%).
  • During the month of June, a total of 4 laboratory-confirmed cases of MERS were reported in Saudi Arabia including 1 associated death (case-fatality rate: 25%). No healthcare associated transmission or hospital outbreak was reported during this month.
  • The demographic and epidemiological characteristics of reported cases, when compared during the same corresponding period of 2013 to 2018, do not show any significant difference or change. Owing to improved infection prevention and control practices in hospitals, the number of hospital-acquired cases of MERS has dropped significantly since 2015.
  • The age group 50–59 years continues to be at highest risk for acquiring infection of primary cases. The age group 30–39 years is most at risk for secondary cases. The number of deaths is higher in the age group 50–59 years for primary cases and 70–79 years for secondary cases.

Clusters of MERS-CoV in Saudi Arabia

WHO

Between 12 January through 31 May 2018, the National IHR Focal Point of The Kingdom of Saudi Arabia reported 75 laboratory confirmed cases of Middle East respiratory syndrome coronavirus (MERS_CoV), including twenty-three (23) deaths.

Details of the cases

Among these 75 cases, 21 cases were part of four distinct clusters (2 health care and 2 household clusters). The details of these clusters are described below, followed by a table listing all 75 laboratory confirmed cases reported to WHO during this time period:

  • Cluster 1: From 2 through 4 February, a private hospital in Hafer Albatin Region reported a cluster of three (3) health care workers in addition to the suspected index case (four [4] cases in total).
  • Cluster 2: From 25 February through 7 March, a hospital in Riyadh reported six (6) cases, including the suspected index. No health care workers were infected.
  • Cluster 3: From 8 through 24 March, a household cluster of 3 cases (index case and 2 secondary cases) was reported in Jeddah. No health care workers were infected.
  • Cluster 4: From 23 through 31 May, a household cluster was reported from Najran region with eight cases including the suspected index case. This cluster is still under investigation at the time of writing. As of 31 May, no health care workers have been infected and the source of infection is believed to be camels at the initial patient’s home.

As of 31 May, the total global number of laboratory-confirmed cases of MERS-CoV reported since 2012 is 2,220, including 1,844 cases that have been reported from the Kingdom of Saudi Arabia. Among these cases, 790 MERS-CoV associated deaths have occurred since September 2012.

The global number reflects the total number of laboratory-confirmed cases reported to WHO under IHR to date. The total number of deaths includes the deaths that WHO is aware of to date through follow-up with affected member states.

WHO risk assessment

Infection with MERS-CoV can cause severe disease resulting in high mortality. Humans are infected with MERS-CoV from direct or indirect contact with dromedary camels. MERS-CoV has demonstrated the ability to transmit between humans. So far, the observed non-sustained human-to-human transmission has occurred mainly in health care settings.

The notification of additional cases does not change the overall risk assessment. WHO expects that additional cases of MERS-CoV infection will be reported from the Middle East, and that cases will continue to be exported to other countries by individuals who might acquire the infection after exposure to animals or animal products (for example, following contact with dromedaries) or human source (for example, in a health care setting). WHO continues to monitor the epidemiological situation and conducts risk assessment based on the latest available information.

WHO advice

Based on the current situation and available information, WHO encourages all Member States to continue their surveillance for acute respiratory infections and to carefully review any unusual patterns.

Infection prevention and control measures are critical to prevent the possible spread of MERS-CoV in health care facilities. It is not always possible to identify patients with MERS-CoV early because, like other respiratory infections, the early symptoms of MERS-CoV are non-specific. Therefore, health care workers should always apply standard precautions consistently with all patients, regardless of their diagnosis. Droplet precautions should be added to the standard precautions when providing care to patients with symptoms of acute respiratory infection; contact precautions and eye protection should be added when caring for probable or confirmed cases of MERS-CoV infection; airborne precautions should be applied when performing aerosol generating procedures.

Community and household awareness of MERS and MERS prevention measures in the home may reduce household transmission and prevent community clusters.

Until more is understood about MERS-CoV, people with diabetes, renal failure, chronic lung disease, and immunocompromised persons are considered to be at high risk of severe disease from MERS-CoV infection. Therefore, in addition to avoiding close contact with suspected or confirmed human cases of the disease, people with these conditions should avoid close contact with animals, particularly camels, when visiting farms, markets, or barn areas where the virus is known to be or potentially circulating. General hygiene measures, such as regular hand washing before and after touching animals and avoiding contact with sick animals, should be adhered to.

Food hygiene practices should be observed. People should avoid drinking raw camel milk or camel urine, or eating meat that has not been properly cooked.

WHO does not advise special screening at points of entry with regard to this event nor does it currently recommend the application of any travel or trade restrictions.


Thailand: A suspected MERS patient from a Middle Eastern country has been quarantined at the Bamrasnaradura Infectious Diseases Institute in Nonthaburi

The Nation

 


An early-stage clinical trial to test the safety of two human monoclonal antibodies (mAbs) designed to treat people infected with MERS-CoV.

NIAID

Friday, May 18, 2018

Experimental MERS treatments enter clinical trial

NIH-sponsored trial to test two human monoclonal antibodies.

Enrollment has begun in an early-stage clinical trial testing the safety of two human monoclonal antibodies (mAbs) designed to treat people infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and is funded in part by the Biomedical Advanced Research and Development Authority, part of the Office of the Assistant Secretary for Preparedness and Response, Department Health and Human Services.

The first recognized case of MERS was reported in Jordan in 2012. Since then, MERS-CoV has spread to 27 countries. As of May, 2,206 laboratory-confirmed cases have been reported to the World Health Organization. Those cases include 787 deaths, a fatality rate of about 36 percent.

“Currently, we lack specific treatments for MERS,” said NIAID Director Anthony S. Fauci, M.D. “Having targeted therapeutics available to treat this unpredictable and frequently fatal respiratory disease would help us reduce MERS-associated deaths and control future outbreaks.”

The mAbs, REGN3048 and REGN3051, were discovered and developed by scientists at the biotechnology company Regeneron, headquartered in Tarrytown, New York.

Subsequently, researchers at Regeneron and the University of Maryland School of Medicine demonstrated the ability of the antibodies to neutralize MERS-CoV in a mouse model of MERS.

The new NIAID trial is the first to test these mAbs in people.

The study will enroll 48 healthy adults between the ages of 18 and 45 years at WCCT Global, a clinic in Cypress, California. Participants will be divided into six groups of eight, with two people in each group receiving an inactive placebo and the remaining six receiving both experimental mAbs delivered intravenously. The study is blinded, meaning neither the study staff nor the participants will know whether a placebo or the mAb is being administered. Participants in the initial cohort will receive the lowest dosage of the experimental antibodies, 1.5 milligrams (mgs) of each mAb per kilogram (kg) of the volunteer’s weight. Participants in successive cohorts will receive increasing dosages until the highest dosage (75 mg/kg of each mAb) is reached in the sixth group.

Decisions to continue the trial and to administer the escalating doses of mAbs will be made by an independent safety review committee (SRC) whose members will have access to safety and tolerability data throughout the trial. The SRC will meet at regularly scheduled intervals to determine if any pre-established criteria have been met that would require the trial to be halted. If there are no safety concerns, the trial will proceed to enroll participants into the next higher dosage cohort. The study is expected to be completed by June 2019.

Additional information about the trial is available at clinicaltrials.gov, using the identifier NCT03301090. The trial is funded through contract HHSN272201500005I.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.


WHO: List of Blueprint priority diseases (i.e. diseases and pathogens to prioritize for research and development in public health emergency contexts)

WHO

2018 annual review of the Blueprint list of priority diseases

For the purposes of the R&D Blueprint, WHO has developed a special tool for determining which diseases and pathogens to prioritize for research and development in public health emergency contexts. This tool seeks to identify those diseases that pose a public health risk because of their epidemic potential and for which there are no, or insufficient, countermeasures. The diseases identified through this process are the focus of the work of R& D Blueprint. This is not an exhaustive list, nor does it indicate the most likely causes of the next epidemic.

The first list of prioritized diseases was released in December 2015.

Using a published prioritization methodology, the list was first reviewed in January 2017.

February 2018 – Second annual review

The second annual review occurred 6-7 February, 2018. Experts consider that given their potential to cause a public health emergency and the absence of efficacious drugs and/or vaccines, there is an urgent need for accelerated research and development for*:

  • Crimean-Congo haemorrhagic fever (CCHF)
  • Ebola virus disease and Marburg virus disease
  • Lassa fever
  • Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS)
  • Nipah and henipaviral diseases
  • Rift Valley fever (RVF)
  • Zika
  • Disease X

Disease X represents the knowledge that a serious international epidemic could be caused by a pathogen currently unknown to cause human disease, and so the R&D Blueprint explicitly seeks to enable cross-cutting R&D preparedness that is also relevant for an unknown “Disease X” as far as possible.

A number of additional diseases were discussed and considered for inclusion in the priority list, including: Arenaviral hemorrhagic fevers other than Lassa Fever; Chikungunya; highly pathogenic coronaviral diseases other than MERS and SARS; emergent non-polio enteroviruses (including EV71, D68); and Severe Fever with Thrombocytopenia Syndrome (SFTS).

These diseases pose major public health risks and further research and development is needed, including surveillance and diagnostics. They should be watched carefully and considered again at the next annual review. Efforts in the interim to understand and mitigate them are encouraged.

Although not included on the list of diseases to be considered at the meeting, monkeypox and leptospirosis were discussed and experts stressed the risks they pose to public health. There was agreement on the need for: rapid evaluation of available potential countermeasures; the establishment of more comprehensive surveillance and diagnostics; and accelerated research and development and public health action.

Several diseases were determined to be outside of the current scope of the Blueprint: dengue, yellow fever, HIV/AIDs, tuberculosis, malaria, influenza causing severe human disease, smallpox, cholera, leishmaniasis, West Nile Virus and plague. These diseases continue to pose major public health problems and further research and development is needed through existing major disease control initiatives, extensive R&D pipelines, existing funding streams, or established regulatory pathways for improved interventions. In particular, experts recognized the need for improved diagnostics and vaccines for pneumonic plague and additional support for more effective therapeutics against leishmaniasis.

The experts also noted that:

  • For many of the diseases discussed, as well as many other diseases with the potential to cause a public health emergency, there is a need for better diagnostics.
  • Existing drugs and vaccines need further improvement for several of the diseases considered but not included in the priority list.
  • Any type of pathogen could be prioritised under the Blueprint, not only viruses.
  • Necessary research includes basic/fundamental and characterization research as well as epidemiological, entomological or multidisciplinary studies, or further elucidation of transmission routes, as well as social science research.
  • There is a need to assess the value, where possible, of developing countermeasures for multiple diseases or for families of pathogens.

The impact of environmental issues on diseases with the potential to cause public health emergencies was discussed. This may need to be considered as part of future reviews.

The importance of the diseases discussed was considered for special populations, such as refugees, internally displaced populations, and victims of disasters.

The value of a One Health approach was stressed, including a parallel prioritization processes for animal health. Such an effort would support research and development to prevent and control animal diseases minimising spill-over and enhancing food security. The possible utility of animal vaccines for preventing public health emergencies was also noted.

Also there are concerted efforts to address anti-microbial resistance through specific international initiatives. The possibility was not excluded that, in the future, a resistant pathogen might emerge and appropriately be prioritized.

 

*The order of diseases on this list does not denote any ranking of priority.

 


Saudi Arabia’s MERS totals since 2012 come to 1,836, including 744 deaths.

28-4-2018-01.jpg


Saudi Arabian Ministry of Health: 1 new case of MERS-CoV related to camel contact.

22-4-2018-01.jpg


Categories

Recent Posts

Archives

Admin