BOA1

4 Jul 2015

#Antigenic #maps of #influenza A/ #H3N2 #virus produced with #human antisera obtained after primary #infection (J Infect Dis., abstract, edited)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Antigenic maps of influenza A/H3N2 virus produced with human antisera obtained after primary infection [      ]

Judith M. Fonville 1,2,3,*, Pieter L. A. Fraaij 3,4, Gerrie de Mutsert 3, Samuel H. Wilks 1,2, Ruud van Beek 3, Ron A. M. Fouchier 3 and Guus F. Rimmelzwaan 3

Author Affiliations: 1Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom 2WHO Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge, United Kingdom 3Department of Viroscience, Erasmus MC, 3015 CE Rotterdam, The Netherlands 4Department of Pediatrics, Erasmus MC-Sophia, 3015 CN Rotterdam, The Netherlands

*Corresponding author contact information: Dr. Judith M Fonville; Center for Pathogen Evolution, Department of Zoology, University of Cambridge, CB2 3EJ, Cambridge, United Kingdom. Fax: +44 1223336676; telephone +44 1223330933+44 1223330933; email: jmf77@cam.ac.uk

 

Abstract

Background.

Antigenic characterization of influenza viruses is typically based on hemagglutination inhibition (HI) assay data of viral isolates tested against strain-specific post-infection ferret antisera. Here, similar virus characterizations were performed using first-infection human rather than ferret serology data.

Methods.

We screened sera collected between 1995 and 2011 from children between 9 and 24 months of age for influenza virus antibodies, performed HI tests for the positive sera against 24 influenza viruses isolated between 1989 and 2011, and measured HI titers of 24 A/H3N2 ferret sera against the same panel of viruses.

Results.

Of the 17 positive human sera, 6 were high-responders, showing HI patterns that would be expected from primary infection antisera, while 11 sera had lower, more dispersed patterns of reactivity that are not easily explained. The antigenic map based on the high-responder human HI data was similar to the results using ferret data.

Conclusions.

Although the overall structure of the ferret and human antigenic maps is similar, local differences in virus positions indicate that the human and ferret immune system might see antigenic properties of viruses differently. Further studies are needed to establish to what degree of detail ferret data provide equivalent patterns to human serological reactivity.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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#HK, #Update on latest #MERS #situation in #Korea and #KSA (CHP, July 4 2015)

[Source: Centre for Health Protection, Hong Kong PRC SAR, full page: (LINK).]

Update on latest MERS situation in Korea and KSA [      ]

The Centre for Health Protection (CHP) of the Department of Health is today (July 4) closely monitoring an additional case of Middle East Respiratory Syndrome (MERS) reported by Korea and six additional cases reported to the World Health Organization (WHO) by the Kingdom of Saudi Arabia (KSA).

According to the preliminary information of the health authority of Korea, the patient is a doctor of Samsung Medical Centre and the source of infection is under investigation.

To date, 184 MERS cases have been confirmed by Korea (including 33 deaths). In addition, another case was exported from Korea to Mainland China.

Meanwhile, according to the WHO, the six cases in KSA involve three men and three women aged 40 to 65 who have underlying illnesses. They had onset of symptoms between May 30 and June 24. A patient is a family relative of a confirmed case, and a patient is a healthcare worker while two other patients had visited healthcare facilities with MERS outbreaks. The remaining two patients' history of exposure to known risk factors in the 14 days prior to the onset of symptoms is ongoing. All patients are currently hospitalised for treatment. In addition, a previously confirmed patient died.

To date, in addition to the 184 laboratory-confirmed MERS cases in Korea and one exported from Korea to Mainland China, 1 181 cases have been reported to the WHO, including at least 454 deaths.

Of note, 1 155 cases globally were confirmed in nine Middle East countries, including 1 037 in the KSA, 76 in the United Arab Emirates, 13 in Qatar, 12 in Jordan, six each in Iran and Oman, three in Kuwait, and one each in Lebanon and Yemen.

"We again urge the public to pay special attention to safety during travel, taking due consideration of health risks of the places of visit," a spokesman for the CHP said.

"In view of the latest situation in Korea, the public should avoid unnecessary travel to Korea, in particular those with chronic illnesses. Travellers in Korea and the Middle East should avoid unnecessary visits to healthcare facilities. In addition, travellers to the Middle East should avoid going to farms, barns or markets with camels, and avoid contact with sick persons and animals, especially camels, birds or poultry," the spokesman advised.

The CHP will maintain close communication with the WHO and the relevant health authorities. Members of the public and the healthcare sector should heighten vigilance and stay alert to the latest situation.

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#Recurrence of #Ebola #transmission in #Liberia (@WHO, July 4 2015)

[Source: World Health Organization, full page: (LINK).]

Recurrence of Ebola transmission in Liberia [      ]

Ebola situation assessment / 3 July 2015

On 9 May 2015, Liberia marked an important milestone in the management of their Ebola outbreak. On that day, the country was declared free of Ebola transmission because no new cases had been identified for 42 days after the safe burial of the last person confirmed to have been infected with Ebola virus disease.

Although transmission of the virus had ceased, Liberia remained at high risk of a recurrence of Ebola due to ongoing transmission in neighbouring Guinea and Sierra Leone. For this reason Liberia then entered a 90-day period of vigilance involving testing anyone with features of Ebola virus disease and testing post-mortem swabs for Ebola virus.

On Monday, 29 June 2015, midway through that 90 day period, a post-mortem swab taken from a seventeen-year-old male who died on June 28 from a febrile illness managed as malaria tested positive for Ebola virus disease. In accordance with standard practice for the current period of heightened vigilance throughout Liberia, a Safe and Dignified Burial team buried the young man’s body safely on the same day that he died. That team also took the swab that later tested positive for Ebola virus.

Every week, Liberia has been testing hundreds of such swabs and blood samples taken from anyone with symptoms that may be caused by Ebola virus disease. When this first sample proved positive, the Liberian ‘incident management system’ immediately activated a team to carry out a detailed investigation in the area, and began tracing people who had been in contact with the young man while he was symptomatic.

The investigation revealed that close to 200 people had been in contact with the young man while he had symptoms of Ebola and these people are now being closely monitored. Two of those people have developed symptoms and have tested positive for Ebola virus. Both of these people are being treated in an Ebola treatment centre that had been kept at the ready as part of the 90-day heightened vigilance period.

People in the community where the young man died - Nedowein, Margibi - are now very involved in ensuring that all people, who have been in contact with others infected with Ebola, do not leave the area and are monitored closely. Where households are quarantined, food and supplies - such as bedding and tents to ease household crowding - are being provided by UN agencies, including UNICEF and the World Food Programme.

The United Nations system and nongovernmental organizations are supporting the Government with necessary supplies such as protective equipment, alcohol-based hand sprays, temperature monitors, and staff already based in Liberia. WHO is sending additional experts in epidemiology and social mobilization to ensure the community is fully involved in identifying contacts and preventing any further disease spread.

The Government has informed the people of Liberia about what is happening, and has reminded them of the key steps needed to keep themselves and their communities safe.

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#Influenza #update - 29 June 2015, - Update no. 240, based on data up to 14 June 2015 (@WHO, July 4 2015, edited)

[Source: World Health Organization, full page: (LINK). Edited.]

Influenza update - 29 June 2015, - Update number 240, based on data up to 14 June 2015 [      ]

--> Open map in new window jpg, 457kb <--

 

Summary

  • Globally, influenza activity has decreased from its peak of influenza activity in early 2015 to low levels in the Northern Hemisphere while there were increases in activity in the Southern Hemisphere.
    • In North America, influenza activity was at low, inter-seasonal levels. Influenza type B continued to be the predominant strain in circulation in recent weeks.
    • In Europe, influenza activity remained low with influenza B predominant in recent weeks
    • In northern Africa, influenza activity remained at low levels in most countries with influenza A activity being predominant throughout the whole season.
    • In western Asia, most countries reported decreasing influenza activity remaining at low levels in recent weeks.
    • In the temperate countries of Asia, influenza activity remained at low levels.
    • In tropical countries of the Americas, low inter-seasonal levels of influenza activity were reported in most countries except Peru where low levels of influenza type A circulation was detected.
    • In tropical Asia, increased influenza activity was reported from Hong Kong(Special Administrative Region, China), Singapore, southern China, Viet Nam, and Sri Lanka with influenza type A viruses predominating in recent weeks.
    • In the Southern Hemisphere, influenza activity increased in most of the regions but remained at low levels. However, South Africa reported high influenza activity with influenza A(H1N1)pdm09 and A(H3N2) co-circulation in recent weeks.

National Influenza Centres (NICs) and other national influenza laboratories from 53 countries, areas or territories reported data to FluNet for the time period from 31 May 2015 to 13 June 2015 (data as of 25/06/2015 12:05 UTC).

The WHO GISRS laboratories tested more than 23 577 specimens during that time period.

1620 were positive for influenza viruses, of which 1117 (69%) were typed as influenza A and 503 (31%) as influenza B.

Of the sub-typed influenza A viruses, 172 (22.8%) were influenza A(H1N1)pdm09 and 582 (77.2%) were influenza A(H3N2). Of the characterized B viruses, 69 (83.1%) belonged to the B-Yamagata lineage and 14 (16.9%) to the B-Victoria lineage.

 

Detailed influenza update

Influenza surveillance outputs

Seasonal update

For regional updates on influenza see the following links

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#Investigation of #cases of #human #infection with Middle East respiratory syndrome #coronavirus (#MERS - CoV) (@WHO, July 4 2015, edited)

[Source: World Health Organization, full PDF file: (LINK). Edited.]

Investigation of cases of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV) - Interim guidance - Updated 3 July 2015 [      ]

WHO/MERS/SUR/15.2

© World Health Organization 2015

All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders@who.int).

Requests for permission to reproduce or translate WHO publications –whether for sale or for non-commercial distribution– should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html).

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement.

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.

All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use.

 

1. Introduction

Coronaviruses are a large family of viruses that can cause a range of illnesses in humans, from the common cold to severe acute respiratory syndrome (SARS). These viruses also cause disease in a wide variety of animal species.

In late 2012, a novel coronavirus that had not previously been seen in humans was identified for the first time in a resident of the Middle East. The virus, now known as the Middle East respiratory syndrome coronavirus (MERS-CoV),1 has (as of 26 June 2015) caused more than 1350 laboratory-confirmed cases of human infection. Thus far, all patients infected with MERS-CoV have had a direct or indirect link to the Middle East, however, local non-sustained human-to-human transmission has occurred in other countries, from people who had recently travelled to the Middle East.

Most MERS-CoV patients have primarily had respiratory disease, although a number of secondary complications have also been reported, including acute renal failure, multi-organ failure, acute respiratory distress syndrome (ARDS), and consumptive coagulopathy. In addition, many patients have also reported gastrointestinal symptoms, including diarrhoea. To date, approximately 30% of infected patients have died. The majority has had at least one comorbid condition, but many have also been in previous good health. As of 2 July 2015, the median age of reported laboratory-confirmed cases is 50 years (Range <1–99 years) and majority (66%) are males.2 A current update of the cases can be found on the WHO MERS-CoV website (http://www.who.int/emergencies/mers-cov/en/ ).

Our current understanding of MERS-CoV is that it is a zoonotic virus, which has entered the human populations in the Arabian Peninsula on multiple occasions from direct or indirect contact with infected dromedary camels or camel-related products. Several studies have shown that MERS-CoV specific antibodies are widespread in dromedary camel populations in the Middle East and Africa. The evidence from animal seroepidemiologic surveys suggests that MERS-CoV has been circulating in camels for decades. However, the reason(s) human cases first appeared in 2012 are unknown and the specific exposures resulting in and modes of transmission from animals to humans have not been fully elucidated3.

Human-to-human transmission has been observed to a limited extent in households. However, the majority of human cases reported to date have resulted from human-to-human transmission in health care settings. Failures in infection prevention and control in health care settings have resulted in sometimes-large numbers of secondary cases, as was seen in KSA in April-May of 2014 and Republic of Korea in May-July 2015. To date, there is no evidence of sustained human-to-human transmission.

In 2015, we observe the same epidemiologic patterns of MERS-CoV: multiple introductions from animals to humans and secondary transmission in health care settings. What is different, however, is that the hospital outbreaks are smaller in size, but more frequent in KSA. Until zoonotic transfer of the virus from animals into the human population is halted, the risk of further nosocomial outbreaks remains.

 

2. Purpose and scope of the document

This document provides a standardized approach for public health authorities and investigators at all levels to plan for and conduct investigations around confirmed and probable cases of MERS-CoV infection. It should be read in conjunction with other detailed guidance referenced throughout the text, such as current laboratory testing guidelines and study protocols. It will be updated as necessary to reflect increased understanding of MERS-CoV transmission and control.

Most of the advice given in this document will apply primarily to countries in which infection is presumed to have originated from an animal or environmental source, and the exposures that result in infection remain the critical questions. In countries that have secondary transmission related to imported cases, however, the recommendations for finding secondary cases and observing subsequent community transmission are still valid, though on a more limited scale. Similarly, the case-control study recommended as a high priority in the second part of the document is not applicable to countries with imported cases, since the purpose of the study is to uncover the non-human exposures leading to infection. However, other studies on health care facility transmission and clinical management are still recommended.

As with nearly all recent emerging novel pathogens, most early cases of MERS-CoV infection will likely be detected by astute clinicians rather than through established indicator or sentinel surveillance systems. Therefore, the most effective tool in detection will be awareness among the health care providers. An effective detection system will also need to include a readily available channel by which clinicians can report suspect cases, and an effective response mechanism. The WHO Regional Office for the Western Pacific has published a guide for event surveillance4.

This document addresses two general categories of activities that need to be undertaken to deal with newly identified cases. The first involves further case finding, case description, and surveillance enhancements in the area where the case is discovered. The primary purpose of these activities is to fully describe the epidemiology of the cases, identify and monitor close contacts of the cases and determine the extent of spread of the virus in the area (sections 3 and 4). The second group of activities is a number of discrete studies aimed at answering critical questions related to MERS-CoV (section 5).

 

3. Key steps for an investigation

3.1 Preparation

A multi-disciplinary team should be assembled. Team members should have experience in field epidemiology, clinical assessment, laboratory specimen collection, infection control, and social mobilization and risk communication. Animal health specialists are also a critical part of the team. Additional team members may include logisticians, laboratory experts, data managers, and environmental health specialists. The size and composition of the initial investigation team may vary depending in part on the size and complexity of the anticipated investigation. Designation of a team leader and attribution of roles and responsibilities is critical to the success of the investigation.

Before deploying, the team should gather preliminary background information, assemble the necessary materials and supplies (e.g. personal protective equipment, specimen collection and transport materials) and inform relevant local public health and animal health authorities.

 

3.2 Objectives

When setting up an investigation, it is critical to clearly define the objectives and use a standardized approach that addresses each of these. These objectives might be to:

  • Public Health Objectives
    • Identify other cases and quickly detect any human-to-human transmission.
    • Reduce onward transmission, morbidity and mortality through rapid identification, isolation, treatment and clinical management of cases and follow-up of contacts.
    • Prevent future cases through identification of potential human, animal, and/or environmental sources of exposure, risk factors for infection, and implementation of appropriate prevention and control measures.
  • Knowledge Objectives
    • Determine the size of geographic area where the virus is transmitting.
    • Determine key epidemiological, clinical, and virological characteristics for cases including clinical presentation and natural history, the mode(s) of transmission and disease diagnosis, incubation period, period of transmissibility, and best practices for treatment.
    • Determine if the efficiency of human-to-human transmission of the virus has changed or increased.

 

3.3 Case identification and interview

Laboratory-confirmation of a MERS-CoV case is an immediate trigger to launch a thorough investigation. However, because collection, shipment, and testing of specimens often require several days or longer, the investigation may need to begin before laboratory test results are available for suspected cases. Even if laboratory-confirmation is not possible, an investigation should still be launched if a patient is strongly suspected to have MERS-CoV infection (e.g. patient with severe acute respiratory infection [SARI] who has a history of travel to Middle East or has been in contact with cases who have died).

The patient and/or family members (if the patient is too ill to be interviewed or has died) should be interviewed within the first 24–48 hours of the investigation to collect basic demographic, clinical, and epidemiological information. A sample questionnaire for the initial interview can be found on the WHO Coronavirus website2 but should be adapted and augmented with questions about practices and exposures in the local community.

 

3.3.1 Essential basic information

The following basic information should be collected, including:

  • Patient ID number/cluster number (if applicable).
  • Relationship between the person answering questions on behalf of the case patient (in the case that the patient is too ill for interview or has died).
  • Date of symptom onset (by symptom, if possible).
  • Date of initial admission/ visit to health care facility.
  • Date of initial WHO notification.
  • Patient contact details (e.g. name, home address, home/mobile telephone numbers).
  • Demographic information (e.g. date of birth/age, sex).
  • Occupation (including specific classification such as healthcare worker, laboratory worker, and farm worker etc.).
  • Date of sample collection, laboratory testing and specimen type (e.g. nasopharyngeal swab, sputum, etc.).

 

3.3.2 Exposure Information and travel history

Possible exposures in the 14 days5 before the onset of symptoms should be thoroughly explored and described, with special focus on:

  • Animal exposures
    • Presence of animals, especially camels, in or around household area where the case patient lives or works (e.g. pets, rats, other rodents, bats, camels, birds, etc.).
    • Activities that result in animal exposures and type of animals exposed to (e.g. keeping livestock, visiting farms, visiting live animal markets racetracks, or practicing falconry, participating in the slaughter or sacrifice of animals etc.).
    • Exposures to animal, especially camel, products or products potentially contaminated by animal excreta or body fluids.
  • Human exposures:
    • Recent contact with individuals with respiratory illness and/or gastrointestinal symptoms, including people who have been severely ill or have died (indicate the type(s) of contact, frequency, and duration of exposure, and location).
    • Recent admission in hospital.
    • Recent visit to outpatient treatment facility.
    • Recent visit to traditional healer.
  • Food exposures
    • Recent consumption of unprocessed, raw foods or drinks.
    • Recent consumption of raw or undercooked meat, or uncooked blood products.
    • Recent preparation of fresh meat for consumption.
    • Use of smoking apparatus such as hookah or shisha.
  • Travel history
    • Dates, destinations and details mode of transport for recent travel (local and international).
    • Activities during the period of travel (including information on animal, human and food exposures as listed above).

 

3.3.3 Clinical Information

Data on the presentation of illness, pre-existing medical conditions, clinical course of illness, and occurrence of complications are critical for refining case definitions and informing clinical management recommendations. As such, detailed clinical data should be collected on each confirmed case and systematically summarized. A clinical collection form has been developed by WHO/ISARIC6; see section 5.6 for more information).

  • Clinical data:
    • Date of illness onset.
    • Signs and symptoms at initial presentation.
    • Time course of illness including time from illness onset to: care-seeking, first hospital admission, deterioration requiring advanced clinical management, and final outcome.
    • Presence of pneumonia and progression to respiratory failure, development of the acute respiratory distress syndrome (ARDS).
    • Occurrence of other complications such as renal failure or other organ system compromise, coagulopathies, secondary infections, sepsis, etc.
    • Presence of pre-existing chronic conditions (immunosuppression, cancer, renal insufficiency, hemoglobinopathies, liver disease, neurological disease, endocrine and metabolic disorders, etc.).
    • Dates and results of any ancillary tests performed (X-Ray, CT scan, etc.).
    • Use of respiratory support (supplemental oxygen and FiO2; non-invasive and invasive mechanical ventilation, prone positioning, use of inhaled nitric oxide, oscillatory ventilation, Extra Corporeal Membrane Oxygenation [ECMO]).
    • Use of other organ support modalities (renal replacement therapy, vasopressors, etc.).
    • Use of antibiotics, corticosteroids, other medical therapies.
    • Documentation of co-infections (viral, bacterial, fungal).
    • Clinical outcomes (recovered, ill, critically ill, duration of intensive care unit admission, duration of hospitalization, deceased).
    • Virological outcomes (if available), including duration of MER-CoV shedding in respiratory tract specimens, and extrapulmonary clinical specimens.
  • Infection control related
    • Where patient was located in health care facility. Which other places (e.g. radiology) may have been visited.
    • Infection control precautions that were used in relation to patient including type of masks, etc.
  • Laboratory data (haematology, biochemistry, and virology)
    • Date specimen taken.
    • Type of test, type of specimen.
    • Test results and date of results.
    • Name of laboratory performing test.
    • Name of national laboratory.
    • Name of reference laboratory (if applicable).

 

3.4 Case finding

3.4.1 Develop a case definition

An additional first step in the investigation is to identify other cases among contacts of the known case and in the community. To do this, the investigation team must first identify the types of clinical presentations or syndromes that will be sought as part of the case finding activity. WHO has developed surveillance case definitions for classification and reporting of human cases globally (http://www.who.int/csr/disease/coronavirus_infections/case_definition/en/) but these are not designed for case finding around newly discovered cases. Definitions for additional case finding must be developed locally and may be shaped by information obtained from the interview with the first case.

These definitions are used to identify patients in the community who should be tested for MERS-CoV infection and should incorporate time periods, localities, illness characteristics, exposure and other information. The criteria used should those that clinicians will find simple, easily understandable, and memorable. The case definition should be sensitive enough during the initial stages of the investigation to capture the majority of cases. An example of a case definition to use for this purpose might include features such as:

  • Location:
    • the local community where the case occurred. This will be defined according to the local situation but should include an area that incorporates other individuals who may have exposures to the same source of virus to which the patient was exposed. As the relevant exposures are currently unknown, they should include the population area that generally includes local markets, places of worship, and health care facilities that the case may have recently visited.
  • Time frame:
    • some retrospective case finding should be conducted and therefore the time period should cover at least two weeks before the onset of symptoms of the case.
  • Patients’ characteristics may include the following, but should be modified according to the latest clinical data on cases:
    • A patient with SARI7 who presents with fever and cough, requires admission to hospital, and whose disease is not completely explained by another pathogen.
    • A patient with SARI whose clinical course is unexpectedly severe even if another pathogen was initially identified and the patient did not respond to appropriate treatment.
    • A patient with SARI with recent exposure to animals.
    • An immunocompromised patient who presents with an acute illness that is not fully explained by another pathogen.

 

3.4.2 Contact monitoring

Close contacts of confirmed or probable cases should be identified and monitored for the appearance of respiratory symptoms for 14 days after last exposure to the confirmed or suspected case, while the case was symptomatic. Any contact that becomes ill in that period of time should be tested for MERS-CoV. If feasible, all contacts especially health care workers and other inpatient hospital contacts, regardless of the development of symptoms should be tested for MERS-CoV.

A line-listing of all contacts and co-exposed persons that records demographic information, date of first and last common exposure or date of contact with the confirmed or probable case, and date of onset if fever or respiratory symptoms develop should be maintained. The common exposures and type of contact with the confirmed or suspected should be thoroughly documented for any contacts that become infected with MERS-CoV.

Initiate active monitoring (e.g. daily visits or telephone calls) for the development of fever and acute respiratory illness or any other symptoms in close contacts for 14 days after the last exposure to the initial case. Contacts should also be advised to contact health care workers as soon as they develop above symptoms. If any of the contacts are confirmed to have MERS-CoV infection, their close contacts should also be monitored.

Collect appropriate clinical specimens (see section 4.4.1) on any close contacts with an acute respiratory illness regardless of severity, and test for MERS-CoV. While under investigation, symptomatic contacts should limit their contact with well individuals and practice good respiratory hygiene to prevent onward transmission. Current advice on preventing transmission both in the household and in health care facilities can be found on the WHO Coronavirus website. The decision of whether to admit symptomatic cases or contacts should be based on clinical judgment and concerns about further transmission. If symptomatic individuals are managed at home, they should be monitored closely for progression of their illness. Currently, it is not possible to predict the course of illness of an individual patient.

Serological investigation of contacts:

In addition to monitoring close contacts for the appearance of acute illness and testing with PCR, it is strongly advised that sera be collected on all close contacts, including health care workers. This will assist in demonstrating the presence of mild and asymptomatic MERS-CoV infections and help in defining common exposures in the environment or exposures to the case that might result in infection. Investigators should collect acute sera on all close contacts immediately after the confirmed or suspected case is identified. Sera collection should be repeated in close contacts 3–4 weeks later, regardless of whether contacts have developed symptoms. Symptomatic contacts should also have appropriate respiratory specimens collected for PCR testing (see section 3.5). If the index case was ill more than 3–4 weeks before the investigation is undertaken, only a single serum specimen needs to be collected from contacts. In addition to the second serum specimen, for each contact collect information regarding:

  • Any illness that may have occurred during the intervening time period, including all signs and symptoms, and their severity.
  • Specific exposures to the confirmed or suspected case including providing care, exposure to body fluids and other physical contact, duration and proximity of exposure, eating with and sleeping in the same room as the case.
  • Exposures to animals, unprocessed food and beverages, and other social and environmental contacts.

A protocol for contact investigation has been developed by WHO and CONSISE and is available at: http://www.who.int/csr/disease/coronavirus_infections/en/

 

3.4.3 Active search for additional cases

Efforts to identify additional cases beyond close contacts are critical for prevention and control of infection, and to determine the total extent of transmission in the community. Active case finding in the area under investigation should focus on:

  • Patients currently admitted to health care facilities in the community where the confirmed MERS-CoV case was discovered. Any patients currently in the hospital with unexplained SARI should be considered for testing for MERS-CoV.
  • Health care providers in the community; health workers should be interviewed about recent cases of unexplained pneumonia and notified to immediately report any patients who have signs and symptoms that meet the case definition developed for the investigation as described above in section 3.4.1. Patients meeting the case definition should be tested for MERS-CoV.
  • Patients who recently died of an unexplained illness consistent with the case definition developed for the investigation should be tested for MERS-CoV infection if appropriate clinical specimens are available.

 

3.4.4 Initiate enhanced surveillance

In addition to case finding activities, surveillance in the area under investigation should be enhanced to detect cases that might arise subsequent to the discovery of the index case. The geographical area targeted will need to be assessed on a case-by-case basis and is defined by the suspected exposures of the case under investigation. The duration of the enhanced surveillance will depend on the findings of the investigation and whether there is evidence indicating that sustained transmission may be occurring in the area. A minimum of one month of enhanced surveillance is a reasonable starting point.

Enhancements include:

  • Introduction of laboratory capacity for MERS-CoV testing in the local health care facility, if feasible, or establishment of mechanisms for rapid transfer of specimens to a capable laboratory.
  • Inform clinicians in the community of the need for vigilance and the case definition for case finding (section 3.4.1).
  • If SARI surveillance is in place, expand to other facilities in the area. If it is not, initiate SARI surveillance at health care facilities in the community of the case. Standards and guidance for SARI surveillance can be found in the ‘WHO Global Epidemiological Surveillance Standards for Influenza’ available at http://www.who.int/influenza/resources/documents/influenza_surveillance_manual/en/
  • Increase the testing for MERS-CoV of SARI cases at local health care facilities in the area under investigation.
  • If resources allow, consider some testing of milder cases of influenza-like illness presenting to surveillance sites.

 

3.5 Biological specimen collection and laboratory testing

3.5.1 Specimen Collection

To confirm the presence of MERS-CoV in suspect cases, collect appropriate clinical specimens for testing:

  • Available evidence suggests that lower respiratory tract specimens contain higher virus titres than upper respiratory tract specimens and are more sensitive for detecting the presence of the virus. Lower respiratory tract specimens include:
    • Sputum, induced or non-induced.
    • Endotracheal aspirate for patients on mechanical ventilation.
    • Bronchial alveolar lavage for those in whom it is indicated for patient management.
  • Upper respiratory tract specimens such as nasopharyngeal and oropharyngeal swabs should be collected if lower respiratory tract specimens cannot be collected. If initial testing of an upper respiratory specimen is negative in a patient suspected of having MERS-CoV infection, repeat testing should be performed.
  • Collect blood for serological testing. For recent cases, an initial blood specimen should be collected and a repeat specimen taken after a period of at least 3 weeks. For cases that had symptom onset more than 3 weeks prior to being investigated, a single blood sample is sufficient.

MERS-CoV has been identified in other body fluids including blood, urine, and stool of infected patients. However, titres of virus in these body fluids are quite low and they may not be useful for diagnostic testing. The presence of virus in these body fluids could have public health implications and could be part of an ancillary study of a case.

Health care workers collecting clinical specimens should exercise appropriate infection control measures including use of personal protective equipment. Current guidelines for infection control and prevention can be found on the WHO MERS-CoV website at http://www.who.int/csr/disease/coronavirus_infections/technical-guidance-infection/en/.

 

3.5.2 Molecular diagnostics

PCR is the most widely used method for detecting the presence of the virus. At least three sites in the virus genome have been identified as suitable targets for such assays, including upE, ORF 1A and ORF 1B, and sequences of the necessary primers have been published. To perform these assays, laboratories should order the primers from their usual suppliers. Positive controls for the UpE screening and the ORF 1A confirmation assays are also available. WHO guidance on laboratory testing for MERS-CoV is available at http://www.who.int/csr/disease/coronavirus_infections/technical-guidance-laboratory/en/.

A confirmed case should either have positive test results for at least two different sites in the virus genome, or a positive result for a single site plus sequencing of a different, appropriate site that shows close similarity to known sequences of the virus. Testing should be carried out in laboratories that are experienced in performing these procedures. Specimens should be sent to a reference laboratory for confirmation.

A BSL2 facility including use of a microbiological safety cabinet (class 1, 2, or 3) is required for the handling of specimens thought to contain MERS-CoV when performing RNA extraction for PCR. Recommendations on the laboratory biorisk management for novel coronavirus have been prepared.

 

3.5.3 Serological testing

Several MERS-CoV specific serologic assays have been developed and are now available and work on further serological assays is continuing in several laboratories around the world. Collection of sera from patients being investigated for infection with MERS-CoV will greatly aid in the validation of assays currently under development and may be useful for confirmation of infection once the validation process is complete.

 

3.5.4 Viral culture

The MERS-CoV virus has been shown to grow in a number of different commonly available cell lines. However, culture of this virus should not be attempted outside of specialised laboratories with appropriate biosecurity level 3 capabilities.

 

3.5.5 Genetic sequencing

Specimens testing positive for MERS-CoV should be genetically sequenced, and the data uploaded to publicly accessible databases. If the laboratory doing the initial test does not have the capacity for genetic sequencing, an aliquot of the specimen should be forwarded to a reference centre. Such centres should attempt to isolate viruses from all cases so that whole genome sequencing can be performed, either in the national or international reference laboratory. Both partial and whole genome sequencing provides crucial information as to the origin and source of exposure to MERS-CoV.

 

4. Data Analysis

The analysis plan will depend on the objectives of the investigation.

At a minimum, descriptive analysis of cases should be performed in terms of person, place, and time. For investigations that yield multiple cases, graphical and/or tabular descriptions of cases by date of onset (i.e. epidemic curve), geographical location (e.g. maps of the locale, case patients’ homes), relationship (i.e. transmission or family trees) and demographic characteristics (e.g. distribution by age and sex) should be developed. Key epidemiological (e.g. estimation of an incubation period, description of transmission patterns, attack rates by age, occupation, exposure history etc.) and clinical (e.g. spectrum of illness severity, proportion of cases who develop pneumonia, require hospitalization, die) parameters should be characterized to enhance understanding of the spectrum and dynamics of disease associated with MERS-CoV infection.

 

5. Studies and specific investigations

Many of the critical questions regarding the clinical manifestation and epidemiological characteristics of MERS-CoV infection will be answered only by careful, detailed formal studies around cases. The following provides some guidance on the types of studies that should be considered.
Useful protocols can be found on the website of the Consortium for the Standardization of Influenza Seroepidemiology (CONSISE) at http://consise.tghn.org/articles/novel-coronavirus-ncov/ . Four CONSISE protocols have been adapted by WHO and are online at http://www.who.int/csr/disease/coronavirus_infections/technical-guidance-surveillance/en/.

This section covers the different epidemiologic study designs and investigations for MERS-CoV, including a brief description of the investigation and the objectives of each.

 

5.1 Case-control studies

Based on the results of initial interviews with cases regarding exposures, risk factors for infection should be further investigated using case-control studies. The purpose of these studies is to determine whether specific exposures occur more frequently in patients infected with MER-CoV (cases), than they do in persons without MER-CoV infection (controls) of the same age and sex in the community during the same time frame. Cases are compared to randomly selected community controls in terms of their recent exposures to other sick individuals, animals, foods and beverages, and other exposures suspected to be the source of infection.

A study protocol has been developed for this purpose and is available at http://www.who.int/csr/disease/coronavirus_infections/MERSCoVCaseControlStudyofExposures.pdf?ua=1. The specific line of questioning for the study, however, should be guided by initial interviews with the cases.

 

5.2 Health care exposures

Several clusters of cases associated with health care facilities have been reported and are thought to represent nosocomial transmission. This transmission was observed between health care workers who work in the same institution, between patients, between patients and health care workers and between patients and visitors in health care settings. The mode of transmission, types of exposures that result in infection and the effectiveness of specific infection control measures in preventing transmission, however, are unknown. For cases admitted to hospital, studies of health care workers and other patients exposed to confirmed cases can provide some of this information. Ideally, these studies would be done prospectively as soon as MERS-CoV infection is suspected. The study will examine the occurrence of infection in persons exposed to the case in the health care environment, using both molecular diagnostics and serological testing and attempt to associate infection with specific types of exposures such as the performance of specific procedures, contact (or not) with body fluids, and proximity of exposure. If performed retrospectively using single sera to reflect probable infection, it is necessary to also use a control group of unexposed health care workers as diagnosis of acute infection cannot definitively be made from a single serum sample.

Specific information to be gathered during these investigations include:

  • Exposures while performing specific procedures on the patient.
  • Use of specific personal protective equipment by the health care worker.
  • Time of exposures in relation to illness of patient.
  • Duration of exposures.
  • Exposure to body fluids, secretions, or excretions.
  • Occurrence of illness in the health care worker.
  • Exposures that may have taken place outside of the work environment as described in the case-control protocol above.

A protocol for investigations in health care workers has been developed by the CONSISE network in collaboration with WHO:

 

5.3 Investigations of close contacts and at risk populations

Two additional seroepidemiologic studies have been developed for MERS-CoV to evaluate risk of infection among close contacts:

 

5.4 Recent respiratory disease trends

In addition to monitoring close contacts for signs of infection, a wider search should be made for evidence of transmission or undetected cases in the community. Local health care facilities and health care practitioners are the focus of this investigation. The objective is to determine if incidence of severe respiratory disease has increased recently or if unusual cases have occurred and not been reported. Investigations include:

  • a. Review of surveillance data for SARI and/or other relevant conditions under surveillance for recent increases in numbers of SARI. If stored specimens of SARI cases are available, they should be tested for MERS-CoV;
  • b. Review of admission records in the intensive care units (ICUs) of local hospitals for evidence of recent increases in numbers of respiratory infection compared to baseline (same time period in previous years). Any cases currently in the ICU whose illness is not entirely explained should be tested for MERS-CoV;
  • c. Review of hospital admission records of local hospitals for evidence of recent increases in numbers of pneumonia. As with patients in ICU, any unexplained pneumonia currently in hospital should be tested for MERS-CoV;
  • d. Review of records of local outpatient treatment clinics for evidence of recent increases in respiratory disease or influenza-like illness;
  • e. Review of hospital records and vital statistics data for evidence of recent increases in mortality due to pneumonia.

 

5.5 Seroprevalence studies

With the appearance of a novel pathogen, often only the most severe cases are detected in the beginning. Seroprevalence studies, which measure the prevalence of antibodies against the novel pathogen in specific populations, can be used to compare relative prevalence of previous infections in different populations, with different types of exposures and to also estimate the incidence of infection in a defined period of time. The first will require samples of individuals from different exposure groups such as market workers, farm workers, health care workers, clerks or business people, etc. The types of activities regularly performed by individuals in each group are compared to the seroprevalence of antibodies to MERS-CoV in each group and to the specific activities that they do. This is then analysed to determine the activities with associated risk of MER-CoV infection.

It should be kept in mind that the likelihood that an individual with a single positive serological test has actually been infected will depend on the specificity of the assay being used. A positive test in a single individual may not represent infection because of cross reactivity with antibodies against other types of coronaviruses. However, the relative differences of prevalence between groups of individuals can be associated with exposures to develop a better understanding of important exposures and the relative risk of infection between different groups. Acute and convalescent titres for individuals recently exposed to sources of infection, however, may be used for specific diagnosis if using an assay which has been validated and for which a significant increase in titer is known as a correlate for infection.

Once the degree to which cross-reactivity with current assays is better understood and the persistence of antibodies in infected individuals is known, population serosurveys may also allow an estimation of background levels of infection in a community. However, even without knowing the exact sensitivity and specificity of an assay, comparison of population seroprevalence over time can be used to estimate incidence. To do this, a cross-sectional seroprevalence survey should be done in a population early in an outbreak. This seroprevalence can then be compared to levels in a repeated survey done after the outbreak to determine incidence of infection over time. (Protocol: Cross-sectional seroprevalence study of novel Coronavirus (nCoV) infection prior and post epidemic periods8).

 

5.6 Animal health and environmental investigations

Investigators in public health and animal health should work together to assess the role of MERS-CoV infection in wild animals (e.g. bats, rodents) or domesticated animals (e.g. camels, sheep, goats, household pets) as sources of possible exposure for human cases.

Field visits to investigate the occurrence of illness among animals can include:

  • The patient's home and its surroundings
  • Local areas where food is produced to be consumed raw/unprocessed (e.g. sun-dried fruits)
  • Farms and live animal markets
  • Places frequented by wild animals (e.g. caves)
  • Any other place of significance that the patient visited in the 14 days prior to illness onset

In addition to animal illness and death, information should be sought on local housing, feeding and animal handling practices.

Before any specimens are collected, it is critical for investigators to be familiar with the correct collection techniques, types and recommended number of specimens to collect and appropriate use of personal protective equipment. Adequate laboratory capacity for processing and testing of specimens must also be determined. Investigators should coordinate their activities so that human and animal specimens can be linked and compared. Guidance from the Food and Agriculture Organization of the United Nations (FAO) and the World Organization for Animal Health (OIE) should be consulted regarding technical issues related to surveillance, prevention, and control of disease in animals.

 

5.6 Clinical management studies

Knowledge of the clinical features of MERS-CoV infection is currently limited, thus clinical management focusses on supportive management of patients who have acute respiratory failure and septic shock as a consequence of severe infection. Guidance is available on the WHO website at http://www.who.int/csr/disease/coronavirus_infections/technical-guidance-infection/en/.

Several possibilities for specific treatment have been studied in cell cultures. A review of literature by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) suggested that use of convalescent sera from recovered patients had the most evidence to support its use, however, more studies are needed. Clinical management protocols are being developed by ISARIC and investigators who have an interest in pursuing these types of investigations are encouraged to contact ISARIC (kajsa-stina.longuere@ndm.ox.ac.uk).

 

6. Infection control

Many of the standard prevention and control measures to reduce opportunities for further transmission of nosocomial infections have been noted previously and are listed below.

  • Strict infection control, the use of personal protection equipment during the delivery of care and isolation of confirmed and probable cases
  • Strict infection control and use of personal protection equipment during collection, transportation and testing of laboratory specimens in patients suspected of having infection with MERS-CoV.

If symptomatic contacts or cases with milder symptoms are cared for at home, infection control measures should be used if. However, because of rapid progression to acute respiratory distress syndrome (ARDS) and other severe life-threatening complications, even otherwise healthy, symptomatic contacts or probable cases should be considered for close observation in a medical facility. Guidance is available on the WHO website at http://www.who.int/csr/disease/coronavirus_infections/technical-guidance-infection/en/.

 

7. Reporting results

7.1 Reporting Cases

WHO requests that probable and confirmed cases be reported within 24 hours of classification, through the Regional Contact Point for International Health Regulations at the appropriate WHO Regional Office. See current definitions for probable and confirmed cases at http://www.who.int/csr/disease/coronavirus_infections/case_definition/en/.

If the local investigators used different case definitions, those should be detailed when reporting cases.

 

7.2 Reporting results of a study investigation

WHO strongly encourages the early reporting of investigation results of MERS-CoV patients, even before analyses are complete. Several networks have been established by WHO that can advise investigators in the conduct of investigations and the interpretation of preliminary results. In addition, even preliminary data can be critical in the early assessment of international spread and inform decision making. Table 1 below shows critical questions that must be answered early in the course of an event and the specific investigations that will inform them.

(…)

 

8. References

  1. Buchholz U, Müller MA, Nitsche A, et al. Contact investigation of a case of human novel coronavirus infection treated in a German hospital, October-November 2012. Eurosurveillance 2013;18(8):pii=20406. Available at http://www.eurosurveillance.org /ViewArticle.aspx?ArticleId=20406.
  2. Corman VM, Müller MA, Costabel U, et al. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Eurosurveillance. 2012;17(49):pii=20334. Available at http://www .eurosurveillance.org/ViewArticle.aspx?ArticleId=20334.
  3. Cotten M, Lam TT, Watson SJ, Palser AL, Petrova V, Grant P, et al. Full-genome deep sequencing and phylogenetic analysis of novel human betacoronavirus. Emerging Infectious Diseases. 2013; 19(5). Available at http://dx.doi.org/10.3201/eid1905.130057.
  4. Gautret P, Charrel R, Belhouchat K, et al. Lack of nasal carriage of novel corona virus (HCoV-EMC) in French Hajj pilgrims returning from the Hajj 2012, despite a high rate of respiratory symptoms. Clinical Microbiology and Infection. 2013; 1469-0691. Available at http://onlinelibrary.wiley.com/doi/10.1111/1469-0691.12174/abstract;jsessionid =53807513DCAB71E6CA099CE6DE6FB212.d02t03.
  5. Guery B, Poissy J, Mansouf L, et al. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus a report of nosocomial transmission. The Lancet. 2013; 2013 (Article in Press DOI: 10.1016/S0140-6736(13)60982-4). Available at http://www.thelancet.com/journals/lancet /article/PIIS0140-6736(13)60982-4/abstract?rss=yes.
  6. Hijawi B, Abdallat M, Sayaydeh A, et al. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. Eastern Mediterranean Health Journal 2013; 19(1): S12-S18. Available at http://www.emro.who.int/emhj-vol-19-2013/s1/novel-coronavirus-infections-epidemiological-findings-from-a-retrospective-investigation.html
  7. Memish Z, Alimuddin Z, Al-Hakeem R, et al. Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections. New England Journal of Medicine. 2013; DOI: 10.1056/NEJMoa13037 29. Available at http://www.nejm.org/doi/full/10.1056/NEJMoa1303729#t=article.
  8. Memish Z, Alhakeem R, Stephens G. Saudi Arabia and the emergence of a novel coronavirus. Eastern Mediterranean Health Journal. 2013; 19(1): S7-S11. Available at http://www.ncbi.nlm.nih.gov /pubmed/23888789
  9. Müller M, Raj V, Muth D, et al. Human Coronavirus EMC Does Not Require the SARS-Coronavirus Receptor and Maintains Broad Replicative Capability in Mammalian Cell Lines. mBio. 2013; 3(6): e00515-12. Available at http://mbio.asm.org/content/3/6/e00515-12.full.html.
  10. Munster V, Wit E, Feldmann H. Pneumonia from Human Coronavirus in a Macaque Model. New England Journal of Medicine. 2013, 368: 1560-1562. Available at http://www.nejm.org/doi /full/10.1056/NEJMc1215691#t=article.
  11. Reusken C, Mou H, Godeke GJ, et al. Specific serology for emerging human coronaviruses by protein microarray. Eurosurveillance. 2013;18(14):pii=20441. Available at http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20441.
  12. Smith, C., Field, H., Wang L. ‘Bat Coronaviruses’ in Investigating the role of bats in emerging zoonoses. Food and Agriculture Organisation of the United Nations. Rome, 2011, pp. 102-122. Available at http://www.fao.org/docrep/014/i2407e/i2407e00.htm
  13. World Health Organization. Case-control study to assess potential risk factors related to human illness caused by novel coronavirus. Geneva, 2013. Available at http://www.who.int/entity/csr/disease/coronavirus_infections/NovelCoronaCaseControlStudyPotentialRiskFactors_17May13.pdf.
  14. World Health Organization. Clinical management of severe acute respiratory infections when novel coronavirus is suspected. Genea, 2013. Available at http://www.who.int/entity/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf.
  15. World Health Organization. Infection prevention and control during health care for probable or confirmed cases of novel coronavirus (nCoV) infection. Geneva, 2015. Available at http://www.who.int/csr/disease/coronavirus_infections/ipc-mers-cov/en/
  16. World Health Organization. Surveillance for human infection with Middle East respiratory syndrome coronavirus (MERS - CoV). Geneva, 2015. Available at http://www.who.int/csr/disease/coronavirus _infections/surveillance-human-infection-mers/en/
  17. World Health Organization. Laboratory testing for Middle East Respiratory Syndrome Coronavirus. Geneva, 2015. Available at http://www.who.int/csr/disease/coronavirus_infections/mers-laboratory-testing/en/
  18. Zaki A, et al. Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia. New England Journal of Medicine 2012; 367: 1814-1820. Available at http://www.nejm.org/doi/full/10.1056 /NEJMoa1211721.

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(1) WHO. Naming of the Novel Coronavirus. Available at http://www.who.int/csr /disease/coronavirus_infections/NamingCoV_28May13.pdf

(2) WHO. Middle East respiratory syndrome coronavirus (MERS-CoV) website. Available at http://www.who.int/csr/disease/coronavirus_infections/en/

(3)  WHO. Weekly Epidemiological Record (WER). 15 May 2015, vol. 90, 20 (pp. 217-252). Available at http://www.who.int/wer/2015/wer9020/en/

(4) WHO Regional Office for the Western Pacific. A Guide to Establishing Event-based Surveillance. Manila, 2008. Available at http://www.wpro.who.int/emerging_diseases/documents/eventbasedsurv/en/

(5) The incubation period of MERS is 2-14 days, median of approximately 5.5-6.5 days.

(6) Available at http://prognosis.org/isaric/documents/WHO_SARI_NewOutbreak_case_record_form_v2.pdf

(7) SARI definition: An acute respiratory infection with history of fever or measured fever of ≥ 38 C⁰ and cough, with onset within the last seven days, that requires hospitalisation.

(8) Available at https://consise.tghn.org/site_media/media/articles/3._CONSISE_nCoV_Serial_cross-sectional_seroprevalence_protocol_8May2013_1.pdf

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[S. #Korea] #MERS #cases keep coming from #Samsung #hospital (Bangkokpost.com, July 4 2015)

[Source: Bangkok Post, full page: (LINK).]

Mers cases keep coming from Samsung hospital [      ]

SEOUL - Another doctor at a major hospital that has been the epicentre of Mers outbreak in Seoul has contracted the deadly virus, the government said Saturday.

(…)

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Middle East respiratory syndrome #coronavirus (#MERS-CoV) [S. #Korea: one new case confirmed] (@WHO WPRO, July 4 2015)

[Source: World Health Organization, Regional Office for the Western Pacific, full page: (LINK).]

Middle East respiratory syndrome coronavirus (MERS-CoV) [      ]

MERS-CoV in Republic of Korea at a glance as of 4 July 2015

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Please refer to the link below for up to date MoHW summary of MERS statistics and list of health facilities where confirmed MERS cases were reported in the Republic of Korea. –> http://www.mers.go.kr/mers/html/jsp/Menu_C/list_C4.jsp <--

 

Related documents

Fact sheet, FAQs and press briefings

News releases

Maps and epicurves

Related links

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A G-quadruplex-binding #macrodomain within the “#SARS-unique domain” is essential for the activity of the SARS- #coronavirus replication–transcription complex (Science Direct, abstract, edited)

[Source: Science Direct, full page: (LINK). Abstract, edited.]

Virology / Volume 484, October 2015, Pages 313–322 / Brief Communication

A G-quadruplex-binding macrodomain within the “SARS-unique domain” is essential for the activity of the SARS-coronavirus replication–transcription complex [      ]

Yuri Kusov a, b, Jinzhi Tan a, Enrique Alvarez 1, c, Luis Enjuanes c, Rolf Hilgenfeld a, b

doi:10.1016/j.virol.2015.06.016

 

Highlights

  • A SARS-CoV replicon encoding Renilla luciferase as reporter protein is constructed.
  • The role of three macrodomains for the replication/transcription complex is analyzed.
  • In contrast to macrodomains X and SUD-N, SUD-M is found indispensable for replication.
  • Site-directed mutagenesis identifies charged SUD-M residues required for replication.
  • These residues have previously been shown to be involved in G-quadruplex binding.

 

Abstract

The multi-domain non-structural protein 3 of SARS-coronavirus is a component of the viral replication/transcription complex (RTC). Among other domains, it contains three sequentially arranged macrodomains: the X domain and subdomains SUD-N as well as SUD-M within the “SARS-unique domain”. The X domain was proposed to be an ADP-ribose-1”-phosphatase or a poly(ADP-ribose)-binding protein, whereas SUD-NM binds oligo(G)-nucleotides capable of forming G-quadruplexes. Here, we describe the application of a reverse genetic approach to assess the importance of these macrodomains for the activity of the SARS-CoV RTC. To this end, Renilla luciferase-encoding SARS-CoV replicons with selectively deleted macrodomains were constructed and their ability to modulate the RTC activity was examined. While the SUD-N and the X domains were found to be dispensable, the SUD-M domain was crucial for viral genome replication/transcription. Moreover, alanine replacement of charged amino-acid residues of the SUD-M domain, which are likely involved in G-quadruplex-binding, caused abrogation of RTC activity.

 

Graphical abstract

Full-size image (23 K)

 

Keywords: SARS-CoV replicon; SARS-unique domain; Macrodomain; X-domain; Reverse genetics; G-quadruplex; MERS-CoV

Corresponding author. Present address: Centro de Biología Molecular Severo Ochoa. Consejo Superior de Investigaciones Científicas. Universidad Autónoma de Madrid (CSIC-UAM). Nicolás Cabrera 1, 28049 Madrid, Spain.

Copyright © 2015 Elsevier Inc. All rights reserved.

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S. #Korea reported one new #MERS-CoV case in the last 24 hours, total now 185 (MoH, July 4 2015, edited)

[Source: South Korea Ministry of Health, full page: (LINK). Automatic translation, extract, edited.]

S. #Korea reported one new #MERS-CoV case in the last 24 hours, total now 185 [      ]

(July 4 2015)

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Middle East respiratory Syndrome Daily Tracking Report

  • To date: 41 patients are currently under treatment (22.2%), 111 patients recovered and discharged from hospital (60.0%), 33 patients passed away (17.8%); cumulative number of confirmed cases: 185.
  • Today: patient under treatment reduced by one, 2 cases have recovered and discharged from hospital, no new death recorded; one new case confirmed.
  • Of the 41 cases under treatment: 30 are in stable condition (73.2%), 11 cases are critical (26.8%).
  • Among confirmed cases: 82 were hospital’s inpatients; 64 inpatients’ relatives or visitors; 39 were health care workers.

(…)

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3 Jul 2015

#Greek #economy close to #collapse as #food and #medicine run short (Guardian, July 3 2015)

[Source: The Guardian, full page: (LINK).]

Greek economy close to collapse as food and medicine run short [   !   ]

by Helena Smith in Athens and Larry Elliott in London  

Greece’s economy is on the brink of collapse after the capital controls imposed ahead of Sunday’s referendum left the country with food and drugs shortages, the tourist industry facing a wave of cancellations and the banks with barely enough money to survive the weekend.

(…)

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