Monday, August 19, 2019

WHO EMRO MERS-CoV Summary - July, 2019


Once a month the WHO's EMRO (Eastern Mediterranean Regional Office) provides a summary of MERS activity in the Middle East - and around the world - based on what is officially reported by individual Ministries of Health to the World Health Organization. 
In this summary WHO EMRO reports 9 new MERS Cases - all from Saudi Arabia - during the month of July.
While a significant decline over the numbers we were seeing last spring, over the past year we've seen a number of studies that have called into question our ability to identify mildly symptomatic, asymptomatic, or atypically presenting MERS infections in the community. 

A few of those studies include:
J. Korean Med Sci: Atypical Presentation Of A MERS Case In A Returning Traveler From Kuwait

mBio: High Prevalence of MERS-CoV Infection in Camel Workers in Saudi Arabia

AJIC:Intermittent Positive Testing For MERS-CoV

JIDC: Atypical Presentation Of MERS-CoV In A Lebanese Patient
And in August of 2018 - in Evaluation of a Visual Triage for the Screening of MERS-CoV Patients - we looked at what has been described as a serious flaw in Saudi Arabia's MERS surveillance program.

First the latest EMRO report, then I'll return with a bit more.

MERS situation update, July 2019

  • At the end of July 2019, a total of 2458 laboratory-confirmed cases of Middle East respiratory syndrome (MERS), including 848 associated deaths (case-fatality rate: 34.49%) were reported globally; the majority of these cases were reported from Saudi Arabia (2067 cases, including 770 related deaths with a case–fatality rate of 37.25%).
  • During the month of July, a total of 9 laboratory-confirmed cases of MERS were reported globally. All the 9 cases were reported from Saudi Arabia with 3 associated deaths. 2 of the cases reported had their the symptom onset in the previous month - June. There were no cluster of cases reported this month. One case had history of contact with camels and consumption of their raw milk while the exposure history of the other cases is still under investigation. Only one case reported this month was a female and one case reported was a non-national. No healthcare workers were a ffected this month.
  • This month, Saudi Arabia has not reported any new cases related to the Al-Khafji city outbreak. The outbreak has presumed to have stopped due to the effective response measures taken by Saudi Arabia. There were no cluster of cases reported this month apart from one secondary case, a health care worker linked to a case reported in the previous month (May).
  • The demographic and epidemiological characteristics of reported cases, when compared during the same corresponding period of 2014 to 2019, do not show any significant difference or change.
  • The age group 50–59 years continues to be at the 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.
While MERS-CoV hasn't embarked on a world tour the way that SARS did 16 years ago, we've seen studies (see A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia) suggesting the virus doesn't have all that far to evolve before it could pose a genuine global threat.

Last year, in the WHO List Of Blueprint Priority Diseases, we saw MERS-CoV listed among the 8 disease threat in need of urgent accelerated research and development.

List of Blueprint priority diseases
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

All of which makes gaining a better understanding of how - and how well - the MERS coronavirus continues to spread in the community a high priority.

Hong Kong CHP Notified Of A Human H5N6 Case In Beijing


In the 2 years since China launched their aggressive nationwide H5+H7 poultry vaccination program, avian influenza reports (in poultry, and in humans) have been greatly suppressed across China.
China reported their only human H7N9 infection of 2019 - after a gap of more than a year - last April (see Taiwan CDC: Travel Alert Level Raised (Level 2) for Inner Mongolia Due to Recent H7N9 Case), while H5N6 cases - which saw a small uptick in the 2nd half of 2018 (n=4) - have been absent since November. 
Although greatly suppressed, we've seen a few poultry outbreaks over the past year, and studies (see OFID: Avian H5, H7 & H9 Contamination Before & After China's Massive Poultry Vaccination Campaign), indicate H5 and H7 avian viruses still circulate at low levels in Chinese livestock

How long this welcome reduction in avian flu activity will last is anyone's guess, but today we have the first reported H5N6 case in 10 months. It is also the first case reported from China's capital; Beijing, and the first to be reported outside of Southern China.
Other than her age (59), gender, and location we are told very little about the case. While most cases have been linked to live poultry, there is no mention of recent poultry exposure in today's announcement. 
First the statement from Hong Kong's CHP, then I'll return with a postscript.

CHP notified of human case of avian influenza A(H5N6) in Beijing 
The Centre for Health Protection (CHP) of the Department of Health (DH) today (August 19) received notification of an additional human case of avian influenza A(H5N6) in Beijing from the National Health Commission, and again urged the public to maintain strict personal, food and environmental hygiene both locally and during travel.
The case involved a 59-year-old female from Beijing. She was hospitalised on August 11. She is now in a critical condition.
From 2014 to date, 24 human cases of avian influenza A(H5N6) have been reported by the Mainland health authorities.
"All novel influenza A infections, including H5N6, are notifiable infectious diseases in Hong Kong," the spokesman said.
Travellers to the Mainland or other affected areas must avoid visiting wet markets, live poultry markets or farms. They should be alert to the presence of backyard poultry when visiting relatives and friends. They should also avoid purchasing live or freshly slaughtered poultry, and avoid touching poultry/birds or their droppings. They should strictly observe personal and hand hygiene when visiting any place with live poultry.
Travellers returning from affected areas should consult a doctor promptly if symptoms develop, and inform the doctor of their travel history for prompt diagnosis and treatment of potential diseases. It is essential to tell the doctor if they have seen any live poultry during travel, which may imply possible exposure to contaminated environments. This will enable the doctor to assess the possibility of avian influenza and arrange necessary investigations and appropriate treatment in a timely manner.
While local surveillance, prevention and control measures are in place, the CHP will remain vigilant and work closely with the World Health Organization and relevant health authorities to monitor the latest developments.
The CHP's Port Health Office conducts health surveillance measures at all boundary control points. Thermal imaging systems are in place for body temperature checks on inbound travellers. Suspected cases will be immediately referred to public hospitals for follow-up.
The display of posters and broadcasting of health messages in departure and arrival halls as health education for travellers is under way. The travel industry and other stakeholders are regularly updated on the latest information.
The public should maintain strict personal, hand, food and environmental hygiene and take heed of the advice below if handling poultry:
  • Avoid touching poultry, birds, animals or their droppings;
  • When buying live chickens, do not touch them and their droppings. Do not blow at their bottoms. Wash eggs with detergent if soiled with faecal matter and cook and consume the eggs immediately. Always wash hands thoroughly with soap and water after handling chickens and eggs;
  • Eggs should be cooked well until the white and yolk become firm. Do not eat raw eggs or dip cooked food into any sauce with raw eggs. Poultry should be cooked thoroughly. If there is pinkish juice running from the cooked poultry or the middle part of its bone is still red, the poultry should be cooked again until fully done;
  • Wash hands frequently, especially before touching the mouth, nose or eyes, before handling food or eating, and after going to the toilet, touching public installations or equipment such as escalator handrails, elevator control panels or door knobs, or when hands are dirtied by respiratory secretions after coughing or sneezing; and
  • Wear a mask if fever or respiratory symptoms develop, when going to a hospital or clinic, or while taking care of patients with fever or respiratory symptoms.  The public may visit the CHP's pages for more information: the avian influenza page, the weekly Avian Influenza Report, global statistics and affected areas of avian influenza, the Facebook Page and the YouTube Channel.
Ends/Monday, August 19, 2019
Issued at HKT 17:00
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It should be noted that surveillance and testing for novel flu is still limited in China - and while H5 and H7 activity undoubtedly remains greatly suppressed - it is still likely that some cases fly under the radar.

Additionally, a number of research studies have suggested the H5N6 virus is becoming better adapted to mammalian hosts, including:
Nature Sci Rpts: H5N6 Viruses Exhibit Varying Pathogenicity & Transmissibility In Mammals
Emerg. Microbes & Inf.: Human Infections With A Novel Reassortant H5N6

J. Virology: Molecular Evolution and Emergence of Avian H5N6

Sunday, August 18, 2019

WHO: Influenza Vaccine Response During The Start Of A Pandemic


We have often talked about the importance of NPIs (Nonpharmaceutical Interventions) like flu hygiene, school closures, and social distancing in the opening months of any pandemic because the creation, mass production, and distribution of an emergency  vaccine is a difficult, uncertain, and time consuming endeavor.
We were lucky in 2009, in that the pandemic virus required a relatively simple `strain change', and it did not require - as first feared - two shots spaced a month apart to produce immunity. 
Even so, the first batches of the emergency vaccine arrived after the peak of the pandemic, and in much smaller quantities than predicted.  Fortunately, the novel H1N1 virus proved to be relatively mild compared to past pandemics.


Last May, in Manufacturing Pandemic Flu Vaccines: Easier Said Than Done, we looked at a Japanese pharmaceutical manufacturer (Daiichi Sankyo Company, Limited) - which in 2011 received a Japanese government contract to supply H5N1 vaccines for 40 million people in the time frame allotted (6 months) - having to formally apologize for being unable to fulfill the terms of the contract.
Illustrating that gearing up to produce a pandemic flu vaccine in quantity, and in a timely manner - even when we are not hampered by an active pandemic - is a tall order.
While novel influenza is - at least based on recent history - the most likely cause of the next pandemic, it isn't the only possibility. And non-influenza vaccines are often harder to create.
Despite 16 years of research, there is still no commercially available SARS vaccine. Seven years after MERS emerged in the Middle East, a vaccine remains elusive (see Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism), and twenty years after its discovery, a Nipah vaccine is still in the works.
None of this is meant to diminish the importance of developing, and distributing, a safe and effective pandemic vaccine in the shortest time frame possible. Even if it isn't made available for the first wave, once it arrives, it could still save millions of lives.
But for that to happen, governments and vaccine manufacturers will have to work together, share information and virus strains, and agree to how (and where) the first vaccines available are allocated.  
The World Health Organization has been working for years to develop a global framework for emergency pandemic vaccine production, and has recently published the results of their Third WHO Informal Consultation, which was held in Geneva, Switzerland, in June of 2017.

This 37-page PDF file outlines the anticipated obstacles and bottlenecks to emergency vaccine production, which includes not only scientific and logistical problems, but political ones as well.

From the Executive Summary:
This meeting report provides an overview of discussions and outcomes from the third WHO informal consultation on influenza vaccine response during the start of a pandemic, held in June 2017. The aim of the meeting was to address challenges and bottlenecks in vaccine response at the start of an influenza pandemic, including issues associated with the decision to start the pandemic vaccine production which might entail the switch from seasonal to pandemic vaccine production.
The first WHO informal consultation on this topic, which took place in 2015, analysed the complexities of vaccine response at the start of an influenza pandemic and provided clarity and understanding among key players on roles and responsibilities of the response. The 2 nd WHO informal consultation in 2016 furthered the discussion to developing principles and processes of decision making of the start of pandemic vaccine production and addressing bottlenecks surrounding the switch. Based on the outcome from the two consultations, the 2013 interim WHO pandemic guidance WHO Pandemic Risk Management Framework (PIRM) was finalized in 2017.

The third informal consultation developed operationalization of the outcomes from the previous two consultations jointly with influenza experts, public health officials, and other stakeholders to address vaccine response at the start of an influenza pandemic, in particular, issues surrounding the potential switch from seasonal to pandemic vaccine production. In addition, the specific challenges for low- and middle-income countries were discussed.

During the consultation, participants drafted an operational framework for pandemic vaccine response, developed a common understanding of an effective pandemic vaccine response, and identified key challenges and potential bottlenecks that would interfere with switching from seasonal to pandemic vaccine production. 

Guiding principles of technical, ethical and political aspects involved in making the decision to start pandemic vaccine production were also elaborated.

Key outcomes from the third informal consultation included the following:

  • A clear, transparent and integrated approach to initiating pandemic vaccine production was proposed; this proposed approach will be further developed by WHO working groups.
  • At the start of a pandemic, WHO will issue recommendations on pandemic vaccine composition and use which will be based on a variety of criteria clearly communicated to all stakeholders involved in the pandemics vaccine response. 
  • Such criteria will be based on risk assessment and to be developed by
    WHO working groups. These will inform the vaccine production decisions.
    Solutions to potential bottlenecks in the pandemic vaccine response at the start of a pandemic should be further prioritized, addressed or operationalized through WHO working groups
  • Communication to clarify the critical responses – including the declaration of a public health emergency of international concern (PHEIC), the declaration of an influenza pandemic, the recommendation to start pandemic vaccine production and subsequent availability of pandemic vaccines should be comprehensively incorporated into global and national pandemic preparedness planning.
These informal consultations clarified critical complexities at national, regional and global levels, and the need for WHO coordinated global response especially the decision to commence the start of pandemic vaccine production based on risk assessment.
The entire document is well worth reviewing, as many of the barriers to developing and distributing an emergency vaccine are not immediately obvious, nor easily solved.

As the chart below illustrates, their 6-months to the first vaccine availability timeline is based on everything going right.
The following timelines represent ideal circumstances, when all staff, facilities, reagents, equipment and process stages are in place and function optimally. If some activities do not go well, they may take longer and this is indicated by the hatched areas of the chart. Due to the interrelatedness of many of the activities, a delay in one activity would delay others in the timeline.

The reality is, even under the best of circumstances, most of the world would not see a pandemic vaccine for a year, maybe longer. Lesser developed countries, particularly those without domestic vaccine production capabilities, would likely find themselves at the back of the line. 
But no one is guaranteed that they'll see a vaccine in a pandemic. 
Last year Johns Hopkins presented a day-long pandemic table top exercise (see CLADE X: Archived Video & Recap), where a vaccine was expected `within 6 months', but turned out to be a failure.
If you don't have the time to watch the (highly recommended) entire 8 hour exercise, I would urge you to at least view the 5 minute wrap up video. It will give you some idea of the possible impact of a severe - but not necessarily`worst case' - pandemic.

Recap Video

While telling people to wash their hands, cover their coughs, avoid crowds, and stay home while sick may seem like an inadequate response to a pandemic - they and other more disruptive measures like school closures, cancellation of public events, etc. - will almost certainly be our most powerful weapons until a pandemic vaccine becomes widely available.

Saturday, August 17, 2019

Japan MAFF: 38th Farm Outbreak Of Classical Swine Fever


The spread of Classical Swine Fever (CSF) continues in Japan, with the 4th farm outbreak announced in just over a week (see Aug 9th's 35th & 36th Farm Outbreak Of CSF and last Monday's 37h Farm Outbreak Of Classical Swine Fever). 

Additionally, since July we've seen two new Prefectures (Mie and Fukui) report their first farm outbreaks.
Classical Swine Fever (CSF) re-emerged in Japan in September of 2018 after an absence of 26 years, initially affecting wild boar and a handful of farms in Gifu prefecture, before spreading to 3 other prefectures.  Exactly how it arrived has never been determined.

While similar to African Swine Fever (ASF), CSF is caused by a different virus (genus Pestivirus, family Flaviviridae). Neither pose a direct threat to human health, although both can be devastating to the swine industry.

First, today's (translated) outbreak report, followed by some excepts from the latest OIE report, which lists the number of infected wild boar that have been detected from 6 prefectures.
Confirmation of suspected affected animals of swine fever in Gifu Prefecture, about (38 case was in Japan)

Ryowa first year August 17,
the Ministry of Agriculture, Forestry and Fisheries

Today, suspected affected animals of swine fever has been confirmed in a farm of wild boar positive confirmation point from there within 10km monitored and made which was Gifu Prefecture Ibi District ibigawa.

We are taken all possible measures for the quarantine measures for the disease.
Interview in the field, thank you for your cooperation as strictly refrain from such that there is a risk that cause the spread of the disease. 

1. Overview of the occurrence farm

Location: Gifu Prefecture Ibi District ibigawa
breeding situation: 3,642 head
2. Background
(1) Gifu Prefecture, August 16 (Friday), from the farm, received a report of a breeding pig has exhibited abnormal, we conducted a site inspection by animal health inspectors.
(2) the same day, because the suspicion of swine fever is caused by the inspection at the Livestock Hygiene Service Center, was subjected to a thorough examination, today (August 17 (Saturday)), turned out to be a suspected affected animals of swine fever want did.
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Summary of the wild boar surveillance (OIE Update #33)
(As of 2nd August) [Gifu prefecture (since 13th of September 2018)] Tested (RT-PCR): 1,783 wild boars (358 dead and 1,425 captured), Positive: 801 (268 dead and 533 captured)
[Aichi prefecture (since 14th of September 2018)] Tested (RT-PCR): 731 wild boars (35 dead and 696 captured), Positive: 59 wild boars (15 dead and 44 captured)
[Nagano prefecture (since 14th of September 2018)] Tested (RT-PCR): 169 wild boars (74 dead and 95 captured) Positive: 39 (19 dead and 20 captured)
[Mie prefecture (since 14th of September 2018)] Tested (RT-PCR): 60 wild boars (11 dead and 49 captured), Positive: 4 (0 dead and 4 captured)
[Fukui prefecture (since 14th September 2018)] Tested (RT-PCR): 39 wild boars (5 dead and 34 captured), Positive: 7 (0 dead and 7 captured)
[Toyama prefecture (since 14th September 2018)] Tested (RT-PCR): 13 wild boars (8 dead and 5 captured) Positive: 2(2 dead and 0 captured)
[Other 37 prefectures (since 14th of September 2018) Tested (RT-PCR): 289 wild boars (259 dead and 30 captured) Positive: 0
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As of May, 2019 the OIE lists the following 36 nations as being free from Classical Swine Fever.

CSF free Members

According to Resolution No. 22 (87th General Session of World Assembly, May 2019)
Members recognised as free from CSF according to the provisions of Chapter 15.2. of the Terrestrial Code :

CDC Clinical Action: Unexplained Vaping-Associated Pulmonary Illness


While we normally think of the CDC's COCA (Clinician Outreach Communication Activity) division as primarily providing monthly continuing education webinars for clinicians, they also send out frequent emails to subscribers on current health issues and best practices.
While these emails are mostly informational, sometimes they are used to alert the healthcare community of a new public health threat, and ask for heightened vigilance and/or action on their part.
In 2018, 4 such `Clinical Action' emails were sent (see below), although 3 of them were related to the same issue (synthetic cannabinoids).
Late yesterday afternoon the CDC issued their first COCA Clinical Action email of 2019, following reports of dozens of unexplained severe pulmonary illness across the country, many of which appear linked to e-cigs or vaping.

CDC Urges Clinicians to Report Possible Cases of Unexplained Vaping-associated Pulmonary Illness to their State/Local Health Department


The following is an updated version of the information posting sent to public health officials via CDC’s Epidemic Information Exchange system (Epi-X) on August 2, 2019.

As of August 14, 2019, 30 cases of severe pulmonary disease have been reported to the Wisconsin Department of Health Services (DHS). Using a case definition drafted by DHS, 15 cases are confirmed (ages 16-34 years) and 15 cases are still under investigation (ages 16-53 years). Patients presented with respiratory symptoms including cough, shortness of breath, and fatigue. Symptoms worsened over a period of days or weeks before admission to the hospital. Other symptoms reported by some patients included fever, chest pain, weight loss, nausea, and diarrhea. Chest radiographs showed bilateral opacities, and CT imaging of the chest demonstrated diffuse ground-glass opacities, often with sub-pleural sparing. Evaluation for infectious etiologies was negative among nearly all patients.

Some patients experienced progressive respiratory compromise requiring mechanical ventilation but subsequently improved with corticosteroids. All patients reported “vaping” (i.e., use of e-cigarette devices to aerosolize substances for inhalation) in the weeks and months prior to hospital admission. Many have acknowledged recent use of tetrahydrocannabinol (THC)-containing products while speaking to healthcare personnel or in follow-up interviews by health department staff; however, no specific product has been identified by all cases, nor has any product been conclusively linked to this clinical syndrome. DHS is working with the Wisconsin State Lab of Hygiene and the U.S. Food and Drug Administration to investigate the possible cause of these illnesses by testing patient specimens and vaping products.

Illinois has identified 24 possible cases. Of these, 10 are considered confirmed, 12 are still under investigation, and 2 have been excluded. Other states such as NY, CA, IN, and UT have also reported possible cases of similar illness and some have issued health alerts to clinicians and healthcare providers in their states. The etiology of this illness is unclear at this time; however, active, state-specific epidemiological investigations are ongoing to better characterize the demographic, clinical, and laboratory features of cases.  

What Clinicians Can Do

Clinicians should always inquire about potential drug (legal and illicit) use as part of a general history. When patients present with respiratory or pulmonary illness, especially of unclear etiology, clinicians should ask about the use of e-cigarette products (devices, liquids, refill pods and/or cartridges) for “vaping”. If possible, inquire about the types of drugs (legal or illicit) used and methods of drug use (e.g., smoking, “vaping”).

CDC recommends that clinicians report cases of significant respiratory illness of unclear etiology and a history of vaping to the appropriate state and/or local health department.

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Although e-cigarettes have been touted as potentially being a `safer' alternative to smoking tobacco products, they use a relatively new delivery system, and contain potentially harmful ingredients (see Surgeon General Vaping Warning). 
The truth is, the long-term health effects of vaping may not be evident for years.
That said, the UK's NHS has more-or-less endorsed vaping as a `safer' alternative to tobacco, stating:
  • An estimated 2.9 million adults in Great Britain currently use e-cigarettes and of these, 1.5 million people have completely stopped smoking cigarettes. They carry a fraction of the risk of cigarettes and can be particularly effective when combined with extra quitting support.
The CDC, however - while acknowledging potential benefit for some adult smokers - has been more cautious.
  • E-cigarettes have the potential to benefit adult smokers who are not pregnant if used as a complete substitute for regular cigarettes and other smoked tobacco products.
  • E-cigarettes are not safe for youth, young adults, pregnant women, or adults who do not currently use tobacco products.
  • While e-cigarettes have the potential to benefit some people and harm others, scientists still have a lot to learn about whether e-cigarettes are effective for quitting smoking.
  • If you’ve never smoked or used other tobacco products or e-cigarettes, don’t start.
  • Additional research can help understand long-term health effects.
Yesterday a number of states issued health advisories on the risks (both known and suspected) of vaping, including the State of New York (see New York State Department of Health Issues Health Advisory on Vaping-Associated Pulmonary Illness).

Since many of these cases appear to be linked to the vaping of THC containing products, including cannabis oils, wax, and buds, it is too soon to know if the same health risks apply across the board for regular `nicotine' vaping.

Stay tuned. 

Friday, August 16, 2019

DRC: WHO Confirms First 2 Ebola Cases in South Kivu Province



A short while ago news broke that 2 people (reportedly a 24 y.o. mother and 7 month old child) in South Kivu Province - several hundred kilometers from the epicenter of the Ebola outbreak - had been confirmed to have the Ebola Virus.  

A few minutes ago (see Dr.Tedros tweet above), those reports were confirmed.
Media reports indicate the mother died on Thursday, while the child is currently receiving treatment. We'll undoubtedly get more information in the hours ahead.  Crofsblog does an excellent job covering the DRC's Ebola outbreak, and I'd invite you to check there often.

The regional spread of Ebola to other provinces (and even neighboring countries) - while disappointing and concerning - isn't unexpected. The WHO's latest risk assessment for the year-long Ebola outbreak in the Eastern DRC reads:

WHO risk assessment

WHO continuously monitors changes to the epidemiological situation and context of the outbreak to ensure that support to the response is adapted to the evolving circumstances. The last assessment, carried out on 5 August 2019, concluded that the national and regional risk levels remain very high, while global risk levels remain low.

Substantial rates of transmission continue within outbreak affected areas of North Kivu and Ituri provinces, with demonstrated extension to new high risk areas and across borders in recent months, although without sustained local transmission in these areas. The high proportion of community deaths, relatively low proportion of new cases who were known contacts under surveillance, existence of transmission chains linked to nosocomial infection, persistent delays in detection and isolation of cases, and challenges in accessing some communities due to insecurity and pockets of community reticence are all factors increasing the likelihood of further chains of transmission in affected communities.

The factors mentioned above, coupled with high rates of population movement from outbreak-affected areas to other parts of the Democratic Republic of the Congo, and across porous borders to neighbouring countries, increase the risk of geographical spread – both within the Democratic Republic of the Congo and to neighbouring countries. Conversely, substantive operational readiness and preparedness activities in a number of neighbouring countries have increased capacity to rapidly detect cases and mitigate local spread. These efforts must continue to be scaled-up and sustained.

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