How a random sampling regime could help detect COVID and highlight infection hotspots


Hannah Peters/Getty Images

Stephen John Haslett, Massey University and Richard Arnold, Te Herenga Waka — Victoria University of WellingtonFor the detection of community transmission of COVID-19, New Zealand currently relies on contact tracing, testing of self-selected people with symptoms and those with permission to travel between different alert levels, and surveillance testing of staff at businesses permitted to operate in higher alert levels.

Surveillance testing has picked up cases before they knew they were contacts of another infected person. But people who are only tested after they feel unwell may have already passed the virus on to several others. Others who have COVID-19 may not display symptoms.

As a supplement to current testing, we suggest a sound, properly designed random sampling regime of certain areas or workplaces to provide a cost-effective way to determine, with known probability, if there is any COVID-19 in a specified area or group.

The critical point is that such COVID Clearance Check surveys must be random.

Continued wastewater testing, contact tracing and community testing stations remain critically important. But they don’t provide any measures of accuracy because currently they don’t incorporate formal sampling designs.

Probability theory behind random sampling

A statistically designed random sampling scheme, based on as few as 100 people or households from key sub-populations, would give a very high probability of detecting if there are any COVID-19 cases. However, to determine this probability, it is critical the sampling is random.

Geographical locations could include certain neighbourhoods and wastewater catchment areas. Workplace sampling could focus on large businesses, rest homes, hospitals and prisons.

COVID Clearance Checks based on random sampling could shorten lockdowns, lessen social impact, save money and support businesses. Once Aotearoa’s borders reopen, they would provide critical information of known accuracy about infection hotspots.




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The formal sampling scheme is based on probability theory, which provides the mathematical connection between COVID prevalence (p₀), sample size (n) and the probability of detecting the virus in the subpopulation (p).

Unless a subpopulation is very small, its size has little effect on the sample size required. For a simple random sample, which selects people or households essentially independently and with equal probability, the probability of detecting COVID is:

p = 1-(1-p₀)ⁿ

For example, for a 3% prevalence of COVID and a random sample of 100, the chance of detecting the virus is over 95%. A larger sample would be required to detect COVID at lower prevalence, for clustered random sampling schemes, or for higher levels of detection probability.

Instead of simple random sampling of households, systematic sampling (which selects households at a fixed interval in a list or along a route) could be used to simplify fieldwork without loss of accuracy.

Survey design and structured fieldwork would provide the mechanism for implementing the random selection of people and safe work conditions for the sampling team. For random sampling, this is now feasible because saliva tests have recently been approved by the Ministry of Health.

Using self-administered saliva tests would reduce close contact between field staff and household members, minimising the risk of spread.

A rapid antigen testing kit
New Zealand has approved the use of rapid antigen testing as a screening tool to protect critical worksites.
Phil Walter/Getty Images

How it would work

Examples where a COVID Clearance Check survey would be useful include towns or city suburbs, and households in catchment areas with positive wastewater results. Sampling areas around MIQ facilities, but not including them, would provide information on possible community transmission.

As a first step, the Ministry of Health would identify particular areas or groups of interest, and then randomly select a sample within it, using statistically sound methods, to ensure every person had a known non-zero chance of being included.

For area sampling, having pre-notified residents, field staff would drop off saliva tests at each sampled household. Household tests would then be collected, either for separate individuals or combined, using set safety protocols.




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Any selected households which do not return test results would be contacted again to reduce non-response bias. Any detected cases would bring other current control mechanisms into play.

Detecting all cases in an area is different and more difficult than detecting whether there are any cases. Cases detected by COVID Clearance Check sampling provide a searchlight rather than fully illuminating the situation. Finding all cases would require much larger sample sizes, which is why such checks supplement rather than replace current surveillance methods.

Using well-designed and implemented random sampling schemes can be an effective, rapid and low-cost way of assessing whether there are any community cases, without testing thousands of people who are not necessarily those of greatest interest. When useful, such surveys can be repeated, using another sample from the same area or group.

As we are now all realising, keeping COVID-19 out of Aotearoa cannot be a long-term plan. Once vaccination rates are high and borders begin to reopen, COVID Clearance Checks using random sampling to monitor possible hotspots will become increasingly useful, even necessary, for surveillance.


Alistair Gray, at Statistics Research Associates, is also a member of the Ministry of Health COVID-19 Expert Advisory Network and has collaborated with us on this article.The Conversation

Stephen John Haslett, Emeritus Professor of Statistics, Massey University and Richard Arnold, Professor of Statistics and Data Science, Te Herenga Waka — Victoria University of Wellington

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Could a test really detect if someone is a COVID-19 ‘superspreader’?


Lara Herrero, Griffith University

Last week we heard Queensland-based biotech company Microbio had developed a test that could, according to media reports, tell whether someone is a COVID-19 superspreader.

While this may sound like an exciting prospect, there are a few questions to answer before we know what role this test might have in managing the spread of COVID-19.

First, what is a superspreader?

It’s important to understand there’s no scientific definition of a “superspreader”.

In the context of COVID-19, the term “superspreader” has been used to describe someone who can spread the virus and cause infection in many people with minimal contact.

There are many factors thought to contribute to what makes someone a superspreader. The most talked about is infectious viral load. Put simply, this is the amount of live infectious virus a person carries.

Current thinking is that people with a higher infectious viral load are more likely to infect others, but it may not be that simple.

An illustration of SARS-CoV-2, the coronavirus that causes COVID-19.
SARS-CoV-2 is the coronavirus that causes COVID-19.
Shutterstock

When a person has a COVID-19 test, the health-care worker uses a swab to collect samples from the back of the person’s nose and throat. These are the areas where the virus likes to live. The swab is then sent to a pathology lab which tests for the presence of viral genomic material.

The test returns as a positive (that is, the virus has been detected) or negative (virus not detected). There’s no indication of how much virus is present, or whether it’s replicating.




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So, back to the new test

Microbio says the newly developed InfectID-COVID-19-R test can detect “replication-competent virus”. This essentially means the test would detect the amount of active live virus a person is carrying. Researchers believe the patient is most likely to be infectious when the virus is replicating.

Like current COVID-19 tests, the test requires a sample of viral genetic material from a patient swab. The genetic material is “extracted” from the swab (termed RNA extraction). The resulting sample is put through a machine to detect an important part of the virus genome which indicates whether the virus is alive and replicating.

InfectID-COVID-19-R claims to accurately detect a virus concentration as low as 1,500 TCID50 per millilitre with 99% specificity. (TCID50 stands for tissue culture infectious dose 50% — it’s currently the accepted standard to quantify the amount of infectious SARS-CoV-2.)

This equation may be tricky to grasp, but the important part to understand is that below this threshold, the person has a lower amount of replicating virus than the test can guarantee to detect. They can’t say for certain the person has no replicating virus.

If a person records a result above the threshold, that tells scientists the virus is alive and replicating.

The suggestion is the test will be able to quantify the amount of replicating virus present in the swab. But exactly what that means — and how the test will achieve this — is uncertain.




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Microbio’s media release is tight-lipped on a few key aspects of this test. We still don’t have answers to some questions, including:

  • what part of the virus genome it is detecting, and how is this different to our current diagnostic tests?

  • how does detecting this part of the virus ensure detection of replicating or “live” virus?

  • how will the test results be presented? For example, will the test provide a reference range and guide on how to interpret the result?

  • how can they prove that if a test comes back below the limit of detection for replicating virus that the person is not infectious?

In response to queries from The Conversation, Microbio’s chief scientific officer Flavia Huygens said the new test “targets the part of the virus’ genome that is present while it is replicating inside the human cell”, and that this target is different to existing COVID-19 tests. She added: “Our test detects the portion of the virus genome that is only present whilst the virus is replicating and hence is indicative that the virus is “live.”

Huygens also said the test has built-in references and guides for clinical laboratories to interpret the results.

It’s early days yet

Without more detail, it’s too early to tell just how useful this test will be.

Certainly, we need to know whether a low replicating viral load means a person is not infectious before using this test to make any decisions around quarantine. Research is still ongoing in this area.

A lecture theatre full of people.
It may be more accurate to describe ‘superspreading events’.
Shutterstock

The test hasn’t yet been approved for use. It has been independently validated by 360 biolabs, a clinical trial laboratory accredited by the Australian National Association of Testing Authorities. Huygens told The Conversation that Microbio is planning further validation of its test using patient samples.

More than a question of viral load

Currently we have no way to know who may be a superspreader. While this test might give us a measure of a person’s replicating viral load, this is only one piece of the puzzle.

As is the case for any virus, spreading SARS-CoV-2 requires more than just high viral load. It requires the right environmental conditions (for example, indoors and lower humidity), proximity to an infected person, and time (more time exposed means more chance of infection).

Therefore it’s more accurate to refer to “superspreading events” rather than to particular people as “superspreaders” more generally. Superspreading events are situations in which one person, aided by the ideal conditions, infects a large number of others.

With this in mind, limiting the time you spend in confined spaces (and wearing a mask if you can’t avoid a closed space), washing your hands and keeping your distance will be your best protection against COVID-19.




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The Conversation


Lara Herrero, Research Leader in Virology and Infectious Disease, Griffith University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

How do we detect if coronavirus is spreading in the community?


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Joanne Macdonald, University of the Sunshine Coast

The daily number of new coronavirus (SARS-CoV-2) cases is now nine times higher outside China than in the country where the disease was first detected.

In Australia, reports this week of local transmission of the coronavirus, which causes the disease now called COVID-19, are a turning point in our disease management.

Our disease surveillance systems are well placed to keep abreast of COVID-19 and provide some reassurance that transmission is unlikely to go undetected in the community. But there’s still more we could do.




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Why is the coronavirus hard to detect?

Detecting all people with COVID-19 is a global problem. There are too many existing respiratory infections, such as colds and flus, in any country to be able to test everyone with coronavirus symptoms.

Each of us gets around two to three upper respiratory tract infections a year. Globally, that amounts to around around 18.75 billion infections a year.

There are not enough testing kits readily available to test people at this scale.

So who is tested?

In Australia, people are currently tested for the coronavirus if they’ve travelled from or through a country considered to pose a risk of transmission in the 14 days before getting sick, or if they have a link to a known case.

This testing criteria has changed as the outbreak progressed, and will continue to do so.

Currently, only those with a relevant travel history or contact with a known case are tested.
Shutterstock

How else do we track possible cases?

Apart from directly testing people suspected of having COVID-19, Australia has a surveillance plan to detect coronavirus in people or populations who don’t know they’re infected.

Australia’s emergency response plan for mitigating COVID-19 says we will use surveillance networks set up for the influenza pandemic emergency reponse plan and some of this is already occurring.




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The Australian Sentinel Practices Research Network (ASPREN) is a network of GPs who log the number of patients they see in total, compared to the number of patients they see with influenza-like illness. These GPs collect samples from a small subset of those patients to see if COVID-19 is circulating. Samples are then sent to SA Pathology for testing.

Another surveillance network that may be activated is FluCAN. This reports on the number of hospitalisations due to a disease, usually influenza, as well as clinical data from the cases. The information helps public health experts get a better picture of how severe the disease is, and the symptoms.

But while these systems can monitor disease levels in those sick enough to seek medical care, they don’t give us an indication of the amount of milder disease that might be circulating in our communities.

It’s unclear how long surveillance systems take to detect community transmission.
James Gourley/AAP

This is where an online surveillance system called FluTracking can help. Anyone in the community can join and answer two simple questions each week about whether they have a fever and/or a cough.

The system provides information on how much influenza-like illness is circulating in the community. If we’re seeing more than usual, it might signify a community outbreak.

FluTracking was activated for COVID-19 surveillance last month.

What else could we be doing?

There are questions, however, about how early in an outbreak the surveillance systems will detect cases.

Will they detect community transmission when an outbreak reaches ten cases? Or will it take hundreds or even thousands of cases to trigger a warning through the network?




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Innovations from other countries suggest there are additional measures Australia could adopt to improve our surveillance networks.

Testing at home or on the road

London adopted a system at the end of January to test mild cases of disease in the patients’ homes. This helps with self-isolation and reducing disease spread.

Meanwhile, Edinburgh has opened a drive-through testing clinic to reduce the chances of viral spreading.

Australia’s emergency response plans include provisions to mobilise flu clinics to help keep patients from overwhelming emergency services. Drive-through services could be an excellent addition to these existing plans.

Rapid testing

One of the biggest concerns with current testing is the time it takes to ship a sample to a laboratory for testing. This can result in a delay of one to two days before getting the results. During peak epidemic times, testing can’t cope with demand.

Researchers in China, however, have reportedly developed a rapid coronavirus test that can detect the virus using a fingerprick of blood in 15 minutes. The test detects if the body has mounted an immune response (Ig M antibodies) to the virus.

While the data is not yet published, the researchers reported success from the 600 samples they tested.

Rapid diagnostic tests are typically cheap to manufacture, can be mass produced, and can be easily used by health workers outside a laboratory.

Reporting on negative test results and surveillance systems

Positive COVID-19 cases from all the surveillance sources are reported as they occur. But while influenza surveillance reports include the number of negative tests results, it’s unclear whether COVID-19 surveillance reports will do the same.

Reporting on negative tests results could help ease community concern that coughs and sneezes people see on the train or in their office are unlikely to be due to the undetected spread of COVID-19.

Local health services should also provide regular updates on the types of COVID-19 surveillance actively being performed, and in which communities. This information can help reduce anxiety levels and assure communities that spread of coronavirus can be effectively monitored.




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The Conversation


Joanne Macdonald, Associate Professor, Molecular Engineering, University of the Sunshine Coast

This article is republished from The Conversation under a Creative Commons license. Read the original article.

‘Pinpricks’ of Truth Making Way into North Korea


Citizens increasingly enlightened about world’s worst violator of religious freedom.

DUBLIN, April 26 (CDN) — As refugees from North Korea and activists from Non-Governmental Organizations (NGOs) gather in Seoul, South Korea this week to highlight human rights violations in the hermit kingdom, there are signs that North Korean citizens are accessing more truth than was previously thought.

A recent survey by the Peterson Institute found that a startling 60 percent of North Koreans now have access to information outside of government propaganda.

“North Koreans are increasingly finding out that their misery is a direct result of the Kim Jong-Il regime, not South Korea and America as we were brainwashed from birth to believe,” Kim Seung Min of Free North Korea Radio said in a press statement. The radio station is a partner in the North Korea Freedom Coalition (NKFC), which is holding its annual North Korea Freedom Week (NKFW) in Seoul rather than Washington, D.C. for the first time in the seven-year history of the event.

“We set out to double the radio listenership of 8 or 9 percent, and we’ve seen a dramatic increase in the number of people who have access to information,” said NKFC Co-Chair Suzanne Scholte. She described the flow of information as “pinpricks in a dark veil over North Korea. Now those pinpricks are becoming huge holes.”

The radio station now air-drops radios into North Korea and broadcasts into the country for five hours a day, adding to information gleaned by refugees and merchants who cross the border regularly to buy Chinese goods.

In recent years the government has been forced to allow a limited market economy, but trade has brought with it illegal technology such as VCR machines, televisions, radios and cell phones that can detect signals from across the border. Previously all televisions and radios available in North Korea could only receive official frequencies. 

“The government hasn’t been able to stamp out the markets, so they begrudgingly allow them to continue,” Scholte confirmed. “This means North Koreans aren’t relying solely on the regime anymore.”

Holding the annual event in Seoul this year sends a significant message, Scholte told Compass.

“This is a spiritual conflict as well as a physical one – some people didn’t want us to call it freedom week,” she said. “But we’re making a statement … God gives us freedom by the very nature of being human and North Koreans are entitled to that too.”

All people say they would never allow the World War II holocaust to be repeated, Scholte said, “but this is a holocaust, a genocide. I firmly believe we will be judged if we fail to intervene.”

The coalition hopes this week’s event will empower the 17,000 strong North Korean defectors in South Korea, awaken the consciousness of the world about human rights conditions in North Korea, and inform all who are suffering in North Korea that others will “work together until the day their freedom, human rights and dignity are realized,” Scholte said in the press statement.

As part of the week’s activities, the coalition will send leaflets into North Korea via balloon stating in part, “In the same year the Universal Declaration of Human Rights was passed, Kim Il-Sung was ensuring that you wouldn’t have any of those rights.”

Religious freedom in particular is almost non-existent. The only accepted belief is Juche – an ideology that strictly enforces worship of the country’s leaders.

“The regime is a perversion of Christianity,” Scholte told Compass. Juche has a holy trinity just as Christianity does, with Father Kim Il-Sung, son Kim Jong-Il, and the spirit of Juche said to give strength to the people.

“Kim Il-Sung is God; a real God can’t replace him,” a former North Korean security agent confirmed in David Hawke’s 2005 report, “A Prison Without Bars.”

While four churches exist in the capital, Pyongyang, experts believe these are largely showpieces for foreign visitors.

The government has allowed token visits from high-profile foreign Christians such as Franklin Graham, president of the Billy Graham Evangelistic Association, who preached at Bongsu Protestant church in Pyongyang in August 2008; and two U.S. Christian bands, Casting Crowns and Annie Moses, attended and won awards at the Spring Friendship Arts Festival in April 2009.

Worship outside limited official venues is simply not tolerated, giving North Korea first place on Christian support organization Open Doors’ 2010 World Watch List for persecution of Christians.

Ordinary citizens caught with a Bible or in a clandestine prayer meeting are immediately labeled members of the hostile class and either executed or placed in prison labor camps, along with three generations of their immediate family. Every North Korean belongs to either the “hostile,” “wavering” or “core” class, affecting privileges from food and housing to education and physical freedom, according to Hawke’s report.

There are no churches outside the capital, but the regime in 2001 estimated there were 12,000 Protestants and 800 Catholics in North Korea. In July 2002 the government also reported the existence of 500 vaguely-defined “family worship centers” catering to a population of approximately 22.7 million, according to a September 2009 International Religious Freedom report issued by the U.S. State Department.

By contrast, South Korea’s Dong-A Ilbo newspaper in July 2009 put the estimate at 30,000 Christians, some NGOs and academics estimate there may be up to several hundred thousand underground Christians.

Uncertain Future

As North Korea celebrated the birthday of Kim Jong-Il on Feb. 16, rumors spread that the elderly leader, currently battling heart problems, had chosen third son Kim Jong-Eun as his successor.

Documents extolling the virtues of Kim Jong-Eun began circulating as early as November, according to the Daily NK online news agency. An official “education” campaign for elite officials began in January and was extended to lesser officials in March. One document obtained by the agency described the “Youth Captain” as being “the embodiment of Kim Il-Sung’s appearance and ideology.”

“Kim picked this son because he’s ruthless and evil,” Scholte said, “but I don’t think they’re quite ready to hand over to him yet. There is an uncertainty, a vulnerability.”

Scholte believes this is the ideal time to “reach out, get information in there and push every possible way.”

“There are many double-thinkers among the elite,” she explained. “They know the regime is wrong, but they have the Mercedes, the education for their kids and so on, so they have no incentive to leave.”

The coalition is trying to persuade South Korea to establish a criminal tribunal, she said.

“North Koreans are actually citizens of South Korea by law,” she said. “We have to let these guys know there’s going to be a reckoning, to create a good reason for them not to cooperate [with authorities].”

Those in other countries have an obligation too, Scholte concluded. “When people walk out of the camps, it will haunt us. They’ll want to know, ‘What were you doing?’ We will be held accountable.”

Article 26 of North Korea’s constitution declares that the people have freedom of religion. The organizers of this year’s freedom week fervently hope that this declaration will soon become a reality.

SIDEBAR

The Cross at the Border: China’s Complicity in Refugees’ Suffering

Non-Governmental Organizations (NGOs) estimate anywhere from 30,000 to 250,000 refugees from North Korea are living in China, either in border areas or deeper inland. Few are Christians when they emerge from North Korea, but the whispered advice among refugees is to “head for a cross,” signaling a Chinese church that may assist them, according to a February 2009 National Geographic report.

Since China will not allow the United Nations High Commissioner for Refugees access to border areas, Chinese Christians work with Christian NGOs to provide an “underground railroad” moving refugees via several routes to safety, most often in South Korea.

Chun Ki-Won, director of Christian NGO Durihana, admits that some of the refugees adopt Christianity to win favor with their rescuers, but others retain and strengthen their faith on arrival in South Korea.

China insists that the refugees are economic migrants and pays police a bounty to arrest and return them to North Korea. On arrival, North Korean officials pointedly question the refugees about contact with Chinese Christians or Christian NGOs. If any contact is admitted, execution or imprisonment is likely, according to David Hawke’s 2005 report, “A Prison Without Bars.”

As one refugee told Hawke, “Having faith in God is an act of espionage.”

Still others choose to return to North Korea with Bibles and other Christian resources at great risk to themselves. For example, officials in June 2009 publicly executed Ri Hyon-Ok, caught distributing Bibles in Ryongchon, a city near the Chinese border, South Korean activists reported.

China remains impervious to the refugees’ plight.

“China fears being flooded by refugees if they show compassion,” said Suzanne Scholte, co-chair of the North Korea Freedom Coalition. “But refugee flows aren’t going to collapse the [North Korean] regime. If that was going to happen, it would have happened already during the famine, so their argument doesn’t hold water.”

She added that North Koreans don’t want to leave. “They leave because of Kim Jong-Il,” she said. “Those [North Korean refugees] in South Korea want to go back and take freedom with them.”

Two U.S. Christians entered North Korea in recent months with the same goal in mind. Robert Park, an evangelical Christian missionary, crossed the border on Dec. 25 with a letter calling for Kim Jong-Il to resign.

Officials immediately arrested Park, according to the regime’s Korean Central News Agency. He was later sentenced to eight years of hard labor but released in late February after making what many experts believe was a forced confession.

Fellow activist Aijalon Mahli Gomes entered North Korea on Jan. 25, the same news agency reported. Officials sentenced Gomes to nine years of hard labor and fined him 70 million new Won (US$518,520). At press time Gomes remained in detention.

Report from Compass Direct News