BROWNSTONEINSTITUTE___________________________________________________

Before Preparing for Pandemics, We Need
Better Evidence of Risk
REPPARE
January 2024

Perceptions of threat
The world is currently reorienting its healthand social priorities to counter a perceived
threat of increased pandemic risk.
Spearheaded by the World HealthOrganization (WHO), the World Bank, and
the Group of 20 governments (G20), thisagenda is based on claims of rapidly
increasing infectious disease outbreaks(epidemics), driven largely by an escalatingrisk of major “spillover” of pathogens fromanimals (zoonosis). To be globally preparedfor such pandemic risk, many quarters havepushed for comprehensive and urgent
action, to avert an “existential threat" tohumanity.

frequency and severity unless urgent action
is taken.
In response, the international public healthcommunity, supported by scientific journals
and major media, is now focused on the taskof preventing, preparing for, and responding
to pandemics and the threat thereof. Over$30 billion annually is being proposed to be
spent on this issue, with over $10 billion in
new funding – three times WHO’s current
annual global budget.
Reflecting a sense of urgency of living in a“pandemic age,” countries will vote on newbinding agreements at the World Health
Assembly in May 2024. These include a setof amendments to the International HealthRegulations (IHRs) as well as a new
Pandemic Agreement (formerly known as
The Pandemic Treaty). The aim of these
agreements is to increase policy
coordination and compliance between
Member States, particularly when the
WHO declares that a Public Health
Emergency of International Concern(PHEIC) represents a pandemic threat.

The G20 has been central to promoting thissense of urgency. As it states in the G20
High Level Independent Panel report ‘A
Global Deal for our Pandemic Age:’“without greatly strengthened

proactive strategies, global
health threats will emerge more
often, spread more rapidly, takemore lives, disrupt more
livelihoods, and impact theworld more greatly than before.”

It is prudent to prepare for public healthemergencies and pandemic risk. It is also
sensible to assure that these preparations arereflective of the best available evidence
concerning pandemic risk, and that any
policy response is proportional to thatthreat. One hallmark of evidence-based
policy is that policy decisions should besubstantiated by rigorously establishedobjective evidence and not based merely on
ideology or common belief. This enables
appropriate allocation of resources among

Moreover,“…countering the existential threat ofdeadly and costly pandemics must be
the human security issue of ourtimes. There is every likelihood thatthe next pandemic will come within adecade…”
In other words, the G20’s report suggeststhat pandemics will rapidly increase in both1

competing health and economic priorities.
Global health resources are already scarceand stretched; there is little doubt thatdecisions about pandemic preparedness will

have significant implications for global andlocal economies, health systems, and wellbeing.

S o, what is the evidence on pandemic threat?
“There has been an acceleration

The G20 declarations from 2022 (Indonesia)
and 2023 (New Delhi) are based on thefindings of its High Level Independent
Panel (HLIP), laid out in a 2022 report
informed by the World Bank and the WHO,and analysis commissioned from a private
data company, Metabiota, and theconsulting firm McKinsey & Company. The
report summarizes the evidence in two
annexes (Figure 1 below), noting in its
Overview that:“Even as we fight this pandemicof zoonotic spillovers over thelast three decades. (See AnnexE.)”
By “zoonotic spillovers,” the report refers to
the passage of pathogens from animal hosts
to the human population. This is thegenerally accepted origin of HIV/AIDS, the2003 SARS outbreak, and seasonal
influenza. Zoonosis is assumed to be themajor source of future pandemics, barringlaboratory releases of pathogens modified byhumans. The basis of the G20 HLIP
report’s sense of urgency is these annexes (Dand E) and their underlying data. In otherwords, it is this evidence base that supports
both the urgency of establishing robust
global pandemic policies, and the level ofinvestment that these policies should
involve.

[Covid-19], we must face thereality of a world at risk of more
frequent pandemics.”
while on page 20:“The last two decades have seen

major global outbreaks ofinfectious diseases every four tofive years, including SARS,
H1N1, MERS and Covid-19.
(See Annex D.)”So, what is the quality of the evidence?
Despite the importance the HLIP report
gives to the data in Annex D, there isactually little data to assess. The Annex
presents a table of outbreaks and the years
they occurred, with no attribution or source
provided. While Metabiota and McKinsey

are quoted elsewhere as primary sources, therelevant McKinsey report does not include
this data, and the data could not be foundwhen conducting searches of publiclyavailable Metabiota material.

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To better understand the implications fromthe data in Annex D, we created acorresponding “best-fit” table of pathogen
outbreaks and year (Figure 1), with official
mortality data for the entire outbreak per
pathogen (some extend beyond 1 year – seesources in Table 1).

“Ebola 2017” was intended to denote in the
Annex D table. In our analysis (Figure 1) we
exclude Covid-19 since its associatedmortality remains unclear and its origin(laboratory-modified or natural) is
contested, as discussed later.
When comparisons are made between the
HLIP outbreaks table and our table of thelast two decades, one mortality event
dominates – the 2009 Swine Flu outbreakthat resulted in an estimated 163,000 deaths.
The next highest, the West African Ebola
outbreak, resulted in 11,325 deaths.

In order to address an apparent oversight in
the Annex D table, we also included the2018 and 2018-2020 Ebola outbreaks in the
Democratic Republic of Congo in our
analysis, since there were no large outbreaksof Ebola reported in 2017. This is likely what

Figure 1. Annex D from the HLIP G20 report showing major outbreaks from 2000 to 2020, and REPPARE’s best
estimate of the outbreaks and associated mortality that the HLIP was alluding to. We have added 2018 and 2018-20
Ebola outbreaks, as we assume these were overlooked by the HLIP. Sources of mortality data are provided at end ofarticle. (Table 1).

Although these absolute numbers areworrisome, in terms of pandemic risk it isnecessary to note that the Ebola virus
requires direct contact for spread and is3

confined to Central and West Africa, where
outbreaks arise every few years and are dealt
with locally. Furthermore, in relative terms,
consider that malaria kills over 600,000
children every year, tuberculosis kills 1.3
million people, while seasonal influenza kills
between 290,000 and 650,000. So, putting
Annex D in context, the West African Ebola
outbreak, the largest in history, thus resulted
in the equivalent of 4 days of global
tuberculosis mortality, while the Swine flu
outbreak of 2009 killed less than influenza
normally does.

the HLIP did not consider sufficiently
significant).
Covid-19 has of course intervened – the firstoutbreak since 1969 to result in greatermortality than seasonal influenza does eachyear. This mortality has occurred
predominantly in the sick elderly, at a
median age above 75 years in highermortality high-income countries, and inpeople with significant comorbidities, acontrast to the predominantly childhood
deaths from malaria and young to middleaged adults who die from tuberculosis.
Excess mortality rose over baseline but
separating out Covid-19 mortality frommortality resulting from the ‘lockdown’measures, reducing disease screening andmanagement in high-income countries andpromoting poverty-related diseases in lowincome countries, makes actual burden
estimates difficult.

The third largest outbreak listed by the G20
HLIP was the cholera outbreak in 2010,
which was confined to Haiti, and thought tohave originated from poor sanitation in a
United Nations compound. Cholera once
caused major outbreaks (peaking between
1852-1859) and was the subject of the firstinternational agreements on pandemics.
Improved water and sewage sanitation has
reduced greatly to a point where the Haiti
outbreak was unusual, and there has been a
consistent overall downward trend since
1859.

However, if we accept Covid-19 (for sake ofargument) as a natural event, then it should
obviously be included when determining
risk. There are meaningful debates about theaccuracy of how deaths were recorded andattributed to Covid-19, yet assuming the
WHO is correct in its estimates, then the
WHO records 7,010,568 deaths attributedto (or associated with) the SARS-CoV-2
virus over 4 years, with most in the first 2
years (Figure 2).

In terms of threat, no other outbreak listedby the HLIP over the 2000-2020 period
killed over 1,000 people. The HLIP
considers this table to show major global
outbreaks every 4-5 years, whereas it actuallyshows mostly small, localized outbreaks ofillness dwarfed by the everyday infectious
and non-infectious diseases that all countries
deal with. There were just 25,629 non-Swine
flu and non-Covid-19 deaths over two
decades from the outbreaks considered by
the HLIP to be severe (it is noted that otheroutbreaks occurred through this period that

Allowing for population increase, this is still
higher than the 1.0 to 1.1 million deaths
attributed to the influenza outbreaks in 195758 and 1968-69, and the largest since the
Spanish flu that inflicted a mortality severalfold higher over a century earlier. With anaverage mortality of 1.7 million per year over4

years of this magnitude, though little
different from major endemic tuberculosis,
and against a background that does notdemonstrate an overall increase in mortality
from outbreak events, it appears to be an
outlier rather than evidence of a trend.

4 years, Covid-19 is not greatly different
from tuberculosis (1.3 million), butconcentrated in a considerably older age
group. Tuberculosis, however, continues
before and will continue after Covid-19,
whereas Figure 2 indicates a rapidly waning
Covid-19 outbreak. As the first event in 100

Figure 2. Covid-19 mortality, as of January 2024 (Source: WHO).
https://data.who.int/dashboards/covid19/deaths?n=c

The second piece of evidence used by the
HLIP to substantiate its claim that we areliving in a “pandemic age” is research
conducted by Metabiota Inc., an
independent company whose epidemiology
team has since been absorbed by Ginkgo
Bioworks. The Metabiota data forms Annex
E of the HLIP report (see Figure 3), whichshows outbreak frequency of zoonotic noninfluenza pathogens over 60 years to 2020,
and influenza ‘spillover’ events for 25 years.

Although Metabiota is cited as the source,
the data itself is not further referenced. Thatsaid, an identical non-influenza data set
appears in an online presentation by
Metabiota to the Center for Global
Development (CGD) on August 25th, 2021
(Figure 4). This dataset also appears in amore recent academic article in the British
Medical Journal in 2023, co-authored by
Metabiota personnel (Meadows et al., 2023).
The authors analyzed the Metabiota
5database of 3,150 outbreaks, including all
outbreaks recorded by WHO since 1963 as
well as “historically-significant” prioroutbreaks (Figure 5). The data used in
Meadows et al. (2023) is available in thearticle’s supplementary information, andformer Metabiota staff confirmed to
REPPARE that the dataset used in that
article, as in the earlier analyses, is now
commercially available through Concentric
by Ginkgo Bioworks.

The data points are summarized in the
HLIP Annex E via two corresponding
claims. Firstly, that there is an “exponential”
increase in non-influenza outbreakfrequency. Secondly, that influenza ‘spillover’(transfer from animals) has increased from“almost none” in 1995 to around 10 events in
2020. Both claims require examination.

Figure 3. Annex E from the HLIP G20 report showing Metabiota Inc. analysis of zoonosis outbreaks 1960-2019(non-influenza) and 1995-2019 (influenza).

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The upper chart in Annex E (Chart 1), if
taken to represent the true frequency ofoutbreaks, does indeed show an exponential
increase since 1960. Yet, as Meadows andco-authors confirm in their later paper, thisincrease in reporting frequency does not take
into account the development of new
surveillance and diagnostic technologies,
which have enabled better (or in some casesany) detection. PCR testing was only
invented in 1983 and has steadily become
more accessible in laboratories over the last
30 years. Antigen and point-of-care serology
tests were only widely available in the past
couple of decades, and genetic sequencing
only very recently.

raises a key issue. Namely, that
advancements in detection technology may
account for the large increase in reported
outbreaks, since most small and localized
outbreaks will have been missed 60 years
ago. As just one example, HIV/AIDS was
missed for at least 20 years before
identification in the 1980s.
What the above suggests is that there arecertainly known spillover effects and thatthese do occur with some frequency anddeadly effect. What is less reliable is theclaim that there is an increased frequency of
zoonosis and/or that the increase inreporting cannot be fully or partly explainedby advancements in detection technologies.
Determining the former would require
further research that could control for thislatter variable.

Since 1960, we also have had significant
improvements in road transport, clinic
access, and digital information sharing. As aresult, this limitation in the Meadows study

Figure 4. Charts from presentation of Metabiota to the Center for Global Development. Chart on right matches theMetabiota non-influenza outbreak chart in the HLIP report.

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In their presentation to the CGD (Figure4), Metabiota included the same frequency
data above, but also included mortality as ameasure of severity. This is important, since
it shows an apparent accompanying
exponential increase in mortality is solely
driven by two recent African Ebola
outbreaks. Again, Ebola is a localized
disease and normally rapidly contained. If
this single disease is removed as a pandemic
threat, the data then shows that, after a few
outbreaks of less than 1,000 deaths 20 years
ago (SARS1, Marburg virus, and Nipah

virus), mortality has decreased (Figure 5).
The world appears to have become muchbetter at detecting and managing outbreaks(and resultant illness) under current
arrangements. The trend in mortality overthe 20 years pre-Covid was downward. A
prominent study of a larger databasepublished in 2014, by Smith et al., found thesame; namely that there was increased
reporting of spillover events but withdecreasing actual cases (i.e. burden) basedon population size

Figure 5. Data from the Metabiota database published by Meadows et al. (2023) (chart 1), and same data with Ebola
virus outbreaks removed (Chart 2).

8The second chart in Annex E of the HLIP
report, of influenza ‘spillover’ events, isdifficult to interpret. Influenza deaths aretrending down in the United States (wheredata is relatively good) over the past few
decades. Furthermore, available global
estimates are relatively flat, with around
600,000 deaths per year for the last few
decades and despite increases in population.

2000 seems unlikely to refer to a real change
in seasonal influenza. It is possible that theincrease refers to advances in detection.
What is more, if only less severe common
influenza variants are considered such as
highly pathogenic avian influenza (HPAI)
types H5 and H7, then mortality has greatly
declined over the past century (see graphic
from Our World in Data site). The WHO
equally notes that mortality from ‘Bird Flu,’of which we most frequently hear, has been
declining (Figure 6).

Thus, Metabiota’s claim of an increase from
1 to 10 spillover events per year from 1995 to

Figure 6. WHO H5N1 influenza (Bord Flu) mortality and cases over the past two decades.

As the HLIP report’s annexes indicate, theclaim of a pre-Covid increase in outbreakrisk appears unfounded. This is good news
from a global health viewpoint but raises
concerns in relation to current G20
recommendations, since they aim to invest
considerable new resources in pandemic
policies while potentially diverting fromexisting programs.

Unfortunately, the McKinsey & Company
report cited by HLIP sheds no further light
regarding risk. With its focus on financing,the McKinsey report merely recommends aninvestment of $15 to $25 billion for two years,
then $3 to $6 billion annually, summarizing
the justification for this investment as:

9

“Zoonotic events, in which
infectious diseases make thejump from an animal to ahuman, touched off some of themost dangerous recent
epidemics, including of Covid19, Ebola, MERS, and SARS.”

dangerous” about an outbreak as well as
what resources and policies would be bestplaced to protect us from these future
dangers.
Elsewhere, publications on pandemic risk
have claimed more than 3 million deaths per
year. These numbers are achieved byincluding the Spanish flu, which occurred
before the advent of modern antibiotics andmainly killed through secondary bacterial
infections, and by including HIV/AIDs, amany-decade event, as an outbreak. Bothinfluenza and HIV/AIDS already have wellestablished international mechanisms forsurveillance and management (although
there could be improvements). As shown
above, influenza mortality has been
dropping with no outbreaks above seasonal
background for 50 years. The type of settingin which HIV/AIDS arose and was able totransmit widely unrecognized for decades
can no longer be found.

Yet, the evidence for this claim is weak. As
shown above, Ebola, MERS, and SARS
caused less than 20,000 global deaths
between them in the past 20 years. This is
the mortality rate of tuberculosis every 5
days. While Covid-19 had much higher
mortality in terms of relative disease burden,
it is not the “most dangerous” health threat
by a considerable margin. In addition,
separating the risks from SARS-CoV-2 virus
from the risks resulting from policy
responses is tricky, and research in this area
remains scant. Yet, understanding thisseparation of Covid-19 risk would be crucial
for determining what is or is not “mostSo, is there an existential risk?
An existential threat is understood assomething that would cause humanextinction or would drastically andpermanently restrain humanity’s potential forsurvival. In this regard, when we think of an
existential threat, we generally think of acalamitous event such as a planet-altering
asteroid or thermonuclear warfare.
Although we agree that it is reckless toargue that there is no pandemic risk, we also
believe that the evidence base to support theclaim of an existential pandemic threat
remains largely underwhelming.

As our analysis shows, the data upon which
the G20 has justified pandemic risk is weak.
The assumptions of a rapidly increasing
threat drawn from that data, which is used
to then justify huge investments in pandemic
preparedness and a substantial reordering ofinternational public health, are not based onsolid ground. Moreover, the likely impact of
the surveillance structures being put in place
to detect natural threats must also bequestioned, as the savings claimed are
predominantly based on historic influenza
and HIV/AIDS, for which mechanisms are
already in place and risks are reducing, while10mortality from spillover events from animalreservoirs, the basis of the G20’s claims ofincreasing risk, is also low.

As we have argued, major shifts in policy
and financing should be based on evidence.
This is currently difficult within theinternational public health community, as
much funding and career opportunities are
now tied to the growing pandemic
preparedness agenda. Moreover, there is a
general feeling within global health policy
circles that it is essential to capitalize on a
“post-Covid moment” without delay, sinceattention on pandemics is high andopportunities for policy agreement more
likely.

Covid-19 alone also presents a poor
justification on various levels. If it is ofnatural origin, then based on the G20 data it
could be understood as an isolated event andnot part of a trend. In addition, Covid-19
mortality is predominantly in the elderly andalready ill, and complicated by changing
definitions of attributable mortality (of, as
versus with, the pathogen). If SARS-CoV-2
is laboratory-modified, as some have argued,
then the massive effort underway to build
surveillance for naturally occurring threats
would not be justified nor appropriate to thetask.

However, to maintain credibility, the onus is
to provide rational and credible evidence ofthe risk of outbreaks in the context of overall
health risks and burdens. This is notreflected in the G20’s statements, indicatingthat the advice on which they base theirclaims is either poor, rushed, and/or being
ignored.

As a result, we must ask ourselves whether
this is an adequate justification for rushingnew international legal agreements that
could divert significant resources from larger
disease burdens that pose everyday risks.
The G20 is basing its recommendation forover $31 billion a year in new pandemic
financing on mortality figures that palebeside the everyday health risks that mosthumans face. In effect the G20 is asking
countries with endemic infectious disease
burdens orders of magnitude higher thanthese small outbreaks to divert limited
resources to intermittent risks largely
perceived to be threats by richer
governments.

There should be time, and urgency, to fix
this evidence gap. Not because the next
pandemic is just around the corner, but
because the costs of getting things wrong
will have long-term implications that may be
far harder to address once wholesalechanges are initiated. As a result, what isprudent is to give the evidence pause forthought, to identify the knowledge gaps,
address them, and to pursue better evidencebased policy.

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Table 1. Derivation of data for REPPARE analysis of HLIP Report Annex D.
2019 SARS-CoV-2

Worldwide…

See main text.

2018 Lassa

Nigeria114

2017 Zika

Brazil362a

https://www.who.int/emergencies/disease-outbreaknews/item/20-april-2018-lassa-fever-nigeria-en
https://www.nejm.org/doi/pdf/10.1056/NEJMoa2101195

2017 Ebola

4bhttps://www.cdc.gov/vhf/ebola/outbreaks/drc/2017-may.html

2014 Chikungunya

DRC (Bas
Uele)
Caribbean0c

https://www.who.int/news-room/fact-sheets/detail/chikungunya

2014 Ebola

West Africa

11,3252012 MERSWorldwide

858

2010 Cholera

Haiti

9,792

2009 H1N1 Influenza

Worldwide

163,000

2004 H5N1 Influenza

Worldwide

32d

2003 SARS-CoV-1

Worldwide

774

2001 Enterovirus 71

Taiwan26

https://www.who.int/emergencies/situations/ebola-outbreak2014-2016-West-Africa
https://www.who.int/health-topics/middle-east-respiratorysyndrome-coronavirus-mers#tab=tab_1
https://www.who.int/emergencies/disease-outbreaknews/item/2022-DON415
https://apps.who.int/iris/bitstream/handle/10665/329438/97892
41516839-eng.pdf?ua=1
https://www.who.int/publications/m/item/cumulative-numberof-confirmed-human-cases-for-avian-influenza-a(h5n1)-reportedto-who--2003-2023-1-november-2023
https://www.who.int/publications/m/item/summary-ofprobable-sars-cases-with-onset-of-illness-from-1-november2002-to-31-july-2003
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188855/

2001 Nipah

Bangladesh,
India

54f

(2018 Ebola)

DRC (Bikoro)

33g(2018-2020)

DRC (NorthKivu, Ituri,
South Kivu)

2287g

TOTAL
TOTAL Excl influenza

https://www.who.int/emergencies/disease-outbreaknews/item/2023-DON490
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323384/
https://www.cdc.gov/vhf/ebola/outbreaks/drc/2018-may.html
https://www.who.int/emergencies/disease-outbreaknews/item/2020-DON284

189,661

25,629a Assumed to refer to the 2016-2017 0utbreak. Mortality not recorded, but derived here from attributable child mortality basedon Brazil data (0.1203 Zika, 0.0105 background, 0.1098 attributable, in 3308 Zika-positive pregnancies, derived from Paixao
et al. (2022); https://www.nejm.org/doi/pdf/10.1056/NEJMoa2101195
b HLIP Report may have intended to reference 2018 (f).
c Attributable chikungunya mortality is normally minimal, predominantly associated with mortality in the sick elderly.
WebArchive includes a now-deleted PAHO report including 194 Caribbean deaths in two small island States, which may be an
attribution error. https://web.archive.org/web/20220202150633/https://www.paho.org/hq/dmdocuments/2015/2015-may15-cha-CHIKV-casos-acumulados.pdf
d Median of range derived from the WHO.
e Avian influenza has low mortality throughout the 20-year period – see Figure 6.
f Includes two outbreaks in that year; 45 in India and 8 in Bangladesh.
g Two 2018 Ebola outbreaks added to table, as this may have been what HLIP intended when referring to a 2017 outbreak.

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REPPARE Team, University of Leeds. January 2024
REPPARE involves a multidisciplinary team convened by the University of Leeds, and led by
two principal investigators.

Garret Wallace Brown
Garrett Wallace Brown is Chair of Global Health Policy at the University of Leeds. He is CoLead of the Global Health Research Unit and will be the Director of a new WHO
Collaboration Centre for Health Systems and Health Security. His research focuses on global
health governance, health financing, health system strengthening, health equity, and estimating
the costs and funding feasibility of pandemic preparedness and response. He has conducted
policy and research collaborations in global health for over 25 years and has worked with NGOs,
governments in Africa, the DHSC, the FCDO, the UK Cabinet Office, WHO, G7, and G20.

David BellDavid Bell is a clinical and public health physician with a PhD in population health andbackground in internal medicine, modeling and epidemiology of infectious disease. Previously,
he was Director of the Global Health Technologies at Intellectual Ventures Global Good Fundin the USA, Programme Head for Malaria and Acute Febrile Disease at the Foundation for
Innovative New Diagnostics (FIND) in Geneva, and worked on infectious diseases andcoordinated malaria diagnostics strategy at the World Health Organization. He has worked for
20 years in biotech and international public health, with over 120 research publications. David isbased in Texas, USA.

Blagovesta Tacheva
Blagovesta Tacheva is a REPPARE Research Fellow in the School of Politics and International
Studies at the University of Leeds. She has a PhD in International Relations with expertise inglobal institutional design, international law, human rights, and humanitarian response. Recently,
she has conducted WHO collaborative research on pandemic preparedness and response costestimates and the potential of innovative financing to meet a portion of that cost estimate. Her roleon the REPPARE team will be to examine current institutional arrangements associated with the
emerging pandemic preparedness and response agenda and to determine its appropriatenessconsidering identified risk burden, opportunity costs and commitment to representative /equitable decision-making.

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Jean Merlin von Agris
Jean Merlin von Agris is a REPPARE funded PhD student at the School of Politics andInternational Studies at the University of Leeds. He has a Masters of Science degree indevelopment economics with a special interest in rural and agricultural development. Recently, he
has focused on researching the effects of non-pharmaceutical interventions during the Covid-19
pandemic. Within the REPPARE project, Jean will focus on assessing the assumptions and therobustness of evidence-bases underpinning the global pandemic preparedness and response
agenda, particularly assumed estimates regarding the frequency and severity of pandemics.

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