Vaccine Derived Poliovirus (VDPV): A review

Abstract

Poliomyelitis is caused by Poliovirus, a member of a large group of enteroviruses. Vaccine-derived polioviruses (VDPVs) stem from mutated live poliovirus, which is contained in the Oral Polio Virus vaccine (OPV). In addition, the emergence of VDPV is one of the global challenges for the eradication of poliomyelitis. VDPVs continue to affect different parts of the world and 1081 cases occurred in 2020 and 682 cases in 2021. There are several reasons that may had caused the increase in circulating Vaccine derived poliovirus (cVDPV) after the “switch” from the trivalent to the bivalent oral polio vaccine. One reason is the low vaccination among the targeted population, and this has further been aggravated by the COVID-19 pandemic. Several strategies could control the spread of VDPV including the use of the monovalent OPV (mOPV-2). The risk of VDPV can be minimized through increased immunization rates and the use of safer vaccine alternatives. The global effort to eradicate polio has made significant progress over the years, but continued vigilance and investment in immunization programs are needed to achieve the ultimate goal of a polio-free world.

Full text

REVIEWS
174
Le Infezioni in Medicina, n. 2, 174-185, 2023
doi: 10.53854/liim-3102-5
Vaccine Derived Poliovirus (VDPV)
Aroop Mohanty1, Ranjana Rohilla2, Kamran Zaman3, Vivek Hada1, Surakchhya Dhakal4,
Abhishek Shah5, Bijaya Kumar Padhi6, Zahra Haleem Al-qaim7, Kauthar Jaffar A. Altawfiq8,
Raghavendra Tirupathi9, Ranjit Sah10,11,12, Jaffar A. Al-Tawfiq13,14,15
1Department of Microbiology, AIIMS Gorakhpur, Uttar Pradesh, India;
2Department of Microbiology, Shree Guru Ram Rai Institute of Medical and Health Sciences, Dehradun,
Uttarakhand, India;
3Department of Microbiology and Molecular Biology, ICMR-National Institute of Traditional Medicine,
Belagavi, Karnataka, India;
4Department of Medicine, Nepal Medical College and teaching hospital, Dharan, Nepal;
5Department of Medicine, B.P. Koirala Institute of Health Sciences, Dharan, Nepal;
6Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education
and Research, India;
7Department of Anesthesia techniques, Al-Mustaqbal University College, Hillah, Babylon, Iraq,
8Department of Medicine, Alfaisal University, Riyadh, Saudi Arabia;
9Internal Medicine Department, Keystone Health, Chambersburg, USA;
10Tribhuvan University Teaching Hospital, Kathmandu, Nepal;
11Dr. D.Y Patil Medical College, Hospital and Research Centre, Dr. D.Y. Patil Vidyapeeth, Pune, Maharashtra, India;
12Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Pune 411018, Maharashtra,
India;
13Infectious Disease Unit, Specialty Internal Medicine, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia;
14Division of Infectious Diseases, Indiana University School of Medicine, Indianapolis, IN, USA;
15Division of Infectious Diseases, Johns Hopkins University, Baltimore, MD, USA
Article received 11 March 2023, accepted 15 May 2023
Corresponding author
Jaffar A. Al-Tawfiq
E-mail: jaffar.tawfiq@jhah.com;
jaltawfi@yahoo.com
Poliomyelitis is caused by Poliovirus, a member of a
large group of enteroviruses. Vaccine-derived poliovi-
ruses (VDPVs) stem from mutated live poliovirus,
which is contained in the Oral Polio Virus vaccine
(OPV). In addition, the emergence of VDPV is one of the
global challenges for the eradication of poliomyelitis.
VDPVs continue to affect different parts of the world;
1081 cases occurred in 2020 and 682 cases in 2021. There
are several reasons that may have caused the increase in
circulating vaccine-derived poliovirus (cVDPV) after
the “switch” from the trivalent to the bivalent oral polio
vaccine. One reason is the low vaccination rate among
the targeted population, which has been further aggra-
vated by the COVID-19 pandemic. Several strategies
could control the spread of VDPV including the use of
the monovalent OPV (mOPV-2). The risk of VDPV can
be minimized through increased immunization rates
and the use of safer vaccine alternatives. The global ef-
fort to eradicate polio has made signicant progress
over the years, but continued vigilance and investment
in immunization programs are needed to achieve the
ultimate goal of a polio-free world.
Keywords: Poliovirus, vaccine derivative poliovirus.
SUMMARY
n INTRODUCTION
Poliomyelitis is caused by Poliovirus, a non-en-
veloped, positive sense, single-stranded RNA
virus, identied in 1908 by Karl Landsteiner and
Erwin Popper [1]. Most of infected patients remain
asymptomatic and less than 1% of the exposed
susceptible children less than 5 years of age gets
paralytic polio (acute accid paralysis (AFP)) [1].
In addition, between 5-10% of children may die
from respiratory failure due to involvement of the
respiratory muscles [2]. The disease transmission
pattern is dependent on the socioeconomic situa-
tion of the country affected. Fecal-oral route in de-
veloping countries and oral-to-oral route through

175Vaccine Derived Poliovirus
saliva and respiratory droplets in developed coun-
tries are the most common routes of transmission
[2, 3].
There are three wild poliovirus types 1, 2 and 3
(WPV-1, 2, 3). Of these types, WPV-1 is responsible
for the majority of the global outbreaks, whereas
WPV-2 and WPV-3 cause limited clusters. The ma-
jor risk factor associated with disease spread is
low sanitation, lack of access to clean drinking wa-
ter, poor hand hygiene and high population den-
sity [4, 5].
Polio is an eradicable disease. The virus causes
acute and short-term infections; in most cases in-
fected cases can only transmit the virus for less
than 2 weeks. The wild poliovirus cannot survive
for long periods outside the human body; if every
single child is vaccinated, virus will eventually die
out. Humans are the only reservoir and there is no
vector involved in the transmission, moreover no
poliovirus transmission has been documented
among animals. There are safe and effective polio
vaccines available. The virus in the oral type of the
vaccine is also excreted in faeces. Mass campaigns
using oral polio vaccine interrupts WPV circula-
tion by boosting population immunity so that
transmission of poliovirus cannot be sustained[6].
When a child is immunized with Oral Polio Vac-
cine (OPV), the weakened vaccine-virus replicates
in the gut for a limited duration, and as immune
system is stimulated, it develops antibodies
against the virus. In areas of crowding and inade-
quate sanitation, this excreted vaccine-virus un-
dergo some replication and can spread in the com-
munity, which also protects other children through
‘passive’ immunization. But if a population is sig-
nicantly under-immunized, the excreted vac-
cine-virus circulates for a longer period of time (at
least 12 months) and it undergoes many genetic
changes. Very rarely, the vaccine-virus can geneti-
cally change into a form that can cause paralysis
similar to the wild poliovirus and is known as a
circulating vaccine-derived poliovirus (cVDPV).
cVDPVs occur when routine or supplementary
immunization activities are poorly conducted,
and population has a low vaccination coverage.
Contrarily, if a population is fully immunized, it is
safe from both vaccine-derived and wild poliovi-
ruses. The development and spread of VDPV are
important hindrance in the journey to the global
eradication of poliomyelitis [7].
Since 2000, more than 10 billion doses of OPV
have been administered to nearly 3 billion chil-
dren globally. As a result, more than 13 million
cases of polio have been prevented, and the dis-
ease has been reduced by more than 99%. Until
2015, over 90% of cVDPV cases were due to the
type 2 component in OPV. As wild poliovirus type
2 had already been successfully interrupted since
the year 1999, in 2016 a switch was implemented
from trivalent OPV (tOPV) to bivalent OPV
(bOPV) in routine immunization programmes.
The removal of the type 2 virus from OPV was as-
sociated with a reduction of the risk of cVDPV2.
Circulating VDPVs in the past have been rapidly
stopped with 2-3 rounds of high-quality immuni-
zation campaigns. To avert all sorts of polio out-
breaks, every child should be vaccinated with the
oral vaccine to stop polio transmission [7].
Types of Vaccine-Derived Poliovirus
VDVPs can spread in communities with incom-
plete polio vaccination, predominantly in places
with poor hygiene, unsanitary conditions or
crowded living situation [8]. It has been well-es-
tablished that the major factor causing polio out-
breaks and incidents is the community at large
with low immunization rate. Lower level of house-
hold literacy and lower maternal education, vac-
cine hesitancy and reluctance are some of the var-
iables that lead to low vaccination coverage or
Table 1 - Classification of Vaccine-derived polioviruses (VDPVs).
VDPVs classification:
–Circulating (cVDPVs): evidence of community transmission
–Immunodeciency-associated VDPVs (iVDPVs): isolation from patients with primary immunodeciency
–Ambiguous (aVDPVs): identity is not known and the virus is not cVDPV nor iVDPV
VDPVs divergence (differences in genetic sequence) from complete viral protein 1 (VP1) genomic coding region of wild OPV:
–VDPV-1 & 3: >1% divergent (≥10 nucleotide)
–VDPV-2: > 0.6% divergent (≥6 nucleotide)

176 A. Mohanty, R. Rohilla, K. Zaman, et al.
uptake [9]. Based on nucleotide changes, VDPVs
are classied based on the divergence from the
wild OPV strain complete viral protein 1 (VP1)
genomic coding region into three types [10-12]
[Table 1].
1. Circulating vaccine-derived poliovirus (cVDPV)
cVDPV is dened when there is evidence of hu-
man-to-human transmission, a previously detect-
ed isolate of VDPV is genetically linked to it, and
the evidence comes from at least two individuals
(not necessarily AFP cases) who are not in direct
contact, at least one individual and one or more
environmental samples, at least two individuals
and two or more environmental samples collected
more than two months apart, or at least one dis-
tinct collection [9]. The nucleotide sequence of the
Sabin strain shows >1% variability from that of the
cVDPV produced from OPV vaccination, indicat-
ing sustained replication with or without circula-
tion in VDPV. The vaccine virus can evolve and
reacquire neurovirulence over the course of 12 to
18 months if it is allowed to circulate for an ex-
tended period without interruption. Because of
insufcient vaccination coverage, cVDPVs can
typically recombine with other enteroviruses in-
creasing their neurovirulence and transmissibility.
Following the elimination of serotype 2 WPV, im-
munization with OPV-2 as part of the tOPV, in-
cluding serotypes 1, 2, and 3 persisted, resulting in
recurrent outbreaks of VDPV-2. Similarly, it result-
ed in outbreaks with VDPV-1 and VDPV-3 [8, 13].
With the course of time, bivalent vaccines (OPV1
& OPV3) were introduced in areas with OPV2
elimination. cVDPVs having a community circula-
tion of more than six months are termed as persis-
tent cVDPVs. Similar to naturally occurring polio-
virus, complete immunization is the primary de-
fense against cVDPV. Two to three rounds of effec-
tive vaccination efforts have effectively stopped
the spread of VDPVs. Regardless of where the vi-
rus originates, the only way to limit the spread of
polio is to vaccinate every child.
2. Ambiguous vaccine-derived poliovirus (aVDPV)
Ambiguous vaccine-derived polioviruses (aVD-
PVs) are VDPV isolates from humans or the envi-
ronment that show no signs of circulation and
come from people who do not have known im-
mune deciencies. The majority of the time, they
are separated from sewage whose ultimate source
is unknown or isolated from persons with no im-
munodeciency and with no evidence of trans-
mission. If subsequently discovered isolates are
genetically connected, it may be reclassied as
cVDPV. One study reported aVDPV in immuno-
competent persons and environmental samples in
seven countries in January 2017-June 2018 [14] and
in 10 countries in January 2016-June 2017 [15].
aVDPV was detected in September 2021 from
wastewater samples in the Jerusalem region [16].
3. Immunodeciency-related vaccine-derived
poliovirus (iVDPV)
After receiving OPV, around 50% of immunocom-
petent individuals excrete poliovirus for two
weeks. Individuals lacking in primary antibodies
are the exception: they could excrete the virus for
3 months [17]. Few individuals with rare immune
deciency syndromes have been found to have
prolonged replication of vaccine-derived viruses
(eg: B cell immunodeciencies) [18-20].
Those individuals fail to mount an immune re-
sponse, which prevents them from being able to
recover from an intestinal vaccine virus infection,
which typically disappears after six to eight weeks
following vaccination. As a result, they continu-
ously excrete iVDPVs [9]. In a study in 2017-2018,
ve countries reported cVDPV and 14 individuals
in nine countries excreted iVDPV [21]. A case of
VDPV-3 with high genetic diversity was found in
2022 in a stool specimen from an infant with pri-
mary immunodeciency disorder in China [22]. In
addition, a Sabin 3/Sabin 1 recombinant of VDPV
was isolated from a child [23]. This issue is even
more problematic with the presence of chronic ex-
cretion of iVDPV2 as described in a patient from
the Philippines [24]. Whether such individuals
may act as reservoirs of such iVDPV and examine
the risks of chronic and prolonged excretions are
being studied in Pakistan [25]. A study from Tuni-
sia showed that the rate of poliovirus detection
was 6.8%, 1.5% and 1.3% in patients with primary
immune deciency, AFP cases, and contacts, re-
spectively [26]. The surveillance of iVDPV showed
16 new cases in ve countries (Argentina, Egypt,
Iran, the Philippines, and Tunisia) from July 2018
to December 2019 [27].
Detection of VDPVs
Detection of poliovirus in stool samples from
acute AFP cases and environmental surveillance

177Vaccine Derived Poliovirus
in the form of sewage sampling are the gold stand-
ard for identifying VDPVs. All AFP cases are in-
vestigated by analyzing stool specimens. If a po-
liovirus is isolated and RNA sequencing is done,
then a VDPV is indicated by the presence of >10
nucleotide differences from the OPV virus. Fol-
lowing conrmation of a VDPV, it is essential to
determine if the VDPV virus is circulating or is an
isolated case. Also, it is important to nd out if the
person who is diagnosed with VDPV has any im-
munodeciency. House-to-house visits are con-
ducted to check on if contacts have been infected
with the VDPV. Epidemiological studies are then
carried out to search for any unrecognized and un-
reported cases in hospitals, in the nearby area [4].
Apart from AFP surveillance and conrmation of
VDPVs, detection of poliovirus in sewage waters
can help detect reintroduction of the WPV in coun-
tries previously declared polio-free [28]. Recently
in the UK and USA, many genetically linked Sa-
bin-like poliovirus 2 were detected from environ-
mental samples, and these samples were classied
as cVDPV-2 [5]. In the USA, the detection of envi-
ronmental viral sequences at two different times,
containing >5 nucleotide changes, and both linked
to the case from Rockland County, was labelled as
cVDVP2. The virus detected in USA is genetically
linked to viruses detected in the UK and Israel.
Figure 6 shows detection of genetically linked
cVDVP2 [5].
Epidemiology
Widespread implementation of OPV led to a re-
duction in the number of AFP cases caused by the
WPV. Subsequently, in the areas with incomplete
vaccination, and the non-availability of inactivat-
ed poliovirus vaccine, the problem of cVDPV per-
sisted. The multiple outbreaks of cVDPV in 2000-
2001 in Haiti and the Dominican Republic were
the rst of their kind with the identication of 21
cases with two fatalities [29].
Though the number of WPV cases has been eclin-
ing in the last 15 years, cVDPV remained endemic
in some regions. This problem was especially sig-
nicant in Africa and the Eastern Mediterranean
region, according to the World Health Organization
(WHO) (Figure 1). There were 24 outbreaks of cVD-
PV with 760 cases between 2000 and 2016 [9]. In
2017, an outbreak attributed to cVDPV2 occurred in
Syria and spanned more than 6 months, and the
virus was isolated from 74 cases of AFP [30].
“Switch and VDPV increase”
It was observed that routine use of OPV contain-
ing poliovirus type 2 was associated with more
risk than benet, especially after the eradication of
WPV-2 in 2015. Therefore, in April-May 2016, the
World Health Assembly authorized a phased ces-
sation of the tOPV, and this strategy was labeled
the “Switch” [31]. The “Switch” was made from
the tOPV (strains 1-3) to the bivalent OPV (b-OPV;
type 1 and 3). OPV-2 however, had been recom-
mended for use during outbreaks [32].
Following the switch, there was an increase in cases
of cVDPV especially in countries in Africa and the
Eastern Mediterranean region. In 2017, an outbreak
attributed to cVDPV2 occurred in Syria and
spanned more than 6 months, and the virus was
isolated from 74 cases of AFP [32]. After adjusting
for gender, level of literacy, and gross domestic
Figure 1 - Showing the Trends
of the WPV cases and cVDPV
cases from 2009 onwards [66].
Source: AFP Polio data. Available
from: https://extranet.who.int/
polis/public/CaseCount.aspx [Ac-
cessed 26th April 2023].
AFR: African Region; AMR: Regions
of the America; EMR: Eastern Med-
iterranean Region; EUR: European;
SEA: South East Asia; cVDPV: circu-
lating Vaccine Derived Poliovirus;
WPV: Wild Poliovirus.

178 A. Mohanty, R. Rohilla, K. Zaman, et al.
product (GDP) per capita, the presence of a low
vaccination coverage was associated with higher
odds of occurrence of cVDPV [9]. The switch may
have contributed to the emergence of cVDPV espe-
cially in 2016-2017, with an associated increase in
the number of outbreaks [9, 21, 33]. In 40 countries
reporting cVDPV, 55% of the countries had low
(<80%) polio vaccination coverage [9]. The number
of cVDPV cases increased from ve in 2016 to 378
in 2019 (Figure 1) and this was associated with an
increase in the number of countries reporting cVD-
PV [29]. The presence of both cVDPV-1 and cVD-
PV-2 was reported in the Republic of the Philip-
pines in 2019 and in Malaysia in 2020 [34].
Several reasons were thought to have caused the
increase in cVDPV after the “switch”, although,
one mathematical model expected a reduction in
cVDPV [35, 36]. The study indicated that the ces-
sation of OPV would eliminate all circulating live
polioviruses, with the caution that population im-
munity is managed appropriately [36]. Managing
immunity at the population level might not be
possible given the variable prevalence of such dis-
orders in any given community. In mathematical
modeling studies, for communities with low vac-
cine-coverage, it is important to attain high cover-
age with the tOPV before the switch [36, 37]. In
countries where cVDPV occurred such as Syria,
Nigeria and Somalia, the coverage rate with tOPV
before the switch was 30-60% [21, 33, 38]. One
study also showed that an increase of 10% in pop-
ulation immunity of children < 5 years of age at
the campaign time and location corresponded to
an 18% decrease in emergence of cVDPV-2 [39]. As
will be discussed later, the use of monovalent OPV
(mOPV-2) is an important strategy to control cVD-
PV outbreaks. However, this intervention should
result in a high-coverage rate to prevent the emer-
gence of cVDPV [37]. It was shown that the num-
ber of cVDPV outbreaks increased from 9 in 2017-
2018 to 29 in 2019 inside and outside of mOPV2
response areas and that 86% of such outbreaks
were due to cVDPV-2 [40].
VDPVs continue to affect different parts of the
world, and a total of 1081 cases were reported in
2020 and 682 cases in 2021 (Figure 2). In 2021, the
highest number of Type 1 cVDVP from AFP cases
had been detected in Madagascar (13) and Yemen
(3). In the same year, the highest number of Type2
cVDVPs had been detected in Nigeria (415), Yem-
en (66), DR Congo (28), and Niger (18).
Figure 2 - Global prevalence of cVDVP2 cases from year
2018-2022 [41].
Source: cVDPV2 Outbreaks and the Type 2 Novel Oral Polio
Vaccine (nOPV2) https://polioeradication.org/wp-content/
uploads/2022/10/GPEI-nOPV2-Factsheet-EN-20221011.pdf
In the year 2022, 185 type 1 cVDVPs, 673 type 2
cVDVPs, and one type 3 cVDVP were detected in
AFP cases. The maximum number of type 1 cVD-
VPs in 2022 has been detected in DR Congo (144),
Mozambique (22), Madagascar (14), and Malawi
(4). The maximum number of Type2 cVDVPs have
been detected from DR Congo (360), Yemen (162),
Nigeria (48), and Chad (44) [41].
Impact of COVID-19 to polio eradication
The occurrence of the COVID-19 pandemic in
March 2020 increased the burden on polio-eradica-
tion programs around the globe. This addition oc-
curred on top of the repeated occurrence of cVD-
PV2 outbreaks in many countries and the presence
of an endemic WPV type 1 (WPV-1) in Afghanistan
and Pakistan [42]. Due to the COVID-19 pandemic,
the Global Polio Eradication Initiative (GPEI) pro-
gram utilized deferred house-to-house visits to ad-
minister supplementary immunization activities in
28 countries between March to May 2020 and GPEI
strived to continue the essential poliovirus surveil-
lance activities. It was noted that the global AFP
cases declined by 34% in January-July 2020 com-
pared with January-July 2019. In addition, there

179Vaccine Derived Poliovirus
was a reduction in the mean number of active envi-
ronmental samples collected in the African and
Eastern Mediterranean regions [43].
An additional impact of the COVID-19 pandemic
on polio eradication was the increase in the num-
ber of cVDPV outbreaks. From 2019 to 2020, the
number outbreaks tripled paralyzing over 1100
children [44]. From the beginning of the COV-
ID-19 pandemic, cases of cVDPV2 among AFP in-
creased in many African countries, including the
Democratic Republic of Congo (DRC), Nigeria,
and Yemen. More than 400 cases were notied
from Nigeria only in 2021 whereas DRC reported
>250 cases last year (Figure 3). Additionally, in the
DRC, >90 cases of cVDPV-1 were reported among
patients with AFP (Figure 4) [45].
On the other hand, in August 2020 and in the
midst of the pandemic, Africa was announced to
be free of WPV, thus leaving Pakistan and Afghan-
istan with such cases [46]. Unfortunately, this vic-
tory was short-lived as in November 2021 a case of
AFP was reported from the Eastern African coun-
try Malawi and the WPV-1was identied from the
stool sample of the patient [21]. Additionally, eight
new cases of WPV-1 were identied from the adja-
cent neighboring country of Mozambique [47, 48].
These two countries had eradicated poliovirus in
1992 and 1993 respectively [49]. Additional rea-
sons cited for the emergence of polio in Africa are
the continued movements and the increase in an-
ti-vaccine activities [50].
A patient with VDPV-2 paralytic poliomyelitis
Figure 3 - Distribution of
cases of cVDPV 2 isolated in
patients with Acute Flaccid
Paralysis from 2020-2023 [66].
Source: AFP Polio data. Available
from: https://extranet.who.int/
polis/public/CaseCount.aspx
AFR: African Region; AMR: Re-
gions of the America; EMR: East-
ern Mediterranean Region; EUR:
European; SEA: South East Asia;
cVDPV: circulating Vaccine De-
rived Poliovirus; WPV: Wild Polio-
virus.
Figure 4 - Distribution of cas-
es of cVDPV 1 & 3 isolated in
patients with Acute Flaccid
Paralysis from 2020-2023 [66].
Source: AFP Polio data. Available
from: https://extranet.who.int/
polis/public/CaseCount.aspx.

180 A. Mohanty, R. Rohilla, K. Zaman, et al.
was reported in an unvaccinated individual resid-
ing in Rockland County, New York, USA in July
2022, and there was no recent international travel
[8, 47, 48, 51]. Similarly, the United Kingdom de-
tected cVDPV-2 from sewage samples in London
with no associated human cases [5].
The number of areas reporting isolation of VDPV
from environmental sampling and surveillance
has increased since the start of the pandemic.
Apart from the African and Eastern Mediterrane-
an region cVDPV-2 have been isolated in the UK,
the USA and Canada (Figure 5), including geneti-
cally linked cVDPV-2 (Figure 6) [5]. Similarly, the
isolation of VDPV-1 and 3 from environmental
samples had increased in the last three years from
10 in 2020 to 44 in 2021, and 122 in 2022. There had
been multiple countries reporting the isolation of
cVDPV-1 from AFP cases for three years suggest-
ing widespread transmission, as discussed above
(Figure 4).
Figure 5 - Distribution of cVD-
PV 2 isolated from environ-
mental samples during the
surveillance related activities
from 2020-2023 [41].
Source: Circulating vaccine de-
rived polio. https://polioeradica-
tion.org/polio-today/polio-now/
this-week/circulating-vaccine-de-
rived-poliovirus/. Accessed on 8th
May 23.
Figure 6 - Countries (in yel-
low) with detection of genet-
ically linked cVDVP-2 [5].
Source: (https://www.who.int/emer-
gencies/disease-outbreak-news/
item/2022-DON408).

181Vaccine Derived Poliovirus
Eradication and control of cVDPV
The GPEI is working to nd new methods of out-
break response to ght mounting threat of cVD-
PV2, so that these cases are detected rapidly and
incidence could be controlled. Various strategies
suggested by GPEI are: improving quality and
speed of outbreak response, targeted political will
of a country, enhanced disease as well as environ-
mental surveillance, the availability of needed in-
frastructure, formation of emergency response
teams, motivated community engagement, amal-
gamation of polio services with other health pro-
grams, and a focus on reaching under-immunized
populations. These strategies can help countries
ght cVDVP outbreaks. Currently, it is of critical
importance that all the countries engage in rapid
and high-quality efforts to detect cVDPV2. The
strategic Advisory Group of Experts on Immuni-
zation (SAGE) of the WHO has recommended that
countries urgently respond to these outbreaks us-
ing available type 2 vaccines: novel Oral Polio Vac-
cine 2 (nOPV2), or monovalent OPV2 (mOPV2). In
situations where there is co-circulation of different
strains, tOPV may be the more suitable vaccine of
choice [52].
nOPV2 has been rolled out by GPEI. The nOPV2 is
a next-generation monovalent OPV2 vaccine, for
which clinical trial data and use in communities
revealed safety and effectiveness in protecting
against type 2 polio [53]. This is particularly im-
portant as 90% of cVDPV outbreaks were caused
by OPV-2 [53]. The vaccine could be used in coun-
tries affected bycVDVP outbreaks. nOPV2,being
a modied version of mOPV2, is less likely to re-
vert into a neurovirulent form in low immunity
settings. Therefore, it carries less risk of starting
newcVDPV2 outbreaksas compared to mOPV2.
GPEI is constantly working to escalate supply of
nOPV2, it supports governments to promote use
of this new vaccine, provides technical assistance
to ensure that Emergency use Listing (EUL) crite-
ria are met. WHO’s Pre-Qualication program
listed nOPV2 in EUL in November 2020 to ag use
of yet-to-be- licensed vaccine after exhaustive val-
idation of stability, efcacy, and safety [52].
Actual use of nOPV2 started in March 2021 in a
few countries under strict criteria of such usage.
By the end of 2022, approximately 500 million dos-
es of this vaccine have been given in more than 30
countries. In a randomized-controlled clinical tri-
al, the nOPV-2 vaccine in infants at birth and 4
weeks of age showed 99% neutralizing antibodies
[54]. Another study showed that antibody sero-
prevalence increased from 26% before nOPV2 to
77% and 83% after one and two doses of nOPV2,
respectively [55]. In another study, there was an
increased stability of the V domain of nOPV2 rel-
ative to mOPV2 [56]. Data on post-usage safety,
efcacy and genetic stability is constantly moni-
tored, and there is proven evidence that it can be
used as a tool to prevent cVDPV2 outbreaks [52].
SAGE also endorsed that nOPV2 can be used in
response to cVDPV2 outbreaks after reviewing it
for the pre-dened period for initial use. Clinical
evaluation studies on nOPV2 in Panama and Bel-
gium have also illustrated that the vaccine is safe
and efcacious and is more stable as compared to
OPV. According to SAGE, the initial use period is
for three months following the rst use of nOPV2
under EUL; but the usage will depend on epide-
miology of the country and its dedication to con-
ducting the strict monitoring of nOPV2’s safety,
and effectiveness during rollout.
GPEI is working with high-risk countries in prepa-
ration to roll out nOPV2. Apart from nOPV2’s ini-
tial use, the GPEI is recommending other strate-
gies to control cVDPV2 outbreaks, such as channe-
ling high-quality outbreak response using mOPV2
or another available vaccine, building a strong
disease surveillance network, strengthening rou-
tine immunization protocols with inactivated po-
lio vaccine (IPV) in high-risk areas, and ensuring
adequate procurement of OPV to reach every child
in remote areas of the world.
Routine vaccination and house-to-house mop up
campaigns have failed to reach all the pediatric
population for so many years, may be due to weak
routine immunization programs, vaccine hesitan-
cy, mobility of populations, poor program man-
agement, political conicts, geographical calami-
ties, a lack of awareness, myths, and misinforma-
tion. Last but not least, in 2020, the setback polio
campaigns suffered because of COVID-19 pan-
demic, had its own unsurmountable impact, it
completely disrupted routine immunization,
which led to new outbreaks of cVDVPs globally.
Fast-paced, high-quality vaccination campaigns
using mOPV2 and nOPV-2 can be utilized to stop
cVDPV-2 outbreaks. However, the use of mOPV-2
was associated with the emergence of cVDPV as
described in the Philippines [57].
The emergence of cVDPV2 in the USA and UK are

182 A. Mohanty, R. Rohilla, K. Zaman, et al.
evidence of the possible occurrence of such events
in countries that had been declared polio-free with
the possibility of re-emergence of polio and subse-
quent AFP in such countries. The vaccine coverage
for three routine doses of polio-vaccine in children
of one year of age, both in the UK and USA was
93% and 92%, respectively in the year 2021 (Figure
7) [58]. It is important to have a polio vaccination
coverage rate of >95% and maintain high quality
surveillance indicators (AFP, percentage of cases
investigated within 48 hours, and percentage of
cases with an adequately obtained sample), man-
datory environmental surveillance, rapid detec-
tion, and rapid response to the emergence or im-
portation of a new virus [52]. It is also important
to have continued surveillance for the emergence
of any polio outbreaks secondary to cVDPVs, and
polio immunization should be updated regularly
[59]. This is especially important as there has been
an increased number of cVDPVs cases which is 7
times more than that caused by the WPV in 2020
[60]. It had been shown that increasing surveil-
lance of non-polio AFP together with adequate
stool collection resulted in an increased speed of
detection of cases [61]. Despite an increase in key
performance indicators in 2021 to 74% of priority
countries compared to 53% in 2020, there is still
national and subnational gaps requiring further
enhancement [62]. A study from 2016 to 2020,
there were 65 outbreak responses to cVDPV. Of the
rst large-scale campaign conducted after Day 0,
only 12 (18.5%) such responses were conducted by
the target date of 28 days after Day 0 of the occur-
rence of the outbreaks [63]. It was well stated that
“without global eradication, there is a risk of re-in-
fection from the importation and spread of wild
poliovirus or VDPV, or the emergence and circula-
tion of VDPV” [64]. It is also important to improve
the surveillance sensitivity and completeness of
AFP case investigations for full detection and in-
terruption of viral transmission [65].
n CONCLUSION
It is important to note that the risk of VDPV emer-
gence is very low, and the benets of OPV far out-
weigh the risks. Nevertheless, the emergence of
VDPV is a cause for concern, particularly in coun-
tries where polio remains endemic, and where the
weakened virus can circulate for longer periods.
To address the risk of VDPV emergence, countries
have developed strategies to increase immuniza-
tion rates and minimize the risk of the vaccine vi-
rus spreading in the environment. These include
the use of IPV instead of OPV, particularly in de-
veloped countries, where the risk of wild poliovi-
rus transmission is low. IPV is a safer alternative to
OPV because it uses inactivated virus particles
and cannot cause VDPV. Additionally, countries
with a high risk of VDPV emergence are using a
Figure 7 - Percentage of Chil-
dren (1 year-old) who received
three doses of Polio-vaccine.
Source: Polio (Pol3) immunization
coverage among 1-year-olds (%)
https://www.who.int/data/gho/
data/indicators/indicator-de-
tails/GHO/polio-(pol3)-immuniza-
tion-coverage-among-1-year-olds-(-)

183Vaccine Derived Poliovirus
different type of OPV that contains a weakened
form of the virus that is less likely to mutate and
cause VDPV. Thus, VDPV is a rare but serious con-
sequence of the use of OPV. The risk of VDPV can
be minimized through increased immunization
rates and the use of safer vaccine alternatives. The
global effort to eradicate polio has made signi-
cant progress over the years, but continued vigi-
lance and investment in immunization programs
are needed to achieve the ultimate goal of a po-
lio-free world.
Conict of interest
None to declare.
Funding
No funding was received for this review.
n REFERENCES
[1] Mehndiratta MM, Mehndiratta P, Pande R. Poliomy-
elitis: Historical Facts, Epidemiology, and Current Chal-
lenges in Eradication. The Neurohospitalist. 2014; 4, 223-
229. doi: 10.1177/1941874414533352.
[2] John J. Role of injectable and oral polio vaccines in
polio eradication. Expert Rev Vaccines. 2009; 8, 5-8. doi:
10.1586/14760584.8.1.5.
[3] Zuckerman NS, Bar-Or I, Sofer D, et al. Emergence of
genetically linked vaccine-originated poliovirus type 2
in the absence of oral polio vaccine, Jerusalem, April to
July 2022. Euro Surveill 2022; 27. doi: 10.2807/1560-7917.
ES.2022.27.37.2200694.
[4] Global Polio Eradication Initiative. Classication
and reporting of vaccine-derived polioviruses (VDPV)
- GPEI guidelines 2016:8. http://polioeradication.org/
wp-content/uploads/2016/09/Reporting-and-Classi-
cation-of-VDPVs_Aug2016_EN.pdf (accessed February
22, 2023).
[5] World Health Organization. Detection of circulating
vaccine derived polio virus 2 (cVDPV2) in environmen-
tal samples - the United Kingdom of Great Britain and
Northern Ireland and the United States of America 2022.
https://www.who.int/emergencies/disease-out-
break-news/item/2022-DON408 (accessed February
22, 2023).
[6] 5 reasons why polio can be eradicated. Available from:
https://polioeradication.org/news-post/5-reasons-why-
polio-can-be-eradicated/. Accessed on 7th May 2023.
[7] Poliomyelitis: Vaccine derived polio. Available from:
https://www.who.int/news-room/questions-and-an-
swers/item/poliomyelitis-vaccine-derived-polio. Ac-
cessed on 5th May 2023.
[8] Al-Tawq JA, Kattan RF, Almoallem SAS, Altawq
KJ, Mohsni E, Memish ZA. Worldwide poliomyelitis
outbreaks: should mass gathering organizers be con-
cerned? J Travel Med. 2022. doi: 10.1093/jtm/taac128.
[9] Lai YA, Chen X, Kunasekaran M, Rahman B, MacIn-
tyre CR. Global epidemiology of vaccine-derived polio-
virus 2016-2021: A descriptive analysis and retrospec-
tive case-control study. EClinicalMedicine. 2022; 50,
101508. doi: 10.1016/j.eclinm.2022.101508.
[10] Hill M, Bandyopadhyay AS, Pollard AJ. Emergence
of vaccine-derived poliovirus in high-income settings in
the absence of oral polio vaccine use. Lancet. 2022; 400:
713-715. doi: 10.1016/S0140-6736(22)01582-3.
[11] Gumede N, Lentsoane O, Burns CC, Pet al. Emer-
gence of vaccine-derived polioviruses, Democratic Re-
public of Congo, 2004-2011. Emerg Infect Dis. 2013; 19,
1583-1589. doi: 10.3201/eid1910.130028.
[12] Alleman MM, Chitale R, Burns CC, et al. Vac-
cine-Derived Poliovirus Outbreaks and Events - Three
Provinces, Democratic Republic of the Congo, 2017.
MMWR Morb Mortal Wkly Rep. 2018; 67, 117-125. doi:
10.15585/MMWR.MM6710A4.
[13] Wringe A, Fine PEM, Sutter RW, Kew OM. Estimat-
ing the extent of vaccine-derived poliovirus infection.
PLoS One. 2008; 3. doi: 10.1371/journal.pone.0003433.
[14] Jorba J, Diop OM, Iber J, Het al. Update on Vac-
cine-Derived Polioviruses - Worldwide, January 2017-
June 2018. MMWR Morb Mortal Wkly Rep. 2018; 67, 661-
672. doi: 10.15585/MMWR.MM6742A5.
[15] Jorba J, Diop OM, Iber J, et al. Update on Vac-
cine-Derived Polioviruses - Worldwide, January 2016-
June 2017. MMWR Morb Mortal Wkly Rep. 2017; 66, 1185-
1191. doi: 10.15585/MMWR.MM6643A6.
[16] Weil M, Sofer D, Shulman LM, et al. Environmental
surveillance detected type 3 vaccine-derived poliovirus-
es in increasing frequency at multiple sites prior to de-
tection of a poliomyelitis case. Sci Total Environ. 2023;
871. doi: 10.1016/J.SCITOTENV.2023.161985.
[17] Module 3 Poliomyelitis; Surveillance Guide for Vac-
cine-Preventable Diseases in the WHO South-East Asia
Region; Module 3 Poliomyelitis. Accessed on 24.4.2023
https://apps.who.int/iris/handle/10665/277459.
[18] Poliomyelits: WHO Vaccine-Preventable Diseases
Surveillance Standards. Accessed on 24.4.2023. https://
cdn.who.int/media/docs/default-source/immuniza-
tion/vpd_surveillance/vpd-surveillance-stand-
ards-publication/who-surveillancevaccinepreventa-
ble-18-polio-r3.pdf?sfvrsn=aa96984f_28.
[19] Aide Memoire - Types of Vaccine-derived Poliovirus
(VDPV). Accessed on 24.4.2023. https://www3.paho.
org/hq/index.php?option=com_content&view=arti-
cle&id=7038:2012-aide-memoire-types-vaccine-derived-
poliovirus-vdpv&Itemid=0&lang=pt#gsc.tab=0,
[20] Schubert A, Böttcher S, Eis-Hübinger AM. Two Cas-
es of Vaccine-Derived Poliovirus Infection in an Oncol-
ogy Ward. N Engl J Med. 2016; 374 (13), 1296-1298. doi:
10.1056/NEJMc1508104. PMID: 27028932.
[21] Mbaeyi C, Wadood ZM, Moran T, et al. Strategic

184 A. Mohanty, R. Rohilla, K. Zaman, et al.
Response to an Outbreak of Circulating Vaccine-De-
rived Poliovirus Type 2 - Syria, 2017-2018. MMWR Morb
Mortal Wkly Rep. 2018; 67, 690-694. doi: 10.15585/mmwr.
mm6724a5.
[22] Yao N, Liu Y, Xu JW, et al. Detection of a Highly
Divergent Type 3 Vaccine-Derived Poliovirus in a Child
with a Severe Primary Immunodeciency Disorder -
Chongqing, China, 2022. MMWR Recomm Reports. 2022;
71, 1148-1150. doi: 10.15585/mmwr.mm7136a2.
[23] Xiao T, Leng H, Zhang Q, Chen Q, Guo H, Qi Y.
Isolation and characterization of a Sabin 3/Sabin 1 re-
combinant vaccine-derived poliovirus from a child with
severe combined immunodeciency. Virus Res. 2022;
308. doi: 10.1016/j.virusres.2021.198633.
[24] Kitamura K, Shimizu H. The molecular evolution of
type 2 vaccine-derived polioviruses in individuals with
primary immunodeciency diseases. Viruses. 2021; 13.
doi: 10.3390/v13071407.
[25] Pethani AS, Kazi Z, Nayyar U, et al. Poliovirus ex-
cretion among children with primary immune decien-
cy in Pakistan: A pilot surveillance study protocol. BMJ
Open. 2021; 11. doi: 10.1136/bmjopen-2020-045904.
[26] Chouikha A, Rezig D, Driss N, et al. Circulation and
molecular epidemiology of enteroviruses in paralyzed,
immunodecient and healthy individuals in tunisia, a
country with a polio-free status for decades. Viruses.
2021; 13. doi: 10.3390/v13030380.
[27] Macklin G, Diop OM, Humayun A, et al. Update on
Immunodeciency-Associated Vaccine-Derived Polio-
viruses - Worldwide, July 2018-December 2019. MMWR
Morb Mortal Wkly Rep. 2020; 69, 913-917. doi: 10.15585/
mmwr.mm6928a4.
[28] Esteves-Jaramillo A, Estivariz CF, Pearanda S, et al.
Detection of vaccine-derived polioviruses in Mexico us-
ing environmental surveillance. J Infect Dis. 2014; 210,
S315-323. doi:10.1093/infdis/jiu183.
[29] Kew O, Morris-Glasgow V, Landaverde M, et al.
Outbreak of poliomyelitis in Hispaniola associated with
circulating type 1 vaccine-derived poliovirus. Science.
2002; 296, 356-359. doi: 10.1126/SCIENCE.1068284.
[30] Burki T. Vaccine-derived poliovirus cases exceed
wild types. Lancet Infect Dis. 2019; 19, 140. doi: 10.1016/
S1473-3099(19)30012-X.
[31] Hampton LM, Farrell M, Ramirez-Gonzalez A, et al.
Cessation of trivalent oral poliovirus vaccine and introduc-
tion of inactivated poliovirus vaccine - Worldwide. 2016.
Morb Mortal Wkly Rep. 2016; 65, 934-938. doi: 10.15585/
mmwr.mm6535a3.
[32] Garon J, Seib K, Orenstein WA, et al. Polio endgame:
the global switch from tOPV to bOPV. Expert Rev Vac-
cines. 2016; 15, 693-708. doi: 10.1586/14760584.2016.1140041.
[33] Wang H. Why Have cVDPV2 Outbreaks increased
globally after the polio immunization strategy switch:
challenges for the polio eradication endgame. China CDC
Wkly. 2020; 2, 176-179. doi: 10.46234/ccdcw2020.046.
[34] Snider CJ, Boualam L, Tallis G, et al. Concurrent
outbreaks of circulating vaccine-derived poliovirus
types 1 and 2 affecting the Republic of the Philippines
and Malaysia, 2019-2021. Vaccine. 2022. 41 (Suppl. 1):
A58-A69 doi: 10.1016/j.vaccine.2022.02.022.
[35] Greene SA, Ahmed J, Datta SD, et al. Progress To-
ward Polio Eradication - Worldwide, January
2017-March 2019. Morb Mortal Wkly Rep. 2019; 68, 458-
462. doi: 10.15585/mmwr.mm6820a3.
[36] Thompson KM, Tebbens RJD. Modeling the dy-
namics of oral poliovirus vaccine cessation. J Infect Dis.
2014; 210, S475-84. doi: 10.1093/infdis/jit845.
[37] Pons-Salort M, Burns CC, Lyons H, et al. Preventing
vaccine-derived poliovirus emergence during the polio
endgame. PLoS Pathog. 2016; 12. doi: 10.1371/journal.
ppat.1005728.
[38] Yang H, Qi Q, Zhang Y, Wen N, et al. Analysis of a
Sabin-strain inactivated poliovirus vaccine response to
a circulating type 2 vaccine-derived poliovirus event in
Sichuan Province, China 2019-2021. JAMA Netw Open.
2023; 6, E2249710. doi: 10.1001/JAMANETWORKO-
PEN.2022.49710.
[39] Gray EJ, Cooper L V, Bandyopadhyay AS, Blake IM,
Grassly NC. The origins and risk factors for serotype-2
vaccine-derived poliovirus (VDPV2) emergences in Af-
rica during 2016-2019. J Infect Dis. 2023. doi: 10.1093/
INFDIS/JIAD004.
[40] Jorba J, Diop OM, Iber J, et al. Update on vaccine-de-
rived poliovirus outbreaks - Worldwide, January 2018-
June 2019. Morb Mortal Wkly Rep. 2019; 68, 1024-1028.
doi: 10.15585/mmwr.mm6845a4.
[41] Circulating vaccine derived polio. https://polio-
eradication.org/polio-today/polio-now/this-week/
circulating-vaccine-derived-poliovirus/. Accessed on
8th May 23.
[42] Chard AN, Datta SD, Tallis G, et al. Progress To-
ward Polio Eradication - Worldwide, January 2018–
March 2020. Morb Mortal Wkly Rep 2020; 69, 784-789. doi:
10.15585/mmwr.mm6925a4.
[43] Burkholder B, Wadood Z, Kassem AM, Ehrhardt D,
Zomahoun D. The immediate impact of the COVID-19
pandemic on polio immunization and surveillance ac-
tivities. Vaccine. 2021. doi: 10.1016/j.vaccine.2021.10.028.
[44] The Lancet. Polio eradication: falling at the nal
hurdle? Lancet. 2022; 400, 1079. doi: 10.1016/S0140-
6736(22)01875-X.
[45] AFP Polio data. Available from: https://extranet.
who.int/polis/public/CaseCount.aspx [Accessed 26th
April 2023].
[46] Mohammed A, Tomori O, Nkengasong JN. Lessons
from the elimination of poliomyelitis in Africa. Nat Rev Im-
munol. 2021; 21, 823-828. doi: 10.1038/s41577-021-00640-w.
[47] World Health Organization(WHO). Wild poliovirus
type 1 (WPV1) - Mozambique 2022; 1: 2003-2005.
https://www.who.int/emergencies/disease-out-
break-news/item/2022-DON395 (accessed February
22, 2023).

185Vaccine Derived Poliovirus
[48] World Health Organization. Wild poliovirus type 1
(WPV1) - Malawi 2022. https://www.who.int/emergen-
cies/disease-outbreak-news/item/wild-poliovi-
rus-type-1-(WPV1)-malawi (accessed February 22, 2023).
[49] Niaz F, Tariq S, Rana MS, et al. The resurgence of
polio: The effect of the Covid-19 pandemic on polio
eradication. Ethics, Med Public Health. 2023; 26, 100858.
doi: 10.1016/j.jemep.2022.100858.
[50] Uwishema O, Elebesunu EE, Bouaddi O, et al. Poli-
omyelitis amidst the COVID-19 pandemic in Africa: Ef-
forts, challenges and recommendations. Clin Epidemiol
Glob Health. 2022; 16. doi: 10.1016/j.cegh.2022.101073.
[51] Rai A, Uwishema O, Uweis L, et al. Polio returns to
the USA: An epidemiological alert. Ann Med Surg 2022;
82. doi: 10.1016/j.amsu.2022.104563.
[52] GEPI. Vaccine-Derived Polioviruses - GPEI n.d.
https://polioeradication.org/polio-today/polio-pre-
vention/the-virus/vaccine-derived-polio-viruses/ (ac-
cessed February 22, 2023).
[53] Martin J, Burns CC, Jorba J, et al. Genetic Character-
ization of Novel Oral Polio Vaccine Type 2 Viruses Dur-
ing Initial Use Phase Under Emergency Use Listing -
Worldwide, March-October 2021. Morb Mortal Wkly Rep.
2022; 71, 786-790. doi: 10.15585/mmwr.mm7124a2.
[54] Zaman K, Bandyopadhyay AS, Hoque M, et al.
Evaluation of the safety, immunogenicity, and faecal
shedding of novel oral polio vaccine type 2 in healthy
newborn infants in Bangladesh: a randomised, con-
trolled, phase 2 clinical trial. Lancet. 2023; 401, 131-139.
doi: 10.1016/S0140-6736(22)02397-2.
[55] Mirzoev A, Macklin GR, Zhang Y, et al. Assessment
of serological responses following vaccination cam-
paigns with type 2 novel oral polio vaccine: a popula-
tion-based study in Tajikistan in 2021. Lancet Glob Health
2022; 10, e1807-814. doi: 10.1016/S2214-109X(22)00412-0.
[56] Wahid R, Mercer LD, De Leon T, et al. Genetic and
phenotypic stability of poliovirus shed from infants
who received novel type 2 or Sabin type 2 oral poliovi-
rus vaccines in Panama: an analysis of two clinical trials.
The Lancet Microb. 2022; 3, e912-921.
[57] Alipon SCB, Takashima Y, Avagyan T, et al. Emer-
gence of vaccine-derived poliovirus type 2 after using
monovalent type 2 oral poliovirus vaccine in an out-
break response, Philippines. West Pacic Surveill Re-
sponse J. 2022; 13, 1-7. doi: 10.5365/wpsar.2022.13.2.904.
[58] Global Health Observatory Data Repository. Polio
Immunization Coverage among 1-year-olds. Www-
WhoInt 2014. http://www.who.int/gho/immuniza-
tion/poliomyelitis/en/ (accessed February 25, 2023).
[59] Kitamura K, Shimizu H. Outbreaks of Circulating
Vaccine-Derived Poliovirus in the World Health Organ-
ization Western Pacic Region, 2000-2021. Jpn J Infect
Dis. 2022; 75, 431-444. doi: 10.7883/yoken.JJID.2022.312.
[60] Sultan MA. Emerging challenges to realizing global
polio eradication and their solutions. East Mediterr Heal
J. 2022; 28, 515-520. doi: 10.26719/emhj.22.045.
[61] Auzenbergs M, Fountain H, Macklin G, Lyons H,
O’Reilly KM. The impact of surveillance and other fac-
tors on detection of emergent and circulating vaccine
derived polioviruses. Gates Open Res. 2022; 5, 94. doi:
10.12688/GATESOPENRES.13272.2.
[62] Wilkinson AL, Diop OM, Jorba J, Gardner T, Snider
CJ, Ahmed J. Surveillance to track progress toward polio
eradication - Worldwide, 2020-2021. Morb Mortal Wkly
Rep. 2022; 71, 538-544. doi: 10.15585/mmwr.mm7115a2.
[63] Darwar R, Biya O, Greene SA, et al. Assessing coun-
try compliance with circulating vaccine-derived polio-
virus type 2 outbreak response standard operating pro-
cedures: April 2016 to December 2020. Vaccine. 2023. doi:
10.1016/J.VACCINE.2023.02.060.
[64] Chong CY, Kam KQ, Yung CF. Combating a resur-
gence of poliomyelitis through public health surveil-
lance and vaccination. Ann Acad Med Singapore. 2023; 52,
17-26. doi: 10.47102/ANNALS-ACADMEDSG.2022390.
[65] Morais A, Morais J, Felix M, et al. Genetic and epide-
miological description of an outbreak of circulating vac-
cine-derived polio-virus type 2 (cVDPV2) in Angola, 2019-
2020. Vaccine. 2023. doi: 10.1016/J.VACCINE.2023.02.035.
[66] AFP Polio data. Available from: https://extranet.
who.int/polis/public/CaseCount.aspx [Accessed 26th
April 2023].
[67] Polio (Pol3) immunization coverage among 1-year-
olds (%). Available from: https://www.who.int/data/
gho/data/indicators/indicator-details/GHO/po-
lio-(pol3)-immunization-coverage-among-1-year-
olds-(-). Accessed 7th May 2023.