Impact of pandemics and disruptions to vaccination on infectious diseases epidemiology past and present

ABSTRACT

Infectious diseases are a leading cause of morbidity and mortality worldwide with vaccines playing a critical role in preventing deaths. To better understand the impact of low vaccination rates and previous epidemics on infectious disease rates, and how these may help to understand the potential impacts of the current coronavirus disease 2019 (COVID-19) pandemic, a targeted literature review was conducted. Globally, studies suggest past suboptimal vaccine coverage has contributed to infectious disease outbreaks in vulnerable populations. Disruptions caused by the COVID-19 pandemic have contributed to a decline in vaccination uptake and a reduced incidence in several infectious diseases; however, these rates have increased following the lifting of COVID-19 restrictions with modeling studies suggesting a risk of increased morbidity and mortality from several vaccine-preventable diseases. This suggests a window of opportunity to review vaccination and infectious disease control measures before we see further disease resurgence in populations and age-groups currently unaffected.

KEYWORDS:

• Infectious disease
• vaccination rates
• COVID-19
• literature review

Introduction

Infectious diseases continue to be one of the leading causes of morbidity and mortality worldwide, accounting for 18.4% of deaths globally in 2019, with a higher proportion of deaths in low- and lower- to middle-income countries.^1,2 Across all age groups, infectious diseases, including infectious diarrhea and lower respiratory infections, were among the top 10 causes of disease burden and deaths globally in 2019.^1,3

Vaccines are recognized as having a critical role in preventing deaths and hospitalizations due to infectious diseases; estimates suggest that vaccines could have prevented nearly one-quarter (21.7%) of the 5.3 million deaths among children under the age of 5 years in 2019.⁴ The role of vaccines in the global eradication of smallpox demonstrates the impact of successful global vaccination efforts, and other successes include the dramatic reduction and near elimination of polio in some regions of the world.^5,6 Decreased rates of other childhood infectious diseases in regions with high vaccination rates have also been observed including diphtheria, pertussis, tetanus, measles, mumps, rotavirus, hepatitis-B, meningococcal, pneumococcal illness and rubella.^7–13 However, vaccine-preventable deaths continue to pose a significant economic burden to society, particularly in resource constrained communities. A 2018 analysis reported that four major vaccine-preventable diseases – rotavirus, pneumococcal disease, measles, and rubella – were estimated to collectively cost Africa (US) $13 billion annually, due to productivity losses resulting from premature death (US $10 billion) and prolonged sickness (US $2 billion), hospitalizations (US $260 million), and outpatient visits (US $73 million).¹⁴

Disruptions in access to healthcare services, including problems with access to national immunization programs (NIP) and low vaccination uptake, can significantly impact the epidemiology of infectious diseases. Vaccine coverage may be impacted by changes to healthcare/vaccination policy, funding, safety concerns, patient noncompliance, and supply and administration issues.^15–18 Historically disruptions in access to NIPs and low vaccination uptake have had major impacts on the epidemiology of infectious diseases. One such recent example is the arrival of the coronavirus disease 2019 (COVID-19) pandemic where non-pharmacological interventions (NPI) were implemented globally to reduce the spread of the virus.^19–21 These included personal protection and hygiene measures (face masks, gloves and other personal protective equipment, hand hygiene, sanitizing contaminated surfaces) and social distancing (e.g., lockdowns, stay-at-home orders, bans/restrictions on travel and group gatherings/events).^19,20,22 However, in addition to controlling the spread of COVID-19, such measures also impacted the epidemiology of non-COVID-19 infectious diseases and the uptake of NIPs. Subsequently, the roll-out of COVID-19 vaccination programs has led to the relaxation of NPIs but the eventual long-term impact of the pandemic on vaccine-preventable diseases globally remains unclear.²¹ It is therefore important to understand the potential impact of the COVID-19 pandemic and associated NPIs on the epidemiology of non-COVID infectious diseases. This targeted literature review (TLR) seeks to 1) identify past pandemics and corresponding NPIs and describe their impact on the epidemiology of infectious diseases; 2) identify historical examples of disruptions to NIPs and low vaccine uptake and characterize their impact on infectious diseases; 3) identify the impact of COVID-19 disruptions on vaccine uptake; 4) understand the impact of COVID-19 restrictions on vaccine preventable infectious disease epidemiology; and finally 5) apply these learnings to the COVID-19 pandemic and associated NPIs to build an understanding of their impact on the uptake of (non-COVID-19) vaccines and the current and future epidemiology of (non-COVID-19) infectious diseases.

Methods

A protocol-driven TLR was conducted to identify key evidence from real-world (observational) and mathematical modeling studies. Extensive literature searches of MEDLINE (OvidSP) and Embase (OvidSP) were conducted from inception to October 2021. Search strategies used a combination of indexing terms (Medical Subject Headings terms in MEDLINE and Emtree terms in Embase) as well as free-text keywords were used to identify studies reporting on factors causing disruption to NIPs and the epidemiology of vaccine-preventable infectious diseases in the general population. Separate search facets were developed using terms for infectious diseases, NPIs, outcomes, and study designs of interest, which were combined using Boolean operators and limited to studies in humans (see Supplemental File 1 for additional details). Gray literature searches were carried out to identify conference abstracts published from 2019 onward (indexed in Embase) and epidemiological/surveillance data reported by key public health websites (World Health Organization [WHO], Gavi, the Vaccine Alliance, United Kingdom Health Security Agency [UKHSA] formerly Public Health England [PHE]), Centers for Disease Control and Prevention [CDC], European Centre for Disease Prevention and Control) were also carried out. Pre-print databases (medRxiv, bioRxiv, Lancet preprints) were also searched for articles posted from 2019 to October 2021 to capture more recent COVID-specific data. Targeted hand searches for updated surveillance data and more recent publications were carried out in June 2022.

Articles at title/abstract and full text were systematically screened using DistillerSR® software and selected for inclusion by one reviewer with a random sample of 20% validated by a second, senior reviewer according to pre-defined population, interventions and comparisons, outcomes, and study design (PICOS) criteria (see Supplemental File 2 for additional details). Studies investigating the impact of NPIs, such as social distancing measures, general face mask use, and policy changes relevant to public health, were considered eligible for inclusion. Observational studies, epidemiological modeling studies (based on real-world data), disease surveillance, and public health reports were included regardless of geographical location if they reported on the dynamics of infectious disease epidemiology (with specific interest in vaccine-preventable diseases) resulting from any disruption to a vaccination program. Examples of disruptions could include any type of NPI, policy changes, vaccine hesitancy, or previous disease outbreaks. From those studies meeting the PICOS inclusion criteria, 50 key articles were prioritized for data extraction. To ensure a representative global sample of key studies across the five research questions, articles were prioritized based on the geographical location (i.e., COVID-related evidence from UK, North America and Europe, and global evidence on past pandemics), infectious disease investigated (i.e., infectious diseases relevant to the United Kingdom (UK)), and time-period of data collection. (i.e., last 10 years) to ensure a representative global sample of key studies across the five research questions. In addition, priority was given to those articles of most importance to public health, within the UK including articles on pneumococcal disease, influenza, human papilloma virus (HPV), pertussis, measles and shingles.²³ Data were extracted into a specially designed Microsoft Excel® spreadsheet by one reviewer and validated by a second reviewer. Key findings of the TLR were summarized qualitatively.

Results

A total of 3,295 records from database searches were screened, and 251 records selected for full-text review, of which 41 records were included. In addition, 102 records were identified from gray literature searches, including searches of websites and citation chasing (Figure 1). From the 143 included records 50 studies were prioritized for data extraction, including studies conducted in the UK (n = 13 studies), US (n = 12), and Europe (n = 10), followed by Africa (n = 6), Asia (n = 4), and Australia (n = 1) with four studies reporting on multiple global regions (Tables 1–5).

Figure 1. PRISMA diagram.

Table 1. Impact of NPIs to tackle pre-COVID disease outbreaks on vaccine-preventable disease epidemiology.

Reference	Population	Country	Type of Disruption (year)	Changes in Vaccination Uptake
Gray^Citation24	General population (Population-level data)	Liberia	Ebola outbreak (2014–2015)	The number of presumptive tuberculosis cases dropped significantly by nearly one-fifth at the beginning of the Ebola outbreak. There was a significant increase in the proportion of smear-positive to presumptive cases in the post-outbreak period, suggesting that the Ebola outbreak negatively affected tuberculosis care services.
Masresha^Citation25	General population (Population-level data)	Liberia, Guinea and Sierra Leone	Ebola outbreak (2014–2015)	In Liberia there were no measles cases in 2013–2014, but incidence rose to 108.5 per million in 2015. Measles immunization activities were postponed to support Ebola outbreak response efforts. Compared to the monthly mean for 2012 (prior to the outbreak), the mean monthly number of vaccinated children (MCV1) reduced by 30% in 2014 and by a further 25% in 2015. In Guinea, the incidence of measles increased from 2.7 per million in 2015 to 11.5 per million in 2016. Prior to the Ebola outbreak, MCV1 coverage averaged 45% (2012–2013) and after the Ebola outbreak (2016–2017) was 48%. In Sierra Leone, there was a decline on MCV1 coverage estimate from an average of 86% for pre-Ebola outbreak (2012–2013) to 83% post outbreak (2016–2017).
Takahashi^Citation26	Children (Population-level data)	Guinea, Liberia, Sierra Leone	Ebola outbreak (2014–2015)	There were an estimated 778,000 children not vaccinated against measles at the start of the Ebola outbreak. The outbreak led to disruptions in health care services, including childhood vaccinations. Assuming a 75% reduction in vaccination rates nationally due to these disruptions, it was estimated that the number of children between 9 months and 5 years of age who are not vaccinated increases by an average of 19,514, reaching 964,346 after 6 months, 1,068,833 after 12 months, and 1,129,376 after 18 months.

Abbreviation: MCV1 = First dose of measles-containing vaccine.

Table 2. Historical disruptions in disease epidemiology due to NPIs (pre-COVID).

Reference	Population	Country	Type of Disruption (year)	Changes in Vaccination Uptake
Measles vaccine
Asaria^Citation27	General population (Population-level data)	UK	Decision not to vaccinate* (1995–2005)	In 1995, uptake of the measles, mumps and rubella (MMR) vaccine was over 90% in the UK. However, MMR vaccine coverage declined in the late 1990s due to controversy over the safety of the vaccine. Coverage with a first dose was 80% among 2-year-olds in England in 2003–2004. The effective reproductive number for measles rose from .47 in 1995–1998 to .82 in 1999–2000.
CDC^Citation28	General population (Population-level data)	Europe	Suboptimal vaccine coverage with no clear reason (2011)	In 2011, measles outbreaks were reported in 36 of 53 countries. France reported the largest number of cases (approximately 14,000), predominantly among not unvaccinated individuals or those whose vaccination history was unknown. MCV1 coverage in France during 2004–2010 ranged from 87%–90%.
Dimala^Citation29	General population (Population-level data)	US	Decision not to vaccinate* (2001–2019)	160 outbreaks were reported between 2001 and 2019 with a yearly median of 6 outbreaks. A median of 36% of cases per year was due to international importation and a median of 15.1% of US cases occurred in vaccinated people. Up to a median of 66.7% of vaccine-eligible cases declined to be vaccinated due to religious beliefs.
Grout^Citation30	Children (Population-level data)	Democratic Republic of Congo	Vaccine schedule issues (2010–2011)	Vaccine coverage was over 89% in Likasi city, Lubumbashi city and Kipushi health zone and below it in all the other health zones. Supplementary immunization activities coverage ranged from 70% to 89% across health zones surveyed.77,241 measles cases were reported during the 2010–2011 outbreaks in the Katanga province. 77,241 measles cases were reported during the 2010–2011 outbreaks in the Katanga province.
Majumder^Citation31	NR	US	Suboptimal vaccine coverage with no clear reason (2014–2015)	Measles outbreak started sometime between December 17 and 20, 2014 and led to rapid growth in cases across the US. This analysis estimated that MMR vaccination rates among the exposed population might be as low as 50% and likely no higher than 86%. MMR vaccination rates in many of the communities that have been affected by this outbreak fell below the necessary threshold to sustain herd immunity, thus placing the greater population at risk as well.
McBrien^Citation32	Children (n = 355)	Ireland	Suboptimal vaccine coverage with no clear reason (1999–2000)	Measles outbreak with 1,407 cases was reported between December 1999 and July 2000. Vaccination rates were suboptimal nationwide, varying from 60% to 88% at 2 years of age with a mean uptake of 79% in 2000.
Rodyna^Citation33	General population (Population-level data)	Ukraine	Decision not to vaccinate* (2016–2019)	Vaccination coverage of MMR1 and MMR2 vaccines has significantly decreased during the period 2008–2016 from 96% to 45% due to challenges in the procurement of vaccines in the country and antivaccination campaigns.
Woudenberg^Citation34	Children (n = 2,766)	Netherlands	Decision not to vaccinate* (2013–2014)	2,766 measles cases were reported during the 2013–2014 outbreak. The first two cases were reported in unvaccinated children attending the same orthodox Protestant primary school. Vaccine coverage in these communities is around 60%, but varies widely between churches, with coverage reaching less than 30% among members of the most orthodox churches.
Polio vaccine
CDC, MMWR^Citation35	General population (Population-level data)	Afghanistan	Decision not to vaccinate* (2020)	During 2019, 29 WPV1 cases were reported, compared with 21 WPV1 cases reported in 2018. During January – July 2020, 41 WPV1 cases were reported compared with 15 in 2019. Nineteen (27%) of the 70 patients had never received OPV, 15 (21%) had received 1 or 2 doses, and 36 (51%) had received ≥ 3 doses each.
Khetsuriani^Citation36	General population (Population-level data)	Ukraine	Decision not to vaccinate* (2015)	There were 0 polio cases between 2008 to 2014. Three cases were identified in 2015 when the vaccination rate decreased to 15%. After a response by the government to increase vaccination rate and strengthen surveillance system, 0 cases of polio were identified in 2016.
TAG on Polio Eradication in Afghanistan^Citation37	General population (Population-level data)	Afghanistan	Decision not to vaccinate* (2020)	Increase in WPV1 cases in 2020, as anticipated given the ongoing ban on polio vaccination by anti-government elements. As of June 26, 2020, 26 cases from 12 provinces, compared to 13 cases from 3 provinces in 2019.
Pneumococcal vaccine
CDC, MMWR^Citation38	Nursing home residents (n = 27)	US	Low vaccination rates in nursing or care homes (2001)	Among 361 long-term care facilities during May 21–July 31, 28 (8%) did not meet the state regulation that requires offering PPV to every resident. Among 52 patients having medical records reviewed, 34 (65%) had no history of having received PPV and no contraindication to the vaccine, none of these patients had documentation of receipt of PPV while hospitalized.
CDC, MMWR^Citation39	Patients at chronic care facilities (n = 267)	US	Low vaccination rates in nursing or care homes (1996)	Death rate among chronic-care facility residents with pneumonia ranged from 20% to 28%, and less than 5% of the residents ≥65 years had vaccination records.
Glanz^Citation40	Children (n = 507)	US	Decision not to vaccinate* (2004–2009)	Among 106 hospitalized children with confirmed pneumococcal infection, 4% had parents who declined all doses of PCV7 vaccination, 1% declined 3 doses, and 1% declined 2 doses.
Health protection report^Citation41	General population (Population-level data)	UK	Suboptimal vaccine coverage with no clear reason (2020)	PPV coverage among people aged ≥65 years has remained constant, between 69.0% and 7.1% between 2014 and 2020. Many of those eligible for PPV vaccination did not receive the vaccine in the first year that they become eligible, but did in the subsequent years, with additional uptake gradually decreasing with age.
Nourti^Citation42	Nursing home residents (n = 84)	US	Low vaccination rates in nursing or care homes (1996)	During an outbreak of pneumococcal infection, 11 out of 84 residents were infected resulting in an attack rate of 13%. Three patients died resulting in a case fatality rate of 27%. Only 4% of the residents had been vaccinated.
Picazo^Citation43	General population (Population-level data)	Spain	Vaccine schedule issues (2007–2015)	From May 2012 to May 2015, the PCV13 vaccine was available only privately for purchase after being excluded from the government-funded regional immunization program. 860 IPD cases were identified between 2007–2015 and estimated vaccine coverages were: 95% from 2007–2008 to 2011–2012, 82% in 2012–2013, 67% in 2013–2014 and 73% in 2014–2015.
Quick^Citation44	Nursing home residents (n = 54)	US	Low vaccination rates in nursing or care homes (1993)	7% of residents had received pneumococcal vaccine. From the survey of 54 nursing homes, 22% of residents were reported to have received the vaccine, and vaccination status was unknown for 66%. Two major barriers to vaccination: low priority among physicians (43%) and difficulty in determining residents’ vaccine history (37%).
Pertussis vaccine
Atwell^Citation45	Children (Population-level data)	US	Decision not to vaccinate* (2005–2010)	Non-medical exemption rate increased from 1.6% in the 2005–2006 school year to 2.4% in the 2009–2010 school year. Reported pertussis cases varied by month from < 100 in January 2010 to a peak of > 1,000 in August 2010.
Varicella vaccine
Glanz^Citation46	Children (n = 626)	US	Decision not to vaccinate* (1998–2008)	133 cases were confirmed of which 7 (5%) had parents who refused all varicella immunizations. The mean age of the cases was 3.9 years, and 55% were female.
Multiple vaccines
Phadke^Citation47	General population (Population-level data)	US	Decision not to vaccinate* (2000–2015)	Measles: 7.6% of those unvaccinated had a nonmedical exemption to vaccination. Higher rates of vaccine exemption were associated with greater measles incidence. Pertussis: In at least 7 statewide pertussis epidemics, a substantial proportion of cases in certain age groups were unvaccinated or under-vaccinated.

*Decisions not to vaccinate included philosophical exemptions, non-medical exemptions, and vaccine safety concerns.

Abbreviations: CDC = Centers for Disease Control and Prevention; IPD = invasive pneumococcal disease; MCV1 = measles vaccination; MMR = measles, mumps, and rubella; NR = not reported; OPV = oral polio vaccine; PCV = pneumococcal conjugate vaccine; PCV13 = 13-valent pneumococcal conjugate vaccine PPV = pneumococcal vaccination; TAG = technical advisory group; UK = United Kingdom; US = United States; WPV1 = wild polio type 1 vaccine.

Table 3. Data on the impact of COVID-19 disruptions on vaccination uptake.

Study	Population	Country (year)	Changes in Vaccination Uptake
Measles vaccine
PHE^Citation48	Infants (Population-level data)	England (2020–2021)	In July 2021, 87% of infants completed the 3-dose course of Hexavalent vaccine by 6 months of age – this was a 2.2% reduction compared with July 2019, but 0.5% increase compared with July 2020. 87.5% of infants were vaccinated with MMR1 by 18 months of age – this was a 0.7% reduction compared with July 2019 and 0.5% increase compared with July 2020.
PHE^Citation49	General population (Population-level data)	England (2020–2021)	For children scheduled to receive the MMR1 vaccine from March 2020 onward, vaccine coverage measured at 18 months of age remained approximately 86.0%. In May 2021, 86.4% of infants were vaccinated with MMR1 by 18 months of age – this was 1.7% and 1.5% lower than May 2019 and May 2020, respectively.
Meningococcal vaccine
PHE^Citation50	Children (Population-level data)	England (2020–2021)	Average vaccine coverage where NHS school-aged providers delivered the MenACWY vaccine to year 9 students in 2019 to 2020 was 58.3% compared to 88.0% in 2018 to 2019.
HPV vaccine
PHE^Citation51	Children (Population-level data)	England (2019–2020)	In 2019 to 2020 the HPV vaccine coverage of the priming dose for year 8 females was 59.2% in England, which was a 28.8% reduction from 2018 to 2019. Coverage was 88.0% in 2018/2019. HPV vaccine coverage of the second dose for year 9 females was 64.7% in England, which was a 19.2% reduction compared with 83.9% in 2018 to 2019.
Td/IPV vaccine
PHE^Citation52	Children (Population-level data)	England (2019–2020)	In 2019 to 2020, the average vaccine coverage in the Las where NHS providers delivered the Td/IPV vaccine to year 9 students was 57.6% compared with 87.6% in 2018 to 2019.Year 10 coverage for the Td/IPV vaccine was 86.4%, compared with 86.0% in 2018 to 2019. Coverage ranged from 35.3% in Bolton to 98.4% in Northamptonshire.
Pertussis vaccine
PHE^Citation53	Pregnant women (Population-level data)	England (2020–2021)	Monthly prenatal pertussis vaccine coverage for the second quarter of 2021 decreased from 66.1% in April to 63.1% in May, and then increased to 64.4% in June 2021. Between April to June 2021, the difference between the highest and lowest prenatal pertussis vaccine coverage by STP for each month was around 50%, which was similar for the first quarter of 2021.
Shingles vaccine
PHE^Citation54	Elderly (Population-level data)	England (2020–2021)	In March 2021, 33.8% of adults turning 70 during quarter 1 were vaccinated, which was a 4.4% reduction compared with March 2020 and 4.5% reduction compared with March 2019. 30.4% of adults turning 70 during quarter 2 were vaccinated, which was a 4% reduction compared with March 2020 and 4% compared with March 2019. 18.5% of adults turning 70 during quarter 3 were vaccinated, which was a 3% reduction compared with March 2020 and 3.7% compared with March 2019.
PHE^Citation55	Elderly (Population-level data)	England (2019–2020)	26.5% of those who turned 70 and 25.8% of those who turned 78 during 2019 and 2020 (from April 1, 2019 to March 31, 2020) were vaccinated by the end of June 2020, compared to 2018 to 2019, vaccine coverage decreased by 5.4% for 70-year-olds and 7.1% for 78-year-olds.
Multiple vaccines
CDC^Citation56	Children (Population-level data)	Worldwide (2021)	From 2010 to 2019, coverage ranged from 89% to 90% for DTP1 and from 84% to 86% for DTP3. From 2019 to 2020, coverage declined from 90% to 87% for DTP1 and from 86% to 83% for DTP3. From 2010 to 2019, coverage with MCV1 stagnated between 84% and 86%, while MCV2 coverage increased from 42% to 71%. From 2019 to 2020, MCV1 coverage decreased to 84%, whereas MCV2 coverage was relatively stable at 71% and 70%, respectively.
WHO^Citation57	Children (Population-level data)	Worldwide (2019–2020)	In 2020 the coverage dropped to 83% for DTP3, leaving 22.7 million children vulnerable. Regions with the strictest COVID-19 response measures experienced the largest increases in zero-dose children, because service provision and especially outreach activities were affected. Only 19 vaccine introductions were reported, less than half of any year in the past two decades. Coverage dropped to 84% for MCV1, the lowest level since 2010, leaving 22.3 million children vulnerable to measles. An additional 18.2 million children received only the first dose

Abbreviations: CDC = Centers for Disease Control and Prevention; COVID-19 = coronavirus disease 2019; DTP = diphtheria-tetanus-pertussis; HPV = human papillomavirus; IPV = inactivated poliovirus vaccine; MCV1 = measles vaccination; MenACWY = meningococcal conjugate vaccine; MMR = measles, mumps, and rubella; NHS = National Health Service; PHE = Public Health England; STP = Sustainability and Transformation Plan; Td = tetanus and diphtheria; UK = United Kingdom; WHO = World Health Organization.

Table 4. Impact of lifting of COVID-19 restrictions on disease epidemiology.

Study	Population	Country	Changes in Disease Epidemiology
Pneumococcal pneumonia
Casanova^Citation58	General population (Population-level data)	Switzerland	From February 2020 (n = 139) to April 2020 (n = 22), a drastic decline of IPD isolates was observed. Numbers remained low from April 2020–February 2021 (n = 19). COVID-19 measures were loosened by the Swiss government on March 1, 2021, and numbers started to increase from March 2021 (n = 31) to May 2021 (n = 49). June 2021, the same number of IPD isolates (n = 47) as for June 2019, 2018, and 2017, was observed.
Perniciaro^Citation59	General population (Population-level data)	Germany	IPD incidence decreased sharply in the second quarter of 2020 and returned to baseline levels in the beginning of the third quarter of 2021.
RSV
Foley^Citation60	Children (n = 917)	Australia	COVID-19 public health measures contributed to a shift in transmission of respiratory viruses, including a delay in the expected RSV season. A summer peak of RSV-positive admissions, 2.5 times the magnitude of the previous mid-winter peak, was observed.
Halabi^Citation61	Children and adolescents (n = 143)	US	The overall number of RSV cases decreased in 2020 to 2021 compared with both previous seasons with inter-seasonal resurgence. Despite lack of known risk factors, a higher proportion of children had severe disease in the 2020 to 2021 season.
Hussain^Citation62	Children (n = 2,922)	UK	In 2020 to 2021 there was a drop in bronchiolitis cases, and no RSV cases were identified. The most likely reason was that of NPIs resulting in reduced transmission of viruses. In Wales, a reemergence of RSV bronchiolitis cases at a rapid rate that is out of sync to the usual seasonal pattern was observed.
van Summeren^Citation63	General population (Population-level data)	Europe	RSV epidemics were only observed in Europe during the 2020–2021 season in France and Iceland, countries that had a policy of keeping their primary schools and daycare facilities open. In the Netherlands, the RSV epidemic started 19 weeks after schools were reopened, suggesting that school closures had an impact on RSV activity.
Norovirus
O’Reilly^Citation64	General population (Population-level data)	England	During the first lockdown until the school reopening stage, the rate of infection for norovirus is sufficiently low that new infections are rare. The third lockdown period corresponds to a reduction in contacts (from 6.61 to 3.47) and the rate of infection falls to low levels again, until schools are reopened. Subsequently, model scenarios predicted a rise in the rate of infection and a resurgence of norovirus in the community resulting in an annual incidence of cases up to 2 times higher than simulations prior to 2020.
Multiple diseases
Baker^Citation65	General population (Population-level data)	US	Following NPIs due to COVID-19, a decline in RSV prevalence was observed beyond mean seasonal levels The 2019–2020 influenza season was more severe than average, with a relative increase in prevalence prior to March 2020; however, there was a decline to below average levels across almost all US states. Models identified that longer periods of NPIs, and subsequently reduce transmission, lead to greater increase in susceptibility and larger resulting outbreaks.
Redlberger-Fritz^Citation66	General population (n = 25,491)*	Austria	A rapid and statistically significant reduction of cumulative cases of influenza viruses, RSV, human Metapneumovirus and Rhinoviruses within short time after the lockdown in March 2020, compared to previous seasons. A reemergence of rhinovirus infections was observed after lifting of lockdown measures.
Wan^Citation67	Hospitalized patients (n = 42,558)**	Singapore	Implementation of NPIs pre-lockdown was associated with a reduction of influenza and RSV and a reduction of enterovirus/rhinovirus and adenovirus was only observed when lockdown was instated. During reopening, low levels of all viruses were sustained for approximately 13 weeks, but a reemergence of enterovirus/rhinovirus occurred in early September and a less pronounced rebound of adenovirus in mid-October.

*Number of nasopharyngeal swabs samples.

**Number of specimens from patients with respiratory symptoms, sent for routine diagnostic purposes.

Abbreviations: COVID-19 = coronavirus disease 2019; IPD = invasive pneumococcal disease; NPI = non-pharmacological intervention; RSV = respiratory syncytial virus; UK = United Kingdom; US = United States.

Table 5. Potential future impacts of vaccination disruptions due to COVID-19 restrictions on disease burden.

Study	Population	Country	Disease	Conclusion
Pneumococcal diseases vaccine
Carter^Citation68	Children (Population-level data)	Ethiopia, India, Nigeria, DRC, Pakistan, Swaziland, Zimbabwe, Laos	Pneumonia	Overall vaccination coverage is a more important driver of vaccine mortality impact than vaccination timing. Irrespective of delays, deaths averted by PCV were comparable when accounting for herd protection. The greatest absolute difference in number of deaths averted was observed for Nigeria, in which two to five weeks of delay and 26% of vaccination coverage resulted in 600 additional deaths. Laos, with 7 to 28 weeks of delay with 78% of coverage had 21 additional deaths. The other five countries had an absolute difference of fewer than 200 deaths and less than 3% relative difference in numbers of deaths averted with delays ranging from 0 to 11 weeks.
Choi^Citation69	General population (Population-level data)	England and Wales	Pneumonia	COVID-19 lockdowns were predicted to offset the increase in IPD cases resulting from a reduction in PCV13 coverage, by reduction in pneumococcal transmission, resulting in a reduction in pneumococcal carriage prevalence and IPD incidence for up to 5 years. The net reduction in cumulative IPD cases over the five epidemiological years from July 2019 was predicted to be 13,494.
Kitano^Citation70	Children (Population-level data)	Japan	Pneumonia	The model analyzing scenarios for the next 10 years indicated reduction in IPD incidence from 11.9 per 100,000 in 2019 to 6.3 per 100,000 in 2020, resulting from reduced transmission following COVID-19 mitigation measures. Assuming a recovery in the transmission rate in 2022, the incidence of IPD is estimated to increase with maximal incidence of 12.1 and 13.1 per 100,000 children under 5 years in a rapid and delayed vaccination scenarios respectively. The difference of incidence was not observed between the two scenarios after 2025.
Polio vaccine
Kalkowska^Citation71	Mixed (Population-level data)	Worldwide	Polio	The COVID-19 pandemic led to disruptions in health services, including immunization campaigns against the transmission of WPV and cVDPV2, posing a challenge to the Global Polio Eradication Initiative. Some resumption in activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021, of all polio immunization activities to pre-COVID-19 levels could mitigate the impact of COVID-19 delays in immunizations campaigns.
Third-dose diphtheria-tetanus-pertussis
Causey^Citation72	Children (Population-level data)	Global (94 countries)	NA	In 2020 there was a relative reduction of 7.7% for DTP3 and 7.9% for MCV1 compared to expected coverage in the absence of the COVID-19 pandemic. These estimates represented an additional 8.5 million children not routinely vaccinated with DTP3 and an additional 8.9 million children not routinely vaccinated with MCV1 attributable to the COVID-19 pandemic. Reductions in vaccine coverage in March and April were identified for all Global Burden of Disease super-region with the most severe impacts in north Africa and the Middle East, south Asia, and Latin America and the Caribbean.
Measles vaccine and yellow fever
Gaythorpe^Citation73	Mixed (Population-level data)	Bangladesh, Chad, Ethiopia, Kenya, Nigeria, South Sudan	Measles and yellow fever	Reductions in vaccination coverage in 2020 may lead to an increase in measles and yellow fever cases. In Ethiopia and Nigeria vaccination delays of one year may significantly increase the risk of measles outbreaks. For yellow fever, delays in vaccination lead to an increase of > 1 death per 100,000 people per year until vaccination campaigns are resumed.

Abbreviations: COVID-19 = coronavirus disease 2019; DRC = Democratic Republic of Congo; DTP = diphtheria-tetanus-pertussis; IPD = invasive pneumococcal disease; MCV1 = measles vaccination; NA = not applicable; OPV = oral polio vaccine; PCV = pneumococcal conjugate vaccine; UK = United Kingdom; WPV = wild-type polio vaccine.

Thirty percent of studies were focused on measles (n = 15), 24% on pneumococcal pneumonia (n = 12), 10% on respiratory syncytial virus (RSV; n = 5), and 8% on polio (n = 4). Thirty-eight percent of the studies (n = 19) reported disease epidemiology in children, while the remainder reported data for the general population or other age-specific groups (e.g., adults, elderly). Out of the 50 included studies 56% were surveillance data studies (n = 28), 22% (n = 11) were modeling studies, 12% (n = 6) were retrospective cohort studies, 6% were (n = 3) literature reviews, and 4% (n = 2) were case–control investigations. One-third of the included articles were public health reports from UK PHE and the US CDC. Articles reported on data gathered before the COVID-19 pandemic and spanned a 20-year period from 1996 to 2019.

Impact of NPIs to tackle pre-COVID disease outbreaks on disease epidemiology

The impact of historical disease outbreaks (pre-COVID) on vaccine-preventable disease epidemiology was reported in three studies all of which focused on the impact of NPIs during the 2014 to 2015 Ebola outbreak across Africa^24–26 (Table 1).

During the Ebola outbreak, the affected countries implemented various NPIs including curfews, border closures, and restrictions on free movement. In addition, the establishment of Ebola treatment centers and the re-deployment of healthcare workers to these centers led to the closure of healthcare facilities and the postponement of vaccination activities resulting in non-Ebola infectious disease outbreaks and a resurgence across various vaccine-preventable diseases.^24–26 In Liberia, the mean coverage of the first dose of measles-containing vaccine (MCV1) during the outbreak in 2015 was 16% lower than in the 2 years preceding the outbreak. Correspondingly, the incidence of measles increased from zero cases in 2013 to 2014, to 108.5 cases per million in 2015.²⁵ The incidence of measles in Sierra Leone increased from 6.9 per million in 2014, to 18.0 per million in 2015, during the Ebola outbreak, and remained high in 2016 and 2017.²⁵ A nationwide measles vaccination effort was initiated in June 2015 to combat the rising case numbers resulting in the vaccination of 1,205,865 children from 9 to 59 months of age (97.2% coverage).²⁵ Following continued outbreaks of measles involving children over 5 years of age, an expanded measles immunization program was implemented in May 2016, which reached 2,795,686 children aged 6 months to 14 years with a coverage at national level of 97.7% (95% confidence interval [CI]: 97.2% to 98%). A post-campaign survey revealed that 20.2% of the children received the vaccination for the first time.²⁵ In Guinea, estimates of coverage for the third dose of diphtheria-tetanus-pertussis (DTP3) vaccine, single-dose yellow fever vaccine, and MCV1 showed declines as a result of the 2014 to 2015 Ebola outbreak. DPT3 coverage was on average 48.5% in 2012 and 2013, 39.5% during the outbreak in 2014 and 2015, and 45% after the Ebola outbreak in 2016 and 2017. The single-dose yellow fever coverage was on average 45% in 2012 and 2013, 35.5% during the outbreak in 2014 and 2015, and 43% after the outbreak in 2016 and 2017. MCV1 was on average 45% in 2012 and 2013, 38% during the outbreak in 2014 to 2015, and 48% after the Ebola outbreak in 2016 and 2017. The incidence of measles increased from 2.7 per million in 2015 to 11.5 per million in 2016.²⁵

Historical disruptions in disease epidemiology due to NPIs (Pre-COVID)

Twenty-one studies reported on the impact of low rates of vaccination on past disease epidemiology (pre-COVID) including eight on measles,^27–34 seven on pneumococcal disease,^38–44 three on polio,^35–37 and three on other infectious diseases (Table 2).^45–47 Low vaccination rates were caused primarily by changes in vaccine schedule^30,43 and individual decisions not to vaccinate, which included philosophical exemptions, non-medical exemptions, and vaccine safety concerns.^{27,29,33,35,36,40,45–47} A number of studies also reported low vaccination rates in nursing or care homes,^38,39,42,44 and some studies reported sub-optimal vaccine uptake with no clear reason despite availability of NIPs (Figure 2).^28,31,32,41

Figure 2. Causes of low vaccination rates.

Abbreviations: MMR = measles, mumps, and rubella; NIP = national immunization program; NPI = non-pharmacological intervention.

Successful NIPs have seen measles and polio effectively eliminated from several regions across the globe, however periodically these diseases have re-emerged in recent years when vaccination rates have fallen below optimal levels. Local and regional outbreaks have resulted in increased disease-related morbidity/mortality in the Netherlands, Ireland, and several other countries across western Europe and Africa.^{28,30,32,34,36} In the Netherlands, a large measles outbreak resulted in 2,766 reported cases, of which, 94% (n = 2,539) were reported in unvaccinated individuals, the majority due to religious reasons (84%; n = 2,135).³⁴ In response to this outbreak, early measles-mumps-rubella (MMR) vaccination was advised in infants too young to have already received their first dose (MMR1), as they represent a highly vulnerable population due to loss of maternal antibodies; a total of 5,800 infants received an early MMR1 vaccination. Another clear example of an outbreak linked to suboptimal uptake of measles vaccination occurred in Dublin from December 1999 to July 2000.³² During this time, 1,407 cases were reported in Ireland, and within a single hospital 111 severely ill children were admitted, with 13 needing treatment in intensive care, seven requiring mechanical ventilation, and three children dying as a result of measles. Of the 111 children, 49 (44%) were >15 months of age and therefore eligible for their first MMR immunization, however only 18 (37%) had received this vaccination.

In 2011, measles outbreaks occurred in 36 out of 53 European countries. France reported the largest outbreak in the region, with 14,025 cases predominantly among individuals who were not vaccinated or those whose vaccination history was unknown.²⁸ In each of these examples, NIPs were in place, however sub-optimal uptake was observed, which resulted in a resurgence of vaccine-preventable illness.

Between 2010 and 2011, measles vaccination rates in the Democratic Republic of Congo (DRC) were poor with only three geographical areas achieving ≥89% coverage; subsequent epidemics resulted in 77,241 measles cases and 1,085 deaths.³⁰ The DRC is prone to measles outbreaks, with supplementary immunization activities (SIAs) having previously been implemented with the aim to increase measles vaccine coverage through catch-up programs targeting young children. Access to vaccinations as well as optimal uptake are critical to reduce the risk of outbreaks. Despite being planned in 2010, the SIAs were not implemented.³⁰

Polio outbreaks have also been observed due to the low uptake of vaccination programs.^36,37 Polio cases were observed in Ukraine following a significant decline in the oral polio vaccine coverage from 91% in 2008 to 15% in 2015, over the subsequent year as vaccination rates and surveillance increased no further cases were reported.³⁶ Several factors contributed to the decline in vaccination against polio in the Ukraine, these included misconceptions around vaccine safety, anti-vaccine sentiments, as well as insufficient funding. Elsewhere in Afghanistan, following an ongoing ban on polio vaccine by anti-government elements, wild type 1 poliovirus (WPV1) cases increased from 13 cases observed in three provinces in 2019 to 26 cases from 12 provinces in 2020.³⁷

In the US, several outbreaks of measles were reported between 2000 and 2015, and vaccine refusal due to non-medical exemptions, such as religious belief, was a contributing factor to these outbreaks.⁴⁷ A detailed review of vaccination data for 970 measles cases revealed that 574 cases occurred in unvaccinated individuals who were eligible for vaccination, with 405 (70.6%) of these individuals having non-medical exemptions.⁴⁷ During this same period, several pertussis outbreaks were observed in the US, including eight outbreaks in populations where 59% to 93% of pertussis cases occurred in children who were intentionally unvaccinated.⁴⁷ Populations, including schools and communities/states with higher vaccination exemption rates, had correspondingly higher rates of pertussis, including among those who were fully vaccinated.⁴⁷

Low vaccination rates have also been associated with several outbreaks of invasive pneumococcal disease (IPD) in nursing homes across the US.^38,39,42,44 Among 361 long-term care facilities assessed in 2001, 8% failed to meet state regulations requiring pneumococcal polysaccharide vaccinations (PPV) to be offered to all residents.³⁸ In addition, a survey of 54 nursing homes found that only 22% of residents had been vaccinated and the vaccination status was unknown for 66% of residents.⁴⁴ The underuse of PPV in nursing homes can be potentially attributed to a lack of prioritization by doctors, skepticism regarding vaccine effectiveness, and challenges when trying to obtain residents’ vaccination history.^38,42,44

Overall, previous evidence suggests young children^30,32 and older adults, including those in nursing homes and long-term care facilities,^38,42,44 have been most affected by disease outbreaks due to low vaccination rates implying the need to maximize efforts on vaccination coverage and uptake in these vulnerable groups.

Impact of COVID-19 disruptions on vaccination uptake

Ten studies reported on the impact of COVID-19 disruptions on vaccination uptake.^48–57 (Table 3). Three studies reported on multiple vaccine types,^55–57 two reported on measles vaccine,^48,49 and the remaining studies reported on HPV,⁵¹ meningococcal (MenACWY),⁵⁰ tetanus and diphtheria (Td)/inactivated poliovirus vaccine (IPV),⁵² pertussis⁵³ and shingles vaccine⁵⁴ individually.

During the COVID-19 pandemic, mitigation measures such as lockdowns and school closures contributed to a sharp decline in the uptake of common childhood vaccinations (e.g., MMR, diphtheria-tetanus-pertussis [DTP], HPV), with the greatest impact felt in those countries with the strictest measures. In England, the operational delivery of all school-aged immunization programs was paused due to the COVID-19 pandemic, resulting in marked reductions in vaccination uptake. For example, a 29.7% reduction in meningococcal conjugate vaccine (MenACWY) was reported in year 9 students from 2019 to 2020 compared to levels in 2018 to 2019.⁵⁰ Similar reductions were reported for the priming dose of HPV for year 8 females (28.8%)⁵¹ and Td/IPV (24%) in year 9 students.⁵² Worldwide data indicated that the 2020 vaccine coverage for DTP3 dropped to 83%, leaving 22.7 million children unprotected.⁵⁷ MCV1 coverage decreased to 84%, whereas the second dose of the measles-containing vaccine (MCV2) coverage was relatively stable at 71% in 2019 and 70% in 2020.⁵⁶

Vaccinations in the older adults were also affected by the introduction of COVID-19 restrictions in England. The shingles vaccination program is open to adults aged between 70 and 79 years, and coverage in all ages was lower in the 2020 to 2021 financial year compared to 2019 to 2020.⁵⁴ For adults turning 70, those newly eligible to the shingles program, coverage dropped from 26.7% in June 2020 to 20.2% in June 2021.⁵⁴ Similarly, coverage decreased by 5.4% in 70-year-olds and 7.1% for 78-year-olds in 2021 compared with 2018 to 2019.⁵⁵

Impact of lifting of COVID-19 restrictions on disease epidemiology

Ten studies reported on changes to infectious disease epidemiology after COVID-19 restrictions were lifted.^58–67 The findings are summarized in Table 4.

Several diseases (especially respiratory diseases) saw a rapid reduction in cases after the introduction of COVID-19 restrictions due to reduced disease transmission rates in light of NPIs reducing social contact. However, research has suggested that although NPI measures have had a beneficial effect in reducing disease incidence, they may also have led to an increase in disease susceptibility, potentially due to waning immunity against some non-COVID-19 infectious diseases.^60,62,63 This immunity gap appears to have ultimately left populations at increased risk of subsequent vaccine-preventable disease outbreaks, with surges in cases, and changes to the seasonality of diseases, such as RSV, influenza, norovirus, and pneumococcal disease.^60,62,63

Low rates of norovirus infections were reported in England during periods where COVID-19 lockdowns were enforced, but this was likely accompanied by an increase in population susceptibility resulting in a rapid increase in infections (9% increase in symptomatic infections) as COVID-19 restrictions began to be lifted. The subsequent estimated annual incidence rate almost doubled when compared to that predicted before the arrival of COVID-19.⁶⁴ Although not a vaccine preventable infectious disease, the change in incidence of norovirus, highlights the impact of the COVID-19 pandemic and lifting of COVID-19 restrictions on infectious disease dynamics.

In Germany,⁵⁹ where NPIs included quarantine after exposure, restrictions on large gatherings, mask wearing, workplace/retail closures and travel restrictions, correlations were reported between reductions in IPD cases and increased stringency to NPIs. IPD incidence dropped sharply in the second quarter of 2020 but rebounded to pre-COVID-19 pandemic levels by the beginning of the third quarter of 2021.⁵⁹ In children ≤4 years of age, IPD levels began to return to pre-COVID-19 pandemic values in April 2021 and exceeded pre-COVID-19 pandemic levels by June 2021, showing a 9% increase over average monthly values for 2015 to 2019.⁵⁹ Similarly, for age groups 5 to 14 years, 15 to 24 years, and >80 years, increases in IPD cases began to be observed in spring 2021, crossing pre-COVID-19 pandemic levels in July 2021.⁵⁹ In Switzerland, a drastic decline in IPD isolates was observed from February 2020 (n = 139) to April 2020 (n = 22) and remained low until February 2021 (n = 19).⁵⁸ COVID-19 measures were relaxed by the Swiss government on March 1, 2021, and by June 2021, the number of IPD isolates had returned to pre-pandemic levels.⁵⁸

Reduced numbers of cases and shifts in seasonality for RSV have been reported globally.^60,65,67 Australia was the first country to report an increase in RSV cases accompanied by a shift in the seasonality and epidemiology of disease.⁶⁰ Similar effects have since been reported across North America and Europe.^62,63,65 A decrease in RSV cases beyond mean seasonal levels was observed in the US following the introduction of COVID-related NPIs. Prediction models have suggested that longer periods of NPI enforcement would subsequently reduce transmission rates, leading to an increase in susceptibility and ultimately resulting in larger RSV outbreaks. For example, modeling suggested that longer durations of NPIs (i.e., one year), would lead to larger RSV outbreak, and more importantly could also result in complex interactions affecting the normal seasonal pattern of disease.⁶⁵ The UK has also reported a rapid reemergence and increase in RSV bronchiolitis cases likely to be out of sync with the usual seasonal pattern of infections.⁶² Conversely, in countries across Europe where a policy of keeping open primary schools and day care facilities was implemented (including France and Iceland), typical pre-COVID-19 pandemic RSV seasonality was observed in 2020 to 2021.⁶³ In the Netherlands, the RSV epidemic started 19 weeks after schools were reopened, also suggesting that school closures had an impact on RSV activity.⁶³

Potential future impacts of vaccination disruptions due to COVID-19 restrictions on disease burden

The potential impacts of COVID-19 restrictions on the future epidemiology of vaccine-preventable diseases including measles, meningitis, polio, and pneumococcal disease were examined in six studies (Table 5).^68–73

Data from the modeling studies suggested that disruptions to vaccination programs experienced during the COVID-19 pandemic could lead to an increase in number of cases and deaths from other infectious diseases. For example, the number of excess deaths due to measles is expected to range from 0.24 to 1.16 per 100,000 persons during 2020 to 2030 using data from Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan.⁷³ During 2020 to 2023, modeling studies have also predicted that the number of polio cases globally is projected to increase from 4,657 to 5,557 cases despite any timely recovery in vaccination programs. Further polio eradication activities are not expected to substantially impact the overall predicted trajectory.⁷¹

COVID-19 lockdowns have had a profound effect on infectious disease incidence in the UK, and modeling studies suggest significant impacts will be felt moving forward. Based on an existing model of pneumococcal transmission in England and Wales, simulating the impact of a 40% reduction in vaccination coverage and 40% reduction in contact rates during the COVID-19 lockdowns introduced in Spring 2020 and Autumn/Winter 2020 to 2021,⁶⁹ a reduction in pneumococcal carriage prevalence and IPD incidence has been predicted to occur over a period of up to 5 years.⁶⁹ The reduction in transmission due to social distancing is predicted to offset any increase in IPD cases due to any reduction in vaccine coverage. Vaccination coverage has been shown to be a more important driver of vaccine mortality than the timing of vaccination, where high vaccination coverage can over-ride the effect of vaccination delay through herd immunity. Model scenarios for seven countries indicated that irrespective of delays, deaths averted by pneumococcal conjugate vaccine (PCV) were comparable when accounting for herd protection.⁶⁸

Discussion

This TLR summarizes key data and learnings from past and current disruptions to human activity and vaccination programs that can impact the epidemiology of infectious diseases to build a better understanding of the potential trend of infectious disease dynamics as we move out of the COVID-19 pandemic era.

Prior to the COVID-19 pandemic (1996 to 2019), disruptions leading to low vaccination rates resulted in numerous disease outbreaks.^{25,26,28–32,34–36,40,43,44,47} Low vaccine uptake and/or coverage can have many causes (e.g., lack of vaccination policy, political conflicts, parental vaccine refusal, vaccine procurement problems, antivaccination sentiments, vaccine safety concerns, and changes in vaccine schedule), but regardless of the cause, evidence gathered in this TLR shows that low vaccination rates have contributed to increased infectious disease burden particularly in vulnerable population groups such as young children and older adults and in some cases leading to local and regional outbreaks of diseases previously brought under control.^24–47

The COVID-19 pandemic is still not completely resolved; however, mitigation measures including lockdowns and school closures have contributed to a sharp decline in vaccination uptake,^{48–53,55–57,72} but also a decrease in disease burden due to reduced social contacts.^58–66

Although causality is difficult to prove especially with regard to individual NPIs, further studies published since completion of the targeted literature search (in October 2021) have provided further evidence that NPIs implemented during the COVID-19 pandemic have coincided with reductions in vaccination rates and disease numbers alongside in some cases changes in the seasonality of disease.^74–78

Overall, evidence suggests that the COVID-19 pandemic has significantly impacted the epidemiology of vaccine preventable infectious diseases at least in the short term and in many cases likely in the longer term.^79–102 As the COVID-19 pandemic has eased and NPIs have been lifted, a small recovery in vaccination uptake has been observed,^53,57 though vaccination coverage still remains generally lower than pre-COVID-19 levels in key populations such as young children. As time progresses the signs of recovery of vaccination rates are variable in the extent and timing of this recovery by geographical region.^{79,81,82,85,86,93,95,97,98,103} In addition, increases in social contact have contributed to the spread of disease with at least initially a likely larger than normal pool of susceptible individuals. Using the example of pneumococcal disease, data from countries such as Germany and Switzerland initially reported reductions in cases during the pandemic, but cases have steadily increased since the relaxation of NPIs.^58,59 Modeling the impact of COVID-19 NPIs on IPD cases in England and Wales predicted reductions in cumulative IPD cases for up to 5 years.⁶⁹ However, recent surveillance data from UKHSA show that the number of IPD cases in 2020/2021 in England has already increased to a similar level as previously reported in 2019/2020 in children less than 2 years (Figure 3) and to a higher level in children less than 15 years compared to pre-pandemic years 2017–2019.^104,106 Within the UK, evidence suggests a similar trend is occurring in meningococcal and other diseases.¹⁰⁷ However, the relative contributions of low vaccination rates, increased population susceptibility, greater social contact, and the lifting of different NPIs is unclear and it is difficult to directly attribute the resurgence of vaccine preventable infectious diseases, like pneumococcal and meningococcal illness, to the lifting of NPIs, and/or the reduced vaccination rates during the pandemic.

Figure 3. Cumulative weekly number of reports of IPD in England due to any of the 13 serotypes covered by 13-valent Pneumococcal conjugate vaccine (PCV13).

Schools reopened on March 8, 2021 (Week 10); outdoor socializing was permitted on March 29, 2021 (Week 13); indoor socializing was permitted on April 12, 2021 1 (Week 15).

Source: Adapted from UK Health Security Agency¹⁰⁴; Institute for Government.¹⁰⁵

Abbreviation: COVID-19 = coronavirus disease 2019.

COVID-19 control measures continue to evolve as the pandemic and vaccination control measures change,²¹ making it difficult to predict future trends in infectious disease epidemiology. However, some data from England (e.g., pneumococcal disease in age <15 years) already suggest that a resurgence in disease levels to pre-pandemic levels is occurring,^104,106 and much earlier than predicted by modeling studies.⁶⁹

Though the studies identified in this TLR were unable to elucidate definitive causality between low vaccination levels, disease rates, and COVID-19 control measures, some speculated on potential causes,^48,50,52,72 with the suggestion of a trend toward larger declines in disease in areas with more stringent COVID-19 response measures and in lower-income countries.⁵⁷ Consistent with this, multi-regional studies have shown that decreases in vaccination rates correlate with socioeconomic status,^{81,88,100,108} suggesting that changes in access to healthcare during the COVID-19 pandemic was a major contributor to decreases in vaccine uptake. Research from 170 countries has shown evidence of substantial disruptions to routine vaccination related to interrupted vaccination demand and supply, including reduced availability of healthcare staff.⁸² The decline in vaccine uptake during the pandemic may also have contributed to a change in attitude toward vaccinations in general and concerns about the safety of vaccines,^109,110 since rates remain low in some diseases despite the relaxation of NPIs.

Further hindering the interpretation of data is the presence of several confounding factors that could contribute to the reported changes in the number of infections after COVID-19 mitigation measures were implemented, including reductions in the reporting capacity of surveillance systems. Uncertainty also exists in general understanding of the measures that are the most influential in causing the observed changes in infectious disease incidence, and whether study designs are adequate to control for confounding factors. The aim of this review was also to capture both historical example of NPIs and the impact of recent COVID-19 related NPIs on disease epidemiology and national immunization programs. Although the electronic databases searches from which the evidence base was generated were conducted in October 2021, pre-print sources were included and additional manual ad-hoc searches for more recent evidence including surveillance data were conducted in June 2022. Given the last of the national lockdown restrictions were lifted in July 2021 the key effects of the COVID-19 restrictions should have been captured but given the target nature of our review our aim was not to capture all data during this period. Despite these issues, the burden of evidence suggests that the recent COVID-19 pandemic and the implementation of NPIs has led to significant impacts on non-COVID vaccine-preventable diseases in a similar manner to past examples such as Ebola.

The recent pandemic may have also positively affected vaccination efforts by encouraging an increase in vaccine awareness,^{109,111–117} which would explain increased vaccine uptake in selected groups (e.g., the elderly)^41,118 and in certain geographical regions.^{80,86,87,103,116,119,120} These positive effects of the pandemic on the public perception of vaccines are ongoing areas of research, but offer a public health opportunity to further improve rates of vaccine uptake and coverage and prevent future outbreaks of vaccine-preventable diseases. As the pandemic progresses, it is important to continue to monitor vaccination uptake and disease rates closely to prevent disease outbreaks. Even though causality is uncertain, a return to normal social mixing suggests the need for vigilance to maintain high vaccination levels and prevent future disease outbreaks. The drop in case numbers also offers a unique opportunity to reset the endemic equilibrium for vaccine-preventable diseases to levels lower than in the pre-COVID era. Consequently, there is a window of opportunity to review vaccination and disease rates before we see further disease resurgence in populations and age-groups currently unaffected. Actions to minimize interruptions in the delivery of immunization services and to plan and implement catch-up vaccinations are needed to mitigate the effects of the COVID-19 pandemic as recommended by a recent WHO report.¹²¹ These actions include improving access to vaccines, increasing the efficiency of vaccination schedules, and harnessing opportunities for the simultaneous administration of multiple vaccines.¹²¹

Abbreviations

CDC	=	Centers for Disease Control and Prevention
CI	=	Confidence interval
DRC	=	Democratic Republic of Congo
DTP	=	Diphtheria-tetanus-pertussis
DTP3	=	Third dose of diphtheria-tetanus-pertussis
HPV	=	Human papilloma virus
ICMJE	=	International Committee of Medical Journal Editors
IPD	=	Invasive pneumococcal disease
IPV	=	Inactivated poliovirus vaccine
MCV1	=	First dose of measles-containing vaccine
MCV2	=	Second dose measles-containing vaccine
MenACWY	=	Meningococcal conjugate vaccine
MMR	=	Measles-mumps-rubella
MMR1	=	First dose of Measles-mumps-rubella
NIP	=	National immunization programs
NPI	=	Non-pharmacological interventions
PCV	=	pneumococcal conjugate vaccine
PHE	=	Public Health England
PICOS	=	Population, interventions and comparisons, outcomes, and study design
PPV	=	Pneumococcal polysaccharide vaccinations
RSV	=	Respiratory syncytial virus
SIA	=	Supplementary immunization activities
Td	=	Tetanus and diphtheria
TLR	=	Targeted literature review
WHO	=	World Health Organization
WPV1	=	Wild type 1 poliovirus
UK	=	United Kingdom
UKHSA	=	United Kingdom Health Security Agency
US	=	United States

Author contributions

All authors participated in data analysis and interpretation and contributed to the development of the manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval of the version to be published.

Compliance with ethical standards

Informed consent was not required for this study.

Acknowledgments

Kate Halsby for contributing to the conceptualization of the TLR and the development of the TLR protocol and Anita Engh for contributing to manuscript writing.

Disclosure statement

EH, TM, JCK, DM, and CC are employed by Pfizer (and may own Pfizer stock or stock options). CF, AP, and PW are employed by Evidera, which provides consulting and other research services to pharmaceutical, medical device, and related organizations. In their salaried positions, they work with a variety of companies and organizations, and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received funding from Pfizer to participate in the study and the development of this manuscript.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2023.2219577.

Additional information

Funding

Pfizer provided the funding for the study and for the manuscript.