-
Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.The Cochrane Database of Systematic... Mar 2021Sickle cell disease (SCD) is a group of inherited disorders that result in haemoglobin abnormalities and other complications. Injury to the spleen, among other factors,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sickle cell disease (SCD) is a group of inherited disorders that result in haemoglobin abnormalities and other complications. Injury to the spleen, among other factors, contribute to persons with SCD being particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person-years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review which was first published in 2002, and previously updated, most recently in 2017. OBJECTIVES: To compare the effects of antibiotic prophylaxis against pneumococcus in children with SCD receiving antibiotic prophylaxis compared to those without in relation to: 1. incidence of Streptococcus pneumoniae infection; 2. mortality (as reported in the included studies); 3. drug-related adverse events (as reported in the included studies) to the individual and the community; 4. the impact of discontinuing at various ages on incidence of infection and mortality.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform (not in 2020 given access issues relating to Covid-19 pandemic). Additionally, we carried out hand searching of relevant journals and abstract books of conference proceedings. Date of the most recent search: 25 January 2021.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug.
DATA COLLECTION AND ANALYSIS
The standard methodological procedures expected by Cochrane were used. Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the certainty of the evidence.
MAIN RESULTS
Six trials were identified by the searches, of which three trials were eligible for inclusion. A total of 880 children, who were between three months to five years of age at randomization were included. The included studies were conducted in centres in the USA and in Kingston, Jamaica. In trials that investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-certainty evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-certainty evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five years. Overall, the certainty of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias).
AUTHORS' CONCLUSIONS
The evidence examined was determined to be of low certainty and suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.
Topics: Age Factors; Anemia, Sickle Cell; Antibiotic Prophylaxis; Bias; Child, Preschool; Hemoglobin SC Disease; Homozygote; Humans; Incidence; Infant; Medication Adherence; Penicillins; Pneumococcal Infections; Randomized Controlled Trials as Topic; Streptococcus pneumoniae; beta-Thalassemia
PubMed: 33724440
DOI: 10.1002/14651858.CD003427.pub5 -
Clinical Infectious Diseases : An... May 2021
Corrigendum to: Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Invasive Disease Caused by Serotype 3 in Children: A Systematic Review and Meta-analysis of Observational Studies.
PubMed: 33576382
DOI: 10.1093/cid/ciaa1767 -
F1000Research 2020: This study aimed to summarise the evidence on the impact of routine administration of 10-valent and 13-valent pneumococcal conjugate vaccines on pneumonia in children...
: This study aimed to summarise the evidence on the impact of routine administration of 10-valent and 13-valent pneumococcal conjugate vaccines on pneumonia in children under five years of age in sub-Saharan Africa. A systematic search of the literature was conducted including primary research reporting on the impact of 10- or 13-valent pneumococcal vaccines on childhood pneumonia in a sub-Saharan African country. Case-control, cohort, pre-post and time-series study designs were eligible for inclusion. Thematic narrative synthesis was carried out to summarise the findings. Eight records were included in the final analysis, 6 records were pre-post or time-series studies, 1 was a case-control study and 1 report combined pre-post and case-control studies. Vaccine impact on clinical pneumonia measured as percentage reduction in risk (%RR) was mostly non-significant. The reduction in risk was more consistent in radiological and pneumococcal pneumonia. Evidence of the positive impact of routine infant pneumococcal vaccination on clinical pneumonia incidence in sub-Saharan Africa is inconclusive. Ongoing surveillance and further research is required to establish the long term trend in pneumonia epidemiology and aetiology after PCV introduction. : CRD42019142369 30/09/19.
Topics: Africa South of the Sahara; Case-Control Studies; Child, Preschool; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia; Vaccines, Conjugate
PubMed: 33335713
DOI: 10.12688/f1000research.25227.2 -
EClinicalMedicine Dec 2020The objective of this systematic review and meta-analysis was to summarise the literature regarding the immunogenicity of pneumococcal conjugate vaccines (PCV) and...
BACKGROUND
The objective of this systematic review and meta-analysis was to summarise the literature regarding the immunogenicity of pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPSV) in adult people living with HIV (PLWH) in the era of advanced combination antiretroviral therapy (cART).
METHODS
The systematic review protocol was published online (PROSPERO ID: CRD 42020153137). We searched Medline (Ovid), EMBASE (Ovid), and the Global Health Library for publications from 2000 to June 11, 2020. We included all studies in adult PLWH that reported vaccine immunogenicity outcomes. The primary outcome was seroconversion rate (SCR) after PCV, PPSV and PCV/PPSV combined. For random-effects meta-analysis, we included studies defining SCR as ≥ 2-fold increase in IgG from baseline, and reporting SCR for serotypes 6B, 14, or overall SCR, 1-3 months after vaccination.
FINDINGS
Our search identified 1597 unique studies, of which 115 were eligible for full-text assessment. Of these, 39 met the inclusion criteria (11 RCTs; 28 cohort studies). A high degree of heterogeneity was observed. Nineteen studies were included in the meta-analysis. Pooled overall SCRs were 42% (95% CI 30-56%), 44% (95% CI 33-55%) and 57% (95% CI 50-63%) for PLWH who received PPSV, PCV or a combination of PCV/PPSV, respectively. Compared to PPSV alone, a combination of PCV/PPSV yielded higher SCRs (OR 2.24 95% CI 1.41- 3.58), whereas we did not observe a significant difference in SCR between PCV and PPSV23 alone. There were no statistically significant differences in geometric mean post-vaccination antibody concentrations between vaccination schedules. Vaccination at higher CD4 cell counts improved immunogenicity in 8/21 studies, especially when PCV was administered. No studies assessed the long-term immunogenicity of PCV followed by PPSV23. Quality of evidence ranged from poor ( = 19) to good quality ( = 7). A limited number of pneumococcal serotypes was assessed in the majority of studies.
INTERPRETATION
We show that the recommended immunisation schedule consisting of a combination of PCV13/PPSV23, is immunogenic in PLWH in the era of advanced cART. However, the durability of this vaccination schedule remains unknown and must be addressed in future research. Vaccination with PCV should be delayed until immunological recovery (CD4>200) in recently diagnosed PLWH for optimal immunogenicity. The evidence gathered here supports wide implementation of the combination of PCV/PPSV23 for all PLWH. We recommend reassessment of this strategy once higher-valent PCVs become available.
FUNDING
HMGG is funded by a public research grant of ZonMw (project number 522004005).
PubMed: 33294820
DOI: 10.1016/j.eclinm.2020.100576 -
The Cochrane Database of Systematic... Nov 2020Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from the middle ear fluid of children with acute otitis...
BACKGROUND
Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from the middle ear fluid of children with acute otitis media (AOM). Reducing nasopharyngeal colonisation of this bacterium by PCVs may lead to a decline in AOM. The effects of PCVs deserve ongoing monitoring since studies from the post-PCV era report a shift in causative otopathogens towards non-vaccine serotypes and other bacteria. This updated Cochrane Review was first published in 2002 and updated in 2004, 2009, 2014, and 2019.
OBJECTIVES
To assess the effect of PCVs in preventing AOM in children up to 12 years of age.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Web of Science, and two trials registers, ClinicalTrials.gov and WHO ICTRP, to 11 June 2020.
SELECTION CRITERIA
Randomised controlled trials of PCV versus placebo or control vaccine.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. The primary outcomes were frequency of all-cause AOM and adverse effects. Secondary outcomes included frequency of pneumococcal AOM and frequency of recurrent AOM (defined as three or more AOM episodes in six months or four or more in one year). We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 15 publications of 11 trials (60,733 children, range 74 to 37,868 per trial) of 7- to 11-valent PCVs versus control vaccines (meningococcus type C vaccine in three trials, and hepatitis A or B vaccine in eight trials). We included one additional publication of a previously included trial for this 2020 update. We did not find any relevant trials with the newer 13-valent PCV. Most studies were funded by pharmaceutical companies. Overall, risk of bias was low. In seven trials (59,415 children), PCVs were administered in early infancy, whilst four trials (1318 children) included children aged one year and over who were either healthy or had a history of respiratory illness. There was considerable clinical heterogeneity across studies, therefore we reported results from individual studies. PCV administered in early infancy PCV7 The licenced 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) was associated with a 6% (95% confidence interval (CI) -4% to 16%; 1 trial; 1662 children) and 6% (95% CI 4% to 9%; 1 trial; 37,868 children) relative risk reduction (RRR) in low-risk infants (moderate-certainty evidence), but was not associated with a reduction in all-cause AOM in high-risk infants (RRR -5%, 95% CI -25% to 12%). PCV7 with the outer membrane protein complex of Neisseria meningitidis serogroup B as carrier protein (OMPC-PCV7) was not associated with a reduction in all-cause AOM (RRR -1%, 95% CI -12% to 10%; 1 trial; 1666 children; low-certainty evidence). CRM197-PCV7 and OMPC-PCV7 were associated with 20% (95% CI 7% to 31%) and 25% (95% CI 11% to 37%) RRR in pneumococcal AOM, respectively (2 trials; 3328 children; high-certainty evidence), and CRM197-PCV7 with 9% (95% CI -12% to 27%) and 10% (95% CI 7% to 13%) RRR in recurrent AOM (2 trials; 39,530 children; moderate-certainty evidence). PHiD-CV10/11 The effect of a licenced 10-valent PCV conjugated to protein D, a surface lipoprotein of Haemophilus influenzae, (PHiD-CV10) on all-cause AOM in healthy infants varied from 6% (95% CI -6% to 17%; 1 trial; 5095 children) to 15% (95% CI -1% to 28%; 1 trial; 7359 children) RRR (low-certainty evidence). PHiD-CV11 was associated with 34% (95% CI 21% to 44%) RRR in all-cause AOM (1 trial; 4968 children; moderate-certainty evidence). PHiD-CV10 and PHiD-CV11 were associated with 53% (95% CI 16% to 74%) and 52% (95% CI 37% to 63%) RRR in pneumococcal AOM (2 trials; 12,327 children; high-certainty evidence), and PHiD-CV11 with 56% (95% CI -2% to 80%) RRR in recurrent AOM (1 trial; 4968 children; low-certainty evidence). PCV administered at a later age PCV7 We found no evidence of a beneficial effect on all-cause AOM of administering CRM197-PCV7 in children aged 1 to 7 years with a history of respiratory illness or frequent AOM (2 trials; 457 children; moderate-certainty evidence) and CRM197-PCV7 combined with a trivalent influenza vaccine in children aged 18 to 72 months with a history of respiratory tract infections (1 trial; 597 children; moderate-certainty evidence). CRM197-PCV9 In 1 trial including 264 healthy daycare attendees aged 1 to 3 years, CRM197-PCV9 was associated with 17% (95% CI -2% to 33%) RRR in parent-reported all-cause otitis media (very low-certainty evidence). Adverse events Nine trials reported on adverse effects (77,389 children; high-certainty evidence). Mild local reactions and fever were common in both groups, and occurred more frequently in PCV than in control vaccine groups: redness (< 2.5 cm): 5% to 20% versus 0% to 16%; swelling (< 2.5 cm): 5% to 12% versus 0% to 8%; and fever (< 39 °C): 15% to 44% versus 8% to 25%. More severe redness (> 2.5 cm), swelling (> 2.5 cm), and fever (> 39 °C) occurred less frequently (0% to 0.9%, 0.1% to 1.3%, and 0.4% to 2.5%, respectively) in children receiving PCV, and did not differ significantly between PCV and control vaccine groups. Pain or tenderness, or both, was reported more frequently in PCV than in control vaccine groups: 3% to 38% versus 0% to 8%. Serious adverse events judged to be causally related to vaccination were rare and did not differ significantly between groups, and no fatal serious adverse event judged causally related to vaccination was reported.
AUTHORS' CONCLUSIONS
Administration of the licenced CRM197-PCV7 and PHiD-CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all-cause AOM is far more uncertain based on low- to moderate-certainty evidence. We found no evidence of a beneficial effect on all-cause AOM of administering PCVs in high-risk infants, after early infancy, and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain and/or tenderness. There was no evidence of a difference in more severe local reactions, fever, or serious adverse events judged to be causally related to vaccination.
Topics: Acute Disease; Age Factors; Child; Child, Preschool; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Male; Otitis Media; Otitis Media with Effusion; Pneumococcal Vaccines; Randomized Controlled Trials as Topic; Vaccines, Conjugate
PubMed: 33231293
DOI: 10.1002/14651858.CD001480.pub6 -
Danish Medical Journal Oct 2020Although acute otitis media (AOM) is a very frequent illness in children, it remains unclear to what extent children with AOM benefit from antibiotics (ABX). This...
INTRODUCTION
Although acute otitis media (AOM) is a very frequent illness in children, it remains unclear to what extent children with AOM benefit from antibiotics (ABX). This systematic review aimed to clarify this subject by including randomised clinical trials (RCTs) from the pneumococcal vaccine era only.
METHODS
We performed a systematic literature search in four databases from 1 January 2000 to 1 January 2019 for RCTs comparing ABX to placebo in patients with AOM. Pain was registered as the main outcome. Adverse events (AE), development of contralateral otitis media, tympanic membrane perforation, late AOM recurrence, abnormal tympanometry and time to resolution of middle ear effusion were registered as secondary outcomes.
RESULTS
Six publications based on five RCTs with 1,862 patients were included. The number needed to treat (NNT) to reduce pain varied from seven (pain at day 7-10) to 28 (pain at day 2-3). The NNT for preventing contralateral otitis was ten. AE were seen in every 13th patient treated with ABX.
CONCLUSIONS
ABX appears to have a limited effect on both primary and secondary outcomes compared with placebo. A substantial number of patients experienced AE. New RCTs are needed to further clarify the effect. Ideally, RCTs could be conducted in Danish general practices in collaboration with practicing ear, nose and throat specialists to obtain large unselected populations with high rates of vaccine coverage. Until more evidence is provided, ABX should be considered among children younger than two years of age with severe symptoms of AOM, i.e. fewer and affected well-being.
Topics: Acute Disease; Anti-Bacterial Agents; Child; Humans; Infant; Neoplasm Recurrence, Local; Otitis Media; Tympanic Membrane Perforation
PubMed: 33215607
DOI: No ID Found -
International Journal of Environmental... Oct 2020Prison inmates are highly susceptible for several infectious diseases, including vaccine-preventable diseases. We conducted a systematic international literature review...
Prison inmates are highly susceptible for several infectious diseases, including vaccine-preventable diseases. We conducted a systematic international literature review on vaccination coverage against hepatitis B virus (HBV), hepatitis A virus (HAV), combined HAV/HBV, tetanus-diphtheria, influenza, pneumococcal, and combined measles, mumps, and rubella (MMR) in prison inmates, according to the PRISMA guidelines. The electronic databases were used Web of Science, MEDLINE, Scopus, and Cinhal. No language or time limit were applied to the search. We defined vaccination coverage as the proportion of vaccinated prisoners. There were no limitations in the search strategy regarding time period or language. Of 1079 identified studies, 28 studies were included in the review. In total, 21 reported on HBV vaccine coverage (range between 16-82%); three on HAV (range between 91-96%); two studies on combined HAV/HBV (77% in the second dose and 58% in the third); three studies on influenza vaccine (range between 36-46%), one of pneumococcal vaccine coverage (12%), and one on MMR coverage (74%). We found that data on vaccination coverage in prison inmates are scarce, heterogeneous, and do not include all relevant vaccines for this group. Current published literature indicate that prison inmates are under-immunized, particularly against HBV, influenza, MMR, and pneumococci. Strengthen immunization programs specifically for this population at risk and improvement of data record systems may contribute to better health care in prisoners.
Topics: Cross-Sectional Studies; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Male; Measles-Mumps-Rubella Vaccine; Prisoners; Prospective Studies; Retrospective Studies; Vaccination; Vaccination Coverage; Viral Hepatitis Vaccines
PubMed: 33086513
DOI: 10.3390/ijerph17207589 -
Vaccine Nov 2020A lower conversion vaccination rate and a more rapid decline in antibody titers over time in dialysis patients raise concerns about the effectiveness of pneumococcal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A lower conversion vaccination rate and a more rapid decline in antibody titers over time in dialysis patients raise concerns about the effectiveness of pneumococcal vaccination (PV) in this population, which has not been systematically reviewed.
METHODS
We searched PubMed, Cochrane Library, Embase and three Chinese databases from inception until February 29th, 2020 for interventional, cohort and case-control studies evaluating PV alone or combined with influenza vaccination (IV) on outcomes (all-cause mortality, pneumonia, cardiovascular events, antibody response and safety). Independent reviewers completed citation screening, data extraction, risk assessment, meta-analysis, and GRADE rating of the quality of evidence.
RESULTS
Five cohort studies and one quasirandomized control trial enrolling 394,299 dialysis patients with high to moderate quality were included. Compared with unvaccinated individuals, those receiving PV had lower risk of all-cause mortality [Adjusted relative risk (RR) 0.73, 95% CI 0.67-0.79, I = 31.1%, GRADE low certainty] and cardiovascular events (adjusted RR 0.80, 95% CI 0.69-0.93, I = 47.2%, GRADE low certainty) without serious adverse effect reported. Compared with no vaccination, lower all-cause mortality was observed in those receiving PV combined with IV (Adjusted RR 0.71, 95%CI 0.67-0.75, I = 63.3%), PV alone (Adjusted RR 0.86, 95% CI 0.78-0.94,I = 0%], and IV alone (Adjusted RR 0.76, 95% CI 0.73-0.79, I = 0%]. There was no difference between pneumococcal vaccinated patients vs non-vaccinated patients with respect to pneumonia. Immune response to pneumococcal conjugate vaccine-13 was weaker in polysaccharide pneumococcal vaccine-23-pre-vaccinated compared with vaccine-naive patients.
CONCLUSIONS
The use of pneumococcal vaccine especially combined with influenza vaccination is associated with lower risks of all-cause mortality but may be affected by residual confounding/healthy vaccinee bias.
Topics: Humans; Influenza Vaccines; Influenza, Human; Pneumococcal Vaccines; Renal Dialysis; Vaccination; Vaccines, Conjugate
PubMed: 33059969
DOI: 10.1016/j.vaccine.2020.09.080 -
Journal of Infection and Chemotherapy :... Jan 2021We conducted a systematic review of the literature to evaluate the reported epidemiology and burden of invasive pneumococcal disease (IPD) and pneumococcal pneumonia... (Review)
Review
We conducted a systematic review of the literature to evaluate the reported epidemiology and burden of invasive pneumococcal disease (IPD) and pneumococcal pneumonia (PP) among children and adults aged 6-64 years in Japan. Studies published from Japan between September 2009 and September 2019 and indexed in the MEDLINE/PubMed or ICHUSHI databases were evaluated. A majority of the studies reported overlapping age ranges, including children aged <6 years and adults aged >64 years. According to the national surveillance data, 19% of the IPD cases were patients aged 5-59 years, and an increasing trend in IPD cases was reported from 2013 to 2017. Comorbidities were consistent with those reported by the Advisory Committee on Immunization Practices. Deaths from IPD appeared to increase nearly 3-fold between 2013 and 2017. Overall, both 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) coverage was higher for IPD compared with PP. All the serotypes known to be prominent in Japan were also identified as common serotypes (3, 6A, 19A: PCV13 serotypes; 12F: outbreak serotype; 15A, 35B: drug-resistant serotypes). This systematic literature review suggests a substantial burden of IPD and PP in Japanese children and adults aged 6-64 years. The burden of comorbidities, hospitalizations, and mortality was particularly high among adults. Concerted pneumococcal vaccination strategies may help to reduce the incidence and burden of IPD and PP in this large proportion of the Japanese population.
Topics: Adult; Child; Humans; Incidence; Infant; Japan; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Serogroup; Streptococcus pneumoniae
PubMed: 33011068
DOI: 10.1016/j.jiac.2020.09.016 -
Vaccines Jul 2020Evidence on costs and health benefits of pneumococcal conjugate vaccine (PCV) for children in Asian countries is limited but growing. As a region with a considerably... (Review)
Review
Evidence on costs and health benefits of pneumococcal conjugate vaccine (PCV) for children in Asian countries is limited but growing. As a region with a considerably high burden of pneumococcal disease, it is prominent to have a comprehensive overview on the cost-effectiveness of implementing and adopting a PCV vaccination program. We conducted a systematic review from Pubmed and Embase to identify economic evaluation studies of PCV for children in Asian countries up to May 2020. Data extraction included specific characteristics of the study, input parameters, cost elements, cost-effectiveness results, and key drivers of uncertainty. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement was followed for this systematic review. The reporting quality of the included studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. After the screening process on both the title and abstract and full text of 518 records, a total of 25 studies fulfilled the inclusion criteria, and were included in the review. The majority of included studies demonstrates that PCV for children is cost-effective in most of the Asian region, and even cost-saving in some countries. Most of the included studies implemented cost utility analysis (CUA) using either quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Overall, the main drivers affecting the cost effectiveness were vaccine price, burden regarding pneumonia-related parameters, and the inclusion of herd effects. The children pneumococcal vaccination program appears to be a cost-effective intervention in Asia, and even cost-saving in certain conditions. Vaccine price, pneumonia-related disease burden, and the inclusion of the herd effect are observed as important key drivers in estimating cost-effectiveness in this region. Incorporating PCV in vaccination programs in this region was found to be highly favorable.
PubMed: 32751569
DOI: 10.3390/vaccines8030426