Systematic Review

Effects of Pneumococcal Vaccination in Children Under

Five Years of Age in the Democratic Republic of Congo:
A Systematic Review
Marcellin Mengouo Nimpa 1 , Abel Ntambue 2 , Christian Ngandu 3 , M. Carolina Danovaro-Holliday 4 ,
André Bita Fouda 5 , Aimé Mwana-Wabene Cikomola 6 , Jean-Crispin Mukendi 6 , Dieudonné Mwamba 3 ,
Adèle Daleke Lisi Aluma 7 , Moise Désiré Yapi 1 , Jean Baptiste Nikiema 1 , Boureima Hama Sambo 1
and Daniel Katuashi Ishoso 1,8, *

1 World Health Organization (WHO) Country Office, Kinshasa P.O. Box 1899, Democratic Republic of the Congo;
nimpamengouom@who.int (M.M.N.); yapimo@who.int (M.D.Y.); nikiemaje@who.int (J.B.N.);
sambob@who.int (B.H.S.)
2 École de Santé Publique, Université de Lubumbashi, Lubumbashi P.O. Box 1825,
Democratic Republic of the Congo; abelntambue@gmail.com
3 National Institute of Public Health, Kinshasa P.O. Box 01206, Democratic Republic of the Congo;
nganduchristian@ymail.com (C.N.); dk.mwamba@umontreal.ca (D.M.)
4 Immunization, Analytics and Insights (IAI), Department of Immunization, Vaccines and Biologicals (IVB),
World Health Organization (WHO), 1211 Geneva, Switzerland
5 World Health Organization African Regional Office, Brazzaville P.O. Box 06, Congo; abita@who.int
6 Expanded Program of Immunization, Kinshasa P.O. Box 01206, Democratic Republic of the Congo;
aimcik@yahoo.fr (A.M.-W.C.); mukendijean2@gmail.com (J.-C.M.)
7 Independent Researcher, Kinshasa P.O. Box 01211, Democratic Republic of the Congo; alumaadele@yahoo.fr
8 Kinshasa School of Public Health, University of Kinshasa, Kinshasa P.O. Box 11850,
Democratic Republic of the Congo
* Correspondence: dishosok@gmail.com; Tel.: +243-821605955

Abstract: Background: In the Democratic Republic of Congo (DRC), the 13-valent

pneumococcal conjugate vaccine (PCV13) was introduced in 2011 through a three-dose
schedule, targeting infants as part of the Expanded Program on Immunization (EPI), to
reduce pneumococcal-related morbidity and mortality. The aim of this study was to
determine the proportion of pneumonia and meningitis cases and deaths prevented
in children under five following the introduction of this vaccine. Methods: This is
Academic Editor: Pedro Plans-Rubió
a systematic review. We synthesized findings from studies carried out in the DRC
Received: 4 February 2025 between 2011 and 2023. We searched scientific articles, published and unpublished
Revised: 3 April 2025
doctoral theses and conference proceedings. Only papers written in French or English
Accepted: 11 April 2025
and those reporting the results of original analytical studies were selected. We assessed
Published: 31 May 2025
the direct effect of PCV13 by calculating the proportion of infections avoided, using
Citation: Nimpa, M.M.; Ntambue, A.;
Odds Ratios or prevalence ratios related to infection or pneumococcal carriage. Results:
Ngandu, C.; Danovaro-Holliday, M.C.;
Bita Fouda, A.; Cikomola, A.M.-W.;
Four studies were included in this review. Regarding pneumococcal carriage, when
Mukendi, J.-C.; Mwamba, D.; Aluma, children received three PCV13 doses, the prevalence of carriage was reduced by 93.3%
A.D.L.; Yapi, M.D.; et al. Effects of (95% CI: 86.3 to 96.6%), while a single dose did not significantly reduce the prevalence
Pneumococcal Vaccination in Children of carriage compared with children who had not received any dose. Concerning
Under Five Years of Age in the
pneumonia prevention, three doses of PCV13 prevented 66.7% (95% CI: 37.2 to 82.2)
Democratic Republic of Congo: A
of cases among vaccinated children. The proportion of meningitis attributable to S.
Systematic Review. Vaccines 2025, 13,
603. https://doi.org/10.3390/
pneumoniae prevented was 75.0% (95% CI: 6% to 93.3%) among children vaccinated
vaccines13060603 with PCV13. S. pneumoniae serotypes 19F and 23F were the most frequent causes of
invasive pneumonia in children. Serotypes 35B/35C, 15B/C, 10A and 11A/D were the
Copyright: © World Health
Organization 2025
most frequently identified causes of morbidity in Congolese children. In 2022, with
(https://creativecommons.org/ PCV13 vaccination coverage at 79.0%, an estimated 113,359 cases of severe pneumonia
licenses/by/4.0/). and 17,255 pneumonia-related deaths were prevented in the DRC, with 3313 cases and

Vaccines 2025, 13, 603 https://doi.org/10.3390/vaccines13060603

Vaccines 2025, 13, 603 2 of 16

1544 deaths attributable to pneumococcal meningitis prevented. Conclusions: There is

clear, but scattered, evidence of reduced colonization by S. pneumoniae and hospital
admissions due to pneumococcal pneumonia and meningitis. The results also show
that S. pneumoniae serotypes 35B/35C, 15B/C, 10A and 11A/D not included in PCV13
were the main cause of pneumococcal disease in unvaccinated or under-vaccinated
children. These data support the need to continue improving vaccination coverage
among children who are unvaccinated or incompletely vaccinated with PCV13 to
reduce the burden of pneumococcal infections in the DRC.

Keywords: pneumococcal conjugate vaccine; PCV13; pneumococcal infections; Streptococcus

pneumoniae; Democratic Republic of the Congo

1. Introduction
Streptococcus pneumoniae, the bacterium responsible for pneumococcal infections, can
lead to severe invasive diseases such as pneumonia, meningitis, septicemia, and acute
otitis media, especially in children under two years of age. These infections are particularly
prevalent among young children and older adults [1,2].
In most cases, pneumococcal illness is preceded by silent colonization of the nasophar-
ynx. Globally, S. pneumoniae is estimated to cause over 318,000 deaths annually (with
an uncertainty range of 207,000 to 395,000) among children aged 1 to 59 months, with
Africa bearing the greatest share of this mortality burden [3].
Prior to the inclusion of pneumococcal conjugate vaccines (PCVs) in national im-
munization schedules, more than 70% of invasive pneumococcal diseases were linked to
serotypes targeted by these vaccines [3]. Pneumonia represents the most common clinical
form of infection caused by this pathogen [4]. Meningitis, although less frequent, accounts
for about 2% of serious pneumococcal cases and contributes to 12% of related fatalities [3,5].
Before vaccine introduction, nasopharyngeal carriage rates in children under five in
low- and middle-income countries ranged from 20% to 90%, making them the principal
reservoir and source of pneumococcal transmission [6].
Over 90 distinct pneumococcal serotypes have been identified, each exhibiting varying
degrees of virulence and antimicrobial resistance [5–7]. The management of these infections
has become increasingly challenging due to the global emergence of strains resistant to
penicillin and other antibiotics [8].
Pneumococcal vaccines target the serotypes most often involved in invasive infections.
There are two types; the first is a conjugate vaccine (PCV13) and contains 13 serotypes 1, 3,
4, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 18C and 23F. It provides protection against pneumococcal
infection and carriage [1]. Moreover, it can be used from the age of six weeks. By reducing
carriage, it provides an indirect (herd) protection effect: unvaccinated children are also
less likely to be infected by pneumococcus [9]. The second vaccine is unconjugated and
contains 23 pneumococcal serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B,
17F, 18C, 19A, 19F, 20, 22F, 23F and 33F). Although this vaccine has a broader spectrum,
it is not effective before the age of two, does not eliminate nasopharyngeal carriage—the
primary source of person-to-person transmission—provides only short-lived protection,
and lacks a booster response upon revaccination [9].
In countries where PCV vaccination is widespread, the number of cases of meningitis
and pneumococcal pneumonia in children under the age of five has fallen markedly [10,11].
An impact has also been observed in unvaccinated children, adults, and the elderly owing
to herd immunity conferred by childhood vaccination. In addition, vaccination has led
Vaccines 2025, 13, 603 3 of 16

to a decline in the rate of antibiotic-resistant pneumococci in meningitis, bacteremia, and

pneumococcal otitis [12].
In the Democratic Republic of Congo (DRC), studies show that pneumonia is the
second leading cause of death in children under the age of five, after malaria [13]. This
bacterium is also responsible for 28.5% of purulent meningitis [14]. In 2011, pneumococcus
was responsible for 41,939 deaths attributable to pneumonia and 9256 deaths attributable
to meningitis in children under five [15].
From April 2011, PCV13 was gradually introduced into the DRC’s Expanded Program
on Immunization (EPI). The vaccination schedule includes three doses of the vaccine: the
first at 6 weeks after birth, the second at 10 weeks, and the third at 14 weeks. However,
children can also be vaccinated at any contact for catch-up if the routine schedule has not
been followed.
In 2011, when PCV13 was introduced into the EPI, under-five mortality was 104 per
1000 live births [16]. It was therefore accepted that vaccination should help to substantially
reduce the burden of morbidity and mortality in this age group [16]. The estimated PCV13
coverage has increased from 9.0% in 2011 to 79.0% in 2022 [15], but we do not know,
in the specific context of the DRC, what effect this vaccine has had on the burden of
disease preventable by PCV13, particularly regarding the number of severe pneumonia
and meningitis cases and related deaths averted.
In the DRC, the scientific literature on the effects of PCV13 is limited [17–28]. What
evidence is available comes from a few studies carried out in limited geographical areas:
children presenting different clinical pictures of pneumococcal carriage [26], invasive
pneumonia [19], and pneumococcal meningitis [22,27] with different inclusion criteria from
one study to another. These results, fragmented and localized, have not yet been pooled
to determine the effects of the introduction of PCV13 on the burden of pneumococcal
infections in the DRC.
The aim of this study was to determine, by synthesizing the available scientific litera-
ture on PCV13 vaccination in the DRC, the fraction of cases of pneumonia and meningitis
and the fraction of deaths in children under five attributable to these diseases prevented by
this vaccine in the DRC, and to determine the evolution of isolated S. pneumoniae serotypes
since the introduction of PCV13.

2. Materials and Methods

This systematic review was carried out in line with the PRISMA group’s recommenda-
tions. A research librarian contributed to the development of the search strategy and the
inclusion criteria. The review protocol was registered in the International Prospective Reg-
ister of Systematic Reviews (PROSPERO) under the registration number CRD42025641327
(https://www.crd.york.ac.uk/prospero/#recordDetails, accessed on 21 January 2020).

2.1. DRC Context

The DRC is one of the most densely populated countries in Africa. In 2022, its
population was estimated at 105 million, occupying an area of 2,345,000 km2 , with a density
of 45 inhabitants per km2 , according to the Statistical Yearbook of the Ministry of Planning
of the DRC. Children under the age of five represented 20% of the total population.
In 2009, two years prior to the rollout of PCV13, pneumococcal infections affected
more than 3000 out of every 100,000 children under five years old, with a mortality rate
ranging between 300 and 500 per 100,000 in the same age group [29]. By 2022, under-five
mortality was recorded at 98 deaths per 1000 live births, and pneumococcal disease was
responsible for 16.0% of these fatalities, based on data from Countdown2030 [13].
 Vaccines2025,
Vaccines 2025,13,
13,603
x FOR PEER REVIEW 44 of
of 16
17

Based
Basedononvaccination
vaccinationcoverage
coveragesurveys,
surveys,and
andusing
usingaalinear
linearinterpolation
interpolationmodel
modelwith
with
Lives Saved Tool (LiST) software, version 6.0, PCV13 vaccination coverage between
Lives Saved Tool (LiST) software, version 6.0, PCV13 vaccination coverage between 2011
2011 and 2022 varied from 9.0% to 79.0% (Figure 1)
and 2022 varied from 9.0% to 79.0% (Figure 1) [30]. [30].

Figure 1.
Figure 1. Trends in vaccination
vaccination coverage
coverage against
againstpneumococcal
pneumococcalinfections
infectionssince
sincethe
theintroduction of
introduction
of PCV13.
PCV13.

2.2. Study
2.2. Study
This study is a systematic review of the literature on the effects of PCV13 (3 doses) and
This study is a systematic review of the literature on the effects of PCV13 (3 doses)
the evolution of S. pneumoniae serotypes since the introduction of this vaccine in the EPI in
and the evolution of S. pneumoniae serotypes since the introduction of this vaccine in the
the DRC. We assessed the effect of the vaccine by summarizing the effects reported in the
EPI in the DRC. We assessed the effect of the vaccine by summarizing the effects reported
literature from scientific research conducted in the DRC and published from 2011 to 2023.
in the literature from scientific research conducted in the DRC and published from 2011
to 2023.
2.3. Documentary Search Strategy
We searched for scientific articles in online journals, local offline journals, published
2.3. Documentary Search Strategy
and unpublished Ph.D. theses, and proceedings of scientific congresses and symposia.
We searched for scientific articles in online journals, local offline journals, published
To locate pertinent studies, we conducted a search across the Medline, Embase,
and unpublished PhD theses, and proceedings of scientific congresses and symposia.
Cochrane Library, and Google Scholar databases, utilizing Medical Subject Headings
To locate pertinent studies, we conducted a search across the Medline, Embase,
(MeSH), controlled vocabulary, and free-text keywords. Additionally, we used keyword-
Cochrane Library, and Google Scholar databases, utilizing Medical Subject Headings
based searches in PubMed to capture articles and publications not indexed in Medline. To
(MeSH), controlled vocabulary, and free-text keywords. Additionally, we used keyword-
ensure comprehensive coverage, we also performed a manual review of reference lists from
based searches in PubMed to capture articles and publications not indexed in Medline. To
relevant systematic reviews to identify any potentially overlooked studies.
ensure comprehensive coverage, we also performed a manual review of reference lists
In these bibliographic databases, the keywords used were as follows: “13-valent
from relevant systematic reviews to identify any potentially overlooked studies.
pneumococcal vaccine AND Democratic Republic of the Congo”; “13-valent pneumococcal
In these bibliographic databases, the keywords used were as follows: “13-valent
vaccine AND Africa”; “PCV13 and Streptococcus pneumoniae serotypes”; “PCV13 and
pneumococcal vaccine AND Democratic Republic of the Congo”, “13-valent pneumococ-
invasive pneumonia in the Democratic Republic of the Congo”; “PCV13 and meningitis in
cal vaccine AND Africa”; “PCV13 and Streptococcus pneumoniae serotypes”; “PCV13 and
the Democratic Republic of the Congo”.
invasive
Afterpneumonia
conductinginallthe theDemocratic
bibliographicRepublic
searchesof the
on Congo”; “PCV13
all published andand meningitis
unpublished
in the Democratic
documents on the DRCRepublic
or in of the Congo”.
Africa, reporting data on the impact of PCV13 vaccination on
the incidence of pneumonia and pneumococcalsearches
After conducting all the bibliographic meningitis,on we
all organized
publishedworking
and unpublished
meetings
documents
with experts on the field
in the DRCoforbacterial
in Africa, reporting
disease data on to
surveillance the impact
search forof PCV13 vaccination
additional reports to
on the the
ensure incidence of pneumonia
completeness and pneumococcal
of the reports meningitis,
collected that could we into
be taken organized
accountworking
in this
meetings with
systematic experts in the field of bacterial disease surveillance to search for additional
review.
reports
We to ensure
used the completeness
the Effective of thePractice
Public Health reports collected that for
Project’s tool could be taken
assessing into
the account
quality of
in this systematic review.
quantitative studies to evaluate the level of risk of bias in each study, as well as its internal
We[31].
validity usedEach
the study
Effective
wasPublic Health
assessed Practice
against eight Project’s tool forcriteria:
methodological assessing the quality
selection bias,
of quantitative studies to evaluate the level of risk of bias in each study, as
study design, confounding factors, blinding if it was a clinical trial, data collection methods, well as its
internal validity [31]. Each study was assessed against
study participant withdrawals, intervention integrity and analysis. eight methodological criteria:
Vaccines 2025, 13, 603 5 of 16

We then assessed the collected papers, with two reviewers first examining the titles
and abstracts, and then the full text. Disagreements about inclusion were resolved by
discussion between the reviewers.

2.4. Inclusion Criteria

We included only papers written in French or English and those reporting original
research results. When meta-analyses included DRC data, we searched for the original
article. Where this was not found, the meta-analysis was not included in this review.
This review considered a range of study designs, including randomized controlled
trials, non-randomized studies, analyses based on surveillance data, and observational
research. Titles and abstracts underwent two rounds of screening, and those addressing
at least one of the four targeted outcomes—carriage, invasive disease, pneumonia or
meningitis, and indirect effects—were subjected to a detailed review using a purpose-
designed data extraction tool.

2.5. Measuring the Effects of PCV13

2.5.1. Measures from Studies
The studies included in this review determined the direct effect of vaccination by
calculating Odds Ratios (ORs) or prevalence ratios of infection or carriage in vaccinated
children (PCV13) compared with those who were not vaccinated (non-PCV13) [18,23,28].
We did not carry out meta-analyses because of the heterogeneity between studies.
From the ORs, we calculated the fraction of infections prevented (FIP) in PCV13 children
according to the formula provided by Bouyer C et al. if the ORs were of less than 1 [32].
However, when the ORs were greater than 1, we used the formula provided by the Global
Burden of Disease (GBD) 2016 Lower Respiratory Infections Collaborators [4].

2.5.2. Estimation of the Burden of Pneumococcal Infections Prevented in the DRC

We modeled the expected direct effect of the vaccine as a function of the effect of
the vaccine reported in the studies included in this review and its coverage in the DRC
population. We derived the total effect of PCV13 on different levels of vaccine coverage
from a report modeling the cohort effect in India [33].
To estimate the number and percentage of cases and deaths attributable to pneumonia
and meningitis caused by S. pneumoniae prevented and averted by PCV13, we established
the effect of this vaccine on the specific causes of morbidity and mortality in children under
five years of age. The effects of the change in PCV13 vaccination coverage were applied to
the number of cases and deaths in children under five years of age as documented since
2000 for DRC, on the assumption that this effect on the population increased linearly with
vaccination coverage [30]. The following formula was used to calculate the number of
infections prevented and deaths avoided in the population (FIPp).

N × I × (P1 − P0)
Deaths averted =
(1 − I × P0)

N = number of cases or deaths with vaccination coverage in the initial year (2011) and
the year before the year under evaluation.
I = percentage by which PCV13 prevents new cases or reduces deaths.
P0 = vaccination coverage in the initial year (2011) and the year before the year under
evaluation.
P1 = vaccination coverage in the year evaluated.
Vaccines 2025, 13, x FOR PEER REVIEW 6 of 17

Vaccines 2025, 13, 603 6 of 16

We consider the herd immunity in the model as the additional proportion of cases or
deaths due to vaccine-susceptible pneumococci that could be prevented by population-
levelWe
PCV coverage,
consider in addition
the herd immunity to in
the cases
the and
model as deaths prevented
the additional directly
proportion of by vaccination.
cases or
deaths due to vaccine-susceptible pneumococci that could be prevented by population-level
Analyses relating to FIP were carried out using NCSS 2020 software, while calcula-
tions coverage,
PCV in addition and
of cases prevented to thedeaths
cases and deathswere
avoided prevented directly
carried by vaccination.
out using the LiST tool in One-
Analyses relating to FIP were carried out using NCSS 2020 software, while calculations
Health software v6.29 [30].
of cases prevented and deaths avoided were carried out using the LiST tool in OneHealth
software v6.29 [30].
3. Results
3. Results
3.1. Selection of Studies
3.1. Selection
In total,ofwe
Studies
identified eleven articles published in online scientific journals and one
In total, we identified eleven articles
doctoral thesis available online relatingpublished in online scientific
to pneumococcal journals
vaccination and
in the one (Figure
DRC
doctoral thesis available online relating to pneumococcal vaccination in the DRC (Figure 2).
2).

Figure 2. Inclusion of studies in this systematic review (PRISMA flow diagram of study selection).
Figure 2. Inclusion of studies in this systematic review (PRISMA flow diagram of study selection).
We excluded four articles (33.3%) that were either systematic reviews or studies based
We excluded
on evaluations using four articles models.
mathematical (33.3%)Ofthat werestudies
the eight eitherbased
systematic reviews
on primary or studies
data, we
based on two
excluded evaluations using
descriptive mathematical
studies that focusedmodels.
either onOf
thethe eight studies
prevalence based on primary
of pneumococcal
data, weorexcluded
disease on PCV13two descriptive
vaccination studies that focused either on the prevalence of pneu-
coverage.
Finally, we excluded two articles
mococcal disease or on PCV13 vaccination due tocoverage.
methodological limitations, such as the
absence of defined
Finally, judgment two
we excluded criteria or undetermined
articles vaccination status
due to methodological in children.
limitations, suchOnly
as the ab-
four studies were included in this review.
sence of defined judgment criteria or undetermined vaccination status in children. Only
four studies
3.2. Profile were included
of Studies Included ininThis
thisReview
review.
and Effects of PCV13
Table 1 shows that two of these three studies were carried out in the province of
3.2. Profile of Studies Included in This Review and Effects of PCV13
South Kivu in a hospital setting; the third study was conducted simultaneously in Kin-
shasaTable 1 shows that
(Kalembelembe two of these
and Kingasani), andthree studies were
in Lubumbashi, carriedHospital.
at Sendwe out in the
The province
first of
South Kivu
study [26] in a hospital
evaluating setting;
the effect the third
of PCV13 on thestudy was
burden conducted simultaneously
of pneumococcal infections was in Kin-
shasa (Kalembelembe and Kingasani), and in Lubumbashi, at Sendwe Hospital. The first
study [26] evaluating the effect of PCV13 on the burden of pneumococcal infections was
carried out in 2013 and published in 2018, i.e., two years after the introduction of PCV13
Vaccines 2025, 13, 603 7 of 16

carried out in 2013 and published in 2018, i.e., two years after the introduction of PCV13 in
the national EPI schedule; the second was carried out in 2016 [19], i.e., five years after, and
the third [27] was carried out in 2023, i.e., 12 years after the introduction of PCV13. Only
the study by Coulibaly et al. used data from sentinel surveillance sites for meningitis and
pneumococcal infections.
The first study [26] was cross-sectional. In this study, the authors compared S. Pneu-
moniae carriage in PCV13 recipients (2–3 doses and 1 dose) versus non-PCV13 children
under five years of age. Coulibaly et al. [19] used a quasi-experimental study in which
they compared the occurrence of pneumococcal infections between children in a province
that had already introduced PCV13 (Kinshasa) and those in another province that had not
yet done so (Katanga). The third study [27], conducted at Panzi Hospital in Bukavu, was
also cross-sectional and was conducted among children admitted to pediatric wards with
confirmed meningitis. It compared the presence of S. pneumoniae as a cause of meningitis
between PCV13-positive children and those who were not.
In the studies included in this review, the burden of pneumococcal infections
was assessed mainly by calculating ORs. As shown in Table 1, the proportion of
children with S. pneumoniae pneumonia was six times lower in children vaccinated
with PCV13 (3 doses) than in those who were not. In the study by Coulibaly et al., the
incidence of invasive pneumonia was five times higher in non-PCV13 than in PCV13
children (95% CI: 0.03–0.14). The study by Manegabe et al. showed that non-PCV13
children had four times the odds of suffering from pneumococcal meningitis than
PCV13 children (three doses).
Table 2 shows that when the FIP was calculated for children with three doses of PCV13
in the Birindwa study, 93.2% (95% CI: 86.3–96.6) of S. pneumoniae carriage cases were
prevented in children who received three doses of PCV13 compared with those who were
not vaccinated. Considering the incidence of invasive pneumonia, the ORs reported by
Coulibaly et al. show that the introduction of PCV13 prevented 66.7% (95% CI: 37.2–82.2) of
cases of invasive pneumonia in vaccinated children compared with unvaccinated children.
According to the measures of association obtained by Manegabe et al., the proportion of
cases of meningitis attributable to S. pneumoniae prevented ranged from 6% to 93.3% in
PCV13 children.

3.3. Overall Effect of PCV13 on the Burden of Pneumococcal Infections in the DRC
Figure 3A–C shows the effect of introducing PCV13 into the EPI schedule as a function
of changes in vaccination coverage. The effect of PCV13 in the general population increased
over time. This effect varied according to vaccination coverage. For example, when PCV13
vaccination coverage was 73.0%, the number of cases of severe pneumonia prevented was
almost 100,000 per year (Figure 3A), while the number of deaths attributable to severe
pneumonia was greater than 12,072 per year (Figure 3B). Thus, with PCV13 vaccination
coverage at 79.0% in 2022, 113,359 new cases of severe pneumonia and 17,255 deaths
attributable to severe pneumonia were prevented in the DRC (Figure 3C).
Figure 4A–C shows similar effects for pneumococcal meningitis. PCV13 vac-
cination coverage of 79.0% prevented more than 3000 new cases of pneumococcal
meningitis (Figure 4A). Unlike pneumonia, where deaths were prevented even with
low PCV13 coverage, for meningitis, only PCV13 coverage of over 60.0% prevented
deaths in children suffering from meningitis (Figure 4B). Thus, in 2022, the number
of new cases and deaths attributable to pneumococcal meningitis prevented in the
DRC owing to PCV13 vaccination coverage at 79.0% were 3313 and 1544, respectively
(Figure 4C).
Vaccines 2025, 13, 603 8 of 16

Table 1. Characteristics of the studies included in this systematic review.

Children’s Study Period (Data Judgment Measurement of

Ref. Author, Year Specific Objective Medium No. Type of Study Comparison
Profile Collection) Criteria Effect
Nasopharyngeal
2–3 vs. 0 doses:
carriage and conditions
South Kivu: aOR = 0.07
predisposing to Healthy
Health Centers S. pneumoniae PCV13 vs. 95% CI: 0.03–0.14
[26] Birindwa, A.M., 2018 pneumococcal children aged 1 794 Cross-sectional 2014 to June 2015
during preschool carriage Non-PCV13 1 vs. 0 dose:
colonization in healthy to 60 months
consultations aOR = 0.84
children after PCV13
95% CI: 0.55–1.27
introduction
To examine the Kinshasa: sentinel
relationship between surveillance sites Sick children
Quasi- Incidence of
childhood PCV13 of Kalembelembe treated in
experimental, invasive PCV13 vs. aOR = 0.33
[19] Coulibaly, A., 2016 immunization rates in and Kingasani, sentinel 380 2009, July 2013
with control pneumococcal Non-PCV13 95% CI: 0.63–0.18
DRC provinces and the and Lubumbashi surveillance
group disease
incidence of invasive at Sendwe sites
pneumococcal disease hospital
Determining the
South Kivu:
presence of bacteria and Children CSF Presence of
pediatric April 2021 to end of PCV13 vs. OR = 4.0
[27] Manegabe, J.T., 2023 viruses in the CSF of hospitalized due 150 Cross-sectional S. Pneumoniae in
department of March 2022 non-PCV13 95% CI: 1.06–15.0
hospitalized children to meningitis children
Panzi hospital
with meningitis
 Concerning serotypes not included in PCV13, all were identified in non-PCV13
Vaccines 2025, 13, 603 dren. In non-PCV13 children, 35B/35C, 15B/C, 10A and 11A/D were the serotypes 9 of 16
id
fied in most children.
In children with pneumococcal meningitis [27], only one serotype included in P
Table 2. Fraction of infections prevented in children vaccinated with PCV13.
was identified—19F among PCV13 children. As in the two previous studies, no sero
included in PCV13 were identified FIP at PCV13 %
Author, Year Outcomes Numberin
of non-PCV13
Children Oddschildren.
Ratio (95%CI)On the other hand, most
(95%CI)
Birindwa, A.M., 2018 [26] types S.not included
pneumoniae carriagein PCV13 identified 794 in PCV13 children
0.07 (0.03–0.14) † were
93.2 not the same as
(86.3–96.6)
Coulibaly, A., 2016 [19] identified
Incidence in children
of invasive pneumococcal suffering
disease from 380
pneumonia 0.33or carrying
(0.63–0.18) only66.7
S. (37.2–82.2)
pneumoniae. In th
Manegabe, J.T., 2023 [27] category, 55.6% of isolated S. pneumoniae were of unknown serotypes.
Presence of S. pneumoniae in children 150 4.0 (1.06–15.0) 75.0 (6.0–93.3)
FIP: Fraction of infections prevented (%); †: 2–3 vs. 0 dose.

Figure 3. Variation in the number of cases of severe pneumonia preventable by PCV13 (A) and
Figure
cases 3.
of Variation inS.the
death due to numberpneumonia
pneumoniae of cases of severe pneumonia
preventable preventable
by PCV13 (B) according to by PCV13 (A) and
vaccination
coverage
of death andto
due year
S. (C).
pneumoniae pneumonia preventable by PCV13 (B) according to vaccination
erage and
We year
found(C).
no studies reporting S. pneumoniae serotypes in the DRC prior to the intro-
duction of PCV13. Of all the studies included in this review (n = 4), only three reported
data on S. pneumoniae serotypes.
 Vaccines 2025, 13, x FOR PEER REVIEW 11 of 17
Vaccines 2025, 13, 603 10 of 16

Figure
Figure 4. Variation in
4. Variation inthe
thenumber
numberofofcases
cases
of of meningitis
meningitis (A)(A)
andand deaths
deaths duedue S. pneumoniae
to S.topneumoniae men-
meningitis preventable by PCV13 (B) according to vaccination coverage and year
ingitis preventable by PCV13 (B) according to vaccination coverage and year (C). (C).

The
Table detailed
3. S. distribution
pneumoniae serotypes of S. pneumoniae
identified in DRCserotypes identified
studies post in theintroduction.
PCV13 vaccine included studies
is presented in Table 3.
This Included in Birindwa,
table presents the resultsA.M.,
of threeBirindwa, A.M., 2020
studies relating Manegabe,serotypes.
to S. pneumoniae J.T., 2023
PCV13 2018 [26] [18] [27]
Children’s Profile Birindwa’s study included healthy children who carried S. pneumoniae and the prevalence
of carriage was 20.5% [26]. Serotype
Healthy analysis showed that more than half of theHospital-
Children
2 to 59 Months Hospi- Children serotypes
identified were not among those currentlytalized
coveredforbyPneumonia ized all
PCV13. Almost withtheMeningitis
serotypes
Children with isolated serotypes(n)
included in PCV13 were identified163 in PCV13 children. 375 37 by 52.2%
Of these, 19F was carried
% with S. pneumoniaeof children. 20.5 77.0 37.8
Included in PCV13 (%) ⱡ Serotypes not included in 46.0 47.4 in 14.8% of vaccinated
the vaccines were identified 10.2 children
Children PCV13 (%) (3 ꬸ doses), while 85.2% were identified
100.0 100.0 100.0
in non-PCV13 children. Among PCV13 children,
1 Yes 0.0
18 was carried by more than two-thirds (66.7%), while 2.8 19A was carried by 0.033.3%. In
19A non-PCV13 children carrying serotypes not included in PCV13, 35B/35C was 0.0
Yes 8.7 13.9 identified in
19F Yes 52.2
almost a third of children (30.4%). 44.4 100.0
14 Yes 4.3 2.8 0.0
23F Yes 8.7 2.8 0.0
9A/V Yes 4.3 5.6 0.0
 Vaccines 2025, 13, 603
Figure
Figure 4.4. Variation
Variation in
in the
the number
number of
of cases
cases of
of meningitis
meningitis (A)
(A) and
and deaths
deaths due
due to
to S.
S. pneumoniae men- 11 of 16
pneumoniae men-
ingitis
ingitis preventable
preventable byby PCV13
PCV13 (B)
(B) according
according to
to vaccination
vaccination coverage
coverage and
and year
year (C).
(C).

Table 3. S. pneumoniae serotypes identified in DRC studies post PCV13 vaccine introduction.
Table
Table 3.
3. S.
S. pneumoniae
pneumoniae serotypes
serotypes identified
identified in
in DRC
DRC studies
studies post
post PCV13
Vaccines
PCV13 vaccine
2025, introduction.
13, x FOR
vaccine PEER REVIEW
introduction.
Vaccines 2025, 13, x FOR PEER REVIEWIncluded in PCV13 Birindwa,A.M.,
A.M., 2018 [26] Birindwa, 11 of 17
Children’s Profile Included
Included inin Birindwa,
Birindwa, A.M., Birindwa,
Birindwa, A.M.,A.M.,
A.M., 20202020Manegabe,
2020 [18] Manegabe,
Manegabe, J.T., J.T., 2023
2023 [27]
J.T., 2023
PCV13
PCV13 2018
2018 [26]
[26] [18]2 to 59 Months
[18] [27]
[27] Hospitalized
Children
Children’s
Children’s Profile
Profile Healthy Children Hospitalized for
with Meningitis
22 to
to 59
59 Months
Months Hospi-
Hospi-
Pneumonia Children
Children Hospital-
Hospital-
Healthy
Healthy Children
Children
Children with talized
talized for
for Pneumonia
Pneumonia ized
ized with
with Meningitis
Meningitis
163 375 37
Children
Children with isolated
isolated
with serotypes(n)
serotypes(n)
isolated serotypes(n) 163
163 375
375 37
37
%
% with S.
S. pneumoniae
% with
with S. pneumoniae
pneumoniae 20.5
20.5 20.5 77.0
77.0 77.0 37.8
37.8 37.8
Included
Included in
in PCV13
Included PCV13
in (%) ⱡⱡ
PCV13(%)
(%) 46.0
46.0 46.0 47.4
47.4 47.4 10.2
10.2 10.2
Children
Children PCV13
PCV13
Children (%) ꬸꬸ
(%)
PCV13(%) 100.0
100.0 100.0 100.0
100.0 100.0 100.0
100.0 100.0
11 1 Yes
Yes
Yes 0.0
0.0 0.0 2.8
2.8 2.8 0.0
0.0 0.0
19A
19A 19A Yes
Yes
Yes 8.7
8.7 8.7 13.9
13.9 13.9 0.0
0.0 0.0
19F
19F19F Yes
Yes
Yes 52.2
52.2 52.2 44.4
44.4 44.4 100.0
100.0 100.0
14
14 14 Yes
Yes
Yes 4.3
4.3 4.3 2.8
2.8 2.8 0.0
0.0 0.0
23F
23F23F Yes
Yes
Yes 8.7
8.7 8.7 2.8
2.8 2.8 0.0
0.0 0.0
9A/V
9A/V 9A/V Yes
Yes
Yes 4.3
4.3 4.3 5.6
5.6 5.6 0.0
0.0 0.0
3 Yes 8.7 0.0
6ABCD Yes 8.7 0.0
5 Yes 4.3 27.8 0.0
Non-PCV13 children (%) 0.0 0.0 0.0
18C Yes 0.0 0.0 0.0
4 Yes 0.0 0.0 0.0
Not included in PCV13 54.0 52.6 89.8
Child PCV13 (%) 14.8 0.0 73.3
Unknown 0.0 0.0 55.6
13 0.0 0.0 11.1
18 100.0 0.0 0.0
23A 0.0 0.0 2.0
22F 0.0 0.0 11.1
33F 0.0 0.0 11.1
15B 0.0 0.0 11.1
Non-PCV13 children (%) 85.2 100.0 26.7
11A/D 21.7 15.0 0.0
10A 8.7 15.0 0.0
15B/C 4.3 17.5 0.0
12 4.3 7.5 0.0
35B/35C 30.4 17.5 0.0
Figure 4. Variation in t
20 Figure 4. Variation in the number0.0of cases of meningitis (A)2.5 0.0
and deaths due to S. pneumoniae
ingitis men-
preventable by P
38 ingitis preventable by PCV13 (B) 0.0
according to vaccination coverage
7.5 and year (C). 0.0
34/17A 13.0 0.0 Table 3. S. pneumoniae
0.0
9N/L Table 3. S. pneumoniae serotypes identified
4.3 in DRC studies post
0.0 PCV13 vaccine introduction.
0.0
Included in
17 4.3 0.0 0.0
Included in Birindwa, A.M., Birindwa, A.M., 2020 Manegabe, J.T., 2023 PCV13
2 4.3[26] 2.5 Children’s Profile66.7
PCV13 2018 [18] [27]
Children’s
7C
Profile 4.3 2 to 59 Months Hospi- Children33.3
7.5 Hospital-
22F
Healthy0.0Children 2.5 0.0
talized for Pneumonia
Children ized with
with isolated Meningitis
serotypes(n)
Children with20isolated serotypes(n) 0.0
163 2.5 % with S. pneumoniae
375 0.0
37
7AF
% with S. pneumoniae 0.0
20.5 2.5Included in PCV13 37.8
77.0 0.0 ⱡ
(%)
Included in PCV13 (%) ⱡ : calculated in relation to the total46.0
number of children in whom the serotype was identified; ꬸ : calculated in
47.4 Children PCV13 10.2
(%)
relation to the total number of children carrying the serotypes included or not in PCV13.
Children PCV13 (%) ꬸ 100.0 100.0 1 100.0 Yes
1 Yes 0.0 2.8 19A 0.0 Yes
19A Yes 8.7 13.9 19F 0.0 Yes
19F Yes 52.2 44.4 14 100.0 Yes
14 Yes 4.3 2.8 23F 0.0 Yes
23F Yes 8.7 2.8 9A/V 0.0 Yes
Vaccines 2025, 13, 603 12 of 16

In children hospitalized for pneumonia [19], the distribution of serotypes according

to their inclusion in PCV13 and the vaccination status of the children was similar to that
observed in healthy carrier children. For example, we noted that in almost half of the
children (47.4%), the serotypes identified were those included in PCV13. Serotypes 19F
(44.4%), 5 (27.8%) and 19A (13.9%) were the most identified in children who had already
been vaccinated with PCV13.
Concerning serotypes not included in PCV13, all were identified in non-PCV13 chil-
dren. In non-PCV13 children, 35B/35C, 15B/C, 10A and 11A/D were the serotypes identi-
fied in most children.
In children with pneumococcal meningitis [27], only one serotype included in PCV13
was identified—19F among PCV13 children. As in the two previous studies, no serotypes
included in PCV13 were identified in non-PCV13 children. On the other hand, most
serotypes not included in PCV13 identified in PCV13 children were not the same as those
identified in children suffering from pneumonia or carrying only S. pneumoniae. In the last
category, 55.6% of isolated S. pneumoniae were of unknown serotypes.

4. Discussion
The studies analyzed in this review primarily examined the impact of PCV13 on
Streptococcus pneumoniae among children under five. Their focus was on how the vaccine
influences bacterial carriage, its role in preventing invasive pneumonia and pneumococcal
meningitis, and the distribution of S. pneumoniae serotypes.

4.1. PCV13 Effects

Regarding carriage, it was noted that when children received three doses of PCV13,
the prevalence of carriage decreased by 93.3%. A single dose of PCV13 did not signifi-
cantly reduce the prevalence of carriage in PCV13-positive children compared with
non-positive children. This level of effect is comparable to what has been observed in
several African settings.
In Burkina Faso, for example, Kaboré et al. observed direct effects ranging from
12.2% to 72.0% [34]. In Laos, Chan J et al. observed that PCV13 coverage was associated
with a reduction in the probability of PCV13 carriage. These authors noted a reduction
of 38.1% (95%CI: 4.1% to 60.0%) in PCV13 children. For each percentage point increase
in PCV13 coverage, the prevalence of carriage fell by 1.1% [35]. In the Republic of South
Africa, the overall effect assessed by the reduction in the prevalence of pneumococcal
colonization was 54.5% (aOR: 0.41; 95%CI: 0.3–0.56) [36].
In relation to the prevention of invasive pneumonia, this review found that PCV13
prevented 66.7% (95%CI: 37.2–82.2) of cases of invasive pneumonia in children. The only
study to assess this effect did not specify the dose at which it was obtained.
This result is in line with those obtained by other researchers in low-income countries.
For example, Bar-Zeev N et al. in Blantyre, Malawi, observed that a reduction in the
total incidence (vaccine serotype plus non-vaccine serotype) of invasive pneumococcal
disease followed PCV vaccine introduction: 19% in infants and 14% in children aged 1 to
4 years [37]. In the Gambia, Mackenzie GA noted that the reduction in the incidence of
invasive pneumococcal disease was related to an 82% reduction in the serotypes covered
by the PCV13 vaccine. In the 2–4-year age group, the incidence of invasive pneumococcal
disease was reduced by 56%, with a 68% reduction in serotypes covered by PCV13. The
incidence of serotypes other than PCV13 in children aged 2–59 months increased by 47%,
with a wide range of serotypes [38].
Taking into account the prevalence of colonization with S. pneumoniae in the DRC, the
incidence of pneumococcal pneumonia and meningitis, and PCV13 vaccination coverage
Vaccines 2025, 13, 603 13 of 16

among children under five years of age, it emerged that in terms of the effects of PCV13
on pneumococcal infections, in 2022, vaccination of 79.0% prevented 113,359 new cases of
severe pneumonia and 17,255 pneumonia-related deaths, and 3313 new cases of meningitis
and 1544 pneumococcal-meningitis-related deaths in children under five in the DRC.

4.2. PCV13 Serotypes

Several studies reported changes in S. pneumoniae serotypes following the introduction
of PCV [5,6,33,39–41]. The available literature does not mention any study of S. pneumoniae
serotypes in the DRC prior to PCV13 introduction. Thus, it was not possible to compare
serotypes before and after PCV13 introduction. According to the studies included in this
review, serotypes 19F and 23F, often carried by children under five, were also frequently
responsible for invasive pneumonia in this age group [18,23,27].
As observed in South African infants, where non-PCV13 serotypes such as 15BC, 10A,
21, and 16F became the most prevalent after the introduction of PCV13 [10], in the DRC,
serotypes 35B/35C, 15B/C, 10A, and 11A/D—although not included in PCV13—were
among the most frequently identified causes of morbidity in children.

4.3. Limitations
The literature on pneumococcal vaccination in the DRC remains limited in volume,
diversity, and geographical representativeness. This review revealed that 12 years after the
introduction of PCV13 into the national immunization program, few scientific studies have
been published on its impact on pneumococcal infection prevention or on S. pneumoniae
serotype evolution. The three articles included in this review were limited in scope. Two
of them [18,27] focused solely on urban areas of a single province, while the third, though
comparing children from two major cities, was not representative of the broader urban or
national population.
The effect reported by Birindwa in the DRC appears greater than that observed in
other countries, which may be explained by the study’s small sample size. Moreover, the
authors did not document the assumptions underlying their sample size calculation [26].
In Coulibaly et al.’s study [19], the effect of PCV13 was not adjusted for common
confounding factors cited in the literature. The external validity of the findings is therefore
uncertain both regarding the broader child population in the studied cities and those who
became ill but did not attend the sentinel sites of Kalembelembe and Kingasani in Kinshasa
or Sendwe in Lubumbashi. Additionally, because data on the number of PCV13 doses were
not collected, it was impossible to assess a dose–response relationship. In the study by
Manegabe et al. [27], statistical power was not considered when calculating sample size,
which was instead determined by available funding.
Regarding analysis methods, vaccine coverage was treated as an estimate and assumed
to be homogeneous, which it is not. Furthermore, many methods used are based on models
incorporating numerous assumptions, such as the Indian model cited in this review.
In addition, the limited number of studies conducted in the DRC on this subject
influenced the sample size used for association measures and, consequently, the overall
estimate of vaccine impact. This estimate could vary as more studies are conducted, more
subjects are included, and vaccine coverage approaches the herd immunity threshold.
However, despite these methodological limitations, the available studies provide
valuable insights that enabled estimation of the vaccine’s effect in the population based on
observed data. The scarcity of robust studies on this vaccine’s effects highlights the need to
conduct further research that reflects the DRC’s geographical and demographic diversity,
as well as the heterogeneity of vaccination coverage.
Vaccines 2025, 13, 603 14 of 16

5. Conclusions
We identified major gaps in the existing literature, including the lack of studies on
the effect of PCV13 conducted in settings with the highest under-five mortality, and the
lack of studies that reflect the geographic and socio-behavioral diversity of the Democratic
Republic of Congo. There is a need for large-scale studies in contexts of high morbidity
and mortality to simultaneously demonstrate the effect of the vaccine on both disease
occurrence and related deaths.
There is clear, but scattered, evidence of reduced Streptococcus pneumoniae colonization
and hospital admissions due to radiologically confirmed pneumonia and pneumococcal
meningitis. Evidence has also shown that S. pneumoniae serotypes 35B/35C, 15B/C, 10A
and 11A/D, which are not covered by PCV13, contribute to pneumococcal disease. These
data support the need to improve vaccination coverage among children with low or zero
coverage to reduce the burden of pneumococcal infections, and to establish and strengthen
sentinel surveillance of invasive bacterial diseases in the Democratic Republic of Congo.

Author Contributions: Conceptualization, M.M.N., D.K.I. and M.C.D.-H.; methodology, M.M.N.,

D.K.I., M.C.D.-H., A.B.F., A.M.-W.C., J.-C.M., D.M., A.D.L.A., M.D.Y., J.B.N. and B.H.S.; formal
analysis, M.M.N., A.N. and C.N.; investigation, A.N. and C.N.; writing—original draft preparation,
M.M.N., A.N. and D.K.I.; writing—review and editing, M.M.N., A.N., C.N., M.C.D.-H., A.B.F.,
A.M.-W.C., J.-C.M., D.M., A.D.L.A., M.D.Y., J.B.N., B.H.S. and D.K.I. All authors have read and
agreed to the published version of the manuscript.

Funding: This research received no external funding.

Institutional Review Board Statement: The present study did not require ethical approval; it was
based on data extracted from published, publicly available articles.

Informed Consent Statement: The present study did not require ethical approval; it was based on
data extracted from published, publicly available articles.

Data Availability Statement: The data presented in this study are available on request from the
WHO-DRC office at the email address “nimpamengouom@who.int”.

Conflicts of Interest: The authors declare no conflicts of interest. The funders had no role in the design
of this study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or
in the decision to publish the results.

Disclaimer: The authors alone are responsible for the views expressed in this article, and they do not
necessarily represent the decisions, policies, or views of the institutions with which they are affiliated.

References
1. Bentley, S.D.; Lo, S.W. Global genomic pathogen surveillance to inform vaccine strategies: A decade-long expedition in pneumo-
coccal genomics. Genome Med. 2021, 13, 84. [CrossRef] [PubMed]
2. Feldman, C.; Anderson, R. Recent advances in the epidemiology and prevention of Streptococcus pneumoniae infections.
F1000Research 2020, 9, 338. [CrossRef] [PubMed]
3. Wahl, B.; O’Brien, K.L.; Greenbaum, A.; Majumder, A.; Liu, L.; Chu, Y.; Lukšić, I.; Nair, H.; McAllister, D.A.; Campbell, H.; et al.
Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines:
Global, regional, and national estimates for 2000–2015. Lancet Glob. Health 2018, 6, e744–e757. [CrossRef] [PubMed]
4. Troeger, C.; Blacker, B.; Khalil, I.A.; Rao, P.C.; Cao, J.; Zimsen, S.R.M.; Albertson, S.B.; Deshpande, A.; Farag, T.; Abebe, Z.; et al.
Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries,
1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect. Dis. 2018, 18, 1191–1210. [CrossRef]
5. Johnson, H.L.; Deloria-Knoll, M.; Levine, O.S.; Stoszek, S.K.; Hance, L.F.; Reithinger, R.; Muenz, L.R.; O’Brien, K.L. Systematic
evaluation of serotypes causing invasive pneumococcal disease among children under five: The pneumococcal global serotype
project. PLoS Med. 2010, 7, e1000348. [CrossRef]
Vaccines 2025, 13, 603 15 of 16

6. Adegbola, R.A.; DeAntonio, R.; Hill, P.C.; Roca, A.; Usuf, E.; Hoet, B.; Greenwood, B.M. Carriage of Streptococcus pneumoniae
and other respiratory bacterial pathogens in low and lower-middle income countries: A systematic review and meta-analysis.
PLoS ONE 2014, 9, e103293. [CrossRef]
7. Russell, F.; Sanderson, C.; Temple, B.; Mulholland, K. Global review of the distribution of pneumococcal disease by age and
region. In WHO Pneumococcal Epidemiology Report 31102011 v3; World Health Organization: Geneva, Switzerland, 2011.
8. Scelfo, C.; Menzella, F.; Fontana, M.; Ghidoni, G.; Galeone, C.; Facciolongo, N.C. Pneumonia and invasive pneumococcal diseases:
The role of pneumococcal conjugate vaccine in the era of multi-drug resistance. Vaccines 2021, 9, 420. [CrossRef]
9. Musher, D.M.; Anderson, R.; Feldman, C. The remarkable history of pneumococcal vaccination: An ongoing challenge. Pneumonia
2022, 14, 5. [CrossRef]
10. Fleming-Dutra, K.E.; Conklin, L.; Loo, J.D.; Knoll, M.D.; Park, D.E.; Kirk, J.; Goldblatt, D.; Whitney, C.G.; O’brien, K.L. Systematic
review of the effect of pneumococcal conjugate vaccine dosing schedules on vaccine-type nasopharyngeal carriage. Pediatr. Infect.
Dis. J. 2014, 33 (Suppl. S2), 152–160. [CrossRef]
11. Reyburn, R.; Tsatsaronis, A.; von Mollendorf, C.; Mulholland, K.; Russell, F.M. Systematic review on the impact of the pneu-
mococcal conjugate vaccine ten valent (PCV10) or thirteen valent (PCV13) on all-cause, radiologically confirmed and severe
pneumonia hospitalisation rates and pneumonia mortality in children 0–9 years old. J. Glob. Health 2023, 13, 05002. [CrossRef]
12. Corcoran, M.; Vickers, I.; Mereckiene, J.; Murchan, S.; Cotter, S.; Fitzgerald, M.; Mcelligott, M.; Cafferkey, M.; O’Flanagan, D.;
Cunney, R.; et al. The epidemiology of invasive pneumococcal disease in older adults in the post-PCV era. Has there been a herd
effect? Epidemiol. Infect. 2017, 145, 2390–2399. [CrossRef] [PubMed]
13. Countdown to 2030. Tracking Progress Towards Universal Coverage for Women’s, Children’s and Adolescents’ Health; The 2017
Report; United Nations Children’s Fund (UNICEF) and the World Health Organization (WHO): Washington, DC, USA, 2017.
Available online: https://www.countdown2030.org/publications/tracking-progress-towards-universal-coverage-for-womens-
childrens-and-adolescents-health (accessed on 30 October 2024).
14. Countdown to 2015. A Decade of Tracking Progress for Maternal, Newborn and Child Survival; The 2015 Report; World Health
Organization: Geneva, Switzerland, 2015.
15. Jo, Y.; Labrique, A.B.; Lefevre, A.E.; Mehl, G.; Pfaff, T.; Walker, N.; Friberg, I.K. Using the Lives Saved Tool (LiST) to Model
mHealth Impact on Neonatal Survival in Resource-Limited Settings. PLoS ONE 2014, 9, e102224. [CrossRef] [PubMed]
16. République Démocratique du Congo, Ministère de la Santé Publique, Programme Élargi de Vaccination. Plan Pluriannuel
Complet du PEV 2013–2015 (Version Révisée); Ministère de la Santé Publique: Kinshasa, Democratic Republic of the Congo, 2015.
Available online: https://extranet.who.int/countryplanningcycles/sites/default/files/planning_cycle_repository/democratic_
republic_of_congo/ppac_rdc_2013-2015_mercredi_12_nov_2012_vf_-_alexis_2.pdf (accessed on 30 October 2024).
17. Lassane, K. Impact Assessment of Childhood Immunization Programs in Limited-Resource Settings: Challenges in Ascertaining
Vaccination Status and Application to Pneumococcal Conjugate Vaccine in Burkina Faso. Ph.D. Thesis, Faculté de Médecine,
University of Geneva , Geneva, Switzerland, 2021.
18. Birindwa, A.M.; Gonzales-Siles, L.; Nordén, R.; Geravandi, S.; Manegabe, J.T.; Morisho, L.; Mushobekwa, S.S.; Andersson, R.;
Skovbjerg, S. High bacterial and viral load in the upper respiratory tract of children in the Democratic Republic of the Congo.
PLoS ONE 2020, 15, e0240922.
19. Coulibaly, A. Impact of Pneumococcal Conjugate Vaccine Thirteen Valent on the Reduction of Invasive Pneumococcal Dis-
ease. Ph.D. Thesis, Walden University, Minneapolis, MN, USA, 2016. Available online: https://scholarworks.waldenu.edu/
dissertations/2116 (accessed on 30 October 2024).
20. Izurieta, P.; Bahety, P.; Adegbola, R.; Clarke, C.; Hoet, B. Public health impact of pneumococcal conjugate vaccine infant
immunization programs: Assessment of invasive pneumococcal disease burden and serotype distribution. Expert. Rev. Vaccines
2018, 17, 479–493. [CrossRef]
21. Muhandule Birindwa, A. Acute Respiratory Infections Among Children in the Democratic Republic of the Congo—Nasopharyngeal
Pathogens, Antibiotic Resistance and Vaccination. Ph.D. Thesis, University of Gothenburg, Gothenburg, Sweden, 2020. Available online:
http://hdl.handle.net/2077/63279 (accessed on 30 October 2024).
22. Mazamay, S.; Bompangue, D.; Guégan, J.F.; Muyembe, J.J.; Raoul, F.; Broutin, H. Understanding the spatio-temporal dynamics
of meningitis epidemics outside the belt: The case of the Democratic Republic of Congo (DRC). BMC Infect. Dis. 2020, 20, 291.
[CrossRef]
23. Birindwa, A.M.; Kasereka, J.K.; Gonzales-Siles, L.; Geravandi, S.; Mwilo, M.; Tudiakwile, L.K.; Mwinja, N.L.; Muhigirwa, B.;
Kashosi, T.; Manegabe, J.T.; et al. Bacteria and viruses in the upper respiratory tract of Congolese children with radiologically
confirmed pneumonia. BMC Infect. Dis. 2021, 21, 837. [CrossRef]
24. Touhami, K.O.; Sakkali, H.E.B.; Maaloum, F.; Diawara, I.; Touhami, M.O.; Bezzari, M.; Zerouali, K.; Belabbes, H. Meningitis
caused by Streptococcus pneumoniae serotype 7a in an infant vaccinated with two doses of 13-valent pneumococcal conjugate
vaccine: A case study. Pan. Afr. Med. J. 2019, 32, 203.
Vaccines 2025, 13, 603 16 of 16

25. Engo, S.M.I. Dynamique Spatio-Temporelle et Écologie des Méningites Bactériennes en Dehors de la Ceinture de la Méningite en
Afrique: Cas de la République Démocratique du Congo. Ph.D. Thesis, Université Montpellier, Montpellier, France, 2019.
26. Birindwa, A.M.; Emgård, M.; Nordén, R.; Samuelsson, E.; Geravandi, S.; Gonzales-Siles, L.; Muhigirwa, B.; Kashosi, T.;
Munguakonkwa, E.; Manegabe, J.T.; et al. High rate of antibiotic resistance among pneumococci carried by healthy children in
the eastern part of the Democratic Republic of the Congo. BMC Pediatr. 2018, 18, 361. [CrossRef]
27. Manegabe, J.T.; Kitoga, M.; Mwilo, M.; Yoyu, J. Identified Bacteria and Virus in the Cerebrospinal Fluid of under Five Years
Hospitalized Children for Clinical Meningitis at Panzi Hospital in the Eastern Part of DRC. Open J. Pediatr. 2023, 13, 676–688.
[CrossRef]
28. Mazamay, S.; Broutin, H.; Bompangue, D.; Muyembe, J.J.; Guégan, J.F. The environmental drivers of bacterial meningitis
epidemics in the Democratic Republic of Congo, central Africa. PLoS Negl. Trop. Dis. 2020, 14, e0008634. [CrossRef]
29. Wang, S. Global burden of pneumococcal disease in children under 5. In Proceedings of the PAHO Regional Symposium of New
Vaccines, Lima, Peru, 1–3 December 2009.
30. Bollinger, L.; Stover, J.; Hecht, K.; Podk, T.; Schmidt, J. Spectrum de Spectrum: Système Spectrum Pour les Modèles de Politiques; Avenir
Health: Glastonbury, CT, USA, 2022.
31. Armijo-Olivo, S.; Stiles, C.R.; Hagen, N.A.; Biondo, P.D.C.G. Assessment of study quality for systematic reviews: A comparison
of the Cochrane Collaboration Risk of Bias Tool and the Effective Public Health Practice Project Quality Assessment Tool:
Methodological research. J. Eval. Clin. Pract. 2012, 18, 12–18. [CrossRef] [PubMed]
32. Bouyer, J.; Cordier, S.; Levallois, P. Épidémiologie. In Environnement et Santé Publique: Fondements et Pratiques; Gérin, M., Gosselin,
P., Cordier, S., Viau, C., Quénel, P., Dewailly, É., Eds.; Edisem: Paris, France, 2003; pp. 89–118.
33. Nagaraj, G.; Govindan, V.; Ganaie, F.; Venkatesha, V.T.; Hawkins, P.A.; Gladstone, R.A.; McGee, L.; Breiman, R.F.; Bentley, S.D.;
Klugman, K.P.; et al. Streptococcus pneumoniae genomic datasets from an indian population describing pre-vaccine evolutionary
epidemiology using a whole genome sequencing approach. Microb. Genom. 2021, 7, e1062–e1070. [CrossRef] [PubMed]
34. Kaboré, L.; Adebanjo, T.; Njanpop-Lafourcade, B.M.; Ouangraoua, S.; Tarbangdo, F.T.; Meda, B.; Velusamy, S.; Bicaba, B.; Aké, F.;
McGee, L.; et al. Pneumococcal Carriage in Burkina Faso after 13-Valent Pneumococcal Conjugate Vaccine Introduction: Results
from 2 Cross-sectional Population-Based Surveys. J. Infect. Dis. 2021, 224, S258–S266. [CrossRef] [PubMed]
35. Chan, J.; Lai, J.Y.R.; Nguyen, C.D.; Vilivong, K.; Dunne, E.M.; Dubot-Pérès, A.; Fox, K.; Hinds, J.; A Moore, K.; Nation, M.L.;
et al. Indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with acute
respiratory infection despite heterogeneous vaccine coverage: An observational study in Lao People’s Democratic Republic. BMJ
Glob. Health 2021, 6, e005187. [CrossRef]
36. Downs, S.L.; Olwagen, C.P.; Van Der Merwe, L.; Nzenze, S.A.; Nunes, M.C.; Madhi, S.A. Streptococcus pneumoniae and other
bacterial nasopharyngeal colonization seven years post-introduction of 13-valent pneumococcal conjugate vaccine in South
African children. Int. J. Infect. Dis. 2023, 134, 45–52. [CrossRef]
37. Bar-Zeev, N.; Swarthout, T.D.; Everett, D.B.; Alaerts, M.; Msefula, J.; Brown, C.; Bilima, S.; Mallewa, J.; King, C.; von Gottberg, A.;
et al. Impact and effectiveness of 13-valent pneumococcal conjugate vaccine on population incidence of vaccine and non-vaccine
serotype invasive pneumococcal disease in Blantyre, Malawi, 2006–2018: Prospective observational time-series and case-control
studies. Lancet Glob. Health 2021, 9, e989–e998. [CrossRef]
38. Mackenzie, G.A.; Hill, P.C.; Jeffries, D.J.; Hossain, I.; Uchendu, U.; Ameh, D.; Ndiaye, M.; Adeyemi, O.; Pathirana, J.; Olatunji, Y.;
et al. Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: A
population-based surveillance study. Lancet Infect. Dis. 2016, 16, 703–711. [CrossRef]
39. Grant, L.R.; Slack, M.P.E.; Theilacker, C.; Vojicic, J.; Dion, S.; Reinert, R.R.; Jodar, L.; Gessner, B.D. Distribution of Serotypes
Causing Invasive Pneumococcal Disease in Children from High-Income Countries and the Impact of Pediatric Pneumococcal
Vaccination. Clin. Infect. Dis. 2023, 76, E1062–E1070. [CrossRef]
40. Deloria Knoll, M.; Bennett, J.C.; Garcia Quesada, M.; Kagucia, E.W.; Peterson, M.E.; Feikin, D.R.; Cohen, A.L.; Hetrich, M.K.;
Yang, Y.; Sinkevitch, J.N.; et al. Global landscape review of serotype-specific invasive pneumococcal disease surveillance
among countries using PCV10/13: The pneumococcal serotype replacement and distribution estimation (PSERENADE) project.
Microorganisms 2021, 9, 742. [CrossRef]
41. Méroc, E.; Fletcher, M.A.; Hanquet, G.; Slack, M.P.E.; Baay, M.; Hayford, K.; Gessner, B.D.; Grant, L.R. Systematic Literature
Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the
20-Valent Pneumococcal Conjugate Vaccine. Microorganisms 2023, 11, 1816. [CrossRef]

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.
Reproduced with permission of copyright owner. Further reproduction
prohibited without permission.