Preventing Pneumonia Deaths in Children Through PCV Vaccination

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Successful introduction of the pneumococcal conjugate vaccination
in developing countries to prevent pneumonia mortality in children:
is it a realistic goal for the international health community in a post-
MDG world?
CONTENTS
LIST OF FIGURES......................................................................................................2
ACRONYMS, ABBREVIATIONS AND SPECIALIST TERMS .............................3
ACKNOWLEDGMENTS.............................................................................................4
ABSTRACT..................................................................................................................5
Background/Rationale ............................................................................................5
Methods ....................................................................................................................5
Results ......................................................................................................................6
Discussion................................................................................................................6
INTRODUCTION.........................................................................................................7
BACKGROUND ...........................................................................................................8
LITERATURE REVIEW........................................................................................... 11
Search inclusion criteria, study selection and quality assessment............... 11
Limitations of literature search ........................................................................... 12
Primary data sources........................................................................................... 14
PROJECT AIMS AND METHODOLOGY............................................................. 17
Research aim:....................................................................................................... 17
Limitations of study: ............................................................................................. 17
Recommendations for further research ............................................................ 18
THE BURDEN OF PNEUMONIA IN UNDER-5s IN DEVELOPING
COUNTRIES ......................................................................................................... 20
The role of changing demographics .................................................................. 21
Fighting under-5 mortality from pneumonia: evaluating potential alternative
interventions to pneumcoccal vaccination............................................................ 23
THE PNEUMOCOCCAL CONJUCATE VACCINE (PCV)................................. 31
The introduction of PCV ...................................................................................... 31
Successful policy, planning and implementation of pneumococcal
immunisation in under-5s........................................................................................ 34
Lessons learnt: strategies to focus efforts on most at risk children ............. 35
Innovations in financing ....................................................................................... 38

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The future of PCV and its role in contributing to child mortality reductions in a
post-MDG world........................................................................................................ 40
CONCLUSION.......................................................................................................... 42
REFERENCES ......................................................................................................... 44
LIST OF FIGURES
Figure 1: Distribution of deaths by cause in under-5s in low-income countries
Figure 2: Contribution of deaths in under-5s from pneumonia by cause
Figure 3: Conceptual framework of the effect of interventions for pneumonia
Figure 4: Care seeking and antibiotic treatment (for % of children with
symptoms of pneumonia), by WHO regions and developing countries
Figure 5: Progress of pneumococcal conjugate vaccine (PCV) introductions
and proportions of birth cohorts living in countries that have introduced PCV
into routine infant immunization schedules, by year
Figure 6: PCV introduction by year

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ACRONYMS, ABBREVIATIONS AND SPECIALIST TERMS
AMC – Advanced Market Commitment
ARIs – Acute Respiratory Infections
ARTIs – Acute Respiratory Tract Infections
ALRTIs – Acute Lower Respiratory Tract Infections
ALRIs – Acute Lower Respiratory Infections
BCG – Bacillus Calmette–Guérin (tuberculosis vaccine)
CHERG – Child Health Epidemiology Reference Group
DALYs – Disability-adjusted Life Years1
DHS – Demographic and Health Survey
DTP – Diphtheria, Tetanus, Pertussis combined vaccine
EPI – Expanded Immunisation Programme
GAPPD – Global Integrated Action Plan for Pneumonia and Diarrhoea
GAVI – The Global Alliance for Vaccines and Immunizations
GBD – Global Burden of Disease
IPD – Invasive Pneumococcal Disease
IMCI - Integrated Management for Childhood Illness
IVAC – International Vaccine Access Centre
LMICs – Low and Middle Income Countries
LSMS – Living Standards and Measurement Survey
MDGs – Millennium Development Goals
MICS – Multiple Indicator Cluster Survey (UNICEF’s microdata source)
NID – National Immunisation Day
PCV – Pneumococcal Conjugate Vaccine
PneumoADIP - The Pneumococcal Vaccines Accelerated Development and
Introduction Plan
SDGs – Sustainable Development Goals
U5MR – Under-5 Mortality Rate
UNICEF – United Nations Children's Fund (formerly United Nations
International Children's Emergency Fund)
UN IGME – United Nations Inter-agency Group for Child Mortality Estimation
1 The sum of years of life lost (YLLs) (years lost due to premature mortality) and years lived
with disability (YLDs). DALYs are also defined as years of healthy life lost (GBD, 2010).

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USAID – United States Agency for International Development
VIMS – Vaccine Introduction Management System
WHO – World Health Organization
ACKNOWLEDGMENTS
I would like to thank my supervisor, Professor Mike Murphy, who provided
invaluable expertise, and advice throughout my dissertation project. I also
thank my programme director Dr Arjan Gjonça, along with Errol Lobo and
Marsha Fu for their guidance and support throughout my three years at LSE.

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ABSTRACT
Background/Rationale
Globally, pneumonia represents the largest cause of under-5 mortality, at
17%, with 99% of this mortality occurring in developing countries (UNICEF,
Child Mortality Report, 2013). Despite large international efforts, reductions in
the incidence of and mortality from pneumonia have been slower than for
other infectious diseases, such as diarrhoeal disease. There are several
reasons why prevention is preferable to intervention as an approach to
pneumonia-associated mortality reduction, especially in resource-constrained
settings where health systems are ill equipped to effectively deal with disease.
Worldwide antibiotic resistance is an emerging and increasing problem (WHO,
2015). The prevention of infection through vaccinating with the pneumococcal
conjugate vaccine (PCV) against some of the pneumococcal serotypes which
are the most common causes of pneumonia will reduce the requirement to
use antibiotics and thereby slow the spread of resistance in all age groups,
not just under-5s. Furthermore, PCV effectiveness of 30% has been
demonstrated for reduction from pneumonia in under-5s of (Webster et al,
2011). It is therefore of importance to undertake a review of the evidence and
an evaluation of the PCV and its potential for success as part of the next 15
years of international health and development goals in relation to reducing
preventable child deaths.
Methods
Methods of research consisted primarily of conducting a literature review. A
pre-defined set of search terms and inclusion criteria were used to locate
relevant studies from a range of sources including peer reviewed journals,
specialist medical databases, as well as primary data sources such as the
WHO Global Health Data Observatory, or Demographic and Health Surveys
(DHS), and microdata sources such as UNICEF’s Multiple Cluster Indicator
Surveys (MICS).

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Results
The PCV is found to be effective both as a public health measure to prevent
incidence, severity and mortality from pneumonia in under-5s in developing
countries, and as a cost-effective intervention to reduce the burden on health
services and economies in low and middle-income countries. Sustainability
and scale-up of vaccination programmes to increase coverage and ensure
long-term availability of the PCV are promising via a number of innovations
including financial, technological and logistical ones. Determinants such as
political will, sociocultural barriers and compounding economic, environmental
and epidemiological risk factors cannot be disregarded in the fight for
preventing pneumonia mortality in those most vulnerable to the disease.
Discussion
Efforts towards increasing coverage, availability and access to PCV should be
targeted to sub-Saharan Africa and the most at risk populations of children.
The most efficient intervention to achieve this would be by targeting
pneumonia prevention by vaccination. The integrated approach to prevention
and treatment by general health-system strengthening and by focusing on
underlying poverty reduction and inequity is supported by robust evidence and
logical arguments, however, in a world where so many preventable child
deaths from pneumonia still occur perhaps more strategic programmes such
as immunisation with PCV are more sustainable in the longer-term, more
realistic, and more likely to achieve the targets due to be set out in the post-
2015 SDGs.

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INTRODUCTION
2015 is a fitting year to be writing about preventable child deaths. Despite the
trends since 1990 showing great progress in reductions in child mortality,
there is still a large degree of unfulfilled promise. Indeed, the target of
Millennium Development Goal 4 2 will not be reached in the majority of
countries (‘Continuing the child survival revival’, The Lancet, 20th April 2013).
Globally, a reduction of 53% in under-5 mortality has been achieved since
1990; however, this falls far short of the two-thirds reduction goal (You et al.,
2015). This insufficient progress has been primarily attributed to the
stubbornly slow reduction of pneumonia mortality.
Establishing the current burden of disease and mortality from pneumonia in
children under-5 is important as a basis for furthering the main arguments
made in this work. The most recent data available from main global players in
child health will be drawn upon, such as the Global Burden of Disease reports
and updates since 2010, and reports from the Global Vaccine Alliance (GAVI),
the WHO Data Observatory, UNICEF and the World Bank. Although the
primary outcome focused on throughout this study is mortality (or, ideally,
survival), establishing the incidence of pneumonia and its aetiologies is
important too. Indeed, preventing disease occurring in the first place (i.e. its
incidence) will mean less chance of the disease featuring as a mortality
statistic.
In addition, because the demographic profile of those countries most at risk of
high under-5 mortality from pneumonia is likely to be young, and with such
countries having some of the largest birth rates, there is a pressing need to
establish better ways to prevent pneumonia in such places. These countries
represent areas where there is the most potential to save lives through, for
example, PCV immunisation strategies (Rudan, Tomaskovic et al., 2004).
2a reduction in child deaths of two-thirds between 1990 and 2015.

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BACKGROUND
There is robust and extensive evidence for vaccination as a highly successful
child health and public health measure. Listed in the past successes of
vaccination have been to eradicate diseases, such as smallpox worldwide,
and polio over entire continents (Foege, 2000). Of the different reasons for the
decline in under-5 mortality, the largest fall has been as a result of reduced
deaths from vaccine-preventable childhood diseases (Norheim et al,. 2015).
This demonstrates the significance of immunisation programmes, both now
and in the future, as part of global child health initiatives and targets. Using
the number of deaths averted or YLL are common measurements for gauging
the success of an intervention such as a certain vaccination (Jaffar et al.,
2003). Since 1990, more than half of the reduction in childhood deaths has
been attributed to vaccination (Andrus et al., 2008). Since 1990, a number of
intervention studies have reported significant reductions in pneumonia in
vaccinated populations of children.
In 1999, the international health community organised a “global mobilization
unmatched in peacetime” initiative to immunise 470 million children under the
age of 5 years (Foege, 2000 p. 20). These gains in coverage were made
easier by targeting the “low hanging fruit” (i.e. those easier to reach children)
first. This was an international, coordinated effort that was vertical in nature,
with a specific focus on immunisation.
There is no reason why the progress made in reducing vaccine-preventable
diseases such as polio should not be extended to other infectious diseases,
with the introduction and scaling up of new vaccinations to protect against
their microbial causes. The challenge now is to target those more
difficult-to-reach children and populations, while maintaining and increasing
the rates of coverage achieved in the past 25 years (PneumoADIP, 2004).
This is unlikely to be achieved, however, without the same specific focus on
immunisation that initially increased coverage and reduced childhood mortality
so greatly. Current difficulties with the eradication of polio in a few problematic
countries, and its resurgence in some of those countries where it had been

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almost totally abolished, demonstrate that governments and the global health
community cannot be complacent about such preventable diseases. Indeed, it
is essential that momentum towards reducing preventable diseases be
sustained, and the priority toward vaccination upheld. This will not happen if
too many and too broad targets are set in the SDGs as are set in the MDGs.
The goals of the MDGs were global in nature, and targets were set as national
and regional averages. For this reason, the MDGs “inadvertently encouraged
nations to measure progress through national averages” (UNICEF, June
2015, p. iii). In attempting to quickly reach these targets, progress may have
actually slowed at a national level, owing to an initial targeting of those easier-
to-reach children. Those most disadvantaged children in a society are also
usually the most at risk from diseases such as pneumonia, and thus may not
have been targeted for vaccination from the offset. Vaccination is named as
an intervention of high priority in relation to the child health MDGs (Brenzel et
al., 2006). Prevention of pneumonia from vaccination is preferable to
treatment for several reasons, especially in resource-constrained settings
where health systems are ill equipped to effectively treat the disease and deal
with pneumonia case management. WHO recommends the implementation of
vaccination for pneumococcal diseases, noting it to be of great benefit to
public health overall, and specifically to tackle increasing antibiotic resistance
of pneumococci (Picazo et al., 2009).
Unlike for other vaccine-preventable diseases, vaccination against pneumonia
will never lead to eradication of the disease (GAPPD, 2013). This is due to the
multiple aetiologies of the disease, meaning that vaccination against one
cause will prevent less than half of cases in under-5’s. Such a seemingly low
rate of potential pneumonia prevention compared to other vaccine-
preventable diseases makes vaccination less attractive as a target for
stakeholders, who are required to show headline-grabbing progress to
investors. For these reasons, there is a strong argument for putting the
emphasis on general strengthening of healthcare facilities and case
management of pneumonia, along with increasing nutritional status and
immune function (Madhi, Levine et al., 2008; Bhutta, Das et al., 2013; Chopra,

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Mason et al., 2013; Gill, Young et al., 2013; and Rice, Sacco et al., 2000).
Recent international consensus on how to reduce pneumonia mortality in
infants uses this argument as justification for the need for interventions
targeting multiple strands, including behavioural and case management
strategies, and not just relying on immunisation alone (UNICEF/WHO,
GAPPD, 2013).
WHO recognised a need for increased momentum towards reducing the
burden of pneumonia and diarrhoeal disease, and produced a Global Action
Plan to advise countries on current recommendations in 2013. The GAPPD
advises a coordinated approach to interventions, using the logic that
pneumonia and diarrhoeal diseases can be addressed in a combined manner
as many of the determinants are the same (UNICEF/WHO, GAPPD, 2013 p.
11). Indeed, during a talk at the WHO Headquarters in Geneva in the first half
of 2015, it was noted that it was an explicit policy of the Organization to leave
the out-of-favour vertical programmes to Public Private Partnerships (PPPs)
such as GAVI or the Global Fund.
Reflecting this trend, there is a gap in the recent literature toward articles on
the assessment of new vaccinations with regard to reducing pneumonia
mortality in developing countries. In comparison, there are a large number of
articles, particularly since 2010, that assess interventions which have tackled
the problem via general strengthening of healthcare systems and improving
underlying causes such as poverty. Prevention by vaccination requires less
effort on overall poverty reduction and healthcare facilities improvement.
These latter aims are admirable but are harder to achieve, and if taken as the
only measure, may translate into stagnation in reducing preventable child
deaths from pneumonia.

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LITERATURE REVIEW
Search inclusion criteria, study selection and quality assessment
A comprehensive literature search of English language resources was
undertaken. Any studies published before the year 2000 were disregarded
due to the nature of the vaccine in question being a relatively new. Only when
studies found in the initial search to meet the criteria used sources before this
date and these were considered to be of possible use (for example informing
policy suggestions via lessons learnt from older vaccines; or large-scale
epidemiological studies of childhood pneumonia that have not been matched
in any study since).
Search terms initially included ‘vaccination’, ‘immunisation’ and the alternative
spelling ‘immunization’, ‘child’, ‘infant’, ‘under-five’, ‘deaths’, ‘mortality’,
‘pneumococcal’ and ‘pneumonia’. Learning from a primary round of results
and using references from initial articles to check if initial results were
comprehensive or not, further terms were added. These were ‘respiratory tract
infections’ (RTIs), ‘acute respiratory infections’ (ARIs) or ‘acute respiratory
tract infections’ (ARTIs), ‘lower respiratory infections’ (LRIs), acute lower
respiratory infections’ (ALRIs), and ‘PCV’, Further searches were made
excluding ‘invasive pneumococcal disease’, ‘otitis media’, ‘meningitis’
‘neonatal’ (time period before the vaccine can be safely given), ‘high income
countries’, ‘developed countries’, and ‘pneumococcal polysaccharide vaccine’.
Therefore the search evolved as lessons were learnt from earlier searches.
Complications occur with comparisons of studies when some studies use
post-neonatal (>1 month) to under 5 (<5) years mortality (as in Arifeen et al,
2004), whereas other studies use ‘child mortality’ (>1 year and <5 years) and
others still use ‘infant mortality’ (risk of dying between birth and exact age 1
year).

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Every study was required to have recorded the following information: whether
the study was community-based or in-patient, study length, co-morbidities and
overlapping risk factors which could confound study results and controls in
place for this, method of diagnosis/diagnostic criteria for pneumonia case
definitions, and pneumonia aetiology, age of children in study, primary
outcome assessed (i.e. mortality or morbidity). Quality was assessed on
length of study (at least one year), whether it is of prospective design and
included follow-up, the number of children in the study, whether there was a
clinical diagnosis made or whether surveillance was undertaken based on
family questionnaires. Ideally the study would be blind or randomised
assessment, be adjusted for confounding factors, a follow-up of more than 5
years (so that reductions in efficacy can be observed), look at direct and
indirect immunity effects, and consider author or publication bias reported or
likely (see Khan et al, 2003; Rudan et al, 2008 and 2004; Madhi et al, 2008
and Webster et al, 2011 for useful explanations of search methodology of
relevance to this present study).
Limitations of literature search
Comparisons between studies can be problematic, owing to how countries or
regions can be classified. The list of regions for which data is compiled for the
World Health Organization (WHO) Global Health Observatory Data
Repository alone includes UN Millennium Development Goals (MDG) regions,
World Bank income groups, World Bank regions, WHO regions, WHO low and
middle-income countries (LMIC) regions, and UNICEF regional groups 3 .
Some studies and literature reviews use low-income countries based on the
World Bank classification system. Although Angola is currently an upper-
middle income country by World Bank categorisation, in the most recent
under-5 mortality figures published by the Lancet on 9th September 2015, it
has the highest infant mortality rate (IMR) in the world, although India, Nigeria,
DRC and Pakistan have larger absolute numbers of under-5 deaths (You D et
al, 2015).
3 See WHO Global Health Observatory Data Repository at
http://apps.who.int/gho/data/node.main.ChildMortREG200?lang=en

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This was the rationale for expanding the initial search to include studies which
met other relevant criteria but that were not included in the original search
results owing to them having been conducted in high income or developed
countries. Indeed, there is much that can be learned from studies conducted
in the developed world that can inform decisions about vaccination strategies
in developing countries. By exclusively focusing on low-income countries, this
work would have disregarded studies in Angola, which has one of the highest
rates of global pneumonia mortality, and the highest rate of child mortality.
Therefore a country having one of the greatest potentials to improve these
rates via PCV vaccination as a method of disease prevention would not have
been included.
In the course of the online research, two studies of interest were found that
had not been picked up via searches using the LSE library catalogue,
PubMed, or Google Scholar. These were Savitha et al. ‘Modifiable risk factors
for acute lower respiratory tract infections’, and Fischer-Walker et al. ‘Diarrhea
as a risk factor for ALRTIs among young children in low income settings’, both
of which were found on the website of suggested further reading of the Child
Health Epidemiology Reference Group (CHERG) pneumonia working group.
CHERG was set up to independently systematically review data on childhood
morbidity and mortality and improve the quality of estimates ( Both studies
were useful for their setting in developing countries, and for their assessment
of risk factors which identified areas for which to target PCV programme
improvevment for greater child mortality reductions. Both were missed from
searches as they did not have mortality as an outcome, nor immunisation as
the main focus.
Many studies received funding from governments, or foundations such as Bill
and Melinda Gates Foundation where potential bias could occur. The studies
were published in peer reviewed journals and risk of bias or competing
interests declared.

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Primary data sources
The Demographic and Health Surveys (DHS) and the United States Agency
for International Development (USAID) have information on under-5 mortality
trends and the split between infant and child rates. However, DHS data are
not disease-specific (DHS child health questionnaires include questions about
DTP, measles, polio and BCG as well as vitamin A supplementation)4. As a
basis for researching the introduction and scaling up of new vaccines, it can
be useful to look at current Expanded Programme on Immunization (EPI) data
and schedules, for example, measles vaccination rates. EPI data is, however,
of limited use as a source of information specifically related to pneumonia.
DHS also has country-specific data, such as the Bangladesh DHS in 2009,
which found pneumonia to be the largest cause of mortality in children under
5 years of age. In itself, however, this data merely helps to justify the
importance of new vaccinations in preventing the disease in a single country.
It does not distinguish between the types of infection site of the Streptococcus
pneumoniae (S. pneumoniae) bacterium (i.e. if the disease is pneumonia or
some other form of pneumococcal disease like otitis media). There is more
evidence in the literature related to outcomes of OM and IPD than pneumonia
caused by pneumococcal disease (WHO, 2001).
The Indicators and Monitoring Framework for the Sustainable Development
Goals (SDGs) suggests: “In general terms, data on health, education and
select aspects of wellbeing can already be disaggregated by gender, age,
geographical region and income (by quintile) in most countries using
international household surveys such as the Demographic Health Surveys
(DHS), Multi-Indicator Cluster surveys (MICS), and Living Standards
Measurement Study (LSMS). Information can also be gleaned from national
census and vital registration information. However, data collection is patchy
(DHS is only collected every 5.88 years) and often data produced by these
different surveys is non-comparable.” (Indicators and Monitoring Framework
for the Sustainable Development Goals, p. 125). Therefore this present study
has used data sources from the WHO, UNICEF, GAVI and full empirical data
4 see http://www.dhsprogram.com/What-We-Do/Survey-Types/KIS.cfm

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from the United Nations Inter-agency Group for Child Mortality Estimation (UN
IGME). 5
In low and middle-income countries primary data sources are mainly from
household surveys and suffer inaccuracies and sampling biases. You et al,
(2015) found that roughly 40 countries have no primary data for child mortality
since 2011. In developing countries, data quality is hindered the assignation
of cause of death is often of questionable accuracy, as the majority of deaths
occur outside of a hospital setting. Consequently, the cause of death is often
established by means of asking the deceased’s relatives about symptoms and
disease progression – a ‘post-mortem questionnaire’ (Jaffar et al, 2003). In
fact, less than 3% of under-5 deaths globally are certified by a medical expert
(Lui et al, 2015).
WHO, UNICEF and GAVI are the lead agencies named in the Sustainable
Development Goals (SDG) working draft. The key primary information
sources recommended for immunisation data are MICS and DHS (Indicators
and Monitoring Framework for SDGs Working Draft, 16th January 2015).
WHO’s Global Health Observatory have yet to add PCV to their Data
Repository, with Hib3 being the most recently incorporated vaccine to the list.
This should be updated with urgency to inform the future targets of the SDGs
with regards to reducing and ending preventable childhood deaths.
Lastly of note, there is a difference between the pneumonia burden estimates
from the Institute for Health Metrics and Evaluation (IHME) and CHERG.
IHME’s Global Burden of Disease (GBD) 2010 Study estimated 0.847 million,
and CHERG estimated 1.396 million, under-5 deaths due to pneumonia. The
GBD used observational studies whereas CHERG relied on vaccine efficacy
studies for modeling pneumonia aetiologies. GBD 2010 used broader
inclusion criteria and assigned cause of death for neonatal infants differently
to CHERG due to distinct data processing methods (Kovacs et al, 2015). The
difference between the two estimates was 49% for the percentage of the
5 see http://childmortality.org

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global burden of mortality in under-5s from pneumonia in 2010. For
aetiologies of the global burden of pneumonia and LRI, mortality in under-5s
was 12.9% higher for S. pneumoniae, the bacteria that PCV targets (Kovacs
et al, 2015). These differences have obvious implications when using such
internationally respected studies and estimates for assessing the potential of
interventions on child mortality such as PCV.

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PROJECT AIMS AND METHODOLOGY
Research aim:
This study aims to provide a systematic literature review of the pneumococcal
conjugate vaccine and its effectiveness as an intervention to prevent and
reduce pneumonia mortality in children under-5 years of age in developing
countries. The analysis will assess current and recent evidence in the areas of
financing, supply and demand-side factors of the PCV to evaluate the
sustainability of the vaccination as the primary immunisation to prevent
pneumonia. It will utilise past evidence from immunisation programmes in
developing countries to ascertain what lessons can be learnt and suggest
future areas for focus by a variety of stakeholders in international health and
development. Finally, it will use this evidence to argue that, although the PCV
has the potential to be the largest and most realistic single intervention
against pneumonia mortality by reducing disease incidence in under-5s in
developing countries, the post-2015 health and development agenda will not
achieve its goal with regards to child mortality reduction without more explicit
focus on the PCV and the most at risk children.
Limitations of study:
Owing to the fact that PCV is still not a basic part of EPIs in all countries
(although it is recommended by WHO), data for PCV are not routinely
recorded, particularly in the developing world. Due to technological
developments in vaccines, and because funding mechanisms for vaccines
that target pneumonia in developing countries are fairly recent (the Advanced
Market Commitment in 2009), the number of studies incorporating the most
recent data is relatively small. Furthermore, studies on the safety and efficacy
of PCV are nearly exclusively located in developed countries (e.g. Adam and
Fehnle, 2008). Despite being located in Germany, this study was included for
two reasons. Firstly, there are scant data on the effectiveness of PCV, and
secondly, the main outcome of interest in this study was pneumonia and not
invasive pneumococcal disease (IPD) or all pneumococcal disease sequelae,

18
such as ear infections. Some thorough studies (e.g. Webster et al., 2011)
evaluate PCV with regards to childhood pneumococcal pneumonia but use
studies from high-income countries in their global study; therefore, although
much of their research is valid here and their conclusions add to this study, it
is problematic to disaggregate the results to tease out that which is relevant
for developing countries alone.
Challenges:
There are a number of variables, determinants and confounding factors when
looking at any one area that this study entails. For example child deaths are
difficult to classify with one cause, and in developing country settings this is
hugely problematic. As is diagnosing pneumonia in the first place and then
discovering the causative agent of each case of pneumonia. In studying
vaccination efficacy itself there are many clinical outcomes to consider, types
of studies such as randomised, blind, or placebo-controlled, which all make
estimating efficacy and comparing results to assess cost-effectiveness of the
PCV a challenge. It is beyond the scope of this study to consider in depth all
determinants, such as socioeconomic, cultural, behavioural, environmental
and political factors. Any public health intervention works through multiple
pathways, which often influence each other. They can suffer from
compounding factors (such as HIV or malaria co-morbidity), which are
problematic to disentangle to evaluate individual interventions such as the
PCV.
Recommendations for further research
Many of the epidemiological studies on pneumonia are from the 1980s and
1990s (Rudan, et al, 2004). Here then, more research is needed to inform the
targeting of interventions such as the prevention of pneumonia by PCV.
This present study identified a number of gaps in the current research relating
to the efficacy of PCV efficacy in developing countries. More resources are
required to assist developing countries in obtaining accurate data on the
efficacy of PCV, with studies incorporating a large number of participants
needed. Some of the populations most at risk of pneumonia mortality are also

19
those with high prevalence of HIV. More studies are required to reflect this
focusing on such at risk groups with regard to PVC efficacy, and policies to
improve coverage (Webster et al, 2011). Furthermore, other groups identified
as those most at risk, such as the lowest income quintile, those furthest away
from health facilities, and those living in households with HIV-positive
members should have studies aimed at them. Because PCV13 – covering 13
pneumococcal seroytpes – has only recently been introduced to vaccination
schedules, most completed studies are of the 7-valent or 9-valent PCV. The
coverage of additional serotypes in PCV13 means further research is needed,
and the health community should not merely rely on studies of earlier
pneumococcal vaccines, as it may not be appropriate to extrapolate the
findings of previous studies to PCV13. Additional research on the indirect
(herd) immunity is needed, particularly in those neonates who are not directly
covered by PCV until 6 weeks of age and have the highest rates of
pneumonia mortality (le Roux, 2015; Fischer Walker et al, 2013; Webster et
al, 2011; Madhi et al, 2008).
Studies on the efficacy of pneumococcal vaccines have mostly focused on
IPD such as septicaemia as the outcome, as it is easier to diagnose and
results in hospital admission more often than does pneumonia, so there is
better data available (see Theodoratou et al, 2010; Webster et al, 2011).
Future research should focus on the closing the gaps in the available data on
pneumococcal vaccine efficacy in pneumonia, as part of efforts to reduce
pneumonia mortality in children by informing international efforts and health
targets.

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THE BURDEN OF PNEUMONIA IN UNDER-5s IN DEVELOPING
COUNTRIES
To be able to accurately assess the benefits of various interventions that
could be used instead of, or in conjunction with vaccines to prevent
pneumonia, it is important to establish the disease burden of pneumonia and
epidemiological profile in under-5s. There is a clear need to focus on
specifically on Sub-Saharan Africa and South-East Asia, as more than 70% of
global under-5 deaths take place in these regions (Rudan et al., 2008). ARIs
are the leading cause of death in under-5s, accounting for 20% of all
childhood deaths, as found in a large study which analysed data on the
clinical incidence of pneumonia from community-based longitudinal studies for
WHO (Rudan et al., 2004). 90% of ARIs occur in developing countries (Rudan
et al., 2004), with 151 million of the 156 million episodes of pneumonia
occurring in developing countries (Rudan et al., 2008). Crucially, of these
episodes, 99.9% of child mortality from pneumonia is located in less and least
developed countries (Madhi et al., 2008).
Figure 1 below shows that pneumonia is the largest cause of death by
distribution in low-income countries (with lower-middle income countries
showing a similar distribution for the top causes). In comparison, pneumonia
in high-income countries accounts for just 4% of the distribution of under-5
deaths (UNICEF, 2013). As the yellow outline shows, communicable diseases
account for the majority of deaths, and of those, a major proportion is from
preventable causes.

21
Figure 1: Distribution of deaths by cause in under-5s in low-income
countries.
Source: UNICEF (2013), Committing to Child Survival, p. 20.
Scaling up supply and demand of PCV and Hib vaccines in these countries
therefore has the potential to save the most lives in a world where inadequate
resources make it impossible to reach all those with the correct diagnostics,
and where vaccine-preventable pneumonia is a real risk. This is the primary
focus of the current study.
The role of changing demographics
The area of the world with the least progress in reducing pneumonia mortality
in under-5s is projected to experience around 40% of births by 2050
(UNICEF, 2014). Sub-Saharan Africa will contain one in three of the world’s
under-5s within the next 15 years (UNICEF, 2015). This region therefore
provides one of the greatest opportunities to prevent pneumonia deaths in
under-5s and achieve the SDG and GAPPD targets for 2025. However,
without further progress in preventing pneumonia incidence as well as
improving treatment interventions, the absolute number of deaths from
Pneumonia,
17%
Diarrhoea,
10%
Malaria, 10%
AIDS, 2%
Pertussis, tetanus,
measles, meningitis, 7%
Sepsis,
5%
Other
neonatal, 26%
Other, 22%
Distribution of deaths, U-5s, low-income countries

22
pneumonia in under-5s will continue to increase here. The proposed post-
2015 goal to reduce under-5 mortality to less than 25 deaths per 1000
livebirths will only be achieved in Sub-Saharan Africa if child mortality
reductions are not merely sustained, but accelerated (You et al., 2015).
Demographics also point toward an advantage to prevention by vaccination,
having the most potential out of the various recommended interventions. All
population growth is projected to be in less and least developed countries and
in urban areas (UNICEF, 2012, Children in an Urban World; UN World
Urbanization Prospects, 2014). This is of relevance as the evidence points to
better uptake and coverage of immunisation in urban areas (Leon, 2008). “It
could be argued that the growth of urban populations has had a multiplier
effect upon the impact of immunization…by increasing the proportion of
children who are readily accessible because they live in towns and cities”
(Leon, 2008 p. 20). Increasing access to and availability of vaccination, and
targeting resources in these areas, thus has the potential to prevent the most
childhood pneumonia cases and save the most lives.

23
Fighting under-5 mortality from pneumonia: evaluating
potential alternative interventions to pneumcoccal
vaccination
Establishing the specific organism responsible for each case of pneumonia is
problematic, and there are no rapid tests. This is true in countries with good
diagnostic capabilities and health systems, let alone in low income countries
that lack even basic infrastructure (Kovacs et al., 2015). Some causes are
bacterial and some viral, thus identifying aetiology is difficult (Webster et al.,
2011).
The number of known pneumococcal serotypes is 93 and the prevalence of
each serotype varies between communities and regions (Rogers and
Klugman, 2011). This makes targeting all causes or even all serotypes of one
bacterial cause problematic, and certainly beyond reach of current vaccine
technology. Pfizer’s (previously Wyeth’s) Prevnar 13-valent PCV, which
covers 13 of the 93 serotype, is the newest version of the vaccine currently
being rolled out by GAVI, although the 7-valent and 9-valent PCV are still in
use in a number of developing countries such as Philippines. This makes the
success of vaccination harder to measure and study (Kovacs et al., 2015).
The difficulties in diagnosing and establishing the causes of pneumonia to
tailor successful treatment of the disease add to the case for prevention in
efforts to reduce pneumonia mortality in under-5s by vaccination.
Although around half of pneumonia and ARI cases are caused by viruses
(Rudan et al., 2008), owing to difficulties with diagnosing the cause, WHO
recommends treatment with antibiotics as standard case management
(UNICEF/WHO, GAPPD, 2013). There is debate over the amount of child
deaths attributable to the different bacterial causes of pneumonia (Dowling,
Root et al., 2014). Vaccination therefore reduces the need for antibiotics that
may or may not be effective against the causative organism, and PCV
specifically has been highlighted as being of significance with regards to
antibiotic resistance (Adam and Fehnle, 2008). Bacterial causes of
pneumonia also have higher case fatality rates (WHO, 2001); therefore,

24
targeting future child mortality by preventing the main causes of pneumonia
therefore has potential to further reduce and sustain reductions in mortality.
The major causes of pneumonia are Haemophillus influenza type b (Hib) and
S. pneumoniae (Picazo et al., 2008).
Figure 2: Contribution of deaths in under-5s from pneumonia by cause.
Source: Adapted from Fichser Walker et al., 2013, p.1409.
PCV therefore has the potential to prevent more cases of pneumonia than any
other single vaccination. However, there are a few exceptions to findings that
S. pneumoniae would be the most effective bacteria to target with vaccination
to prevent pneumonia mortality. For example, Falade et al. (1997) in The
Gambia, found Mycobacterium tuberculosis to be a major cause of lobar
pneumonia from lung aspirate cultures. Additionally, Mimica et al. (1971) and
Ashgar et al. (2008) both found Staphylococcus aureus to be the cause of the
most significant proportion of cases of pneumonia. A study by O’Brien (2009),
which was used to inform CHERG’s results, assumed that the proportion of

25
under-5 pneumonia mortality caused by S. pneumoniae is the same globally,
as did Rudan et al., who put the proportion at 33%, and did not factor any
regional variations in proportions of disease aetiology (Rudan et al., 2013).
Some estimates put the S. pneumoniae bacterium as the cause of
approximately 50% of pneumonia mortality in under-5s, either alone or in
combination with HIV, or of respiratory infections of viral cause (Bernatoniene
and Finn, 2005). In a number of microbiology-based studies, Rudan et al.
(2008) found S. pneumoniae to be the cause identified in between a third and
half of all pneumonia cases in a number of different settings (Rudan, Boschi-
Pinto et al., 2008 p. 411). The potential of PCV and Hib immunisations to
reduce childhood incidence and mortality from pneumonia is clear.
Children with HIV are more susceptible to, and have a higher case-fatality rate
from pneumonia, particularly infections caused by s. pneumoniae and h.
influenzae (Fischer Walker et al., 2013; Webster et al., 2011; Theodoratou et
al., 2010; Madhi et al., 2008). Therefore targeting children specifically in high
burden HIV settings such as many sub-Saharan African countries with
vaccination from PCV and Hib would produce the largest reductions in
mortality in populations where the coverage is particularly low.

26
Figure 3: Conceptual framework of the effect of interventions for
pneumonia
Source: adapted from Bhutta, Das Lancet April 20, 2013.
Figure 3 charts the dynamics of interventions for pneumonia leading to the
two possible outcomes of interest, “Survival” or “Death” via a relevant
conceptual framework. The boxes in blue represent three areas of public
health intervention that affect the dynamics of transmission. Vaccines such as
PCV reduce incidence of pneumonia and prevent it before we reach the pink
“Treatment” box by which point the interventions that affect child survival are
known to be less effective.
The practicalities of treating pneumonia in the community must be considered
when considering the advantages of prevention via immunisation. Realities

27
such as high rates of diarrhoea in the populations most at risk of pneumonia
in developing countries mean that the effectiveness of oral antibiotic treatment
is impaired, likely due to a lack of absorption of the therapy. Additionally, only
roughly “half of children with acute pneumonia receive antibiotics” (Gill, Young
et al, 2013).
Figure 4: Care seeking and antibiotic treatment (for % of children with
symptoms of pneumonia) 6 by WHO regions and developing countries
Source: UNICEF, 2013. Committing to Child Survival, p. 24.
Even though it is widely acknowledged which interventions are needed to
reduce the incidence of, and mortality from, pneumonia in childhood, there is
a lag with successful outcomes of these interventions in case fatality.
Much of the recent literature combines pneumonia and diarrhoea with regards
to approaches to both research into burden of disease and interventions to
reduce this burden (see Bhutta, Das et al., 2013; Gill, Young et al., 2013;
Chopra et al., 2013; Kovacs, Mullholland et al., 2015; Fischer-Walker et al.,
6
Care-seeking for children w ith symptoms of pneumonia – % of children <5 w ith symptoms of pneumonia (cough and
fast or difficult breathing due to a problem in the chest) in the 2 w eeks preceding the survey forwhomadvice or
treatment w as sought froma health facility or provider.
Antibiotic treatment for children w ith symptoms of pneumonia – % of children <5 w ith symptoms of pneumonia in the
2 w eeks preceding the surveywho received antibiotics. NB: This indicator refers to antibiotic treatment among
children w hose caretakersreport symptoms that are consistent with pneumonia. These children have not been
medically diagnosed and thus this indicator should be interpreted w ith caution (State of the World’s Children, 2015, p.
53).
0
20
40
60
80
100
Sub-Saharan
Africa
Eastern and
Southern
Africa
West and
Central
Africa
Middle East
and North
Africa
South Asia Latin
America and
Caribbean
Least
developed
countries
Percentage(%)
Pneumonia (2009 - 2013)
Care seeking for children with symptoms of pneumonia (%)
Antibiotic treatment for children with symptoms of pneumonia (%)

28
2013; Madhu, Pradhan and Maskey, 2010; and Mihrshahi, Ichikawa et al.,
2007). The Lancet published a series of articles in 2013 with key
recommendations for healthcare systems. A key emphasis of this series was
on targeting the “horizontal determinants” of the diseases (i.e. the underlying
causes such as housing, nutrition and access to care) (Gill, Young et al,.
2013, p. 1503). Many international and multilateral agencies suggest both
preventing and treating diarrhoea and pneumonia in similar ways. The biggest
example of this is the WHO’s Global Action Plan on Pneumonia and
Diarrhoea (WHO/UNICEF, 2013). This is because they share a large number
of associated risk factors (Bhutta, Das et al., 2013). These include “Risk
factors that are common to both conditions include undernutrition, suboptimal
breastfeeding, poor hygiene and zinc deficiency. A clean home environment,
including access to safe water and to adequate sanitation, helps prevent both
pneumonia and diarrhea” (UNICEF, 2013, p. 24). The diseases are also
treated successfully in similar manners, with strengthening community health
worker and primary care systems.
Using the example of diarrhoeal disease as a comparison can justify the use
of prevention of pneumonia as the figures for mortality and incidence of
diarrhoea have continued to decrease at faster rates than pneumonia, leading
to the conclusion that perhaps these measures are more successful for
diarrhoea than pneumonia, which would be better prevented than treated.
There is no denying that there has been significant progress in reducing infant
and child mortality in the developing world, specifically in countries such as
Bangladesh and Rwanda (Chopra, Mason et al, 2013). Rwanda was the first
developing country to introduce the PVC nationally in 2009 (GAVI, 2009).
Bangladesh is a country often cited for its significant achievements in child
mortality reductions, mostly from communicable diseases, with annual
reductions of its under-5 mortality rate of 5.6% since 1990 (UNICEF, 2014 p.
16). To illustrate its progress using absolute numbers, the total rate has fallen
from 241 per 1000 livebirths in 1965 to 41 per 1000 in 2015 (World Bank,
2015). Bangladesh is highlighted as one of the eight countries classified as

29
‘high mortality’ that has reduced their under-five mortality rate by the two-
thirds required to achieve MGD 4 (Luby et al., 2008). The level of mortality
cause-specific to pneumonia has, however, not contributed in a meaningful
way to these reductions (Liu et al, 2014). Pneumonia is the main cause of
child mortality in Bangladesh, overtaking diarrhoea, which has decreased in
incidence by more than 90% since 1975 (albeit from a particularly high level)
(Luby et al, 2008).
Lessons can be learned from how such countries achieved this. With mortality
reductions from pneumonia has not been as great as progress as from
diarrhoeal disease (even though they have similar underlying causes). Given
that Bangladesh only introduced PCV to childhood immunisation schedules in
2015 (WHO Global Immunization Data, July 2015) there is hope for greater
progress in prevention of pneumonia and therefore the main cause of child
mortality in the country.
Focus on case management as a mortality reduction strategy has been
ineffective in the case of Bangladesh (Luby et al., 2008). “For both indicators
of pneumonia treatment, all 15 countries failed to meet the 90% GAPPD
coverage targets (Fig. 3). The coverage rates for care by a health care
provider were as low as 26% (Chad) and as high as 79% (Uganda), while the
rates for antibiotic treatment ranged even more widely, from 7% (Ethiopia) to
71% (Bangladesh)” (IVAC, 2014 p 10). This illustrates the ineffective nature of
antibiotic treatment and case management as a method of reducing under-5
mortality without the correct healthcare input. With the highest coverage rates
for treatment, Bangladesh has made no gains in reductions of child
pneumonia mortality. Often, this is due to care-seeking occurring too late in
disease progression (UNICEF/WHO, 2013). This is a clear argument in favour
of focusing on the prevention of pneumonia by vaccination.
The inclusion of surveillance and statistics for both care-seeking for under-5s
with pneumonia symptoms, along with data from those receiving treatment for

30
pneumonia symptoms with antibiotics 7 is a clear indication that the
international health community has put pneumonia in under-5s as a priority to
improve child health.
However, the MDGs included other infectious disease as specific sub-targets,
for example HIV or malaria, when their overall burden to child mortality in low
income countries is 2% and 10% respectively, whereas pneumonia is 17%
(UNICEF, 2013). MDG6 ,with its target of having “halted by 2015 and begun
to reverse the spread of HIV/AIDS and the incidence of malaria and other
major diseases” has specific indicators to be measured that include HIV,
malaria and tuberculosis but Lomazzi et al. (2014) suggest adapting the
framework used for the MDGs to make a more thorough and accurate
framework for the post-2015 goals. With relevance to PCV, this will enable
inequities between localities and population within countries to be better
addressed. Supply of vaccines would be improved by better productivity, and
using local and more accurate data to improve the efficiency of immunisation
programmes for children most at risk of pneumonia and those most at risk of
missing routine immunisations.
The SDGs are likely to name specific targets for malaria, HIV and
tuberculosis; and have 35 health-related “Complementary National
Indicators”, of which none are for pneumonia, one mentions diarrhoea
incidence, 10 involve communicable diseases, and 11 involve children
(Indicators and Monitoring Framework for SDGs Working Draft for
Consultation, pp. 20-22).
7Care-seeking for children with symptoms of pneumonia – % of children <5 with symptoms of
pneumonia (cough and fast or difficult breathing due to a problem in the chest) in the 2 weeks
preceding the survey for whom advice or treatment was sought from a health facility or
provider (UNICEF, 2014 p.53). Antibiotic treatment for children with symptoms of pneumonia
– % of children <5 with symptoms of pneumonia in the 2 weeks preceding the survey who
received antibiotics. NB: This indicator refers to antibiotic treatment among children whose
caretakers report symptoms that are consistent with pneumonia. These children have not
been medically diagnosed and thus this indicator should be interpreted with caution (UNICEF,
2014, p.53).

31
THE PNEUMOCOCCAL CONJUCATE VACCINE (PCV)
The introduction of PCV
PCV is included as one of GAVI’s “new and underused vaccines” (GAVI,
2015). The State of the World’s Children 2015 publication includes newer
vaccines such as rotavirus and PCV38 as part of its Health Statistics “Basic
Indicators” (UNICEF, 2014, pp. 48-53). GAPPD recommends 90% coverage
for each of the following vaccines: pertussis, measles, Hib and pneumococcal
vaccines (UNICEF/WHO, 2013). It is significant that these newer vaccinations
have been made available as standard as part of the international health
community’s basic standards, and that there is an obligation to collect data in
all countries, not just in the developed world.
Figure 5: Progress of pneumococcal conjugate vaccine (PCV)
introductions and proportions of birth cohorts living in countries that
have introduced PCV into routine infant immunization schedules, by
year
Source: WHO, 2013, Pneumococcal vaccination information sheet
8PCV3 – Percentage of surviving infants who received three doses of pneumococcal
conjugate vaccine. (UNICEF, 2014 State of the World’s Children, pp. 53).

32
Figure 5 provides evidence of both the relatively rapid progress PCV has
made, but also by the proportion of the birth cohort in each country which has
introduced the PCV, that there are great challenges remaining with regard to
increasing coverage to prevent pneumonia in children in developing countries.
Figure 6: PCV introduction by year
Source: IVAC/VIMS, 2015 p. 10.
There are still a number of important countries with regards to reducing child
mortality from pneumonia in developing countries. Figure 6 shows that both
India and China do not yet have a full national or subnational PCV
immunisation programme. It does, however, show great progress across
much of sub-Saharan Africa and Latin America with regards to introduction.
Focus must now be on strengthening these programmes and targeting those
children still lacking access to the vaccination despite their national
governments introducing the vaccine officially.
10 countries plan to introduce PCV in 2015: 6 in Africa (Algeria, Lesotho,
Nigeria, Gabon, Guinea-Bissau and Eritrea), two in South Asia (Bangladesh

33
and Nepal), one in the Western Pacific Region (Soloman Islands) and one in
the Eastern Mediterranean (Lebanon). Bangladesh and Nigeria are
highlighted as those with the greatest burdens of pneumonia mortality in
children globally (GAPPD, 2013). Therefore the introduction in these countries
will likely significantly reduce the incidence, severity, and mortality in under-5s
in these countries and therefore the total number of deaths from pneumonia in
children globally. Additionally, these countries are projected to have large
increases in birth cohorts so if scaling up of the introduction of PCV into
national programmes to increase coverage can be achieved quickly the
potential to reduce under-5 pneumonia mortality will be significant.

34
Successful policy, planning and implementation of
pneumococcalimmunisation in under-5s
Although 130 countries globally have achieved the 90% coverage target for
the first dose of the DTP vaccine (UNICEF, 2012), Seth Berkley of GAVI
writes that despite efforts and progress to reach all children with basic
immunizations, there are still 22 million who are not fully immunized (State of
the World’s Children 2015, interactive version)9. This fact in itself is relevant to
any discussion of pneumonia prevention because the diphtheria and pertussis
components of the vaccination, along with measles vaccination, are the basis
of any immunisation programme. They also reduce mortality from pneumonia
in their own right (Brenzel et al., p. 389).
The MDGs use coverage rates for measles immunization as one of the
targets toward reducing child mortality (UNICEF, 2015). It has more data
available than other vaccines to put to use to inform the addition of new
vaccines to the schedule and continue to target pneumonia prevention in
children. Furthermore, any newer vaccines, such as Hib and PCV will be
added to these existing DTP schedules so if there are a significant number of
children not receiving the recommended primary doses of long-established
vaccines then the new vaccinations will not reach these children either.
Dynamics of uptake and coverage should be considered, including both
supply-side and demand-side incentives and barriers. Household-level
determinants such as the price of vaccine services or taking services directly
to households should be considered. Incomplete coverage in rural areas
demonstrates how governments cannot rely on individuals bringing their
children to the facility (Barham and Maluccio, 2009). Points for consideration
with regard to improving immunisation programmes have been identified as:
“supply management, cold chain capacity, health worker training, outreach, or
in the demand by parents for vaccines” (IVAC 2014 p. 7). In 2001 there were
5 PCV manufacturers, just one of them based in a developing country. In
9 See http://sowc2015.unicef.org/stories/a-healthy-future-through-innovation/

35
2014 those figures were 16 and 10 respectively (GAVI, 2014). This shows that
working on incentives to support manufacturers and developers of PCV on the
supply side in low-income countries has been a success and will help towards
increasing coverage and therefore preventing many more under-5 deaths
than would have been achieved without such work.
Supply-side and demand-side factors that affect the uptake of vaccinations
are similar for all vaccinations so studies on factors pre-PCV introduction.
Because PCV3 can be added to existing programmes, the need for
strengthening capacity and success of these existing programmes is
important. The WHO’s “Adopting Global Vaccine Management Policies for
National Use” recommends using data from GAVI assessments, DHS, MICS
and NID reports to note trends and assess policy successes and failures
(WHO, 2001, pp. 6). These data can be used to inform future policy with
accuracy and contribute to the success of adding vaccines such as PCV to
the EPI of all countries. Further to this, is the aim to get developing countries
collecting their own data on PCV coverage and information about high-risk
districts or populations. India has started to collect data to fill these current
gaps in knowledge. Both India and Nigeria are attempting to evaluate the
performance of interventions that reduce pneumonia incidence, including Hib
and PCV immunisations (IVAC, 2014). All of these new strategies will target
scale-up of PCV coverage in populations with the highest risk of under-5
pneumonia mortality. They will also ensure future sustainability of the
immunisation programmes by giving developing countries the ability to
analyse trends and assess programme successes and failures.
Lessons learnt: strategies to focus efforts on most at risk children
Effects of common comorbidities are not often considered in research and
literature but are an important advantage to prevention with immunisation. For
example, interactions between malaria and pneumonia lead to higher chances
of mortality, but also cause complications in attributing the death to one or
other disease or its aetiologies (Fischer Walker et al., 2013; Rudan et al.,
2008). Another study showed that undernutrition contributes to 44% of all

36
under-5 pneumonia deaths (GBD 2004, p.14). A large prospective study in
Germany on infants with one or more physical risk factors for pneumonia (e.g.
preterm infants or underlying diseases such as cardiovascular conditions)
found that the PVC7 had an effectiveness of 38%, some 27% more than in
infants without risk factor (Adam and Fehnle, 2008).
A report by UNICEF found that investing in the more disadvantaged children
in a community can be more cost-effective than focusing on reaching targets
as quickly as possible (UNICEF, June 2015 Progress for Children p. iii). This
must be considered in the final SDG for health, and targets be drafted in such
a way as to inform policy relating to the administering of PCV.
In the last 5 years, there is more evidence that “disaggregating data and
targeting programmes to reach the most disadvantaged and overcome the
barriers that exclude them from critical services – can accelerate progress”
(UNICEF, 2015, p. iii). Learning from some drawbacks noted with the MDGs,
the SDGs recommend “possible” disaggregation of data for Goal 3 indicators.
This additional detail required for data collection should be made explicit in
the SDGs and governments given assistance to collect such data. This will
help vaccine suppliers, stakeholders and international health agencies to set
more specific population-based local and regional targets which will focus on
the most disadvantaged (and therefore in the case of pneumonia mortality,
the most at risk).
It has also been found that children who live in a household with a HIV -
positive member, as well as maternal and postnatal tobacco exposure, are all
negatively associated with pneumonia. Exclusive breastfeeding for the initial 6
months after birth and higher levels of maternal education are noted to have
positive effect on the incidence, severity and mortality of under-5 pneumonia
(le Roux et al., 2015).
Although most pneumonia mortality in under-5s occurs in the first 2 years of
life (Fischer Walker et al., 2013; UNICEF/WHO, 2013; Lucero et al., 2009),
the proportion of deaths from pneumonia caused by S. pnemoniae is greatest

37
in those older under-5s (Fischer Walker et al., 2013). Therefore, to achieve
global health targets like the SDGs, although it is advised that more efforts
need to be targeted at children under-2 with regards to interventions to reduce
mortality from pneumonia, for the PCV it seems prudent to consider ensuring
efforts focus on catching up children that missed the initial introduction of the
PCV in their country’s EPI schedule. National immunisation days have proven
to be effective for this in a number of Latin American countries, including
Brazil, Nicaragua, and Bolivia, and could be replicated in other world regions
with sufficient funding, political will and social mobilisation.
PCV has made significant progress in some developing countries.
Nicaragua’s introduction of the 13-valent PCV in 2010 was the first in a
developing country “Within the first 2 years of a PCV-13 immunization
program in Nicaragua, we observed lower rates of hospitalisations and
ambulatory visits for pneumonia among children of all ages and a lower infant
mortality rate. Lower rates of pneumonia among age groups not eligible to
receive PCV-13 suggest an indirect effect of the vaccine” (Beker-Dreps et al.,
2014). The Health advisor to the Nicaraguan government ascribes this in part
to the organised social mobilisation and volunteers and health workers
involved in ensuring all children are reached (Bill and Melinda Gates
Foundation, 2015). This is reminiscent of the previous successes of gaining
high coverage rates for immunisations in the late 1990s in Nicaragua and
other Latin American countries by drawing on their strong traditions of family
health, social mobilisation.
National Immunisation Days (NIDs) have played an important role in past
strategy of increasing coverage. This has been particularly the case in Latin
America where the Pan American Health Organization (PAHO) effectively
used them in the 1990s when a more targeted approach was advocated by
WHO, over an overall strengthening of health systems and combined
approach as currently advocated. Nicaragua now has graduated from needing
GAVI support and has a coverage rate of 98% for PCV3, with only Albania,
Bahrain, Kuwait and Turkmenistan achieving greater at 99% (WHO/UNICEF,
State of the World’s Children 2015 pp. 48-52).

38
GAVI’s next phase of development for the period 2016-2020 aims to:
“contribute to improving integrated and comprehensive immunisation
programmes, support improvements in supply chains, health information
systems, demand generation and gender-sensitive approaches, and to
strengthen engagement of civil society, private sector and other partners in
immunisation” (GAVI, 2015, Phase IV p. 2). The adjustment toward a more
integrated approach in their post-2015 phase, which considers a broader
health system strengthening, is both a sign of GAVI’s success in its more
narrow focus during its first decade in operation, and a sign of its commitment
to work alongside the recommendations of international health organisations
and global consensus that is currently shaping the finalised SDGs. It also
emphasizes strategies that target those previously identified in this work as
both most at risk and hardest to reach, such as mobilization of civil society. To
achieve this equity the inclusion of gender and locally sensitive approaches
will be important and help to ensure that the demand is there in the more
vulnerable populations.
Innovations in financing
The economic benefits of PVC have been assessed as very cost-effective in
countries with high under-5 mortality (Sinha et al., 2007). The majority of low-
income countries fall into this category. However, it has been noted that “new,
more expensive vaccines are challenging previous notions of the cost-
effectiveness of immunization” (Brenzel et al., p. 389). The price of PCV
(US$54 per dose) is a barrier to access for the poorest countries (Andrus et
al., 2008). From a cost-effectiveness or development perspective, considering
outcomes other than mortality, with regards to the benefits of preventing
pneumonia by vaccination, is essential (Brenzel et al., p. 408). The impact on
child development and economic potential of preventing morbidity and
mortality from pneumonia by PCV should be considered (IVAC, 2014).
Most figures and studies do not take into consideration the herd effect of the
vaccination, which would be expected to further increase any efficacy figures

39
and reduce disease burden. Herd effects have been noted in unprotected
children in a number of studies in developed countries. There are fewer
studies in developing countries due to the later introduction of PCV in these
countries but notably, studies of the PCV13 in Nicaragua (Becker-Dreps et al.,
2014) and South Africa (le Roux et al., 2015), and PCV9 in The Gambia in
2005 (Cutts et al., 2005) all found indirect effects on pneumonia incidence and
mortality.
New mechanisms have been put in place to increase both supply and
demand of the PVC. The Advance Market Commitment (AMC) is an
innovation in finance for vaccinations and guarantees large purchases in
exchange for a low price. GAVI countries secured a new lowest price for PCV
of US$3.30 per dose from 2014 onwards. Due to the successes of the AMC
42 developing countries introduced PCV as of September 2014, and 15 more
have been approved for 2015 (UNICEF, State of the World’s Children 2015,
interactive version, 2015).
With the help of GAVI and the AMC, in a study on 72 developing countries, if
the coverage rates of PCV could be increased to match those of DTP3 7% of
all-cause mortality in children aged 3-29 months would be prevented
This amounts to 8.34 million DALYs per year (Sinha et al., 2007). This
would prevent a substantial amount of future economic loss. This, in turn,
would help to break the poverty and disease cycle found in many at risk
populations and developing countries and reduce future incidence and
mortality of pneumonia in under-5s in these countries.

40
The future of PCV and its role in contributing to child
mortality reductions in a post-MDGworld
It is as yet unclear if efficacy declines in some or all populations in the years
post immunisation. For example, a 26% reduction in efficacy was found in HIV
positive children 6 years after immunisation with PCV9 (for all pneumococcal
disease) (Webster et al., 2011), In high income countries studies have found a
reduction in efficacy as serotype replacement has occurred (Webster et al.,
2011). This means that the strong case for focusing on increasing PCV
coverage as an intervention to prevent pneumonia mortality and increase
rates of reduction in under-5s could be called into question at a later date.
Demographics in low- and middle-income countries are not in favour of
reducing overall child and infant mortality from pneumonia: “countries that
have lagged in vaccine introduction are often larger countries with large birth
cohorts” (IVAC, 2014 p. 5). For example, Nigeria, India and the Democratic
Republic of the Congo fall into this group. Sustaining coverage levels is
therefore likely to be problematic in the coming decades (‘Brenzel et al., 2006,
p. 408). Additionally, “by 2018, Asia will have more people living in urban
areas than in rural areas; that change will come to Africa by 2037” (UNICEF,
2015, Progress for Children, p. 5). This will partly be due to urbanisation and
partly due to urban growth. For Asia, taking advantage of the population
change in the post-2015 global health agenda is realistically too late;
however, this time-scale of the projection for Africa gives the potential to
prevent many pneumonia deaths by strengthening capacity and supply of
vaccination, as well as targeting for immunisation those most at risk, such as
infants in households with HIV positive members. This should be where global
efforts focus with regard to PCV coverage to prevent and reduce pneumonia
mortality in under-5s.
GAVI explain how the future of their PCV scale-up and improvement of
access and coverage looks by innovating vaccine delivery and supply chains
to help get coverage to the most at risk and difficult to reach children:

41
“Allowing real-time data of stock levels in remote facilities to filter back
up the chain can help prevent unnecessary stock-outs and ensure that
vaccines are available when infants and children are brought in to be
immunized. Meanwhile, the technology will also enable health-care
workers in the field to access health records and schedule
appointments using their phones. They can even issue automated text
reminders to parents about when to bring their children in for
vaccination” (UNICEF, 2015).10
For the future of health goals in a post-MDG world, the pertinent suggested
targets and indicators relating to child health and mortality in developing
countries are as follows:
“3.2 By 2030, end preventable deaths of newborns and children under 5 years
of age”.
“3.3 By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected
tropical diseases and combat hepatitis, water-borne diseases and other
communicable diseases.”
“3.8 Achieve universal health coverage, including financial risk protection,
access to quality essential health-care services and access to safe, effective,
quality and affordable essential medicines and vaccines for all.”
(UN, Indicators and Monitoring Framework for SDG Working Draft, 16th
January 2015, p. 9).
Once again, as with the MDGs, the overarching goals to guide the health and
development communities have neglected to name the largest killer of under-
5s globally, pneumonia. This is a loss of potential and much needed continues
impetus on the fight against pneumonia mortality in under-5s in developing
countries. The PCV will be the most important intervention in this fight
10 Taken from: http://sowc2015.unicef.org/stories/a-healthy-future-through-
innovation/

42
between 2016 and 2030 but will not reach its full potential without the
international health community giving explicit recognition on pneumonia as a
preventable cause of child mortality.
CONCLUSION
A panel of global health experts for The Lancet concluded that if the MDG for
child mortality were extended as part of the SDGs, it would be possible to
achieve and maintain the reduction of mortality by communicable diseases by
the goal of two-thirds. The group suggests that future strategies need to
consider “epidemiologically efficient” ways to achieve this (Norheim et al.,
2015). This means going further than scaling up health service delivery as
the focus of mortality reduction efforts. The dynamics of disease transmission
must be considered, and the R&D into improved efficacy of pneumococcal
vaccinations increased.
Improvements in approaches to data collection and analysis in areas of
quality, scope and quantity will help inform the next GBD results, and will
better assist international health stakeholders to prioritise interventions to
achieve the SDGs post-2015 (Kovacs et al., 2015). There is need for
serotypes more commonly found in developing countries to be added to PVC.
Alternatively, a better approach would be for PCVs that are produced
regionally or at country level to contain more locally prevalent serotypes
seeing as those in Asia differ from those in Africa or Latin America so efficacy
may differ (Webster et al., 2011). With regards to other causes of pneumonia,
specifically viral ones such as influenza or respiratory syncytial virus (RSV),
there is little promise of these being routinely vaccine-preventable so as to
play any part in the post-2015 health and development agenda (Rudan et al.,
2008). For this reason the focus on improving PCV in efficacy, supply and
uptake is imperative to continue improving child mortality rates up until 2030
and beyond. It is the world’s best hope for the prevention of mortality from the
largest contributor to under-5 deaths globally and has more potential than that

43
of any other single intervention to protect the most vulnerable children in a
post-2015 world.
The interaction between the various underlying elements is often hard to
untangle, in both directing interventions to reduce disease burden, and in
quantifying the reductions those interventions will achieve. This depends, at
least in part, on behavioural and cultural factors on the demand side, which
are hard to predict and alter to prevent pneumonia mortality in children (for
example, early care-seeking for antibiotic treatment). This makes targeting
pneumonia mortality by prevention with PCV all the more attractive.
Prevention by vaccinating against the most common causes of these
diseases requires less effort to be focused on the underlying causes of
disease, such as overall poverty reduction or strengthening infrastructure
such as sanitation. Difficulties with resurgence of polio or measles in some of
those countries where it had been almost totally eradicated show that
governments cannot be complacent about vaccine-preventable infectious
diseases by losing focus. The momentum must continue and the priority
sustained, but this will not happen if too many and too broad targets are set.
In an ideal world, the new SDGs would prevent many millions of child deaths
with the all-encompassing nature of their objectives. They are noble and
idealistic and hopeful, but whether they are realistic, achievable or sustainable
is questionable.

44
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