Risk factors for community-acquired pneumonia among adults in Kenya: a case–control study
Muthumbi et al. Pneumonia
Risk factors for community-acquired pneumonia among adults in Kenya: a case-control study
Esther Muthumbi 0
Brett S. Lowe 0 2
Cyprian Muyodi 1
Esther Getambu 1
Fergus Gleeson 4
J. Anthony G. Scott 0 3
0 KEMRI-Wellcome Trust Research Programme, Center for Geographical Medicine Research Coast , Kilifi , Kenya
1 Coast Provincial General Hospital , Mombasa , Kenya
2 Centre for Tropical Medicine & Global Health, University of Oxford , Oxford , UK
3 Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine , London , UK
4 Department of Radiology, Churchill Hospital, University of Oxford , Oxford , UK
Background: Pneumonia is a leading cause of morbidity and mortality among adults worldwide; however, the risk factors for community-acquired pneumonia in Africa are not well characterized. Methods: The authors recruited 281 cases of community-acquired pneumonia and 1202 hospital controls among patients aged ≥15 years who attended Kilifi District Hospital/Coast Provincial General Hospital in Kenya between 1994 and 6. Cases were admissions with an acute illness with ≥2 respiratory signs and evidence of consolidation on a chest radiograph. Controls were patients without signs of pneumonia, frequency matched by age, sex and hospital. Risk factors related to socio-demographic factors, drug use, clinical history, contact patterns and exposures to indoor air pollution were investigated by questionnaire, anthropometric measurements and laboratory assays. Associations were evaluated using a hierarchical logistic regression model. Results: Pneumonia was associated with human immunodeficiency virus (HIV) infection (Odds Ratio [OR] 2.06, 95% CI 1.44-3.08), anemia (OR 1.91, 1.31-2.74), splenomegaly (OR 2.04, 95% CI 1.14-3.41), recent history of pneumonia (OR 4.65, 95% CI 1.66-12.5), history of pneumonia >2 years previously (OR 17.13, 95% CI 5.01-60.26), coryza in the 2 weeks preceding hospitalization (OR 2.09, 95% CI 1.44-3.03), current smoking (2.19, 95% CI 1.39-3.70), use of khat (OR 3.44, 95% CI 1.72-7.15), use of snuff (OR 2.67, 95% CI 1.35-5.49) and contact with several animal species. Presence of a Bacillus Calmette-Guerin (BCG) scar was associated with protection (OR 0.51, 95% CI 0.32-0.82). The risk factors varied significantly by sex. Conclusion: Pneumonia in Kenyan adults was associated with global risk factors, such as HIV and smoking, but also with specific local factors like drug use and contact with animals. Intervention strategies should account for sex-specific differences in risk factors.
Community acquired pneumonia; Adults; Africa; Risk factors; Air pollution
Community-acquired pneumonia (CAP) is a common
cause of morbidity and mortality worldwide. In Africa, CAP
is associated with an in-hospital mortality of 6–15% among
adults, as reported from hospital-based studies [
Studies from high-income countries have identified
several risk factors for CAP including smoking [
age > 65 years [
4, 8, 9
], immunosuppression by any
cause , underlying lung diseases such as chronic
obstructive pulmonary disease (COPD) [
], recent viral
upper respiratory infections (URTI) [
] and the
presence of co-morbidities . In addition, low
bodymass index (BMI), contact with children and poor dental
hygiene were identified as risk factors for CAP in a
systematic literature review and meta-analysis from studies
in Europe [
Different environmental and socio-economic
circumstances in sub-Saharan Africa are likely to give rise to
different risks for pneumonia, including younger age at
presentation, which has been observed [
]. There is a
single published study of pneumonia risk factors in
tropical Africa, which is confined to human
immunodeficiency virus (HIV)-infected adults in Kenya. This
identified additional risk factors as being single,
widowed or divorced (i.e. not married), being of low
socio-economic status and experiencing overcrowding
in the home [
]. Here the authors present an analysis
of a previously unpublished dataset from 1994 to
1996, exploring the risk factors for pneumonia among
adults in Kenya.
This case–control study was conducted at Kilifi District
Hospital (KDH), and Coast Provincial General Hospital
(CPGH) in Kenya among patients who presented either
to the outpatient clinic or the casualty department. Cases
were adult patients aged ≥15 years who were admitted with
CAP. CAP was defined as an acute illness (<14 days),
characterized by at least two respiratory symptoms (cough,
sputum, breathlessness, chest pain, hemoptysis or fever) and
evidence of consolidation on a chest radiograph. The
radiographs were read by a study physician and later
confirmed, independently, by a consultant thoracic radiologist.
Controls were adults aged ≥15 years who presented to
the outpatient clinics of the same hospitals who did not
meet the clinical case definition of CAP. They were
frequency matched on age, sex and hospital of presentation
in a ratio of 4:1 with cases. Controls with diagnoses that
were strongly associated with the exposures of interest
(e.g. meningitis, septicemia, tuberculosis, Kaposi’s
sarcoma, sickle cell crisis, diabetic ketoacidosis or
oropharyngeal candidiasis) were excluded.
A target sample size of 1500 (300 cases: 1200 controls)
was sought for the study. The study was powered to
detect relevant odds ratios using a range of prevalence
estimates for a wide variety of exposures included in the
study (Additional file 1).
Patients were questioned on clinical history, lifestyle habits
and contact history using a standard questionnaire.
Anthropometry and a physical examination were performed
for all participants in a standardized manner. Venous blood
was collected and tested for HIV-1 antibodies by
enzymelinked immunosorbent assay (ELISA), malaria parasites by
microscopy, and sickle cell status. A full hemogram,
glycosylated hemoglobin (HbA1C) test and blood grouping
(ABO) were also performed.
Associations with case status were analyzed using
logistic regression, adjusting for the matching variables (age,
sex and route of presentation) in each model. Because
this was the first study of risk factors for pneumonia in
an unselected population in Africa, a wide range of
potential exposures were explored. A hierarchical process
was used to define the final model, whereby related
exposures were first examined in intermediary models before
the best representative exposures were selected for a final,
multi-variable model. The intermediary models examined
5 categories of related variables (Table 1). Within each
category, univariate analysis was performed and variables
were selected with a likelihood ratio (LR) p-value of <0.1
to include in the intermediary multivariable model. Risk
factors contributing significantly (LR test, p = <0.05) to
the intermediary multivariable models were subsequently
included in a final multivariable model. Backward stepwise
analysis was used in each of the multivariable analyses. In
addition, prompted by the presence of sex-specific
exposures (e.g. pregnancy) and several instances of effect
modification due to sex, two sex-restricted models were
developed following a similar hierarchical process.
Some variables, e.g. BMI and presence of a scar following
Bacillus Calmette-Guerin (BCG) vaccine, were introduced
shortly after the study had begun, leading to some missing
data (Additional file 1). However, this is unlikely to have
caused bias unless there was a systematic difference in the
HIV, human immunodeficiency virus; TB, tuberculosis; URTI, upper respiratory tract infection
Number of children in the household, contact with children of different ages, with or without an URTI, number of
adults in the household, size of house, hours of childcare, sharing a room with children when sleeping, contact with
a case of pneumonia, recent travel beyond the immediate residential vicinity, use of public minibuses for transport
(matatu), frequenting social places and contact with selected animals, working and living in different locations
Quantified alcohol consumption and use of traditional brews (matingas, busaa, changaa, mnazi, muratina), quantified
present and past cigarette smoking, use of ground tobacco (snuff), use of Khat (miraa).
Exposure to cooking fuel smoke in the home, use of mosquito coils, ventilation in the cooking room, use of air
conditioning, passive smoking and occupational exposure during welding
Chronic bronchitis, recent history of viral URTI (<14 days), previous history of pulmonary TB, previous pneumonia,
body mass index, mid upper-arm circumference, anemia, splenomegaly, malaria parasitemia, sickle cell status, HIV
sero-positivity, ABO blood group, Glycosylated hemoglobin (HbA1c) and current pregnancy status.
admissions across the time periods of the study; therefore,
data imputation was not used.
All statistical analysis were performed using STATA V.13
(Stata Corp, College Station, Texas, United States [US]).
Between March 1994 and May 1996, 301 cases and 1202
controls were recruited. After review of the chest
radiographs by the radiologist, 20 of the original cases were
excluded as non-CAP. Among the 281 remaining cases,
177 (63%) were male and 22 (7.8%) were aged ≥55 years.
The matching achieved a similar distribution of age, sex
and route of recruitment across cases and controls
(Table 2). Among controls, malaria was the most common
presenting diagnosis, accounting for 26% (316/1202,
Additional file 1: Table S3).
The results of the univariate analysis for 72 variables, by
category of exposure, are listed in the Additional file 1:
Tables S4–S8. In Table 3 the results of the intermediary
and final adjusted models are presented for 25 variables,
with significant results at the intermediary model stage.
Previous history of pneumonia was a major risk factor
for current pneumonia. This risk was almost 20-fold
higher among those whose history of pneumonia was more
than 2 years ago (Table 3). History of previous URTI, HIV
infection, splenomegaly and anemia were all associated with
a 2-fold increase in risk of pneumonia; HIV was present in
30% (356/1202) of the controls. Malaria and presence of a
BCG scar was associated with a reduced risk of pneumonia.
The risk of pneumonia was reduced by 35% for every cm
increase in mid-upper arm circumference (MUAC, Table 3,
Additional file 1: Table S4). For most of the significant
clinical variables, there was no evidence of confounding
by variables in other categories as the effect sizes varied
little between intermediary and final models. Of note
from the univariate analyses, there was no association
Route of recruitment CPGH Filter clinic
between pneumonia and sickle cell trait, Blood group A
or history of previous tuberculosis (Additional file 1:
In the intermediate model, pneumonia was inversely
associated with the number of years in education and with
current employment. However, these associations did
not remain significant in the final model. In the
univariate analysis, there was no evidence of an association
between pneumonia and ethnicity, religion or economic
status measured either as amount of income or type of
roofing (Additional file 1: Table S5).
Air pollution and related factors
Among a wide range of air-pollution variables, only two
were significant in the univariate analyses; cooking in a
room with only one ventilation exit (the door) was more
common among cases; cooking for oneself was more
common among controls (Additional file 1: Table S6).
Pneumonia was not associated with indoor cooking, nor
sleeping in the cooking room, nor with the type of fuel
used for cooking.
Drug use and related factors
The prevalence of drug use differed by sex. Males
accounted for 87% (268/307) of alcohol consumers and
97% (312/321) of current smokers. Females were the largest
consumers of snuff (60% vs. 40% in males), but did not
report consumption of busaa and matingas (traditional
brews). Current smokers and ex-smokers had a 2-fold
increased risk of pneumonia compared to never-smokers;
recent ex-smokers had a 10-fold increase in risk (Table 3).
There was no evidence of increased risk with an increase in
smoking pack-years. Passive smoking and alcohol intake
were not associated with pneumonia.
Exposure to animals was reported in 43% (519/1202) of
the controls. Significant associations in the intermediary
model included exposure to monkeys, chickens, ducks
and goats, of which only the latter two remained
significant in the final model (Table 3). Adults frequenting
cafés or working at a different location from home were
at slightly increased risk of pneumonia; those using
public minibuses (matatus) or visiting nightclubs had lower
risks of pneumonia. In the univariate analysis, pneumonia
was associated with the total number of other people in
the home, and with the number of co-resident girls aged
<5y. Contact with a child under the age of 5 years with
coryza or sleeping in the same room as a child were not
associated with pneumonia.
OR = Odds Ratio; aOR = adjusted odds ratio;
afirst stage multivariable model adjusted results (within-category)
bsecond stage multivariable model adjusted results
camong those cooking indoors
Risk factors by sex
After restricting the analysis by sex, HIV infection, history
of coryza, splenomegaly and anemia were independent
risk factors shared by both sexes (Table 4). Decreasing
MUAC, history of tuberculosis, smoking, use of khat and
exposure to chickens were risk factors unique to males.
Among females, use of snuff and exposure to ducks and
sheep were unique risk factors. The presence of a BCG
scar was a protective factor among males only.
These results suggest that several of the risk factors for
pneumonia are common to both developed and
developing countries. These include smoking tobacco, exposure
to animals, recent URTI and anemia. The results have
also identified novel modifiable risk factors, such as the
use of snuff (ground tobacco) and khat, which are
particular to this population.
Smoking is a well-established risk factor for CAP [
The risk was highest among recent ex-smokers; this was
interpreted to mean that their decision to stop smoking
was influenced by an ailing respiratory system—a form of
reverse causality. Passive smoking was not associated with
an increased risk of pneumonia. Passive cigarette smoke
exposure is a known risk factor for lower respiratory tract
infections (LRTIs) among children [
], but not
Use of snuff and khat are novel associations found
among women and men, respectively. Snuff use is a risk
factor for oral cancer [
], while khat, a natural
amphetamine, is associated with a range of effects from tooth
decay to psychosis [
]. Khat, Catha edulis Forsk, is
a shrub whose leaves and twigs are chewed for their
stimulant effect and there is no obvious biological
explanation of this association. Overall, however, drug use
appeared to be a major avoidable risk factor.
History of coryza (representing URTIs) was associated
with pneumonia [
]. Viral URTIs suppress immune
function leading to increased susceptibility to secondary
infections. Influenza vaccine can reduce both primary
pneumonia and secondary bacterial pneumonia [
and may be useful to prevent CAP in adults.
Patients with a previous history of pneumonia were at
a higher risk of CAP in the current study, especially
those whose initial episode occurred more than 2 years
previously; in previous studies the risk was higher for
more recent episodes [
]. Childhood pneumonia is
associated with development of chronic lung disease and
later hospitalizations with pneumonia [
] and in
this study, 40% of cases were <30 years of age. In
addition, patients with recent episodes of pneumonia are
more likely to recognize the symptoms and the
seriousness of the illness, and therefore more likely to seek
early treatment, averting hospital admission. In Kenya,
pneumococcal vaccines are rarely used in adults;
however, post-hospitalization vaccination could potentially
reduce the rate of recurrence with pneumonia [
The authors found that low social economic status
(SES), measured directly by level of income and indirectly
by proxy measures like the materials used for house
construction, was not associated with pneumonia. However,
higher education, increased use of matatus (minibuses for
public transport) and frequent visits to a nightclub, which
are all likely to be indicators of higher SES, were
associated with a reduced risk of disease despite also implying
more human contact and therefore, potentially, a greater
risk of infection.
Indoor air pollution is a leading risk factor for
respiratory diseases [
], including pneumonia, in children
] though evidence in adults is weak [
]. In this
study, exposure to air pollution, including biomass fuels,
was not associated with an increased risk of pneumonia.
However, this study relied upon questionnaire methods
to ascertain exposure to air pollution and this is likely to
admit significant misclassification. More direct
measurements of air quality would be useful to estimate the role
of this risk factor [
As in other studies from developed countries [
HIV infection was associated with a 2-fold increase in
risk of CAP. This effect size is likely to be an
underestimate due to the use of hospital controls, despite
attempts to exclude from the control population those
with HIV-related diseases. The prevalence of HIV among
controls was 30.3%; population-based estimates of HIV
sero-prevalence at the same time were 7.5% . Use of
hospital controls also explains the seemingly protective
effect of malaria infection. Infection with malaria parasites
in the tropics is a common cause of presentation to
hospitals with non-pneumonia syndromes. Interestingly, markers
of chronic malaria infection, anemia and splenomegaly
were strongly associated with pneumonia, suggesting that
chronic or recurrent malaria may in fact be a risk factor for
pneumonia, although splenomegaly may also be a marker
of HIV or tuberculosis, both common in this population.
Evidence of BCG vaccination was associated with a
70% reduction in risk of pneumonia among men. The
effect in women was smaller and non-significant. In the
complementary study of pneumonia etiology conducted
in the same cases, Mycobacterium tuberculosis was
found in 9% [
]. Several vaccines have demonstrated
non-specific protective and harmful effects, which differ
by sex [
]. For example, those who develop a BCG
scar following vaccination are known to be less likely to
get sepsis, with the beneficial effect occurring
predominantly in girls . These benefits have been observed to
extend into adulthood [
]. The WHO suggests these
heterologous effects of vaccines are intriguing, currently
inexplicable and “warrant further research” [
The limitation of this study is that it is an analysis of
historical data and therefore, due to changes in
epidemiology in the ensuing years, the relative importance of
some of the observations may have changed. First,
several risk factors that were identified have changed in
prevalence; for example, HIV-infection and malaria have
both declined and smoking has increased. While this
alters the public health importance of these factors and
invalidates any attempt to calculate the current
population-attributable fraction for pneumonia, it does
not invalidate the etiological association.
Second, temporal changes may have modified the effect of
risk factors; for example, the introduction of anti-retroviral
therapy reduces the risk of pneumonia in HIV-infected
]. Third, changes in urbanization and lifestyle
habits may have introduced new risk factors for pneumonia,
which are not captured by the dataset that has been
analyzed. Nonetheless, historical data such as these can offer
unique insights into the epidemiology of pneumonia and
can stimulate and inform new studies.
The authors believe this is the only case–control study
on the risk factors of CAP ever conducted in an
unselected adult population in Africa. As the major risk
factors were unknown at the outset, the study examined
many different exposures simultaneously. Although this
leads to a risk of false-positive associations, the purpose
was to scan a broad range of potential risks that could
be explored and confirmed in subsequent focused
studies. As such, several key risk factors have been identified
that are amenable to vaccination or to changes in
lifestyle habits. Furthermore, in this setting the study has
demonstrated that the risk factors for pneumonia among
men and women were sufficiently different that they
should be investigated and managed separately.
This study was designed as a hypothesis-generating study.
It has identified a number of potential risk factors that
suggest that interventions that induce changes in lifestyle
habits (especially smoking and the use of other drugs)
may have a beneficial impact on the incidence of
pneumonia in this population—these are worth considering in
confirmatory studies. Previous history of pneumonia was
the strongest risk factor of all in this study, suggesting a
target for post-discharge vaccination.
Additional file 1: Supplementary information on the risk factors for
pneumonia in Adults. (DOCX 142 kb)
We would like to thank the nursing and clinical staff of Coast Provincial General
Hospital and Kilifi District Hospital, and the patients and their families. This paper
is published with the approval of the Director, Kenya Medical Research Institute.
The work was supported by the Wellcome Trust through fellowship support
for JAS (098532).
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.
EM conducted the data analysis and wrote the manuscript. BL, CM, EG
coordinated the hospital and lab aspects of the study. FG read and interpreted
the radiographs. JAS conceived the study, coordinated the data collection and
has contributed to data analysis and manuscript writing. All authors read and
approved the final manuscript.
Ethics approval and consent to participate
Ethical approval for the study was obtained from the National Ethics Review
Committee of the Kenya Medical Research Institute and the London School
of Hygiene & Tropical Medicine Ethics Review Committee.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
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