Summary

Background: An analysis of trends and spatial distribution of pneumonia hospital admissions among children <5 years in Uganda,2013–2021 indicated a high incidence of severe pneumonia in Kasese District. However, data on the factors associated with developing severe pneumonia in this area was limited. We, assessed factors associated with severe pneumonia among children <5 years in the Kasese District, January to April 2023 to inform effective evidence-based control and prevention strategies.

Methods: We conducted an unmatched hospital-based case-control study with a 1:1 ratio among children aged 2-59 months presenting with pneumonia at the outpatient department at 5 high-volume health facilities in Kasese District. Cases were selected based on presenting with severe pneumonia defined as pneumonia with any danger signs including oxygen saturation <90%, central cyanosis, severe respiratory distress, inability to drink or breastfeed or vomiting everything, altered consciousness, and convulsions. Controls were selected based on presenting with pneumonia as defined as lower chest wall indrawing or fast breathing (respiratory rate ≥50 breaths per min if aged 2–11 months; ≥40 breaths per min if aged 12–59 months) and without signs of severe pneumonia. Risk factors assessed included: caregiver’s, child’s health, health-seeking behaviour, and environmental exposure characteristics. Logistic regression analysis was used to identify risk factors associated with severe pneumonia.

Results: A total of 336 children <5 years presenting at 5 high-volume facilities in Kasese District with pneumonia between January to April 2023 were included in the study. Of these 199 were cases while 174 were controls. The median age of children was 12 months, interquartile range; of 6-24 months. After adjusting for covariates, having diarrhoea only (aOR=2.88,95% CI:1.69-4.89), malaria and diarrhoea (OR: 3.41,95% CI:1.98-5.86), not being exclusively breastfed at least 6 months (aOR=1.97,95% CI:1.1-3.34), and exposure to indoor air pollution through proximity to cooking combustion sources during home cooking with the child in the kitchen (aOR=2.89,95% CI:1.77-4.72) were associated with severe pneumonia.

Conclusion: Having diarrhoea only, malaria and diarrhoea, not being exclusively breastfed for at least 6 months and exposure to indoor air pollution through proximity to cooking combustion sources during home cooking with the child in the kitchen were associated with developing severe pneumonia. These results can be used to develop tailored interventions for reducing morbidity and mortality due to severe pneumonia.

Background

Pneumonia, a largely preventable disease persists as a major public health problem among children <5 years. By 2019, pneumonia was the leading infectious cause of death among children <5 years accounting for 14% of all deaths in this age group. (1) Half of pneumonia cases and deaths are reported in Sub-Saharan Africa(2) .

Pneumonia is classified based on clinical severity and risk of poor outcomes into non- severe and severe pneumonia. Severe pneumonia often requires hospitalisation and has a higher case fatality rate than non-severe pneumonia. Severe pneumonia is also linked to long-term morbidity and life-long disability(3,4). Between 2015-2019, McAllister et al documented a worrying trend of severe pneumonia among children <5 years in Sub-Saharan Africa with a seven-fold increase in severe pneumonia cases(2). This suggested a growing burden of severe pneumonia in this region. In Uganda, the incidence of severe pneumonia was 108 per 100,000 children under five years in 2022 based on the routinely-collected weekly national surveillance data. Furthermore, a 2013-2021analysis of trends and spatial distribution of pneumonia hospital admissions and mortality among children under five years in Uganda, indicated a particularly high incidence of pneumonia admissions (> 3000 per 100,000 children<5 years in all years with the highest of 7,421 cases per 100,000 in 2019) in the Kasese District indicating a high burden of severe pneumonia in this area.

This growing burden of severe pneumonia creates a need to understand the factors associated with severe pneumonia among children <5 years in order to implement effective evidence-based control and prevention strategies. Previous studies by Rudin et al(5) found that about 7-13% of pneumonia cases develop severe pneumonia, but the reasons why they do remains a unclear. Although there is reasonable data on the risk factors for pneumonia, data on risk factors for development of severe pneumonia is limited. In developing countries, documented risk factors for the development of severe pneumonia include bacterial aetiology, immunisation status, low weight for age, low caregiver education, low wealth quintile delayed care seeking, household crowding, co- morbidities, exposure to household crowding, malnutrition, and young age(6–8).

However, these were inconsistent and varied with unique contextual differences observed in different settings. Little is documented on the factors associated with severe pneumonia among children <5 years in Uganda especially in high burden areas such as Kasese District. We identified the factors associated with development of severe pneumonia among children < 5 years in Kasese District in to inform control and prevention strategies.

Methods

Study setting

We conducted the study from January to April 2023 in Kasese District located in western Uganda. Kasese is one of the districts where the integrated community case management for childhood illnesses including diarrhoea, malaria, and pneumonia are implemented(9). Kasese District has 139 health facilities, out of which 81 were health centre IIs, 48 health centre IIIs, 6 health centre IVs and 4 general hospitals. As per the revised package of basic health services for Uganda, 2014, severe pneumonia can only be managed at health centre IIIs, health centre IV, and general hospitals(10). We specifically conducted the study in in five health facilities reporting the highest number of severe pneumonia cases. These included Kagando Hospital, Bwera Hospital, Kasanga PHC Health Centre III, St Francis of Assis-Kitabu Health Centre III. These facilities offer both in-patient and outpatient child care services.

Case control study

We conducted an unmatched hospital-based case control study between January to April 2023. We defined severe pneumonia cases as a child aged 2-59 months presenting with pneumonia with any danger signs including: oxygen saturation <90%, central cyanosis, severe respiratory distress, inability to drink or breastfeed or vomiting everything, altered consciousness, and convulsions(11). Controls were defined as a child aged 2-59 months presenting with lower chest wall indrawing or fast breathing (respiratory rate ≥50 breaths per min if aged 2–11 months; ≥40 breaths per min if aged 12–59 months), and without signs of severe pneumonia at the health facility during the same period as cases.

We determined the sample size using the Fleiss et al (12) formula using Open Epi software. We assumed a two sided confidence level (CI) =95%, power =80%, 1:1 ratio of cases to controls, taking non-exclusive breastfeeding as a main predictor for severe pneumonia in developing countries with an odds ratio of 2.7(13), and percentage of exposed controls at 9%(14). We obtained a total sample of 153 cases and 153 controls.

Using a structured questionnaire, we collected data regarding socio-demographics, child’s health, health seeking behaviour, environmental related factors from both the cases and controls. We further reviewed medical records and child health cards to obtain more details on the clinical characteristic including the immunization status of the children. Socio-demographic factors included 1) age categorised into infants 2–11 months, young children 12–23 months, toddlers 24–59 months, 2) sex categorised as male and female ,3) birth order categorised as1– 2, 3–4 and ≥5 caregiver’s 4) education level categorised based on the Uganda Education system to include: none, primary, O’level and A ‘level and 5) wealth status, a composite variable constructed using principal component analysis of data on ownership of consumer items and livestock, characteristics of the dwelling unit, water sources and sanitation facilities. Child health factors included 1) nutritional status categorised into normal stunting, wasting, underweight and overweight.

This was assessed by the following MUAC (in cm), weight for age Z score (WAZ), weight -for height/length Z score (WHZ), height-for-age Z score (HAZ), 2) breast feeding status defined based on WHO classification of breastfeeding was used to categorize patients as exclusively breastfed for at least 6months and those who were not ,3) underlying illness was defined as having diarrhoea, measles, malaria or HIV during the current illness, 4)immunisation status was defined age-appropriate receipt of vaccines (including Pneumococcal Conjugate Vaccine (PCV), DPT- HebB+Hib2, measles and polio vaccines) as indicated in the Uganda Immunisation schedule 5) previous respiratory illness. Environmental factors included 1) type of cooking fuel used at home 2) exposure to household air pollution from cooking fuel assessed using proximity to cooking combustion sources during home cooking with child in the kitchen and 3) exposure to tobacco smoke defined as staying with a cigarette smoker in the same household. Health seeking behaviour factors included1) duration in days to seeking care following caregiver’s recognition of illness 2) healthcare sought for this episode of illness prior to enrolment in the study, yes or no and 3) place where health care was sought for this episode of illness prior to enrolment in the study: home remedies, village health team, clinic, drug shop, health centre II, health centre III, and health centre IV.

Data analysis

We calculated frequencies with percentages for categorical variables(birth order, wealth status, nutrition status, breast feeding status, underlying illness, immunisation status, type of cooking fuel and exposure to indoor air pollution during home cooking exposure to tobacco to smoke and place where health care was sought prior to enrolment in the study) while medians with interquartile ranges (IQR) for continuous skewed variables (duration of seeking care following caregiver’s recognition of illness). We used logistic regression to obtain independent variables significantly associated with the outcome variable. The independent variables with p-values ≤0.2 at bi-variate analysis were used to develop a multivariable logistic regression model using a forward stepwise approach. The strength of association between outcome variable and the independent variables of interest were assessed by calculating Odds ratios (ORs) with 95% confidence intervals. Variables with 95% confidence intervals not including 1 and p<0.05 were considered statistically significant.

Ethical Considerations

The MoH of Uganda through the office of the Director General Health Services gave the administrative clearance to carry out this investigation and access anonymised patient data. Additionally, the MOH has also granted the program permission to disseminate the information through scientific publications. In addition, the Office of the Associate Director for Science, U.S. Centers for Disease Control and Prevention, determined that this study was not a human subjects research with the primary intent of guiding public health planning and practice. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§

• See e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. §241(d);

Results 

Socio-demographic characteristics of children <5 years in a hospital-based case- control study assessing factors associated with severe pneumonia in Kasese District, Uganda

The study comprised of 366 children <5 years, including 174 cases and 192 controls. The median age of children was 12 months, IQR:6- 24 months with 60% males and 44% in the ≤ 11 months age group. Forty-eight percent (48%) of children were in the 1-2 birth order with 62% with primary caregivers whose highest level of education was primary level education and 21% from households in the highest wealth quintile. Slightly more controls were in 1-2 birth order category (54% Vs 41%) and female (44% Vs 36%) (Table 1).

Table 1: Socio-demographic characteristics of children <5 years in a hospital- based case-control study assessing factors associated with severe pneumonia in Kasese District, Uganda

Characteristic	Cases		Controls
	n	%	n	%	P-value
Gender
Male	112	64	107	56	0.092
Female	62	36	85	44
Age group
≤11 months	78	45	84	44	0.489
12–23 months	47	27	44	23
≥24months	49	28	64	33
Birth order
1– 2	72	41	103	54	0.063
3–4	60	35	53	28
≥5	42	24	36	19
Primary care giver’s level of education
None	22	12	26	14	0.689
Primary level	113	65	115	60
Second	36	21	45	23

Tertiary	3	2	6	3
Wealth Status
Upper tercile	52	30	73	38	0.248
Middle tercile	59	34	60	31
Low tercile	63	36	59	31

Factors associated with severe children <5 years in a hospital-based case-control study assessing factors associated with severe pneumonia in Kasese District, Uganda

At the bivariate analysis level, , birth order, being in the lowest wealth tercile, not being exclusively breast fed to at least 6 months, and exposure to indoor air pollution through proximity to cooking combustion sources during home cooking with child in the kitchen were associated with having severe pneumonia. Seeking care from a VHT reduced the odds of having severe pneumonia. Gender, age group, primary care giver’s education, nutrition status, immunisation status, type of fuel used for cooking, and staying with a tobacco smoker in the same house did not have a statistically significant relationship with pneumonia development. Following adjusting, children who were not exclusively breast feed had twice the odds (OR=1.97,95% CI:1.13-3.36) of having severe pneumonia compared to children who were exclusively breast fed for at least 6 months; Children with diarrhoea only had 3 times the odds (OR:2.88,95% CI:1.69-4.89) of having severe pneumonia compared to children with no underlying disease at the time of their pneumonia-related diagnosis. Children with malaria and diarrhoea had 3 times the odds (OR:3.41,95% CI:1.98-5.86) of having severe pneumonia compared to children with no underlying disease at the time of their pneumonia-related diagnosis. Children who were exposed to indoor air pollution through proximity to cooking combustion sources during home cooking with child in the kitchen had 2 (OR: 2.89,95% CI:1.77-4.73) times higher odds of developing severe pneumonia.

Table 2: Factors associated with severe children <5 years in a hospital-based case-control study assessing factors associated with severe pneumonia in Kasese District, Uganda 

Characteristic	Case		Control		Unadjusted Odds Ratio				Adjusted OR
	n		n		OR	95% CI	P-value		OR		95% CI		P-value
Birth order
1-2	72		103		Ref
3-4	60		53		1.62	1.01-2.61	0.047*		1.55		0.82-2.93		0.176
≥5	42		36		1.67	0.98-2.86	0.062		1.40		0.72-2.70		0.331
Wealth Status
Upper tercile		52		73	Ref
Middle tercile		59		60	1.37	0.83-2.27		0.212		1.05		0.56-1.96		0.185
Low tercile		63		59	1.74	1.05-.90		0.032*		1.51		0.82-2.78		0.889
Exclusive breast feeding for at least 6 months
Yes		50		75	Ref
No		124		117	1.80	1.13-2.87		0.013*		1.97		1.13-3.46		0.017*
Underlying illness
None		65		108	Ref
Malaria only		13		4	0.85	0.49-1.48		0.575		0.99		0.88-1.12		0.937
Diarrhoea only		52		37	2.54	1.63-3.93		<0.001*		2.88		1.69-4.89		<0.001*
Malaria and
diarrhoea		44		33	2.76	1.69-4.56		<0.001*		3.41		1.98-5.86		<0.001*
Place of first care
Health Facility		70		55	Ref
VHTs		65		102	0.50	0.31-0.80		0.004*		0.78		0.44-1.39		0.404
Home		27		22	0.96	0.50-1.87		0.915		1.33		0.63-2.80		0.449
remedies
Exposure to indoor air pollution through proximity to cooking combustion sources during home cooking with child in the kitchen
Yes		98		79	1.89	1.19-2.98		0.007*		2.89		1.77-4.72		<0.0001*
No		54		76	Ref

Note: Gender, age-group, primary care giver’s education, vaccination status appropriate for age, previous respiratory illness, main source of energy used for cooking and staying in a household with a tobacco smoker were not associated with severe pneumonia at bivariate analysis with p>0.2.

Discussion

We assessed factors associated with severe pneumonia among children <5 years in five high volume health facilities in Kasese District. Our findings indicated that children who were not exclusively breast feeding, having diarrhoea only and diarrhoea and malaria at the pneumonia diagnosis and exposure to indoor air pollution through proximity to cooking combustion sources during home cooking with child in the kitchen were associated with severe pneumonia.

Children who were not exclusively breast fed for at least 6months had twice the odds of developing severe pneumonia compared to those that were exclusively breastfed. This is consistent with a systematic review of studies largely outside the African Region done by Lamberti et al that found that children who were not exclusively breast fed had a 5- fold increased risk in developing severe pneumonia which often requires hospitalisations(15). Breast milk contains Immunoglobulin G (Ig) and Immunoglobulin A (IgA) antibodies which enhance the child’s immune system and strengthens defence mechanisms against infectious agents protecting the child from developing severe disease (14,15). Our findings highlight the need for exclusive breast feeding in order to prevent severe pneumonia.

Children with diarrhoea only and malaria or diarrhoea, had higher odds of getting severe pneumonia compared to children with no underlying illness. Previous studies have indicated that malaria predisposes children to bacterial infections of common pneumonia causing organisms such as Streptococcus Pneumoniae and Klebsiella Pnemoniae often with severe forms of disease(16). Similarly diarrhoea may predispose children to pneumonia(17). Due to their immature immune system, children already suffering from an illness are more likely to suffer from severe illness if they get another coinfection(18).

Children who were exposed to indoor air pollution through proximity to cooking combustion sources during home cooking with child in the kitchen had twice the odds of developing severe pneumonia compared to those who were not. In the study setting, like other parts of Africa solid fuels such as firewood and charcoal are the main source of energy(19). Combustion of wood during cooking releases air pollutants such as PM2.5(20). A previous study conducted in Ugandan kitchens where charcoal and firewood was used indicated PM2.5 concentrations higher than the World Health Organization 24-h Air Quality Guideline(21). Under these circumstances, children whose caregivers cook with them often get exposure to these air pollutants. Such exposure compromises their immune response against invading pathogens in the respiratory tract which predisposes them to more severe disease(22).

Other previously documented risk factors for severe pneumonia such as younger age, immunisation status, and health seeking behaviour were not associated with severe pneumonia in our study. This could be attributed to the similar baseline characteristics in terms of age, immunisation status, and health seeking behaviour among cases and controls.

Study limitations

Our findings should be interpreted with the following limitations, to ensure case ascertainment, we selected hospital-based controls. Hospital-based pneumonia cases maybe different from community controls(23). Due to the differences in the diagnostic capacities of the selected health facilities, we did not explore clinical features and causative microorganisms associated with severe pneumonia.

Conclusion

In conclusion, having an underlying illness, not being exclusively breast fed for at least 6 months, and exposure to indoor air pollution through proximity to cooking combustion sources during home cooking with child in the kitchen were associated with developing severe pneumonia. These results can be used to develop tailored interventions in reducing morbidity and mortality due to severe pneumonia.

Conflict of interest

The authors declare that they had no conflict of interest.

Authors’ contribution

MW, RM, KA and KP: Participated in the conception, design, analysis, interpretation of the study and wrote the draft bulletin; RM reviewed the report, reviewed the drafts of the bulletin for intellectual content and made multiple edits to the draft bulletin; RM, DK, BK, LB, and ARA reviewed the bulletin to ensure intellectual content and scientific integrity.

Acknowledgments

We thank the Ministry of Health, Kasese District Local Government, and the Administration of the following health facilities: Kagando Hospital, Bwera Hospital, Kasanga PHC Health Centre III, St Francis of Assis-Kitabu Health Centre III and Kyarumba Health Centre III for supporting this assessment. We appreciate the technical support provided by the Ministry of Health. Finally, we thank the US-CDC for supporting the activities of the Uganda Public Health Fellowship Program (UPHFP) under which this assessment was conducted.

Copyright and licensing

All materials in the UPHB is in the public domain and may be used and reprinted without permission; citation as to source; however, is appreciated. Any article can be reprinted or published. If cited as a reprint, it should be referenced in the original form.

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