Introduction
Pneumonia in children aged <5 years is a major public health problem and is one of the leading causes of childhood deaths worldwide,1 mostly in low-income and middle-income countries (LMICs). In 2021, pneumonia claimed the lives of 725 557 children aged <5 years, primarily in LMICs.2
The Democratic Republic of Congo, Ethiopia, India, Nigeria and Pakistan contribute a substantial proportion of pneumonia cases and related deaths.3 4 Furthermore, beyond mortality, childhood pneumonia contributes to long-term respiratory complications and impaired lung function.5 The Global Burden of Disease Study reported over 97 million disability-adjusted life years lost globally in 2019, with children aged <5 years bearing a substantial portion of this burden.6
Effective management of childhood pneumonia is crucial for reducing morbidity and mortality in children.3 WHO revised pneumonia management guidelines in 2012, recommending outpatient treatment of chest indrawing pneumonia with oral amoxicillin based on findings from clinical trials.7–10 The WHO Integrated Management of Childhood Illnesses (IMCI) chart booklet was revised in 2014.11 The IMCI proposes a comprehensive approach to the management of childhood pneumonia, including prompt assessment and classification, appropriate treatment with antibiotics, supportive care and referral for severe cases.11 In 2018–19, a WHO survey reported that 45 (30%) out of 154 countries had embraced the revised WHO pneumonia guidelines. Among them, 39 (87%) recommended oral amoxicillin as the primary treatment for chest indrawing pneumonia.12
It is essential to consider the broader context of childhood pneumonia management in LMICs. Childhood pneumonia takes a significant toll on children’s health and places a substantial economic burden on families. This burden arises from healthcare expenses related to frequent healthcare visits, hospitalisations and productivity losses resulting from recurrent illnesses. A study conducted in India, for instance, estimated that the direct out-of-pocket cost of hospitalised acute respiratory infections consumed approximately one-third (34%) of the annual per capita income.13 Implementation of the revised WHO pneumonia management guidelines has been shown to reduce 39.5% of treatment costs, alleviating the significant financial strain on both families and healthcare systems, particularly in nations facing resource limitations.13
In addition, healthcare challenges in LMICs are multifaceted and often daunting. These regions grapple with inadequate access to essential healthcare services, resulting from a lack of healthcare infrastructure and geographic barriers.14 Moreover, the burden of preventable diseases, inadequate sanitation and malnutrition persists, contributing to high rates of morbidity and mortality, particularly among vulnerable populations such as children and pregnant women.15 16
These financial and healthcare challenges are exacerbated by a range of systemic issues in LMICs. These challenges include pervasive poverty, limited access to healthcare facilities, a shortage of trained healthcare providers and suboptimal quality of care.17 Moreover, concerns persist about the overuse and misuse of antibiotics, which undermine treatment effectiveness and contribute to the development of antimicrobial resistance (AMR).18 The AMR compounds the healthcare challenges in LMICs. The overuse and misuse of antibiotics in these regions have led to a growing threat of AMR, making previously treatable infections increasingly difficult to manage. This poses a serious public health risk, as it limits the effectiveness of essential antibiotics and threatens the success of medical interventions, including surgeries, chemotherapy and the prevention of infections in childbirth.19 Addressing AMR is a critical component of improving healthcare in LMICs, and it necessitates prudent antibiotic use and investments in infection control and surveillance.
Against this backdrop, the implementation of revised guidelines for the management of WHO-defined pneumonia in an outpatient setting holds immense promise. By addressing these challenges head-on, the revised guidelines have the potential to alleviate the economic burden on families, improve access to quality care and promote judicious antibiotic use, ultimately benefiting children’s health outcomes.
In 2018, a retrospective analysis of data concerning hospitalised children with pneumonia in Kenya revealed a notably elevated mortality rate among children who exhibited mild to moderate palmar pallor, had a weight-for-age z-score below −3 SD and displayed lower chest indrawing.20 These findings raised concerns among the authors and other experts, prompting a recommendation for these children to receive hospital-based treatment, diverging from the outpatient approach advocated by the revised WHO guidelines.
Therefore, it is important to evaluate the current management and outcomes status of children aged 2–59 months with chest indrawing pneumonia in a few selected LMICs using the updated WHO pneumonia guidelines. This prospective observational study in selected primary healthcare facilities in selected countries in Africa and Asia where the burden of disease is the highest would enable us to collect data about outpatient management of children with chest indrawing pneumonia and its associated outcomes.
Methods and analysis
Study design and setting
This is a prospective, observational cohort study in six countries, four in Africa (Ethiopia, Nigeria, Uganda and Zambia) and two in Asia (India and Pakistan). These countries were selected due to the high prevalence of childhood pneumonia, and they have updated national policies that recommend oral amoxicillin at the outpatient level for the treatment of chest indrawing pneumonia in children aged 2–59 months. Moreover, these countries have functional primary-level health facilities with staff trained according to the updated WHO IMCI case management tool (figure 1).11 Tables 1 and 2 show the details of each study site.
Details of Ethiopia, India and Nigeria study sites
Details of Pakistan, Uganda and Zambia study sites
Current Integrated Management of Childhood Illnesses clinical guidelines pneumonia standard case management.11
Study population
Children aged 2–59 months presenting to selected primary-level healthcare facilities with cough and/or breathing difficulty and presence of lower chest indrawing will be enrolled. Written informed consent will be obtained from parents when the child has been diagnosed with chest indrawing pneumonia, and treatment has been initiated by the healthcare provider. Children will be excluded if they are aged <2 months or >5 years, displaying any general danger sign (eg, convulsions, inability to drink or breast feed, persistent vomiting, lethargy, unconsciousness), stridor when calm, severe malnutrition oxygen saturation (SpO2) levels below 90% (where pulse oximeter is available),11 live in an area where the follow-up is not feasible or currently enrolled in another study.
The study investigators at each site, in agreement with the Ministry of Health, will select a suitable number of facilities to achieve the sample size.
Participant and recruitment
The recruitment process involves both the initial assessment and subsequent follow-up evaluations of the outcome.
Initial assessment
At the primary-level healthcare facility, healthcare providers will follow the IMCI chart booklet to assess children presenting with cough and/or breathing difficulty. Based on the assessment, children aged 2–59 months will be classified as having no pneumonia, fast breathing (respiratory rate above the age-specific cut-off per minute), chest indrawing or severe pneumonia.11 Video recording of children with chest indrawing pneumonia may be done with parental consent to evaluate the providers’ assessments. The face of the child will not be videographed to protect the privacy of the study patients. Healthcare providers will attend to all patients seeking care in routine and record all essential patient information, such as patient name, age, address, caregivers’ phone number, clinical findings and diagnosis, in the daily outpatient register. Additionally, the healthcare providers will also be involved in screening children aged 2–59 months who present with cough and/or breathing difficulty and will use the IMCI tool for assessing, classifying and managing children and will enrol those eligible with chest indrawing pneumonia. During this process, the healthcare provider will be assisted by the research staff, who will collect basic demographic information and will also obtain consent for the enrolment procedure.
Follow-up and outcome assessment
On day 15 after enrolment, the independent data collector (not involved in the diagnosis and treatment of the enrolled children) will contact the parents or caregivers using the provided phone number or mobile number that was obtained at the time of enrolment. The outcome data collectors will introduce themselves and inquire about the possibility of conducting an outcome assessment visit or call. Based on this phone call, the research team will visit the child’s home or any facility/hospital where the child is admitted or follow-up telephonically (figure 2). During the visit, the data collector will gather details regarding the child’s treatment during the illness, including the name, route of administration, duration, frequency of antibiotic use, treatment adherence and whether the child was treated on an outpatient basis or referred for hospitalisation. If the child was hospitalised, then the name, route of administration, frequency and duration of antibiotic therapy will be recorded. The survival status (outcome) of the child will be recorded. The window period for the follow-up is within the range of ±2 days. An Outcome and Treatment Record Form will be completed. In the unfortunate event of child death, a verbal autopsy will be conducted to determine the apparent cause of death. The hospital notes about the death will be prioritised over verbal autopsy whenever they are available. Online supplemental table S1 details the implementation strategy of all the research study sites in the selected countries.
Supplemental material
Visual representation of the study data collection process. IMCI, Integrated Management of Childhood Illnesses.
IMCI refresher training
Before implementing the study, all healthcare providers at selected primary-level facilities will undergo a 2-day to 3-day refresher training programme based on the IMCI chart booklet. The training will focus on assessing and classifying children aged 2–59 months presenting with cough and/or difficult breathing.11 Subsequently, it will be ensured that health workers have an IMCI chart booklet and facilitation materials, including pictorial guides, to assist them in their daily work. An orientation of all health workers on the study’s objectives, design, methods, consent forms, ethical considerations regarding data collection, etc will be done to facilitate enrollment.
Sample size
The sample size for the descriptive analysis has been calculated to be 292 for each study site (not each health facility at each study site). This calculation is based on assumptions of a 5% case fatality ratio for chest indrawing (5% taken from primary care data from Malawi, personal communication), with a margin of error of 3% and a confidence level of 95%. Accounting for a 5% loss to follow-up, a total of 310 children aged 2–59 months with chest indrawing pneumonia will be enrolled and followed up at each study site.
Statistical analysis
The analysis will be performed using STATA V.17. The analysis will start with the calculation of frequency and percentage distributions for categorical variables, including sex, clinical signs, treatment received and vital outcomes based on IMCI.11 The case fatality risk and 95% CIs will be calculated and reported separately for each study site. Additionally, we will conduct a pooled analysis to estimate the case fatality risk with 95% CI for all children enrolled in this study. Additionally, continuous variables such as age and duration of treatment will be evaluated by calculating the mean and median, accompanied by measures of dispersion such as SD and IQR, respectively. The site-specific data analysis will be conducted, followed by a pooled analysis of de-identified data from all sites using predefined core variables. The selection of these core variables will occur in the subsequent phases of the study.
Ethics
The study protocol, enrolment forms and consent forms will undergo ethical review by the Institutional Review Boards of the University of Gondar, Gondar, Ethiopia; The INCLEN Trust International Independent Ethics Committee, New Delhi, India; Ethical Review Committee of the University of Ibadan, Ethical Review Committees of Lagos State and Ethical Review Committee of University College London, UK; Institutional Review Board, International Research Force, Islamabad, Pakistan; Institutional Review Board, People’s Primary Healthcare Initiative-Sindh, Karachi and National Bioethics Committee, Islamabad, Pakistan; Makerere University School of Biomedical Sciences Research Ethical Committee, Kampala, Uganda; University of Zambia Biomedical Research Ethics committee, Lusaka, Zambia and Ethical Review Committee of WHO, Geneva, Switzerland approved the study.
Written informed consent will be obtained from the parent or guardian of each child with chest indrawing pneumonia for enrolment, follow-up and video-recording of clinical examination. Apart from Nigeria, the healthcare provider will present the consent document to the parents/caregivers of eligible children in the local language to ensure their understanding of the study and its procedures. Parents/Caregivers of the eligible child will receive comprehensive information about the study and will be invited to provide consent for their child’s participation. Children meeting the eligibility criteria will be enrolled if their parents/caregivers provide informed consent. In cases where parents/caregivers are illiterate, they will be asked to make a thumbprint on the consent form in the presence of a witness, while literate parents/caregivers will be requested to sign it. Children diagnosed with chest indrawing pneumonia requiring hospitalisation will either be admitted or referred to the appropriate hospital for treatment, and the quality of the care they receive will not be influenced by whether they provide consent for video recording or their participation in the study. Participation in the study will be voluntary, and participants will be allowed to withdraw if they are not comfortable with the study. The study will adhere to all local and national regulations concerning research involving human subjects by obtaining approval from the relevant ethical review committees before commencing data collection. Potential risks to the participating children and their families will be identified and addressed by the research teams in the study design to ensure an ethically responsible approach throughout the research process.
Confidentiality
All collected data will be de-identified and stored securely in a location accessible only to the site-specific research team to ensure privacy and confidentiality. Participants will be assured of the confidentiality of the data collected from them. Any data shared beyond the research team will be presented in aggregated form, with no identifiable information included.
Dissemination
The findings of this study will be disseminated locally, nationally and internationally to various stakeholders, including government officials, policymakers, academics, researchers, the local community and voluntary organisations involved in community-based services. Dissemination efforts will include a district-level seminar for healthcare staff, providers and local non-governmental organisations. Meetings with community leaders and members will directly communicate findings, raise awareness and encourage discussions. The study’s results will also be published in open-access, peer-reviewed journals, with local researchers as lead authors, promoting local expertise. Additionally, key findings will be summarised in abstracts for national and international conferences, expanding the reach and fostering collaborations with experts from diverse backgrounds.
Patient and public involvement
The development of the research question was informed by the high pneumonia-related mortality. Patients neither were advisers in this study nor were involved in the design, recruitment or conduct of the study. Results of this study will be made publicly available through open-access publication where study participants may access them.
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