Pneumonia hospitalizations and mortality in children 3 - 24-month-old in Nigeria from 2013 to 2020: Impact of pneumococcal conjugate vaccine ten valent (PHiD-CV-10).

Pneumococcal conjugate vaccine ten valent (PCV 10) was introduced into Nigeria in three phases. Phase 3 introduction started in August 2016. However, its impact on pneumonia admissions and mortality among vaccinated Nigerian children has not been determined. Data in the period before PCV-10 introduction (3 August 2013-2 August 2016), and after (3 August 2017-2 August 2020) were retrospectively extracted from the medical charts of eligible patients aged 3-24 months with hospitalized radiological pneumonia at the University College Hospital (UCH), Ibadan; National Hospital (NH), Abuja; and Federal Teaching Hospital (FTH), Gombe, allowing for an intervening period of 1 year. Proportions of the patients with hospitalized pneumonia and case fatality rates were determined during both periods. The results were compared using z-test, multiple logistic regression analysis and p < .05 was considered significant. Adjusted pneumonia hospitalization rates between the two periods increased at the NH Abuja (10.7% vs 14.6%); decreased at the UCH, Ibadan (8.7% vs 6.9%); and decreased at the FTH, Gombe (28.5% vs 18.9%). Case fatality rates decreased across all the sites during the post-PCV introduction period: NH Abuja, from 6.6% to 4.4% (p = .106); FTH, Gombe, 11.7% to 7.7% (p = .477); and UCH, Ibadan, 2.0% to 0% (p = .045); but only significant at Ibadan. Overall, proportion of hospitalized pneumonia cases decreased after 3 years of PCV 10 introduction into the National Immunization Programme in Nigeria. The case fatality rate during post-PCV 10 introduction decreased at all the three sites, but this difference was significant at the UCH, Ibadan.

Pneumonia is the commonest killer of Nigerian children aged less than 5 years. Pneumonia vaccine (PCV 10) was introduced into Nigeria Vaccination Program between 2014 and 2016, but up till now the value has not been confirmed. We conducted a retrospective study in which data before and after PCV 10 introduction were compared. The study sites were the University College Hospital (UCH), Ibadan; National Hospital (NH), Abuja; and Federal Teaching Hospital (FTH), Gombe. The data were extracted from the medical charts of eligible patients aged 3­24 months who were admitted for severe pneumonia with evidences on lung radiographs. We found that the proportion of hospitalized pneumonia cases decreased after 3 years of PCV 10 introduction into the National Immunization Program in Nigeria. The death rate during post-PCV 10 introduction decreased at all the three sites, but was only significantly decreased at the UCH, Ibadan.

Oxygen systems and quality of care for children with pneumonia, malaria and diarrhoea: Analysis of a stepped-wedge trial in Nigeria.

OBJECTIVES: To evaluate the effect of improved hospital oxygen systems on quality of care (QOC) for children with severe pneumonia, severe malaria, and diarrhoea with severe dehydration. DESIGN: Stepped-wedge cluster randomised trial (unblinded), randomised at hospital-level. SETTING: 12 hospitals in south-west Nigeria. PARTICIPANTS: 7,141 children (aged 28 days to 14 years) admitted with severe pneumonia, severe malaria or diarrhoea with severe dehydration between January 2014 and October 2017. INTERVENTIONS: Phase 1 (pulse oximetry) introduced pulse oximetry for all admitted children. Phase 2 (full oxygen system) (i) standardised oxygen equipment package, (ii) clinical education and support, (iii) technical training and support, and (iv) infrastructure and systems support. OUTCOME MEASURES: We used quantitative QOC scores evaluating assessment, diagnosis, treatment, and monitoring practices against World Health Organization and Nigerian standards. We evaluated mean differences in QOC scores between study periods (baseline, oximetry, full oxygen system), using mixed-effects linear regression. RESULTS: 7,141 eligible participants; 6,893 (96.5%) had adequate data for analysis. Mean paediatric QOC score (maximum 6) increased from 1.64 to 3.00 (adjusted mean difference 1.39; 95% CI 1.08-1.69, p<0.001) for severe pneumonia and 2.81 to 4.04 (aMD 1.53; 95% CI 1.23-1.83, p<0.001) for severe malaria, comparing the full intervention to baseline, but did not change for diarrhoea with severe dehydration (aMD -0.12; 95% CI -0.46-0.23, p = 0.501). After excluding practices directly related to pulse oximetry and oxygen, we found aMD 0.23 for severe pneumonia (95% CI -0.02-0.48, p = 0.072) and 0.65 for severe malaria (95% CI 0.41-0.89, p<0.001) comparing full intervention to baseline. Sub-analysis showed some improvements (and no deterioration) in care processes not directly related to oxygen or pulse oximetry. CONCLUSION: Improvements in hospital oxygen systems were associated with higher QOC scores, attributable to better use of pulse oximetry and oxygen as well as broader improvements in clinical care, with no negative distortions in care practices. TRIAL REGISTRATION: ACTRN12617000341325.

Diagnosis of pneumonia and malaria in Nigerian hospitals: A prospective cohort study.

BACKGROUND: Pneumonia and malaria are the leading causes of global childhood mortality. We describe the clinical presentation of children diagnosed with pneumonia and/or malaria, and identify possible missed cases and diagnostic predictors. METHODS: Prospective cohort study involving children (aged 28 days to 15 years) admitted to 12 secondary-level hospitals in south-west Nigeria, from November 2015 to October 2017. We described children diagnosed with malaria and/or pneumonia on admission and identified potential missed cases using WHO criteria. We used logistic regression models to identify associations between clinical features and severe pneumonia and malaria diagnoses. RESULTS: Of 16 432 admitted children, 16 184 (98.5%) had adequate data for analysis. Two-thirds (10 561, 65.4%) of children were diagnosed with malaria and/or pneumonia by the admitting doctor; 31.5% (567/1799) of those with pneumonia were also diagnosed with malaria. Of 1345 (8.3%) children who met WHO severe pneumonia criteria, 557 (41.4%) lacked a pneumonia diagnosis. Compared with "potential missed" diagnoses of severe pneumonia, children with "detected" severe pneumonia were more likely to receive antibiotics (odds ratio [OR], 4.03; 2.63-6.16, P < .001), and less likely to die (OR, 0.72; 0.51-1.02, P = .067). Of 2299 (14.2%) children who met WHO severe malaria criteria, 365 (15.9%) lacked a malaria diagnosis. Compared with "potential missed" diagnoses of severe malaria, children with "detected" severe malaria were less likely to die (OR, 0.59; 0.38-0.91, P = 0.017), with no observed difference in antimalarial administration (OR, 0.29; 0.87-1.93, P = .374). We identified predictors of severe pneumonia and malaria diagnosis. CONCLUSION: Pneumonia should be considered in all severely unwell children with respiratory signs, regardless of treatment for malaria or other conditions.

Providing oxygen to children and newborns: a multi-faceted technical and clinical assessment of oxygen access and oxygen use in secondary-level hospitals in southwest Nigeria.

BACKGROUND: Oxygen is an essential medical therapy that is poorly available globally. We evaluated the quality of oxygen therapy in 12 secondary-level Nigerian hospitals, including access to oxygen equipment, equipment functionality, healthcare worker knowledge and appropriateness of use. METHODS: We conducted a three-part evaluation of oxygen access and use involving: (1) facility assessment (including technical evaluation of oxygen equipment), (2) clinical audit (children and neonates admitted January 2014-December 2015) and (3) survey of healthcare worker training and experience on the clinical use of oxygen (November 2015). RESULTS: Oxygen access for children and newborns is compromised by faulty equipment, lack of pulse oximetry and inadequate care practices. One hospital used pulse oximetry for paediatric care. Eleven hospitals had some access to oxygen supplies. Testing of 57 oxygen concentrators revealed two (3.5%) that were 'fit for use'. Overall, 14.4% (3708/25 677) of children and neonates received oxygen some time during their admission; 19.4% (1944/10 000) of hypoxaemic children received oxygen; 38.5% (1217/3161) of children who received oxygen therapy were not hypoxaemic. CONCLUSIONS: Oxygen access for children in Nigerian hospitals is poor, and likely results in substantial excess mortality. To improve oxygen access for children globally we must focus on actual provision of oxygen to patients-not simply the presence of oxygen equipment at the facility level. This requires a systematic approach to improve both oxygen (access [including equipment, maintenance and affordability]) and oxygen use (including pulse oximetry, guidelines and continuing education).

Hypoxaemia in hospitalised children and neonates: A prospective cohort study in Nigerian secondary-level hospitals.

BACKGROUND: Hypoxaemia is a common complication of pneumonia and a major risk factor for death, but less is known about hypoxaemia in other common conditions. We evaluated the epidemiology of hypoxaemia and oxygen use in hospitalised neonates and children in Nigeria. METHODS: We conducted a prospective cohort study among neonates and children (<15 years of age) admitted to 12 secondary-level hospitals in southwest Nigeria (November 2015-November 2017) using data extracted from clinical records (documented during routine care). We report summary statistics on hypoxaemia prevalence, oxygen use, and clinical predictors of hypoxaemia. We used generalised linear mixed-models to calculate relative odds of death (hypoxaemia vs not). FINDINGS: Participating hospitals admitted 23,926 neonates and children during the study period. Pooled hypoxaemia prevalence was 22.2% (95%CI 21.2-23.2) for neonates and 10.2% (9.7-10.8) for children. Hypoxaemia was common among children with acute lower respiratory infection (28.0%), asthma (20.4%), meningitis/encephalitis (17.4%), malnutrition (16.3%), acute febrile encephalopathy (15.4%), sepsis (8.7%) and malaria (8.5%), and neonates with neonatal encephalopathy (33.4%), prematurity (26.6%), and sepsis (21.0%). Hypoxaemia increased the adjusted odds of death 6-fold in neonates and 7-fold in children. Clinical signs predicted hypoxaemia poorly, and their predictive ability varied across ages and conditions. Hypoxaemic children received oxygen for a median of 2-3 days, consuming ∼3500 L of oxygen per admission. INTERPRETATION: Hypoxaemia is common in respiratory and non-respiratory acute childhood illness and increases the risk of death substantially. Given the limitations of clinical signs, pulse oximetry is an essential tool for detecting hypoxaemia, and should be part of the routine assessment of all hospitalised neonates and children.

Oxygen systems to improve clinical care and outcomes for children and neonates: A stepped-wedge cluster-randomised trial in Nigeria.

BACKGROUND: Improving oxygen systems may improve clinical outcomes for hospitalised children with acute lower respiratory infection (ALRI). This paper reports the effects of an improved oxygen system on mortality and clinical practices in 12 general, paediatric, and maternity hospitals in southwest Nigeria. METHODS AND FINDINGS: We conducted an unblinded stepped-wedge cluster-randomised trial comparing three study periods: baseline (usual care), pulse oximetry introduction, and stepped introduction of a multifaceted oxygen system. We collected data from clinical records of all admitted neonates (<28 days old) and children (28 days to 14 years old). Primary analysis compared the full oxygen system period to the pulse oximetry period and evaluated odds of death for children, children with ALRI, neonates, and preterm neonates using mixed-effects logistic regression. Secondary analyses included the baseline period (enabling evaluation of pulse oximetry introduction) and evaluated mortality and practice outcomes on additional subgroups. Three hospitals received the oxygen system intervention at 4-month intervals. Primary analysis included 7,716 neonates and 17,143 children admitted during the 2-year stepped crossover period (November 2015 to October 2017). Compared to the pulse oximetry period, the full oxygen system had no association with death for children (adjusted odds ratio [aOR] 1.06; 95% confidence interval [CI] 0.77-1.46; p = 0.721) or children with ALRI (aOR 1.09; 95% CI 0.50-2.41; p = 0.824) and was associated with an increased risk of death for neonates overall (aOR 1.45; 95% CI 1.04-2.00; p = 0.026) but not preterm/low-birth-weight neonates (aOR 1.30; 95% CI 0.76-2.23; p = 0.366). Secondary analyses suggested that the introduction of pulse oximetry improved oxygen practices prior to implementation of the full oxygen system and was associated with lower odds of death for children with ALRI (aOR 0.33; 95% CI 0.12-0.92; p = 0.035) but not for children, preterm neonates, or neonates overall (aOR 0.97, 95% CI 0.60-1.58, p = 0.913; aOR 1.12, 95% CI 0.56-2.26, p = 0.762; aOR 0.90, 95% CI 0.57-1.43, p = 0.651). Limitations of our study are a lower-than-anticipated power to detect change in mortality outcomes (low event rates, low participant numbers, high intracluster correlation) and major contextual changes related to the 2016-2017 Nigerian economic recession that influenced care-seeking and hospital function during the study period, potentially confounding mortality outcomes. CONCLUSIONS: We observed no mortality benefit for children and a possible higher risk of neonatal death following the introduction of a multifaceted oxygen system compared to introducing pulse oximetry alone. Where some oxygen is available, pulse oximetry may improve oxygen usage and clinical outcomes for children with ALRI. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617000341325.

A prospective validation study in South-West Nigeria on caregiver report of childhood pneumonia and antibiotic treatment using Demographic and Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) questions.

BACKGROUND: Childhood pneumonia is the single largest infectious cause of death in children under five worldwide. Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) provide health information on care sought for sick children in resource poor settings. Despite not being primarily designed to identify childhood pneumonia, there are concerns that reported episodes of "symptoms of acute respiratory infection" in DHS and MICS are often interpreted by other groups as a "proxy" for childhood pneumonia. Using DHS5 and MICS5 survey tools, this study aimed to assess how accurately caregivers report of "symptoms of acute respiratory infection" reflect pneumonia episodes and antibiotic use in children under five. METHODS: Children aged 0 to 59 months presenting with cough and/or difficult breathing were recruited from four study hospitals in Ibadan, Nigeria from August 2015 to March 2017. Children were assessed using World Health Organization (WHO) standard criteria by study physicians to identify whether they had pneumonia. Three hundred and two matched children in each category of 'pneumonia' and "no pneumonia" were followed up at home, either two or eight weeks later, using questions from DHS5 and MICS5 surveys to assess the accuracy of caregiver recall of pneumonia. RESULTS: The specificity of DHS5 and MICS5 questions for identifying childhood pneumonia were 87.4 (95% confidence interval (CI) = 83.1-91.0) and 86.1 (95% CI = 81.7-89.8) respectively and the sensitivity of questions were 37.1 (95% CI = 31.6-42.8) and 37.1 (95% CI = 31.6-42.8). Correct recall of antibiotic treatment was poor (kappa statistic = 0.064) but improved with the use of medicine pill boards (kappa statistic = 0.235). CONCLUSIONS: DHS5 and MICS5 survey questions are not designed to identify childhood pneumonia and this study confirms that they do not accurately discern episodes of childhood pneumonia from cough/cold in children under five. The proportion of pneumonia episodes appropriately treated with antibiotics cannot be accurately assessed using current DHS and MICS surveys. If these results are used to guide programmatic decisions, it is likely to encourage overuse and inappropriate prescribing of antibiotics for episodes of cough/cold. International agencies who continue to use these household data to monitor the proportion of children with pneumonia who receive antibiotic treatment should be discouraged from doing this as these data are likely to mislead national and global programmes. Medicine pill boards are used in a number of DHS surveys and should be promoted for wider use in national population surveys to improve the accuracy of antibiotic recall.

Care seeking behaviour and aspects of quality of care by caregivers for children under five with and without pneumonia in Ibadan, Nigeria.

BACKGROUND: This study aimed to investigate the differences in reported care seeking behaviour and treatment between children with pneumonia and children without pneumonia with cough and/or difficult breathing. METHODS: Three hundred and two children aged 0-59 months with fast breathing pneumonia were matched with 302 children seeking care for cough and/or difficult breathing at four outpatient clinics in Ibadan, Nigeria. After follow up at home, Demographic and Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) questionnaires were administered in the community by trained field workers to gather information around care seeking delay, patterns of care seeking, appropriateness of care seeking and treatment provided once care was sought. Multivariable analysis was carried out to determine significant factors associated with care seeking delay. RESULTS: Children with pneumonia had a significantly longer delay (median = 3d) before seeking care than those without pneumonia (median = 2d; P = 0.001). The length of the delay was 21% (95% confidence interval (CI) = 1%-42%) greater in those aged 0-1 month and 11% (95% CI = 5%-42%) greater in those aged 2-11 months compared to those aged 12-59 months. The length of delay was 17% (95% CI = 5%-30%) greater in rural locations than urban ones, and 33% (95% CI = 7%-51%) shorter in fathers with only primary education compared to higher education, adjusted for covariates. The range of places where care was sought showed the same distribution in those with and without pneumonia. Twenty two per cent of those with pneumonia sought care first from inappropriate providers. The number of children for whom caregivers reported having received antibiotic treatment was 92% for those with pneumonia and 84% for those without pneumonia. CONCLUSIONS: Given that children with pneumonia and cough/cold had similar patterns of reported care seeking information gathered on care seeking (type of provider visited) from DHS and MICS surveys on those with 'symptoms of acute respiratory infection' in this setting provide a reasonably valid indication of care seeking behaviours in children with pneumonia. There are high levels of antibiotic overuse for children with cough/cold in this setting which risks worsening antibiotic resistance.

Improving oxygen therapy for children and neonates in secondary hospitals in Nigeria: study protocol for a stepped-wedge cluster randomised trial.

BACKGROUND: Oxygen is a life-saving, essential medicine that is important for the treatment of many common childhood conditions. Improved oxygen systems can reduce childhood pneumonia mortality substantially. However, providing oxygen to children is challenging, especially in small hospitals with weak infrastructure and low human resource capacity. METHODS/DESIGN: This trial will evaluate the implementation of improved oxygen systems at secondary-level hospitals in southwest Nigeria. The improved oxygen system includes: a standardised equipment package; training of clinical and technical staff; infrastructure support (including improved power supply); and quality improvement activities such as supportive supervision. Phase 1 will involve the introduction of pulse oximetry alone; phase 2 will involve the introduction of the full, improved oxygen system package. We have based the intervention design on a theory-based analysis of previous oxygen projects, and used quality improvement principles, evidence-based teaching methods, and behaviour-change strategies. We are using a stepped-wedge cluster randomised design with participating hospitals randomised to receive an improved oxygen system at 4-month steps (three hospitals per step). Our mixed-methods evaluation will evaluate effectiveness, impact, sustainability, process and fidelity. Our primary outcome measures are childhood pneumonia case fatality rate and inpatient neonatal mortality rate. Secondary outcome measures include a range of clinical, quality of care, technical, and health systems outcomes. The planned study duration is from 2015 to 2018. DISCUSSION: Our study will provide quality evidence on the effectiveness of improved oxygen systems, and how to better implement and scale-up oxygen systems in resource-limited settings. Our results should have important implications for policy-makers, hospital administrators, and child health organisations in Africa and globally. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12617000341325 . Retrospectively registered on 6 March 2017.