An assessment of the clinical effectiveness of World Health Organization guidelines for the management of pneumonia among hospitalised children in Kenya

Background: The effectiveness of World Health Organization (WHO) guidelines for pneumonia case management in sub-Saharan Africa has been contested. This thesis aims to determine the clinical effectiveness of these guidelines among children admitted to Kenyan hospitals in a period after the introduction of the pneumococcal and Haemophilus influenzae type B (Hib) conjugate vaccines. The studies focus on the treatment of children with chest indrawing pneumonia, who were previously regarded to be at high-risk requiring inpatient treatment but were reclassified as lowrisk (non-severe) in the WHO guidelines updated in 2013. Methods: This thesis consists of: (i) A systematic review linked to a national guidelinedevelopment exercise appraising the evidence for the WHO pneumonia guidelines, (ii) a prospective observational study evaluating adherence to, and effectiveness of the pneumonia guidelines in the national referral hospital in Kenya, (iii) a multi-centre pragmatic randomised controlled trial (RCT) comparing amoxicillin versus benzyl penicillin for chest indrawing pneumonia (iv) a cohort study comparing treatment effects among children enrolled in the antibiotic RCT with a similar group who received routine care, and (v) a multi-centre retrospective cohort study of children hospitalised with pneumonia describing factors associated with mortality, focusing on characteristics that increase risk of death among children who would, under current guidance, be assigned a non-severe classification. Results: Although evidence from clinical trials supported the adoption of oral amoxicillin for severe pneumonia over benzyl penicillin (the standard treatment) for chest indrawing pneumonia, a Kenyan guideline development panel raised concerns of generalizability citing the limited data from sub-Saharan African populations in whom mortality was argued to be high. This concern was explored using prospectively collected observational data from 385 children. Treatment failure and mortality were infrequent (16000 children suggested that the presence of commonly-occurring clinical signs may be associated with increased risk among children with non-severe pneumonia. Specifically, very low weight-for-age Z score (WAZ) or pallor in children with non-severe pneumonia were shown to be associated with absolute risks of mortality as high as those for severe pneumonia. Conclusions: Findings from locally-conducted observational studies and a clinical trial indicate low risks of treatment failure and mortality among children with chest indrawing pneumonia following treatment with benzyl penicillin monotherapy or amoxicillin. In contrast, mortality for severe pneumonia was greater than 10 percent. These results are consistent with the updated WHO recommendations and have more recently informed the revision of the national policy for pneumonia case management in Kenya. However, these guidelines may apply to sub-populations of children with non-severe pneumonia and either very low WAZ or pallor. This evidence is expected to contribute to ongoing debates on the adoption of WHO guidance for pneumonia case management in similar settings across sub-Saharan Africa where coverage of the Hib and pneumococcal conjugate vaccines is high

Regional and temporal trends in malaria commodity costs: an analysis of Global Fund data for 79 countries

BACKGROUND: Although procurement consumes nearly 40% of Global Fund’s money, no analyses have been published to show how costs vary across regions and time. This paper presents an analysis of malaria-related commodity procurement data from 79 countries, as reported through the Global Fund’s price and quality reporting (PQR) system for the 2005–2012 period. METHODS: Data were analysed for the three most widely procured commodities for prevention, diagnosis and treatment of malaria. These were long-lasting insecticide-treated nets (LLINs), malaria rapid diagnostic tests (RDTs) and the artemether/lumefantrine (AL) combination treatment. Costs were compared across time (2005–2012), regions, and between individual procurement reported through the PQR and pooled procurement reported through the Global Fund’s voluntary pooled procurement (VPP) system. All costs were adjusted for inflation and reported in US dollars. RESULTS: The data included 1,514 entries reported from 79 countries over seven years. Of these, 492 entries were for LLINs, 330 for RDTs and 692 for AL. Considerable variations were seen by commodity, although none showed an increase in cost. The costs for LLINs, RDTs and AL all dropped significantly over the period of analysis. Regional variations were also seen, with the cost for all three commodities showing significant variations. The median cost for a single LLIN ranged from USD 4.3 in East Asia to USD 5.0 in West and Central Africa. The cost of a single RDT was lowest in West and Central Africa at US$0.57, and highest in the Latin American region at US$ 1.1. AL had the narrowest margin of between US$0.06 per tablet in sub-Saharan Africa and South Asia, and US$ 0.08 in the Latin American and Eastern Europe regions. CONCLUSION: This paper concludes that global procurement costs do vary by region and have reduced overall over time. This suggests a mature market is operating when viewed from the global level, but regional variation needs further attention. Such analyses should be done more often to identify and correct market insufficiencies

Regular measurement is essential but insufficient to improve quality of healthcare

Background: Evidence on the detrimental effect of low quality health systems on preventable mortality worldwide has accelerated investments in large scale healthcare improvement. Regular measurement of quality of care is a core principle of quality improvement programmes that has been promoted in some low resourced settings as the primary means to improve quality of healthcare— that is, the degree to which health services for individuals and populations are effective, safe, and people centered

Extending the measurement of quality beyond service delivery indicators.

Assessing the quality of healthcare services is a priority in low-resource and high-resource settings alike. It is, however, a complex endeavour. Outcome measures are subject to case-mix variation, often require lengthy follow-up periods to manifest, and are generally costly to monitor. Therefore, structure and process measures are routinely considered reliable alternatives under the assumption of a causal link between the provision of care and improved health status. In this edition of BMJ Global Health, Giorgio et al used such structure and process measures—that is, service delivery indicators (SDI)—to assess the quality of healthcare across 10 African countries.2 The SDI programme was set up to conduct crosssectional nationally representative surveys that examine service delivery performance in education and health in Africa. The health indicators assess health worker availability, health worker knowledge on the management of common ailments, and availability of selected essential equipment and treatments. These surveys are aimed at providing high-level snapshots of the quality of health services in target countries. In this editorial, we discuss some of the limits of using data from a platform such as the SDI programme to make sense of quality of care and highlight complementary approaches that are aligned with emergent thinking in the field

Comparable outcomes among trial and nontrial participants in a clinical trial of antibiotics for childhood pneumonia: a retrospective cohort study.

OBJECTIVES: We compared characteristics and outcomes of children enrolled in a randomized controlled trial (RCT) comparing oral amoxicillin and benzyl penicillin for the treatment of chest indrawing pneumonia vs. children who received routine care to determine the external validity of the trial results. STUDY DESIGN AND SETTING: A retrospective cohort study was conducted among children aged 2-59 months admitted in six Kenyan hospitals. Data for nontrial participants were extracted from inpatient records upon conclusion of the RCT. Mortality among trial vs. nontrial participants was compared in multivariate models. RESULTS: A total of 1,709 children were included, of whom 527 were enrolled in the RCT and 1,182 received routine care. History of a wheeze was more common among trial participants (35.4% vs. 11.2%; P < 0.01), while dehydration was more common among nontrial participants (8.6% vs. 5.9%; P = 0.05). Other patient characteristics were balanced between the two groups. Among those with available outcome data, 14/1,140 (1.2%) nontrial participants died compared to 4/527 (0.8%) enrolled in the trial (adjusted odds ratio, 0.7; 95% confidence interval: 0.2-2.1). CONCLUSION: Patient characteristics were similar, and mortality was low among trial and nontrial participants. These findings support the revised World Health Organization treatment recommendations for chest indrawing pneumonia

Risk factors for death among children aged 5-14 years hospitalised with pneumonia: a retrospective cohort study in Kenya.

INTRODUCTION: There were almost 1 million deaths in children aged between 5 and 14 years in 2017, and pneumonia accounted for 11%. However, there are no validated guidelines for pneumonia management in older children and data to support their development are limited. We sought to understand risk factors for mortality among children aged 5-14 years hospitalised with pneumonia in district-level health facilities in Kenya. METHODS: We did a retrospective cohort study using data collected from an established clinical information network of 13 hospitals. We reviewed records for children aged 5-14 years admitted with pneumonia between 1 March 2014 and 28 February 2018. Individual clinical signs were examined for association with inpatient mortality using logistic regression. We used existing WHO criteria (intended for under 5s) to define levels of severity and examined their performance in identifying those at increased risk of death. RESULTS: 1832 children were diagnosed with pneumonia and 145 (7.9%) died. Severe pallor was strongly associated with mortality (adjusted OR (aOR) 8.06, 95% CI 4.72 to 13.75) as were reduced consciousness, mild/moderate pallor, central cyanosis and older age (>9 years) (aOR >2). Comorbidities HIV and severe acute malnutrition were also associated with death (aOR 2.31, 95% CI 1.39 to 3.84 and aOR 1.89, 95% CI 1.12 to 3.21, respectively). The presence of clinical characteristics used by WHO to define severe pneumonia was associated with death in univariate analysis (OR 2.69). However, this combination of clinical characteristics was poor in discriminating those at risk of death (sensitivity: 0.56, specificity: 0.68, and area under the curve: 0.62). CONCLUSION: Children >5 years have high inpatient pneumonia mortality. These findings also suggest that the WHO criteria for classification of severity for children under 5 years do not appear to be a valid tool for risk assessment in this older age group, indicating the urgent need for evidence-based clinical guidelines for this neglected population

Regular measurement is essential but insufficient to improve quality of healthcare.

Ambrose Agweyu and colleagues argue that large scale improvements in quality of healthcare require strong change management as well as health information systems that can provide continuous and rapid feedbac

Modelling the cost-effectiveness of essential and advanced critical care for COVID-19 patients in Kenya.

BACKGROUND: Case management of symptomatic COVID-19 patients is a key health system intervention. The Kenyan government embarked to fill capacity gaps in essential and advanced critical care (ACC) needed for the management of severe and critical COVID-19. However, given scarce resources, gaps in both essential and ACC persist. This study assessed the cost-effectiveness of investments in essential and ACC to inform the prioritisation of investment decisions. METHODS: We employed a decision tree model to assess the incremental cost-effectiveness of investment in essential care (EC) and investment in both essential and ACC (EC +ACC) compared with current healthcare provision capacity (status quo) for COVID-19 patients in Kenya. We used a health system perspective, and an inpatient care episode time horizon. Cost data were obtained from primary empirical analysis while outcomes data were obtained from epidemiological model estimates. We used univariate and probabilistic sensitivity analysis to assess the robustness of the results. RESULTS: The status quo option is more costly and less effective compared with investment in EC and is thus dominated by the later. The incremental cost-effectiveness ratio of investment in essential and ACC (EC+ACC) was US$1378.21 per disability-adjusted life-year averted and hence not a cost-effective strategy when compared with Kenya's cost-effectiveness threshold (US$908). CONCLUSION: When the criterion of cost-effectiveness is considered, and within the context of resource scarcity, Kenya will achieve better value for money if it prioritises investments in EC before investments in ACC. This information on cost-effectiveness will however need to be considered as part of a multicriteria decision-making framework that uses a range of criteria that reflect societal values of the Kenyan society

Building Learning Health Systems to Accelerate Research and Improve Outcomes of Clinical Care in Low- and Middle-Income Countries.

Mike English and colleagues argue that as efforts are made towards achieving universal health coverage it is also important to build capacity to develop regionally relevant evidence to improve healthcare

Prevalence and fluid management of dehydration in children without diarrhoea admitted to Kenyan hospitals: a multisite observational study

OBJECTIVES: To examine the prevalence of dehydration without diarrhoea among admitted children aged 1-59 months and to describe fluid management practices in such cases. DESIGN: A multisite observational study that used routine in-patient data collected prospectively between October 2013 and December 2018. SETTINGS: Study conducted in 13 county referral hospitals in Kenya. PARTICIPANTS: Children aged 1-59 months with admission or discharge diagnosis of dehydration but had no diarrhoea as a symptom or diagnosis. Children aged <28 days and those with severe acute malnutrition were excluded. RESULTS: The prevalence of dehydration in children without diarrhoea was 3.0% (2019/68 204) and comprised 15.9% (2019/12 702) of all dehydration cases. Only 55.8% (1127/2019) of affected children received either oral or intravenous fluid therapy. Where fluid treatment was given, the volumes, type of fluid, duration of fluid therapy and route of administration were similar to those used in the treatment of dehydration secondary to diarrhoea. Pneumonia (1021/2019, 50.6%) and malaria (715/2019, 35.4%) were the two most common comorbid diagnoses. Overall case fatality in the study population was 12.9% (260/2019). CONCLUSION: Sixteen per cent of children hospitalised with dehydration do not have diarrhoea but other common illnesses. Two-fifths do not receive fluid therapy; a regimen similar to that used in diarrhoeal cases is used in cases where fluid is administered. Efforts to promote compliance with guidance in routine clinical settings should recognise special circumstances where guidelines do not apply, and further studies on appropriate management for dehydration in the absence of diarrhoea are required