Integrated paediatric fever management and antibiotic over-treatment in Malawi health facilities: data mining a national facility census

Since the 1990s, the World Health Organization (WHO) and United Nations Children’s Fund (UNICEF) have promoted the Integrated Management of Childhood Illness (IMCI) strategy in low- and middle-income countries to effectively manage the most common causes of child morbidity and mortality in an integrated manner [1]. It is well recognized that integrated protocols are critical for optimally managing the sick child in order to address co-morbidities and to differentiate among illnesses with overlapping symptoms [2].

Fever is a common symptom of many childhood illnesses in sub-Saharan Africa. For many years however, the IMCI strategy promoted presumptive malaria treatment of paediatric fevers in malaria-endemic African settings given high malaria mortality rates and the lack of other defining features for clinical management. While additional IMCI algorithms have been available to clinically differentiate other fever causes, the presumption of all fevers as ‘malaria’ has often impeded probing for these other conditions [3].

In 2010, WHO revised malaria treatment guidelines to recommend diagnosis of all suspected malaria cases prior to treatment given the increasing availability of malaria rapid diagnostic tests (RDT) [4]. This policy shift has great potential to improve rational drug use and quality fever care [5], although studies indicate common inappropriate treatment of RDT-negative patients with anti-malarial or antibiotic drugs [6]. These findings suggest poor integration of RDT into the IMCI framework, although few studies have explicitly examined integrated paediatric fever management and available evidence is largely derived from limited hospital settings [7‐12]. There is also limited understanding of factors associated with non-adherence to clinical guidelines, notably antibiotic over-treatment, which is a particular concern in the era of test-based malaria case management [13]. This concern reflects studies showing widespread antibiotic prescriptions for test-negative cases and not according to established clinical guidelines [1, 6, 8].

Malawi recently adopted the ‘test and treat’ strategy in its National Malaria Strategic Plan and began nationwide RDT deployment in July 2011 [14]. A national facility study conducted prior to RDT implementation showed low availability of functional microscopy for malaria diagnosis [15], and common non-compliance to negative blood smear results [16]. Similar evidence is needed from the post-RDT implementation period in Malawi with an expanded analysis of how RDT and IMCI are used together during outpatient consultations.

In this paper, a national facility census conducted in Malawi in 2013–2014 was analyzed to examine integrated paediatric fever management using RDT and IMCI, including other presenting complaints, completed assessments, diagnoses/classifications, and treatment prescriptions [17]. The large number of facilities audited coupled with the broad data collection scope provides a unique opportunity to investigate the association between RDT results and antibiotic over-treatment. Classification trees are well suited for such an analysis since numerous influences on different levels may shape the complex nature of the clinical encounter and there may be complicated inter-relationships among variables that are not well defined in advance or easily detected using standard statistical methods [18]. Indeed, traditional regression models assume a uniform influence of the exposure on an outcome unless an interaction is specified, which is unrealistic in real-life contexts and complicates results interpretation. It is also a challenging situation to model if numerous variables may influence an examined relationship and there is limited a priori knowledge of these potentially complex interactions in order to define a clear hypothesis for statistical testing.

The Malawi Service Provision Assessment 2013–2014 included 977 facilities out of 1060 on the Ministry of Health master facility list with non-response due to refusal (3 %), closure (2 %), inaccessibility (2 %), or other issue (1 %). A total of 2950 sick child clients met inclusion criteria and 1981 reported fever complaints (Fig. 1). Additional files 1, 2 describe characteristics of febrile clients with RDT results and receiving antibiotic over-treatment respectively.

Integrated paediatric fever management was sub-optimal in terms of fever assessments completed and poor antibiotic targeting, although findings suggest common compliance to malaria treatment guidelines. The RDT negative result was strongly associated with antibiotic over-treatment conditioned by CDB complaints.

In this study, only 6 % of clients with fever complaints had no other complaint or danger sign underscoring the critical need for integrated protocols to manage sick children [1‐3]. It was further shown that most clients with fever complaints received a malaria test or were referred for diagnosis, and RDT-guided malaria treatment seemed common according to provider reports. This finding suggests compliance with new malaria treatment guidelines in Malawi in 2013–2014 and contrasts with previous studies showing poor adherence to negative blood smear readings prior to nationwide RDT deployment [16]. This result should be viewed in light of data limitations described later in this section and additional studies are needed to corroborate this finding.

Yet general fever assessments were less commonly conducted despite being essential for differential diagnosis. This finding is consistent with other research showing poor IMCI implementation in Malawi and other settings [28, 29]. There was also poor antibiotic targeting with both under- and over-treatment that is in part due to poorly assessing clients to identify antibiotic need. Poor antibiotic targeting in low-income settings has been documented in other research [7‐12]. This study, however, is the first to our knowledge to provide large-scale evidence of integrated paediatric fever management using RDT and IMCI during outpatient consultations, including the important relationship between RDT results and antibiotic over-treatment.

These findings demonstrate the strong influence of RDT-negative results on antibiotic over-treatment and an inter-relationship with CDB complaints, which reinforces the primary importance of patient symptoms and diagnostic test results on clinical treatment decisions. This is consistent with research showing widespread antibiotic prescriptions for RDT-negative cases [8‐11], and cough complaint as a main predictor of incorrect malaria treatment in Malawi [16]. The relatively small sample size may have limited detection of other inter-relationships, notably over-treatment previously documented among urban clients [30]. Nevertheless, data mining tasks are well suited to discover inter-relationships among variables with respect to an outcome, particularly if there is limited a priori knowledge of these associations [18]. These methods have been widely used in business and biomedical research but their application in global health research has been limited and should be increasingly considered where appropriate [31‐35].

Taken together, these results underscore growing concerns about irrational antibiotic prescription practices in the era of test-based malaria case management [13], particularly given recent research showing viral disease is a far more common cause of paediatric fevers in various African settings compared to bacterial or parasitic infections [36, 37]. A recent World Health Assembly resolution urges countries to develop action plans to combat antibiotic resistance in the coming years [38]. A main focus for low-income countries will be to extend the reach of health systems to expand access to life-saving medicines while simultaneously strengthening quality care at facilities that could in turn improve antibiotic targeting [39]. These results highlight the need to implement IMCI and RDT together to strengthen integrated paediatric fever management and rational use of both anti-malarial and antibiotic medicines.

To this end, the IMCI algorithm has been adapted to reflect test-based malaria treatment guidance, and there are efforts to further strengthen these guidelines based on recent etiology studies [36, 37], and in recognition of its poor implementation to date [29]. However, this new IMCI adaptation lacks clarity on antibiotic indications in the fever algorithm that could in turn inadvertently promote antibiotic over-treatment [40], which has been demonstrated in other recent research [9]. It is critical that IMCI guidelines clearly indicate when antibiotics are (or are not) recommended for sick children, particularly for RDT-negative cases, and additional review of these guidelines from this perspective may be needed.

These results should be viewed in light of data limitations. First, client selection is based on sick child attendance on the interview date and do not represent clients visiting facilities on different dates/seasons, nor all sick children in Malawi. Second, providers may perform better during observations than in routine conditions biasing results towards better practices, including RDT compliance [41]. Third, assessments recorded do not include all IMCI fever assessments, notably asking about fever duration or measles history. There is also no recording of assessment quality or clinical findings. Fourth, it may be difficult for observers to recognize that certain assessments were conducted, such as checking for neck stiffness, which could underestimate results. Fifth, the re-examination was a limited protocol that only assessed the sick child for a raised respiratory rate, signs of anaemia and fever presence based on a thermometer reading. Other assessments that could potentially indicate pneumonia or antibiotic need were not assessed in the re-examination, such as chest indrawing or hypoxia.

Measurement limitations for main predictors and the outcome should also be highlighted. First, RDT results are based on provider reports without supporting documentation. The provider reports RDT results after providing information on diagnoses and prescriptions. Some providers may misreport a negative result as positive if anti-malarial medicines were prescribed to seem in compliance with guidelines. Misclassification of the positive result as negative seems less likely in this scenario. This could potentially explain common RDT compliance found in this assessment and these results should be corroborated by additional studies. Second, RDT compliance estimates are only for clients diagnosed by the consultation time and do not include blood smear or RDT results not available by the initial consultation. Facilities conducting RDT prior to the consultation may be systematically different from other facilities in ways that influence compliance, such as larger facilities with more staff and better quality care. Third, antibiotic over-treatment is notoriously difficult to measure in settings without diagnostics to differentiate bacterial from other pathogenic causes. This paper defines ‘need’ according to IMCI antibiotic indications for pneumonia and provider reported diagnostic categories requiring antibiotics: sepsis, dysentery, mastoiditis, acute ear infection, abscess, or severe malnutrition. Urinary tract infection is not a diagnostic category and is not included in this definition. Clients assigned these diagnoses may not have the underlying condition and may not need antibiotics. The ‘without antibiotic need’ definition in this study therefore underestimates true lack of need. Fourth, IMCI pneumonia can be difficult to assess even by a trained provider leading to some misclassification in either direction [42].

Based on 977 facilities and 1981 eligible clients, study findings demonstrate sub-optimal integrated paediatric fever management practices in Malawi health facilities in 2013–2014. While malaria-specific assessments and RDT-guided treatment seemed common, other fever assessments were not often completed and poor antibiotic targeting was demonstrated. RDT-negative results were strongly associated with antibiotic over-treatment conditioned by CDB complaints. These results suggest moving beyond malaria-focused ‘test and treat’ strategies toward ‘IMCI with testing’ to improve quality fever care and rational use of both anti-malarial and antibiotic medicines. Integrated paediatric fever management using RDT and IMCI together is critical to improve antibiotic targeting in line with recent commitments to combat antibiotic resistance, and should be considered for inclusion in national action plans developed by malaria-endemic African countries in the next year.