Background
Access to prompt and effective malaria diagnosis and treatment is one of the foundations of malaria prevention and control strategies [
1]. While substantial progress has been made in reducing malaria burden since mass intervention scale-up in the early 2000s, progress has since stalled [
2]. It is essential that National Malaria Programs review their performance regularly to assess if existing policies are appropriate, and that patients are receiving quality diagnosis and treatment of malaria [
3]. Effective malaria case management is characterized by parasitological testing of all suspected malaria cases and prompt provision of quality-assured treatment, including identification and management of severe malaria [
4]. Prompt and effective treatment of malaria is particularly important among children under 5 years; this age group accounted for 61% of global malaria deaths in 2017 [
2]. Use of confirmatory diagnostics and ensuring appropriate dosing of quality-assured first-line antimalarials improves malaria treatment outcomes and reduces the risk of drug resistance. Improved algorithms for management of patients who test negative for malaria are also important in management of acute febrile illness more broadly [
5].
Mali adopted a policy of artemisinin-based combination therapy (ACT) for treatment of uncomplicated malaria in 2005, replacing chloroquine [
6]. Artemether-lumefantrine (AL) is the first-line ACT, with artesunate-amodiaquine (AA) the second-line. National treatment guidelines indicate that children with severe malaria should receive an injection of either artesunate, artemether, or quinine (according to availability), followed by a full dose of ACT as soon as they are able to safely take oral medication [
7].
The public health system in Mali is divided into 65 functional health districts, with each health district comprising one referral health center (
Centres de Santé de Réference, CSRef) and multiple community health centers (
Centres de Santé Communautaire, CSCom). The health district is led by a medical chief, with a malaria focal person allocated to every health district. CSRefs comprise the first reference level of the health system, with a second reference level consisting of eight regional hospitals, and third reference level comprising five national reference hospitals. Health system governance is decentralized, with a strong emphasis on community participation to extend health service coverage [
8]. There is a shortage of staff at all levels of the public health system, but particularly at facilities below national level [
8]. A program of “medicalization” of CSComs began in 2011, aiming to appoint medical doctors at CSComs. In 2014, 100% of CSComs in Bamako were staffed by a medical doctor, but only 19–28% of CSComs in the regions of Kayes, Koulikoro, Segou and Sikasso [
9]. CSComs operate on a cost recovery system based on the Bamako Initiative and are managed by community health associations, who are responsible for managing the CSCom staff and operations, paying salaries, purchasing diagnostic and treatment commodities, and collecting income from drug sales and user fees [
8]. Community health workers (CHWs) have been introduced to increase access to basic health services in areas > 5 km from a CSCom, and report to CSComs. CHWs in Mali are supported by various donors including Global Fund, UNICEF and USAID, or by financial incentives from local political authorities. Diagnosis of malaria by rapid diagnostic test (RDT) is free for all, but microscopy diagnosis is free only for children under 5 years (U5) and pregnant women. Malaria treatment is free for U5s and pregnant women at all levels of the health system. Other members of the population must pay for malaria treatment, but the price is kept low to minimize financial barriers to treatment. A 2015 national malaria survey indicated that there were differences in treatment seeking between rural and urban areas: while 67% of children under 5 years with fever in an urban area were taken to a health provider, the equivalent value in rural areas was only 45% of febrile children [
10].
Mali has implemented seasonal malaria chemoprevention (SMC) policies since 2012, reaching national scale in 2017. Children aged 3–59 months receive up to four rounds of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) during the peak malaria season, at one-month intervals. Children with fever on the day of the SMC campaign are tested using an RDT, and those with a positive RDT receive the standard dose of ACT instead of SP and AQ.
Monitoring of malaria case management procedures allows malaria control programs to assess if diagnosis and treatment policies are being followed; particularly the use of confirmatory diagnostics, adherence to test results when prescribing treatment, and choice of appropriate drug and dosing for the patient. While household surveys such as the Malaria Indicator Survey collect information about caregivers’ report of care received by recently febrile (fever in the last 2 weeks) U5s, alternative tools such as health facility surveys and patient exit interviews give a more direct assessment of procedures applied by healthcare providers, and End User Verification surveys (EUV) combine information on commodity availability with review of patient records at facilities. Systems effectiveness approaches combine ACT efficacy, treatment-seeking, malaria testing rate, proportion of test-positives prescribed ACT, and patient comprehension of the ACT regimen [
11,
12]. Other studies evaluating malaria case management have focused on procedures at the facility: assessment of fever or fever history, malaria testing, treatment prescribed and dose [
13,
14].
Limitations in case management identified by previous studies included failure to perform diagnostic testing on all suspected malaria cases [
13‐
15], prescription of antimalarial drugs for test negative patients [
14,
16,
17], or ACT not being prescribed to patients with confirmed malaria [
18,
19]. Additional shortcomings in other settings include ‘poly-pharmacy’ whereby multiple antimalarials are given at once, incorrect dose prescription [
13,
20], and lack of referral/admission or pre-referral treatment for severe malaria [
21]. Presence of substandard or degraded drugs at facilities also impacts case management effectiveness. Stock-out of key commodities, or ‘rationing’ in anticipation of future stock-outs also likely contribute to some of these shortcomings, in addition to the beliefs and preferences of health workers, patients, and caregivers [
22,
23].
Data from supervision visits to health facilities in Mali suggest that adherence to negative test results is lower than adherence to positive results, suggesting lack of trust in test results by health workers [
24]. Stock outs of RDTs are thought to be responsible for underperformance in confirmatory testing, but stock outs of ACT do not appear to be responsible for lack of adherence to positive test results, suggesting either deviation from the case management protocol or record-keeping problems [
25]. EUV in Mali in 2017 found that although some facilities did not follow case management protocols, overall adherence by facilities was good, but 19% of facilities had experienced a stockout of RDTs in the previous month lasting more than 3 days, and 15% had experienced a stockout of one of the ACT doses used for U5s [
26].
Consequences of deficiencies in case management can include increased progression to severe malaria if patients with malaria are not adequately identified and treated; wastage of drugs if prescribed to malaria-negative patients, increasing costs for the malaria control program and reducing supply of drugs for those in need; failure to clear infection or promotion of drug resistance if incorrect drugs or doses are prescribed; and failure to address other potential causes of fever such as typhoid fever, diarrhea and pneumonia.
This paper reports malaria case management practices recorded during a treatment recall validation study in a high transmission setting in Mali, including public health facilities in urban and rural areas, CHW sites, and private health facilities in urban areas [
27]. The aim was to conduct secondary analysis of existing data collected from different types of health provider and locations for a treatment recall validation study to describe malaria testing and treatment practices among febrile U5s. Specifically, we report data on use of parasitological testing among U5s attending with complaint of fever, adherence to diagnostic test result by health workers, medicines prescribed to children in the study, and explore factors associated with deviation from malaria case management guidelines.
Discussion
This study provides a snapshot of management of malaria in febrile children U5 in Mali at urban private and public health facilities and at rural public facilities and community health worker sites. While the primary aim of the original data collection was to explore validity of caregiver recall of drugs received during consultations [
27], this secondary analysis explored malaria diagnostic procedures and medications prescribed in further detail, aiming to describe adherence to national malaria diagnosis and treatment guidelines and to explore factors associated with deviation from guidelines. Use of parasitological testing among the study population of febrile children U5 was inconsistent, with particularly low testing rates at public facilities in rural areas and private facilities in urban areas. The most common deviation from national treatment guidelines was prescription of antimalarial drugs other than ACTs; drugs such as artesunate injection or artemether were given to some children in combination with ACT, and to others in place of ACT. When considering both diagnostic and treatment procedures, more than three-quarters of enrolled febrile children under 5 years received inappropriate malaria case management during their consultation.
Use of parasitological testing varied by type of site, with low testing rates at public rural and private urban facilities in the study. There was some evidence of a decrease in confirmatory testing in the peak transmission season (September–October) compared to the early transmission season (July), which could be attributable to health worker assumptions that fever is more likely attributable to malaria in the peak season, or simply a result of increased patient load and limited human resources for testing. OPSANTE data indicate that while some study facilities experienced low stock or stockouts of RDTs during the study period, this does not fully explain low use of parasitological testing at other facilities and time periods with no apparent RDT stock problems. Failure to use parasitological diagnosis has been identified as one of the main gaps in malaria case management in several other settings [
13‐
15,
31,
32], with some hypothesizing that high patient load at facilities has a detrimental impact on diagnostic testing rates [
13,
15].
In addition to recording microscopy or RDT result, the study collected the health worker’s final diagnosis of malaria or not malaria. Discrepancies where a test was negative but the health worker diagnosed malaria were observed primarily at the public urban health facilities. While there was no association between this type of discrepancy and type of diagnostic, we cannot exclude that there was a lack of trust in both RDT and microscopy, or that specific clinical presentations led to the health worker disagreeing with the test result. While data were not collected on characteristics of health workers, odds of incorrect management were lower at CHW sites than public urban and rural sites, and evidence from other settings indicates that more senior health workers are more likely to deviate from standard case management guidelines [
17]. Interestingly, when reviewing prescription according to the health worker’s diagnosis of malaria or not malaria, irrespective of diagnostic test result, health workers did not consistently give ACT to all children they ultimately diagnosed as malaria cases, and some children that they thought did not have malaria did received antimalarials. This indicates that lack of adherence to treatment guidelines is not solely due to lack of trust in the diagnostic test result, but may reflect health worker or caregiver preference for antimalarial drugs, or a desire to provide antimalarial treatment even if malaria is not thought to be primary cause of current febrile illness. Other studies have found that individual health worker training is more influential in determining adherence to guidelines than commodity supply issues [
33], but the need for health worker autonomy to deviate from guidelines was highlighted in a study in Madagascar [
34], where clinicians justified prescribing antimalarial to test-negative individuals who may have self-treated prior to attending the facility. Patient flow has also been shown to be relevant in some settings, where drugs may be prescribed before laboratory test results are available [
35].
Non-ACT antimalarials were prescribed to febrile children U5 participating in this study, most commonly drugs recommended for treatment of severe malaria: injectable artesunate, artemether or quinine. Children with signs of severe malaria or other severe illness were not eligible for inclusion in the study, and while there is a possibility that children with signs of severe malaria were erroneously included, it is very unlikely that this can explain the full extent of injectable antimalarials in this setting. It is not possible to determine the precise motivations for prescription of non-ACT antimalarials in the current study, but injectables were more commonly prescribed to older children (within the study range of one to 59 months) and those with higher axillary temperatures. It is possible that health workers and caregivers are concerned about severe malaria in this high transmission setting and consequently take a cautious approach to treatment of malaria in under-fives, choosing to give drugs for severe malaria to those perceived to be at higher risk of progression to severe disease. The use of injectables could also be explained by caregiver or clinician preferences for injectables over oral drugs [
34]. The use of injectable antimalarials in the current study is in contrast to findings from other settings. ACT Consortium studies across five countries found a substantial proportion of patients with confirmed uncomplicated malaria receiving drugs other than ACTs; but most commonly amodiaquine, chloroquine or SP rather than injectable antimalarials [
19]. Two studies in Sudan identified relatively high proportions of children with uncomplicated malaria receiving injectable quinine [
36], but with receipt of injectables more frequent in those over five than under 5 years [
37]. Monotherapy was also more common in those aged older than five in studies in Nigeria [
15] and Equatorial Guinea [
18].
When monotherapy is prescribed for severe malaria, parenteral drugs should be given for a minimum of 24 h and always followed by a full oral course of ACT [
4,
38]. While some children in this study were prescribed both ACT and an injectable, some received only the injectable. No follow up data are available to determine if children given injectable monotherapy subsequently returned to the facility for a course of ACT. A further factor that should be considered when interpreting prescription practices is the cost-recovery model used at health facilities in Mali. Both diagnostic testing and ACT are free for children under 5 years, but other antimalarial drugs and injectable drugs generally require payment. Drug and service charges support the facility operating costs, therefore there may be economic motivations from health workers to prescribe additional drugs for children under five with malaria. Prescribing artemisinin monotherapies intended for severe malaria drugs to patients with uncomplicated malaria is a concern due to risk of drug resistance [
39,
40], particularly when injectable monotherapy is not followed by a full course of ACT, but also has immediate consequences in increased wastage and drug costs for the facilities, and represents an increased risk to the patient due to use of an invasive treatment when safe and effective oral drugs are available.
Polypharmacy was common in this study, particularly the prescription of an antimalarial drug together with an antibiotic. This finding likely reflects the challenge of managing febrile illness in children in a high malaria transmission setting, where
P. falciparum parasite rate by RDT in children aged six to 59 months was estimated at 25.5% in 2015 [
10]. In such settings, health workers must assess if clinical signs and symptoms are due to malaria or another cause. Prescription of multiple drugs for uncomplicated malaria was found to be common in Nigeria, with antimalarials often prescribed in combination with analgesics, antibiotics or vitamin preparations, leading to concerns about potential drug interactions [
15]. In Tanzania, U5s were more commonly prescribed antimalarials and antibiotics together than older children [
41], while a study in Burkina Faso found that antibiotics are prescribed to 84% of all U5s attending rural public health facilities in the dry season [
42]. Challenges remain in management of febrile illness in the tropics, particularly in rural areas with limited diagnostic capacity [
43]. In the current study, the prescription of antimalarials to children with negative malaria test could be an indication of lack of alternative diagnostic tools to determine fever etiology, consequently these children may not be treated for the true cause of their fever. Antibiotic prescription has been shown to increase following scale up of RDTs and increased malaria testing, however, this has prompted concerns regarding use of appropriate antibiotics for the most common bacterial causes of fever, and over-use of antibiotics promoting development of antimicrobial resistance [
44]. Identification of biological markers of severe disease or likelihood of progression to severe disease could be of great value, allowing health workers to identify children who require rapid referral, admission or supportive care [
45]. Ongoing research using electronic decision trees in combination with point of care tests and clinical signs show promise in improving health workers’ ability to identify severe disease and prevent unnecessary antibiotic prescription [
46], but further evidence is required.
Description of malaria case management practices in Mali was not the primary aim of the study which collected these data, therefore the findings presented are limited by failure to collect additional indicators which would have been of interest to the current analysis. Description of health worker characteristics (gender, qualifications, years of experience, role at facility), consistent recording of drug formulation type or administration route, and stock of malaria drugs and diagnostic materials at the facilities could have added useful detail to the current study and aided interpretation of results. Additional description of patient clinical signs and comorbidities would also have aided interpretation of drug choices made by health workers, particularly in relation to co-prescription of antimalarials and antibiotics, or the use of injectable antimalarials. All data describing diagnostic method used, test results and drugs prescribed were recorded by the health worker without independent validation. Additionally, no follow up data were collected to determine if children given injectable monotherapy subsequently returned to the facility for a full course of ACT. While study team members were present at the facilities, they did not observe the consultation or conduct exit interviews with caregivers to avoid introducing bias in the primary study assessing caregiver recall of treatment, and there was no independent validation that children with signs of severe disease were excluded. Finally, this study is limited by the relatively small number of health facilities and health workers participating, therefore the findings may not be generalizable to the broader context in Mali.
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