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Erschienen in: Malaria Journal 1/2021

Open Access 01.12.2021 | Research

Factors associated with access and adherence to artemisinin‐based combination therapy (ACT) for children under five: a secondary analysis of a national survey in Sierra Leone

verfasst von: Kristin Banek, Emily L. Webb, Emily Bostick Doogue, Samuel Juana Smith, Daniel Chandramohan, Sarah G. Staedke

Erschienen in: Malaria Journal | Ausgabe 1/2021

Abstract

Background

Access and adherence to artemisinin-based combination therapy (ACT) are key challenges to effective malaria treatment. A secondary analysis of the Sierra Leone malaria Knowledge, Attitudes, and Practices (mKAP) survey was conducted to investigate access and adherence to ACT for the treatment of fever in children under-five.

Methods

The mKAP was a nationally representative, two-stage cluster-sample survey, conducted in 2012. Thirty primary sampling units per district were randomly selected using probability proportionate to size, based on national census estimates; 14 households were subsequently randomly selected and enrolled per sampling unit. The analysis was restricted to children under-five with fever in the past two weeks. Factors associated with access and adherence were assessed using multivariate logistic regression.

Results

Of 5169 enrolled households, 1456 reported at least one child under-five with fever in the past two weeks. Of the 1641 children from these households, 982 (59.8%) received any treatment for fever and were analysed for access to ACT; 469 (47.6%) received ACT and 466 were analysed for treatment adherence. Only 222 (47.4%) febrile children received ACT and completed 3-day treatment. In an adjusted analysis, factors associated with ACT access included knowledge of ACT (odds ratio [OR] 2.78, 95% CI 2.02–3.80; p < 0.001), knowledge of insecticide-treated nets (ITNs) (OR 1.84, 95% CI 1.29–2.63; p = 0.001), source of care (public health facility vs. other; OR 1.86, 95% CI 1.27–2.72, p = 0.001), geographic region (East vs. West; OR 2.30, 95% CI 1.20–4.44; p = 0.025), and age (24–59 vs. 0–23 months; OR 1.45, 95% CI 1.07–1.96; p = 0.016). The only factor associated with ACT adherence was time to treatment; children treated within 24 h were less likely to adhere (OR 0.55, 95% CI 0.34–0.89; p = 0.015).

Conclusions

In 2012, access and adherence to ACT remained low in Sierra Leone. Knowledge of ACT and ITNs, and seeking care in the public sector, were most strongly associated with ACT access. National surveys provide important information on anti-malarial access and could be expanded to measure treatment adherence.
Hinweise

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Abkürzungen
ACT
Artemisinin-based combination therapy
AL
Artemether–lumefantrine
AOR
Adjusted odds ratio
AQAS
Fixed-dose combination amodiaquine–artesunate
AQ+AS
Co-packaged amodiaquine plus artesunate
CRS
Catholic Relief Services
DHS
Demographic Health Survey
FHCI
Free Health Care Initiative
GFATM
The Global Fund to Fight AIDS, Tuberculosis, and Malaria
ITN
Insecticide-treated net
KAP
Knowledge, attitudes, and practices
MIS
Malaria Indicator Survey
MICS
Multiple Indicator Cluster Survey
mKAP
Malaria Knowledge, Attitudes, and Practices Survey
NMCP
National Malaria Control Programme
OR
Odds ratio
PCA
Principal component analysis
PPS
Probability proportional to size
PSU
Primary sampling units
WHO
World Health Organization
95% CI
95% confidence interval

Background

Malaria remains a serious health problem in sub-Saharan Africa and is particularly dangerous for children under-five [13]. Prompt access to effective treatment is critical to malaria control. The World Health Organization (WHO) malaria treatment guidelines recommend that all laboratory-confirmed malaria cases be treated promptly (within 24 h of onset) using artemisinin-based combination therapy (ACT) [4]. Despite this recommendation, access to prompt and effective treatment remains sub-optimal (on average, 65%) across sub-Saharan Africa [3]; with access to ACT influenced by availability, affordability, and acceptability [5]. Weak health systems are adversely impacted during global public health emergencies, such as Ebola and COVID-19, leading to disruptions in service provision, supply chain, and health-seeking behaviour [6, 7]. During the Ebola outbreak 2014–2015 in Sierra Leone, pre-existing gaps in reporting and service delivery worsened [8], and changes to service delivery had a lasting impact on access in neighbouring Liberia [9]. Although access to ACT is essential, multiple factors influence the effectiveness of treatment, including the efficacy of ACT regimens, targeted testing and treatment, and patient (or caregiver) adherence to treatment [10, 11].
In Sierra Leone, malaria is the leading cause of morbidity and mortality in children under-five, accounting for 47% of outpatient visits [12]. Although amodiaquine plus artesunate (AQ + AS) was recommended as the first-line treatment for uncomplicated malaria in 2004 [13], access to ACT remained low, with only 19.2% of children with fever receiving ACT in 2010 [14]. Furthermore, probable adherence to co-packaged AQ + AS in Sierra Leone was reported to be only 48.7% in 2008 [15]. In the 2016 Malaria Indicator Survey (MIS), 40% of children aged 6–59 months tested positive for malaria; parasite prevalence was twice as high in rural compared to urban areas (49% vs. 25%) and was highest in the northern region (52%) [16].
In 2010, the government of Sierra Leone recognized the importance of improving access to essential medications, including anti-malarials, to reduce childhood morbidity and mortality. Two initiatives were rolled out to improve access to health care: (1) The Free Health Care Initiative (FHCI), which provides services and medications free of charge to pregnant women, lactating mothers and children under five at government health facilities along with supportive supply-side interventions, such as improved drugs and medical supply chains; health workforce strengthening; governance; infrastructure for service delivery; communication; monitoring and evaluation; and health financing [17]; and (2) a malaria treatment policy advocating for free malaria testing and treatment with ACT for all malaria cases [18].
These initiatives only addressed health system factors that impact access and targeting of ACT, steps at the beginning of the effectiveness pathway, and did not focus on the quality of care provided [10, 11, 19]. To be truly effective, health workers must follow malaria treatment guidelines, and patients and caregivers must adhere to the prescribed ACT regimens. If these last steps of the pathway, focusing on adherence, are not realized, effective treatment and control of malaria cannot be achieved. Therefore, it is critical to measure and understand factors associated not only with access, but also adherence to ACT.
Although a number of national surveys between 2013 and 2016 documented access to ACT in Sierra Leone, ranging from 77–97% [14, 16, 20, 21], none of these surveys measured treatment adherence nor factors associated with access and adherence to ACT. In 2012, a nationwide malaria knowledge, attitudes, and practices (mKAP) survey was carried out in Sierra Leone, which included not only questions about treatment access but also treatment adherence [22]. To further explore access and adherence to ACT, a secondary analysis of the mKAP dataset was conducted to quantify, and determine factors associated with, access and adherence to ACT in Sierra Leone.

Methods

Study design

The mKAP was conducted in 2012 by Catholic Relief Services in partnership with the National Malaria Control Programme (NMCP), supported by Statistics Sierra Leone. The primary objective of the survey was to gather information to inform and update the national malaria communication strategy. Additionally, data from the survey was used to establish a baseline for malaria control activities that were to be subsequently implemented with support from the Global Fund to Fight AIDS, Tuberculosis, and Malaria [22]. This study is a secondary analysis of a subset of data collected from the mKAP survey.
The mKAP survey was a nationally representative two-stage cluster sample survey conducted in all 14 districts of Sierra Leone. Thirty primary sampling units (PSU) per district were randomly selected using probability proportional to size (PPS) based on estimates from the National Census [23]. This resulted in 5880 randomly chosen households (14 households per PSU; 420 households per district). The questionnaire was based on the Roll Back Malaria standardized guidelines for core population-level indicators [24]. All respondents answered questions about household demographics and assets, malaria knowledge and prevention practices, recent pregnancy experiences, and whether the household contained one or more children aged under-five who had a fever in the previous two weeks. Information on fever treatment was collected on up to three such children per household. The mKAP survey was conducted in 2012 before a question about receiving a blood test was universally introduced into national surveys, and therefore did not include a question on whether the child had “blood taken from his/her finger or heel for testing.”

Data collection

Data were collected by trained field staff using Apple iPhones provided by Catholic Relief Services. The devices were programmed using the iFormBuilder mobile platform (Zerion Software, Inc., Herndon, VA, USA) [25]. All electronic data were transferred from the Apple devices into a cloud database regularly while in the field using the local 3G mobile network. Upon completion of the fieldwork, any remaining forms that needed to be transferred were uploaded via wireless internet connections at Statistics Sierra Leone and Catholic Relief Services offices in Freetown.
Paper questionnaires were provided to teams to use only as a backup in case of electronic equipment failure. When necessary, data entered onto paper forms were then entered into an iPhone as soon as it was possible. Backup files of the database were stored on two external servers (iFormBuilder and a specially created Google email account). Additionally, data were stored on the iPhones until completion of the study. For quality control, validation and built-in skip logic were written into the iFormBuilder program.

Outcome variables and predictors

The objectives of this study were: (1) to quantify the level of access and adherence to ACT in children less than five in Sierra Leone, (2) to assess factors associated with access to ACT for children under-five with fever in the two weeks preceding the survey, and (3) to identify factors associated with adherence to ACT in those children that received ACT for their fever. Access was defined as receiving ACT for the treatment of the most recent fever. Adherence was defined as taking the treatment for the recommended 3 days. The methodology used to assess adherence was similar to that used in two previous cross-sectional household studies in Kenya, which utilized a self-report question to assess whether the duration of treatment with ACT was correct (i.e. 3 days) [26, 27]. Those taking ACT for 3 days were considered to have completed treatment and were classified as adherent, while those taking ACT for less than 3 days or more than 3 days were classified as non-adherent.
Using the available variables from the survey dataset, along with the factors identified in the ACT adherence literature, a list of a priori predictors were identified and evolved into a conceptual framework (Fig. 1). Four categories of potential predictors of access and adherence were identified: (1) socioeconomic status (i.e. wealth class and education); socio-demographic characteristics (i.e. child age, religion, household size, place of residence); (2) knowledge of malaria (i.e. knowledge of protective measures and treatments); and (3) health practices (i.e. accesses prompt treatment for fever, ITN utilization, and source of health care).

Data analysis

Stata Version 12 (StataCorp, College Station, TX USA) and Excel (Microsoft Corp. Redmond, WA, USA) were used for data processing and analysis. In all analyses, the “svy” commands were used to account for the survey design, including clustering by PSU and stratification by the location of the PSU (urban/rural). Descriptive statistics were used to summarize household and respondent characteristics as well as treatment-seeking behaviour for children with fever. Household socioeconomic status was based on a principal component analysis (PCA) of household assets, split into tertiles [28].
Logistic regression models were used to estimate the crude and adjusted odds ratios and their 95% confidence intervals to assess the strength of the association between the a priori predictors and the two outcomes (access and adherence to ACT). All predictor variables were included in multivariable analyses regardless of p-values, with the exception that for any pair of covariates identified to be strongly correlated (Pearson’s correlation r ≥ 0.8), one was removed from the final model. Associations between the predictors and outcomes were considered significant if the p-value was < 0.05.

Ethical considerations

The original study protocol was approved by the Sierra Leone Ethics and Scientific Review Committee prior to the commencement of activities. Ethical approval to conduct this secondary analysis of the mKAP data set was obtained from the London School of Hygiene & Tropical Medicine. Permission to use this data for secondary analysis was obtained from CRS and the NMCP in Sierra Leone.

Results

Survey profile

Of 5169 enrolled households, 1456 reported at least one child under-five with fever in the past two weeks and were included in the analysis (Fig. 2). Access to ACT was assessed in 1641 children residing in these households who had a recent history of fever and data on treatment available. Of these children, factors associated with access to ACT were estimated for children whose caregiver sought and received any treatment for their child’s fever (n = 982). Factors associated with adherence to ACT were assessed for children who received ACT and had data on treatment duration (n = 466).

Characteristics of households and their children

Overall, households that reported fever in a child under-five within the past two weeks were similar to other households, as were the adult respondents from these households (Table 1). Households with febrile children were primarily located in rural areas (87.6%), practiced the Islamic faith (81.0%), and owned at least one bed net of any type (87.2%). The average age of the adult caregiver respondents was 39.2 years, and 66.8% reported not having any formal education. Three out of four adult respondents (76.6%) reported sleeping under an insecticide-treated net (ITN) the previous night. Although most respondents were knowledgeable about malaria, some information gaps were identified, specifically regarding the prevention and treatment of malaria. Only 606 (41.8%) respondents were aware that ACT was the recommended treatment for malaria.
Table 1
Household and individual-level characteristics of survey participants, stratified by the presence or absence of a child under five with fever in the preceding 2 weeks
Variable
Categories
Under-five Households with fever (N = 1456)
Under-five Households without fever (N = 1199)
n(%)
95% CI
n(%)
95% CI
Household
 Location
Urban
191 (12.4%)
10.6–14.4%
184 (14.8%)
12.8–17.0%
Rural
1265 (87.6%)
85.6–89.4%
1015 (85.2%)
83.0–87.2%
 Region of Sierra Leone
North
672 (46.9%)
41.4–52.5%
368 (30.6%)
25.8–35.9%
South
371 (25.4%)
21.1–30.3%
427 (35.7%)
30.4–41.4%
East
291 (19.5%)
15.7–24.1%
236 (19.8%)
15.9–24.5%
West
122 (8.2%)
5.8–11.3%
168 (13.9%)
10.6–18.0%
 Number of household residents
1–5
430 (29.3%%)
26.5–32.2%
440 (36.6%)
33.6–39.8%
6–10
795 (54.7%)
51.8–57.5%
602 (50.4%)
47.3–53.5%
11+
231 (16.1%)
13.9–18.5%
157 (12.9%)
11.0–15.2%
 Religion
Christian
284 (19.0%)
16.2–22.2%
261 (21.9%)
18.9–25.4%
Muslim
1172 (81.0%)
77.8–83.8%
938 (78.1%)
74.8–81.2%
 Socio-economic status
1 (poorest)
508 (35.4%)
31.9–39.0%
400 (33.4%)
30.0–37.1%
2
532 (36.2%)
33.3–39.1%
410 (34.2%)
31.2–37.4%
3 (least poor)
416 (28.5%)
25.2–31.9%
389 (32.3%)
28.6–36.3%
 Ownership of bed nets
Own any net
1272 (87.2%)
10.1–15.1%
1045 (86.9%)
84.4–89.1%
Net is an ITN
1214 (83.1%)
80.5–85.5%
989 (82.2%)
79.2–84.9%
Mean ITNs
2.6
2.5–2.8
2.5
2.4–2.6
Household adult respondents
 Mean age (years)
 
39.2
38.4–40.1
38.7
37.8–39.6
 Gender
Male
684 (47.1%)
44.0–50.2%
577 (48.2%)
45.0–51.5%
Female
772 (52.9%)
49.8–56.0%
622 (51.8%)
48.5–55.0%
 Education
None
967 (66.8%)
63.9–69.6%
779 (64.7%)
61.4–67.9%
Primary
173 (11.8%)
10.1–13.8%
124 (10.7%)
8.9–12.7%
Secondary/highera
279 (18.7%)
16.4–21.2%
277 (23.0%)
20.3–25.9%
Arabic/Other
37 (2.7%)
1.9–3.8%
19 (1.7%)
1.0–2.8%
 ITN use previous night
Respondent
1129 (76.6%)
73.7–79.3%
913 (76.2%)
72.9–79.2%
Knowledge of malaria-related topics
 Ever hear of the illness called “Malaria”
Yes
1492 (98.1%)
97.0–98.8%
1167 (97.4%)
96.1–98.3%
 At least one sign or symptom of malaria
Yes
1374 (94.2%)
92.5–95.6%
1116 (93.0%)
91.1–94.6%
 All are susceptible to malaria
Yes
1065 (73.2%)
70.3–75.9%
884 (73.4%)
70.3–76.3%
 At least one malaria protective measure
Yes
1244 (85.2%)
82.6–87.5%
1026 (85.4%)
82.7–87.8%
 ITNs can prevent malaria
Yes
865 (59.6%)
56.3–62.9%
741 (60.9%)
57.1–64.5%
 At least one antimalarial drug
Yes
1268 (86.9%)
84.7––88.8%
1021 (85.1%)
82.5–87.3%
 Recommended treatment with ACTs
Yes
606 (41.8%)
38.5–45.3%
527 (43.7%)
40.2–47.2%
aSecondary or higher includes technical and vocational school

Treatment for children under‐five with fever

Of the 1641 children under-five with a fever episode in the last 2 weeks, care was sought for 1038 (63.4%) (Table 2). The majority of children (82.2%) were taken to a public health facility. Of those children for whom treatment was sought, most (n = 982) received any treatment, the majority of which were anti-malarials (n = 780). Of these children, 469 (47.6%) received ACT, most of whom (n = 314; 67.8%) were treated within 24 h of onset. Only 222 (47.4%) children with fever received ACT and completed 3-day treatment, and only 137 (31.6%) received prompt treatment (within 24 h) with ACT and completed the 3-day treatment.
Table 2
Treatment and treatment-seeking behaviors for children under-five with fever (n = 1641)
 
Observations
n/N
%
Linearized SE
95% CI
Treatment seeking for fever
 Caregiver sought treatment
1038/1641
63.4 %
1.67%
60.1–66.6%
 Caregiver sought prompt treatment ( 24 h)
571/1038
55.9%
1.87%
52.2–59.6%
First treatment sourcea
 Public health facility
854/1038
82.2%
1.48%
79.1–84.9%
 Otherb
184/1038
17.8%
1.48%
15.1–20.9%
Treatment of fever
 Received any treatment
982/1038
94.6%
0.83%
92.7–96.1%
Type of treatment
 Artemisinin combination therapy (ACT)
469/982
47.6%
2.11%
43.4–51.7%
 Chloroquine
472/982
48.7%
2.19%
44.5–53.1%
 Sulfadoxine-pyrimethamine (SP)
153/982
15.0%
1.37%
12.5–17.9%
 Paracetamol
770/982
78.4%
1.67%
74.3–80.9%
 Herbs
141/982
14.4%
1.36%
11.6–17.0%
 Otherc
136/982
13.5%
1.32%
11.1–16.3%
ACT treatment timed
 Received ACT same/next day ( within 24 h)
314/469
67.8%
2.33%
63.0–72.2%
 Received ACT on day 2
93/469
19.4%
2.00%
15.8–23.7%
 Received ACT 3 + days
29/469
6.0%
1.07%
4.2–8.5%
 ACT treatment time unknown
33/469
6.8%
1.21
4.8–9.6%
ACT durationd
 Took ACT for 3 days (correct duration)
222/469
47.4%
2.56%
42.4–52.4%
 Did not take ACT for 3 days
244/469
52.0%
2.53%
47.1–57.0%
 ACT duration unknown
3/469
0.57%
0.03%
0.19–1.74%
 Mean duration of ACT treatment (days)
 
3.62
0.80
3.47–3.78
Prompt and effective treatment with ACTe
 Children who received ACT < 24 h & Completed 3-day treatment course
137/433
31.6%
2.57%
27.3–37.4%
aThe denominator is the number seeking treatment for the fever in the last 2 weeks (n = 1038)
bOther sources of treatment include: Community Health workers [Community Health Worker (CHW), Traditional Birth Attendant (TBA), Blue Flag Volunteer (BFV)] = 39; Informal Health workers (drug peddler, traditional healer) = 31; Drug shops/Pharmacy = 96; private clinics/doctors = 9 and self-treatment = 9
cOther drugs received include other antimalarial–mono-therapy: quinine and amodiaquine (4), antibiotics (34), antidiarrheal/ORS (17), other antipyretic (7), cough medicine (2), deworm (1), vitamins (12), iron (16), unnamed syrup (6), injection (11), routine medication (10), unspecified/unknown (16)
dThe denominator is the number who received ACT (n = 469)
eThe denominator is the number who received ACT and who have information on the timing and duration of treatment (n = 433)

Factors associated with access

In a multivariate analysis restricted to children who received any treatment for fever (n = 982), five factors were found to be significantly associated with receiving ACT (access), including geographic region, the knowledge that ITNs protect against malaria, knowledge of ACT, older child age, and seeking care at a public health facility (Table 3). ACT access was highest in the eastern region. Knowledge of ACT was the strongest predictor; children with caregivers who were knowledgeable about ACT had almost three times the odds of receiving an artemisinin-based combination for treatment of fever than children whose caregivers lacked this knowledge (OR: 2.78; 95% CI 2.02–3.80; p < 0.001). Similarly, children whose caregiver knew that ITNs provide protection from malaria were more likely to receive ACT (OR: 1.84; 95% CI 1.29–2.63; p = 0.001). Children treated at a public health facility had nearly twice the odds of receiving an artemisinin-based combination compared to those treated elsewhere (OR: 1.86; 95% CI 1.27–2.72; p = 0.001), and older children (24–59 months) were more likely to receive ACT than children aged 0–23 months (OR: 1.45; 95% CI 1.07–1.96; p = 0.016).
Table 3
Factors associated with receiving an ACT among febrile children under-five who received any treatment (n = 982)
Variable
n/N
%
Unadjusted analysis
Adjusted analysis
OR (95% CI)
p value
OR (95% CI)
p value
Location
 Rural
386/835
46.3%
Ref
0.181
Ref
0.899
 Urban
83/147
54.9%
1.41 (0.85–2.33)
1.03 (0.63–1.69)
Region
 West
36/75
47.8%
Ref
0.253
Ref
0.025
 North
203/452
45.0%
0.89 (0.51–1.56)
1.20 (0.64–2.26)
 South
125/268
45.9%
0.93 (0.51–1.70)
1.48 (0.79–2.83)
 East
105/187
56.4%
1.41 (0.75–2.66)
2.30 (1.20–4.44)
Household size
 1–5
146/269
52.2%
Ref
0.058
Ref
0. 178
 6–10
257/548
47.6%
0.83 (0.59–1.17)
0.95 (0.68–1.33)
 11+
66/165
39.9%
0.61 (0.41–0.91)
0.69 (0.46–1.04)
Household religion
 Muslim
375/796
46.9%
Ref
0.402
Ref
0.579
 Christian
94/186
50.7%
1.17 (0.81–1.67)
0.90 (0.62–1.30)
Socio-economic status
 1 (poorest)
131/317
41.0%
Ref
0.001
Ref
0.237
 2
175/382
46.1%
1.23 (0.87–1.73)
1.00 (0.68–1.47)
 3 (least poor)
163/283
57.0%
1.91 (1.31–2.77)
1.41 (0.88–2.24)
Respondent education
 None
290/644
45.1%
Ref
0.059
Ref
0.930
 Primary
63/123
51.2%
1.28 (0.87–1.89)
1.03 (0.68–1.58)
 Secondary or higher
107/196
53.8%
1.42 (0.99–2.03)
1.00 ( 0.66–1.50)
 Arabic school or Other
9/19
47.9%
1.12 (0.44–2.87)
1.41 (0.49–4.08)
Everyone is at risk
 No
120/250
47.4%
Ref
0.948
Ref
0.380
 Yes
349/732
47.6
1.01 (0.73–1.39)
0.85 (0.60–1.22)
ITNs protect from malaria
 No
129/370
35.0%
Ref
< 0.001
Ref
0.001
 Yes
340/612
55.2%
2.29 (1.66–3.15)
1.84 (1.29–2.63)
Under 5 slept under ITN
 No
119/287
40.2%
Ref
0.009
Ref
0.061
 Yes
350/695
50.6%
1.53 (1.11–2.10)
1.41 (0.98–2.02)
Knowledge of ACTs
 No
187/537
34.7%
Ref
< 0.001
Ref
< 0.001
 Yes
282/445
63.0%
3.20 (2.36–4.35)
2.78 (2.02–3.80)
Child age (months)
 0–23 months
136/321
42.6%
Ref
0.047
Ref
0.016
 24–59 months
333/661
49.9%
1.34 (1.00–1.79)
1.45 (1.07–1.96)
Prompt treatment (< 24 h)
 No
209/440
47.2%
Ref
0.842
Ref
0.866
 Yes
260/542
47.9%
1.03 (0.77–1.37)
1.03 (0.76–1.38)
Public health facility
 No
57/159
36.4%
Ref
0.004
Ref
0.001
 Yes
412/823
49.7%
1.73 (1.19–2.52)
1.86 (1.27–2.72)

Factors associated with adherence

In a multivariate analysis restricted to children who received ACT and had data on treatment duration (n = 466), only one factor was found to be significantly associated with adherence (Table 4). Children receiving ACT within 24 h of symptom onset were less likely to complete treatment than those who received ACT treatment beyond this window (OR: 0.55; 95%CI 0.34–0.89; p = 0.015). Due to collinearity with ‘knowledge of ACT,’ ‘knowledge of at least one anti-malarial’ and ‘knowledge of at least one sign or symptom of malaria’ were removed from the multivariable models. Similarly, ITN use was retained, while ITN ownership and knowledge of any malaria protective measures were removed. As knowledge of the term ‘malaria’ was collinear with both knowledge of ACT and ITN utilization, it was removed from both final multivariable models.
Table 4
Factors associated with adherence to ACTs among febrile children under-five who received treatment with an artemisinin-based combination (n = 466)
Variable
n/N
%
Unadjusted analysis
Adjusted analysis
OR (95% CI)
p value
OR (95% CI)
p value
Location
 Rural
178/385
46.2%
Ref
0.233
Ref
0.245
 Urban
44/81
55.3%
1.44 (0.79–2.64)
1.49 (0.76–2.95)
Region
 West
11/35
30.1%
Ref
0.355
Ref
0.211
 North
98/202
47.9%
2.13 (0.83–5.50)
2.58 (0.99–6.77)
 South
60/124
49.3%
2.26 (0.87–5.89)
2.83 (1.04–7.68)
 East
53/105
50.8%
2.40 (0.91–6.32)
2.76 (1.04–7.32)
Household size
 1–5
63/144
45.3%
Ref
0.487
Ref
0.620
 6–10
122/256
47.3%
1.08 (0.72–1.62)
1.13 (0.73–1.73)
 11 +
37/66
54.2%
1.43 (0.79–2.59)
1.35 (0.73–2.50)
Household religion
  Muslim
172/373
46.0%
Ref
0.158
Ref
0.058
 Christian
50/93
54.7%
1.42 (0.87–2.30)
1.61 (0.98–2.65)
Socio-economic status
 1 (poorest)
62/131
46.5%
Ref
0.883
Ref
0.930
 2
83/175
47.0%
1.02 (0.64–1.63)
1.07 (0.66–1.75)
 3 (least poor)
77/160
49.4%
1.13 (0.68–1.86)
1.12 (0.60–2.08)
Respondent education
 None
138/288
48.1%
Ref
0.984
Ref
0.854
 Primary
30/63
48.5%
1.02 (0.58–1.80)
0.87 (0.46–1.64)
 Secondary or higher
50/106
46.5%
0.94 (0.57–1.54)
0.80 (0.46–1.38)
  Arabic or other
4/9
42.3%
0.79 (0.18–3.49)
0.74 (0.17–3.26)
Know everyone is at risk
 No
60/120
51.3%
Ref
0.390
Ref
0.329
 Yes
162/346
46.4%
0.82 (0.53–1.29)
0.79 (0.49–1.27)
Know ITNs protect
 No
62/128
48.4%
Ref
0.844
Ref
0.943
 Yes
160/338
47.4%
0.96 (0.63–1.47)
0.98 (0.63–1.54)
U5 slept under ITN
 No
58/118
48.8%
Ref
0.779
Ref
0.829
 Yes
164/348
47.3%
0.94 (0.61–1.44)
0.95 (0.60–1.50)
Knowledge ACTs
 No
88/187
46.9%
Ref
0.805
Ref
0.866
 Yes
134/279
48.2%
1.05 (0.70–1.57)
1.04 (0.67–1.60)
Child age (months)
 0–23 months
60/135
43.9%
Ref
0.276
Ref
0.270
 24–59 months
162/331
49.2%
1.24 (0.84–1.81)
1.26 (0.83–1.90)
Prompt treatment (< 24 h)
 No
102/207
49.5%
Ref
0.744
Ref
0.150
 Yes
119/258
45.9%
1.05 (0.79–1.39)
1.25 (0.92–1.70)
Public health facility
 No
28/57
48.3%
Ref
0.926
Ref
0.951
 Yes
194/409
47.6%
0.97 (0.55–1.74)
0.98 (0.53–1.81)
ACT within 24 h
 No
85/154
55.0%
Ref
0.047
Ref
0.015
 Yes
137/312
44.1%
0.65 (0.42–0.99)
0.55 (0.34–0.89)
Data for ACT duration was available for 466 children out of the 469 that received ACT

Discussion

The pathway to effective malaria case management depends on timely access to ACT and patient (or caregiver) adherence to treatment regimens. ACT has been recommended as the first-line treatment in Sierra Leone since 2004; however, in 2012, uptake remained suboptimal. To further investigate access to ACT and adherence to treatment guidelines in Sierra Leone, a secondary analysis of the national 2012 mKAP survey was undertaken. In a previous nationwide survey conducted in 2010, only 19.2% of febrile children received ACT, and only 50.3% received any anti-malarial within 24 h [14]. Assuming that a large proportion of febrile illness in children under five in Sierra Leone is due to malaria, these results suggest that challenges to delivering prompt and effective malaria treatment still remained in 2012.
In 2012, most children under-five with fever in the 2 weeks before the survey did not receive an artemisinin-based combination. ACT access varied geographically and was highest in the eastern region of the country. Similar to findings reported from Thailand, Kenya, and Uganda [2931], this study found that children were more likely to receive ACT if their caregiver had prior knowledge of ACT and ITNs, suggesting that health education interventions could improve patient access to ACT. Additionally, this analysis found that seeking care from a public health facility doubled the odds of receiving ACT, suggesting that price or limited availability may impact access to ACT in the private sector. This is similar to other studies in sub-Saharan Africa, which have reported improved access to ACT for children treated in the public sector [32, 33].
This study also demonstrates a difference in access based on age, with older children (2–4 years) more likely to receive ACT than younger children (< 2 years). While removing user-fees removes the cost barrier of accessing care for individuals, it can strain weak health systems when demand increases. Higher patient loads require more resources to provide adequate service delivery. Although Sierra Leone had a relatively high availability of amodiaquine + artesunate (the ACT of choice at the time) compared to other post-conflict countries [34], the number of infant doses has often been insufficient due to improper forecasting and provision of pediatric formulations [35, 36]. Such challenges could be even more significant with the recent Ebola outbreak and ongoing pandemic [7, 8].
Of those febrile children who received artemisinin-based combination, less than half completed the recommended 3-day course of treatment (47.6%). However, no significant association between knowledge of ACT, malaria, or prevention practices and adherence was found, despite suggestions that patient knowledge, attitudes, and beliefs may be strong predictors of adherence [15, 31, 3740]. Although Bruxvoort et al. reported that age, higher household income, higher education level, malaria knowledge, and treatment-seeking behavior are factors facilitating anti-malarial adherence [41], none of the a priori socioeconomic or demographic factors were associated with adherence in this study.
Unlike the findings reported for access, this analysis found no association between the source of care and treatment adherence. Unexpectedly, poor adherence to ACT was associated with accessing ACT promptly (within 24 h from the onset of symptoms). Lemma et al.. reported similar results; participants that delayed 1 day before seeking treatment were more adherent than those seeking prompt treatment (OR: 5.39; 95% CI 1.83–15.88) [37]. In contrast, a study in Uganda reported that prompt access to ACT was associated with higher treatment adherence [30]. Similarly, patients in Kenya seeking treatment greater than 1 day after the start of fever were 27% less likely to be adherent [31]. Given these mixed results, the association between prompt treatment for fever and lower ACT adherence should be interpreted with caution. Those accessing treatment early may have had lower parasite loads, which was cleared more quickly, resulting in fewer symptoms and possibly lower treatment adherence. Moreover, as the mKAP survey did not capture information on confirmatory malaria diagnosis, the child may have had a non-malaria febrile illness, and their symptoms may have resolved at the same time as receiving ACT, thus leading the caregiver to discontinue the treatment.
National cross-sectional household surveys such as the Demographic Health Survey (DHS), Multiple Indicator Cluster Survey (MICS), and the Malaria Indicator Survey (MIS) routinely collect information on the treatment of fever. These surveys including questions on treatment-seeking behavior for fever, medications received for that fever, and how soon after the onset of symptoms, the treatment was initiated. Additionally, since 2013, most surveys have gathered information on whether a blood test was received. However, the test question is not malaria-specific, nor is information on the test result collected due to concerns about the reliability of the data [42, 43]. Without this vital specific information, caution should be taken when interpreting results on fever case management from these surveys, as these data would represent the treatment of fever and not necessarily malaria. Ashton et al.. recently found that caregiver recall surrounding testing and diagnosis to be valid; therefore, the recommendation regarding confirmed malaria cases may need to be reviewed [44].
The fever case management sections of these national surveys could be expanded to include questions related to ACT treatment adherence, such as duration and/or completion of treatment, as was done in this study. Including these additional questions would allow a population-level estimate of adherence to be measured, as well as information on access to ACT, providing a more complete picture of the malaria treatment pathway. Collecting ACT adherence data through national surveys would be simple to implement, sustainable, and cost-effective. However, the use of national surveys to assess ACT adherence has several limitations: (1) the method assumes that respondents know and recognize which anti-malarial or artemisinin-based combination was prescribed for their child; (2) the data is relying on self-reported outcomes; and (3) unless surveys collect information about diagnostic testing specifically for malaria along with those test results, then the utility of adherence data would be limited as it would apply only to children with fever who may or may not have malaria.
Although this was a national survey, which allows generalizability of the findings to the entire country, there were some limitations. First, the data presented here were collected in 2012. Despite the delay in reporting these results, ACT adherence at the national level remains unknown in 2020, and factors impacting access and adherence to ACT have yet to be evaluated in Sierra Leone. Second, the study cannot provide a causal relationship between improved access and government programs rolled out to improve access to health services. However, the successful implementation of the FHCI in certain districts may have contributed to better access to medicines and services [19]. Third, the analysis was limited to the variables collected and may not have captured all the factors plausibly associated with receiving or completing treatment with ACT. In particular, this secondary analysis did not contain information on ACT and malaria rapid diagnostic tests stock-outs, confirmatory diagnosis of malaria, the quality of care at the health facility (including if the health worker provided information on how to administer the medication), or treatment completion. Additionally, questions on the number of tablets taken or whether treatment was completed were not included in this survey and would have contributed to a more precise quantification of adherence. Finally, although the sample size was large, it may not have provided the optimal power needed to detect associations between adherence and the a priori socioeconomic or demographic factors identified.

Conclusions

This study demonstrates that poor access and adherence to ACT remained key challenges to ensuring effective malaria case management in Sierra Leone in 2012 and continues to be a challenge in the face of public health emergencies such as Ebola and COVID-19. While efforts have been made to improve access to key health services in Sierra Leone, such as malaria treatment, further emphasis on ACT adherence is still needed. Optimizing the supply chain, implementation of the Free Health Care Initiative, and scaling up malaria communication campaigns to include messages on adherence could improve malaria treatment effectiveness in Sierra Leone. Finally, national household surveys could be expanded to capture key indicators on ACT access and adherence to help guide malaria case management in the future.

Acknowledgements

The Authors thank the initial study team for their hard work in completing the initial survey. In particular, we thank the CRS program manager Nancy Mansary and our college at Statistics Sierra Leone Sahr Yambasu for leading the field teams and assisting with the sampling frame. We are also very grateful for the support of the National Malaria Control Programme and the district health teams. Finally, we are grateful for the participants for agreeing to take part in the initial study.
The original survey protocol was reviewed and approved by the Sierra Leone Ethics and Scientific Review Committee. All participants provided informed consent at the time of the mKAP interview. Catholic Relief Services and the National Malaria Control Program granted permission to use the survey data for this secondary analysis. The LSHTM Research Ethics Committee approved the secondary analysis protocol.
Not applicable.

Competing interests

The authors declare that they have no competing interests.
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Metadaten
Titel
Factors associated with access and adherence to artemisinin‐based combination therapy (ACT) for children under five: a secondary analysis of a national survey in Sierra Leone
verfasst von
Kristin Banek
Emily L. Webb
Emily Bostick Doogue
Samuel Juana Smith
Daniel Chandramohan
Sarah G. Staedke
Publikationsdatum
01.12.2021
Verlag
BioMed Central
Erschienen in
Malaria Journal / Ausgabe 1/2021
Elektronische ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-021-03590-9

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