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ORIGINAL ARTICLE
Year : 2022  |  Volume : 25  |  Issue : 6  |  Page : 903-908

Uptake and usage of proguanil as malaria chemoprophylaxis and the socio-economic determinants of proguanil usage in children with sickle cell anemia in Benin City


1 Department of Paediatrics, College of Medical Sciences, Edo State University, Uzairue; Institute of Child Health, University of Benin, Edo State, Nigeria
2 Department of Child Health, University of Benin Teaching Hospital; Department of Child Health, University of Benin, Edo State, Nigeria

Date of Submission15-Nov-2021
Date of Acceptance01-Apr-2022
Date of Web Publication16-Jun-2022

Correspondence Address:
Dr. I G Enato
Department of Paediatrics, College of Medical Sciences, Edo State University, Uzairue, Edo State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_1938_21

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   Abstract 


Background: Proguanil is currently the recommended drug used for malaria chemoprophylaxis in children with Sickle cell anaemia (SCA). Aims: This study aims to determine the uptake and usage of proguanil as malaria chemoprophylaxis and the socioeconomic determinants of its usage in children aged 6–59 months. This was a descriptive cross-sectional study carried out in two major sickle cell clinics in Benin City, Edo state, Nigeria. A total of 420 participants were interviewed using semistructured questionnaires. Patients and Methods: Descriptive, bivariate, and multivariate analysis of quantitative data were done using SPSS version 21. Results: The uptake of proguanil among study participants was 67.4%; of these number, 268 (94.7%) reported daily use of proguanil. Only 3 (0.7%) used pyrimethamine as chemoprophylaxis, while 134 (31.9%) used no form of malaria chemoprophylaxis. Having mothers with higher level of education (LOE) (P = 0.013, odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.15–3.17), attending clinic at the University of Benin Teaching Hospital (UBTH) (P = 0.044, OR = 2.15, 95% CI = 1.02–4.54), older age group (36–59 months) (P = 0.015, OR = 1.67, 95% CI = 1.11–2.51), and owning insecticide-treated net (ITN) (P = 0.000, OR = 3.11, 95% CI = 1.98–4.88) were significant positive predictors for the usage of proguanil. Conclusion: Proguanil uptake was low. Attending sickle-cell clinic at UBTH, having mothers with tertiary LOE, and owning ITN were social factors associated with high usage of proguanil amongst children with SCA. Continuous monitoring and evaluation of the uptake and usage of proguanil in children is important, so as to aid policy implementation and review.

Keywords: Drug adherence, malaria chemoprophylaxis, malaria prevention, proguanil, sickle cell anemia, socioeconomic factors, uptake


How to cite this article:
Enato I G, Odunvbun M E. Uptake and usage of proguanil as malaria chemoprophylaxis and the socio-economic determinants of proguanil usage in children with sickle cell anemia in Benin City. Niger J Clin Pract 2022;25:903-8

How to cite this URL:
Enato I G, Odunvbun M E. Uptake and usage of proguanil as malaria chemoprophylaxis and the socio-economic determinants of proguanil usage in children with sickle cell anemia in Benin City. Niger J Clin Pract [serial online] 2022 [cited 2022 Jul 5];25:903-8. Available from: https://www.njcponline.com/text.asp?2022/25/6/903/347618




   Introduction Top


In children with SCA, malaria is a significant cause of severe morbidity and death.[1],[2],[3],[4] It is essential that all children born with SCA in malaria-endemic regions, such as Nigeria, be protected from malaria as much as possible. The use of malaria chemoprophylaxis/chemoprevention has been shown to be efficacious in reducing malaria-related deaths and morbidities in children with SCA.[5],[6],[7],[8],[9] Proguanil is currently the recommended drug for malaria chemoprophylaxis in persons with SCA in Nigeria.[10] This recommendation was first made in Nigeria by the Ministry of Health (MOH) in 1990.[10] In 2011, due to ineffectiveness of proguanil, insecticide-treated net (ITN)/long-lasting insecticide-treated net (LLITN) was recommended in place of proguanil for malaria prevention.[11] Proguanil may have been considered ineffective due to the problems of drug resistance and the fact that its uptake in adults was low despite more than 20 years after the first recommendation of proguanil for chemoprophylaxis.[12],[13] However, 3 years following this policy change, the recommendation was reviewed and proguanil was reintroduced as the recommended drug for malaria chemoprophylaxis in Nigeria, in 2014.[14] With the reintroduction of proguanil as malarial prophylaxis in persons with SCA, the rate of uptake is yet to be determined hence this study.

In addition, factors that affect the usage of proguanil are not known. Such data can be used to determine and monitor progress on the uptake rate and usage of proguanil in children with SCA. Also, information derived from this work can aid in determining the challenges associated with the uptake and usage of proguanil and guide prompt intervention to promote rapid and effective uptake and usage of proguanil for malaria chemoprophylaxis in children with SCA living in Nigeria, especially Benin City.


   Materials and Methods Top


Ethical consideration

Ethical approval for the study was obtained from the Ethics and Research Committee of the University of Benin Teaching Hospital (UBTH), Benin City, Edo State. Permission was also obtained from the Director of Medical Services, MOH, Edo State office. A written informed consent was obtained from parents or guardians of the study participants by the researcher/assistants before questionnaires were administered.

Study design

Selection and description of study participants

This was a cross-sectional study carried out in two major sickle cell clinics in Benin City, Edo State, Nigeria: the sickle cell center (SCC) and the sickle cell clinic of the UBTH. The sickle cell clinic in UBTH is held once a week on Mondays. The clinic in UBTH has two pediatric hematologists who run clinic once weekly along with other resident doctors in training. SCC is attached to the Central Hospital, Benin City. There are two senior medical officers who attend to patients in the SCC. SCC provides secondary health-care services to population within and outside Benin City. The SCC manages only sickle cell disease patients (children and adults); clinics are run daily. The center also operates a support group that meets on the last Thursday of every month. A semistructured questionnaire/interview was used to obtain information from the parents or guardians of children with SCA aged 6–59 months, after obtaining a signed or thumb-printed written informed consent from parents/guardians.

Sample size

The minimum sample size was estimated using an expected proportion of persons with SCA using proguanil as chemoprophylaxis (69% as found in the study by Kotila et al.).[13] This sample had a margin of error of 5% and confidence interval of 95%. This was calculated using the formula:



where

n is the minimum required sample size; z is the standard normal deviation corresponding to 95% confidence interval, which equals to 1.96; P is the proportion of persons with SCA who received proguanil (uptake of proguanil as found in the study by Kotila et al.);[13] E is the margin of error on P estimated to be at 5%.

Therefore:



n = 238. Adjusting for 10% of nonresponse rate, the minimum sample size needed for the study was a total of 262 participants.

Sampling method

A total of 420 participants were recruited for the study. A total of 361 children aged 6–59 months were recruited from the SCC and 59 children aged 6–59 months were recruited from the sickle cell clinic in UBTH. Study participants were recruited consecutively until a total of 420 participants were recruited.

Measurement

The questionnaire included information on the child's biodata: age, sex, parent's sociodemographic data (mother's level of education [LOE] and occupation, father's occupation), age at diagnosis of SCA, ownership and utilization of ITNs/LLITNs, type of malaria chemoprophylaxis being used, and frequency of use of proguanil reported in the preceding week by participants.

Uptake of proguanil was measured by[15]:

Number of patients using proguanil × 100

Total number of children in study

Usage of proguanil was defined as

Number of patients using proguanil × 100

The number of children who used proguanil only + those who did not use any prophylaxis.

Statistical analysis

All data generated were collated, checked, and analyzed using statistical package for social sciences (SPSS) version 21 (SPSS for Window, Inc., Chicago, IL, USA). Descriptive statistics was used to analyze and present sociodemographic parameters (age, sex, LOE, socioeconomic status, and ownership of ITN/LLITN), type of malaria chemoprophylaxis used, and frequency of proguanil usage reported in the preceding week. The association between the uptake of proguanil and independent variables (age group, age at first diagnosis of SCA, educational status of mother, socioeconomic status, clinic attended [SCC or UBTH], ownership, and utilization of ITNs) was assessed using the Chi-square test. Multiple logistic regressions model was used to identify predictors of usage of proguanil. Statistical significance was set at P < 0.05.


   Results Top


Sociodemographic characteristics of study participants

The age and sex distribution of the study participants are shown in [Table 1]. Majority of the study participants 270 (64.29%) were aged between 36 and 59 months, while only 10 (2.38%) were less than 1-year old. There were more males 61.19% than females 38.81%; about half (211) (50.24%) of study participants belonged to the middle class; and 52.62% of mothers had secondary LOE.
Table 1: Sociodemographic characteristics

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Type of malarial chemoprophylaxis used and proguanil uptake in study participants

Majority of the study participants 283 (67.4%) used proguanil for chemoprophylaxis. Only 3 (0.7%) used pyrimethamine, while 134 (31.9%) did not use any form of malaria chemoprophylaxis. Thus, the uptake of proguanil among the study participants was 67.4% [Figure 1].
Figure 1: Type of malarial chemoprophylaxis used and proguanil uptake in study participants

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Number of days per week of proguanil usage reported

Of the 283 children that used proguanil, 268 (94.7%) used it daily, while only 10 (3.5%) used proguanil twice weekly, 1 (0.4%) used proguanil thrice weekly, and 4 (1.4%) used proguanil for 4 days in the preceding week [Figure 2]. The use of proguanil once or five times weekly was not reported by study participants [Figure 2].
Figure 2: Number of days per week of proguanil usage and adherence in children on proguanil

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Determinants of proguanil usage

Only 30.0% of children aged 6–11 months used proguanil for malaria chemoprophylaxis, while 65.0% and 70.8% of those aged 12–35 months and 36–59 months, respectively, used proguanil. This difference was statistically significant (χ = 8.15, P = 0.017). Seventy one point six percent (71.6%) of those diagnosed before the age of 1 year used proguanil, compared to 68.0% and 62.8% of those diagnosed at 12–35 months and 36–59 months, respectively (χ = 1.70, P = 0.427). More of the children who attended the sickle cell clinic in UBTH 81.4% used proguanil compared to 65.6% of those who attended the SCC (P = 0.017); see [Table 2].
Table 2: Determinants of proguanil usage

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Seventy three point eight percent (73.8%) of those belonging to low socioeconomic class (SEC) used proguanil, while only 87 (60.0%) of those in the high SEC used proguanil. This difference was statistically significant (χ = 6.41, P = 0.041); see [Table 2]. Of the children whose mothers attended tertiary institution, 79.8% used proguanil, compared to 57.7% of children whose mothers had primary LOE/no education. This difference was statistically significant (χ = 12.34, P = 0.002).

Of the 417 participants, 206 (49.4%) owned ITN/LLITN, while the rest did not. Of the 206 that owned ITN/LLITN, 166 (80.6%) used proguanil for their children, while of the 211 participants who did not own ITN/LLITN, only 117 (55.5%) used proguanil. This difference was statistically significant (χ = 30.19, P = 0.000); see [Table 2].

Also, of the 206 participants that owned ITN/LLITN, 117 (83.6%) slept under the net in addition to using proguanil, while of the 66 participants who owned but did not sleep under their ITN/LLITN, 49 (74.2%) used proguanil. However, this difference was not statistically significant (χ = 2.50, P = 0.114); see [Table 2].

Multiple logistic regressions model for predictors of usage of proguanil

Logistic regression was performed to ascertain the effects of age, clinic attended, ownership of ITNs, SEC status, and mother's LOE on the usage of proguanil for malaria chemoprophylaxis. Children aged 36–59 months were 1.67 times more likely to use proguanil compared to those in younger age groups (P = 0.015, 95% confidence interval [CI] = 1.11–2.15). Children with mothers having tertiary LOE were 1.91 times more likely to use proguanil (P = 0.013, 95% CI = 1.15–3.17); see [Table 3]. SEC had no significant impact on the usage of proguanil. Those who attended clinic at UBTH were 2.15 times more likely to use proguanil compared to those attending the SCC (P = 0.044, 95% CI = 1.02–4.54). Ownership of ITN/LLITN was associated with a 3.11-fold increase in usage of proguanil (P = 0.000, 95% CI = 1.98–4.88); see [Table 3].
Table 3: Multiple logistic regressions model for predictors of usage of proguanil

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   Discussion Top


Uptake of proguanil was low, as only 67.4% of the study participants used proguanil. There seems to have been no significant progress in the uptake of proguanil in SCA over the years; as a similar (but slightly higher) uptake rate of 69% was found in a study by Kotila et al.,[13] in 2007. In addition to the low uptake of proguanil found in this study, 31.9% of participants did not use any form of malaria chemoprophylaxis. This value is higher than that found in the previous studies, where only 22% of study participants did not use any form of malaria chemoprophylaxis.[13],[16] A possible explanation for the increase in the number of persons not on malaria chemoprophylaxis over the years could be due to the brief interruption in the recommendation of proguanil as chemoprophylaxis in SCA.[11],[14] Only three (0.7%) of patients in this study used pyrimethamine, unlike 9% found in the study by Kotila et al. in 2007.[13] Thus, the use of pyrimethamine for prophylaxis seems to have declined over the years.

Despite the low uptake of proguanil, the number of children reported to have used proguanil daily was high. This could be due to the fact that drugs utilization in this age group in usually supervised by the parents/caregivers, unlike that seen in older children and adults.[17],[18],[19]

A higher usage of proguanil was found amongst those who attended clinic in UBTH compared to those who attended the SCC; in addition, all children who used pyrimethamine attended the SCC, while none attending clinic at UBTH used pyrimethamine. This higher usage of proguanil in those attending clinic in UBTH could be due to the fact that the clinic at UBTH is run by pediatric hematologists and several resident doctors. Thus, it is expected that the level of care, counseling, and informed consent will be higher, compared to that given in the SCC, which is run by only two trained senior medical officers. In addition, the patient-to-doctor ratio is higher in SCC, compared to that in the UBTH clinic; thus, counseling on malaria prevention may not have been as detailed in SCC compared to that in UBTH clinic.

LOE of mothers was found to be an independent predictor of usage of proguanil in this study, as higher usage of proguanil was found in children whose mothers had high (tertiary) LOE compared to those with none/primary LOE. This inequity in the usage of proguanil with respect to maternal LOE seen in this study was not found in a similar study involving uptake/usage of seasonal malaria chemoprevention (SMC) in young children in Cameroon, where uptake was similar in all children irrespective of their mothers' educational status.[15] This may be due to the door-to-door delivery of SMC, which enhances uptake/usage and adherence of SMC.[15]

The uptake of proguanil was higher in children from low SEC, compared to those from high SEC. This is unexpected, considering the cost implication of proguanil use. However, following multiple logistic regression, SEC was not a significant predictor of usage of proguanil.

Children in households with ITN were more likely to use proguanil compared to those who did not own an ITN. This may imply that the uptake of one method of malaria prevention promotes the uptake of the other methods. In addition, the use of ITN for vector control has been established over the years and the knowledge of the benefits of sleeping under ITN by children aged under 5 years and pregnant women is broadly disseminated across Nigeria and Africa.[1],[20]

In this study, age was a significant predictor for the uptake of proguanil; older children aged 36–59 months were 1.67 times more likely to use proguanil compared to the younger age group of 6–11 months. This could be due to the fact that older children have been taking the drug over the years and have become used to the daily routine medication, compared to infants. Thus, it becomes easier for their parents/guardians to administer drugs to them than to infants. This was also demonstrated in this study, as the use of proguanil was higher in children diagnosed during infancy than in those diagnosed at older age (36–59 months). Similarly, a study on SMC coverage in children in Burkina Faso showed that compared with those aged 3–11 months, children aged 12–59 months had higher coverage.[21]


   Conclusion Top


The uptake of proguanil in children with SCA is low and even lower than that found prior to the brief discontinuation of proguanil as the recommended malaria prophylaxis in 2011. Older age group, higher LOE in mothers, ownership of ITN/LLITN, and attending the clinic in UBTH all significantly influence the usage of proguanil in children with SCA in Benin City.

Acknowledgements

We wish to thank all study participants and their parents/guardians for participating in this study. We also thank the staff and management of the sickle cell clinic, the University of Benin Teaching Hospital, and the sickle cell center, Benin City, for caring for patients with sickle cell disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Key messages

Proguanil is currently the recommended drug used for malaria chemoprophylaxis in children with SCA. The uptake and usage of proguanil as malaria chemoprophylaxis in children is not known. The uptake of proguanil found in this study was 67.4%. Attending sickle cell clinic at the University of Benin Teaching Hospital, having mothers with tertiary LOE, and owning an ITN were social factors associated with high usage of proguanil amongst children with SCA.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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