Available online on 15.10.2021 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2021 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                     Research Article 

Preventive and Curative treatment of malaria during pregnancy in Mali: Evaluation of the Healthcare Professionals based on the Malian National Malaria Control Program (NMCP) Guidelines 

 Ballo Mahamadou1*, Traoré Karim1, Sidibé Sambou1, Seidina Diakité2, Guindo Abdoulaye1, Daou Fatoumata1, Sangaré Modibo2, Konaté Drissa2, Diakité Mahamadou2, Youl Estelle3 and Bah Sekou1

1 Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali 

2 Faculty of Medicine and Odontostomatology, University of Sciences, Techniques and Technologies of Bamako, Mali

Faculty of Pharmacy, Université Joseph Ki-ZERBO. Burkina Faso

Article Info:

_________________________________________

Article History:

Received 06 August 2021      

Reviewed 14 September 2021

Accepted 19 September 2021  

Published 15 October 2021  

_________________________________________

Cite this article as: 

Ballo M, Traoré K, Sidibé S, Seidina D, Guindo A, Daou F, Sangaré M, Konaté D, Diakité M, Youl E, Bah S, Preventive and Curative treatment of malaria during pregnancy in Mali: Evaluation of the Healthcare Professionals based on the Malian National Malaria Control Program (NMCP) Guidelines 

, Journal of Drug Delivery and Therapeutics. 2021; 11(5-S):71-76

DOI: http://dx.doi.org/10.22270/jddt.v11i5-S.5092       

_________________________________________

*Address for Correspondence:  

Mahamadou BALLO, Faculty of Pharmacy, University of Sciences, Techniques and Technologies of Bamako, Mali

ORCID iDhttps://orcid.org/0000-0002-6369-1852 

Abstract

______________________________________________________________________________________________________

Malaria infections in pregnancy should be treated promptly with safe and efficacious antimalarial drugs to prevent harmful effects on the mother and fetus. To succeed, the Malian has developed NMCP guidelines for the management of malaria cases in pregnant women. The study aimed at the analysis of the prescription of antimalarial drugs based on the Mali's NMCP guidelines. 

We conducted a cross-sectional study during malaria transmission season from June to August 2020. The sampling concerned all prescriptions for pregnant women containing at least one antimalarial drug.

The frequency of prescription of antimalarial drugs was 85%. 132 (74.16%) were preventive treatments and 46 (25.84%) curative treatments. 30 (90.91%) of pregnant women in the first trimester received one dose of Sulfadoxine-Pyrimethamine. 6 (12.5%) received three doses in the third trimester. Of the 46 antimalarial drugs prescribed for the treatment of uncomplicated malaria, 30 (65.22%) were Artemether-lumefantrine (tablet), 10 (21.74%) were Quinine (tablet). 29 (63.04%) were compliant with NMCP guidelines and 17 (36.96%) were not. The non-compliances concerned 3 prescriptions of Artemether-lumefantrine in the first trimester, 3 and 5 prescriptions of Quinine (tablet) in the second and third trimester respectively and at the end 2 and 4 non-compliances respectively for the prescription of injectable dosage forms of Quinine and Artesunate.

This study showed a great noncompliance with the Mali's NMCP guidelines in the prescription of antimalarial in pregnant women. Chemoprophylaxis should be prohibited in the first trimester.   

Keywords: Curative and Preventive Treatment, Malaria in Pregnancy, Malaria Transmission, Mali

 


 

INTRODUCTION

Despite the progress made in the fight against malaria over the past decade, including a significant reduction in malaria-related morbidity and mortality in most sub-Saharan Africa countries, ~ 228 million cases and ~ 405’000 deaths were still recorded worldwide in 2018.1 Children under 5 and pregnant women are the most vulnerable and therefore the most affected by malaria.1 In 2018, there were an estimated 39 million pregnancies in sub-Saharan Africa, of which over 11 million (29%) were exposed to P. falciparum.1 The majority of women residing in malaria-endemic areas of sub-Saharan Africa are partially immune and do not develop symptoms when infected with P. falciparum during pregnancy. However, even in the absence of symptomatic disease, malaria in pregnancy is associated with maternal anemia and adverse birth outcomes such as low birth weight, preterm delivery, and stillbirth.2–4 Pregnancy is associated with various physiological changes that can alter the absorption, disposition, metabolism, and excretion of drugs.5 These pregnancy-related changes in pharmacokinetic properties could result in overexposure or underexposure to antimalarial drugs. These pregnancy-related changes in pharmacokinetic properties could result in overexposure or underexposure to antimalarial drugs. Overexposure might lead to maternal and fetal toxicity and underexposure could cause therapeutic failures, resulting in poor pregnancy outcomes, maternal death, and increased risk of drug resistance.5,6 Malaria infections in pregnancy should be treated promptly with safe and efficacious antimalarial drugs to prevent harmful effects on the mother and fetus.7,8 For P. falciparum malaria infections during the first trimester, WHO recommends quinine with clindamycin for 7 days (or quinine alone if clindamycin is not available.8 Guidelines for the treatment of P falciparum malaria in the second and third trimester are the same as for non-pregnant adults; this means any ACTs that are recommended as first-line treatment—namely, artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine, or artesunate plus sulfadoxine-pyrimethamine can be used in pregnancy.8 

 To control malaria in Mali, the National Malaria Control Programme (NMCP) recommends intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) in pregnant women and to use quinine (first trimester) and artemether –lumefantrine (AL) or artesunate-amodiaquine (second and third trimester) for the treatment of confirmed cases. The Malian has developed NMCP guidelines with protocols for the management of uncompleted and severe malaria cases in pregnant women.9

The prescriber's responsibility is to initiate properly an early antimalarial treatment for confirmed malaria cases. Chemoprophylaxis and curative treatment should comply with current standards and guidelines to reduce morbidity during pregnancy and adverse birth outcomes. The success of these recommendations in the treatment policy will depend on the adherence and compliance of healthcare professionals and their patients.10

METHODS

Our study took place in seven health centers of commune VI of district of Bamako in Mali, where malaria is endemic. We conducted a cross-sectional study during malaria transmission season from June to August 2020. The sampling concerned all prescriptions for pregnant women containing at least one antimalarial drug and recorded in a medical register in one of the seven health centers.

The nature of the antimalarial drugs, its dosage, the duration of treatment and the type of prescribed antimalarial combination according to the age of pregnant were analyzed based on the NMCP guidelines.9 A non-compliant prescription was defined as any breach of one or more of the parameters listed above with respect to the NMCP guidelines. In the registries, we also collected information about biological diagnosis and the socio-demographic characteristics (age and sex of the patient). In addition, prescriber’s qualification was reported.

Drug according to the age of pregnant, dosages and duration of treatment prescribed by the NMCP are shown below (Table 1).

Ethical aspects

The Faculty of Pharmacy of the University of Sciences, Techniques and Technologies of Bamako validated the protocol. Anonymity and confidentiality were respected.

Statistical analysis

Data were collected on a report form, entered into Excel and analyzed using the statistical software Epi info 6.04.


 

 

Table 1 : Drug, presentation, dosage, duration of treatment for uncomplicated malaria according to the age of pregnant by the NMCP.

First trimester of pregnancy: Quinine salt tablet 10mg / kg every 8 hours for 7 days.

Second and third trimester of pregnancy: Artemether 20 mg - Lumefantrine 120 mg  

Age/weight

Presentation

Day 1

Day 2

Day 3

≥ 35 Kg (≥13-years-old)

Tablet

Morning

Evening

Morning

Evening

Morning

Evening

4 tablets

4 tablets

4 tablets

4 tablets

4 tablets

4 tablets

Second and third trimester of pregnancy: artesunate-amodiaquine

Age/weight

Presentation

Day 1

Day 2

Day 3

≥ 18kg to <36kg

(6 to 13 years-old)

100mg/270 mg blister 3 tablets

1 tablet 

1 tablet 

1 tablet 

≥36kg

(≥14 years-old)

100mg/270 mg blister 6 tablets

2 tablets 

2 tablets

2 tablets 

Note : Artesunate injection is the drug of choice for the treatment of severe malaria. In case of unavailability, artemether is preferable to quinine. 













 


 

RESULTS 

The study population consisted of 210 prescriptions given to 208 pregnant women seen in prenatal consultations.

Socio-demographic data and frequency of prescribing of antimalarials in pregnant women

Among the 210 prescriptions, 178 had an antimalarial, a frequency of 0.85 (85%). The most represented age group was 21-30 years with 58.43%. The average age was 24.16±5.83 years with extremes ranging from 13 to 37 years. Prenatal consultations were performed by midwives and matrons respectively 172 (96.63%) and 6 (3.37%). The Pregnant women were more in the second and third trimester with 53.98% and 27.27% respectively.

Type of treatment of malaria in pregnant women 

Among the 178 prescriptions prescribed to 176 pregnant women, 132 (74.16%) were preventive treatment and 46 (25.84%) curative treatment (Table 1). Sulfadoxine purimethamine (SP) was the only molecule used in chemoprophalaxis. The international non-proprietary name prescription was respected in 16.85% and not respected in 83.15%. The tablet and injectable forms were the prescribed forms with 96.63% and 3.37% respectively. The dosage indication appeared on 88.77% of the prescriptions. Side effects occurred in 12 (6.82%) of 176 pregnant women (Table 2). 


 

Table 2 : Evaluation of antimalarial prescription

Socio-demographic data

Effectifs

Pourcentage

 

Age ranges

13-20 years-old

30 

16,85 

21-30 years-old

104 

58,43 

31-37 years-old

44 

24,72 

Total 

178

100

 

Qualification

Physician

0

0

Midewife 

172

96,63

Obstetric Nurse

6

3,37 

Total 

178

100

 

Gestational age

1er Trimestre 

33

18,75

2ème Trimestre      

95

53,98

3ème Trimestre      

48

27,27

Total 

176

100

Prescription in International Nonproprietary Name

Conform

30

16,85

Non conform

148

83,15

Total 

 

 

 

Galenic forms

Comprimé 

172 

96,63 

Injectable  

6

3,37 

Total 

 

 

 

Types de traitement

Preventif    

132 

74,16

Curatif  

46 

25,84

Total

 

 

 

Dosage indication

Yes 

150 

88,77 

No  

28 

15,73 

Total 

 

 

 

Onset of side effects

Yes 

12 

6,7 

No

166 

93 

Total

 

 

 

Malaria curative treatment duration

Conform

46

100

Non conform

0

0

Total

 

 

 

Malaria diagnostic confirmed by RDT

Yes 

46

100

No

0

0

Total

 

 

RDT : rapid diagnostic test 

 


 

Preventive treatment of malaria in pregnant women 

75% of the 176 pregnant women received pyrimethamine sulfadoxine. 30 (90.91%) of first trimester pregnant women received one dose of Sulfadoxine-Pyrimethamine. Of those in the second trimester, 54.74% received one dose of Sulfadoxine-Pyrimethamine and 15.79% received two doses. 60.42% of those in the third trimester received two doses and 12.5% received three doses (Table 2).

Curative treatment of uncomplicated malaria according to pregnancy age and compliance with Mali NMCP guidelines 

Out of the 46 antimalarials prescribed for the treatment of uncomplicated malaria, 30 (65.22%) were Artemether-lumefantrine (Tablet), 10 (21.74%) were Quinine (Tablet), Artesunate (Injectable) in third position with 8.69% and Quinine (Injectable) with 4.35%. 29 (63.04%) were compliant with NMCP guidelines and 17 (36.96%) were non-compliant. The non-compliances concerned 3 prescriptions of Artemether-lumefantrine (Tablet) in the first trimester, 3 and 5 prescriptions of quinine (Tablet) respectively in the second and third trimester and at the end 2 and 4 non-compliances respectively for the prescription of injectable pharmaceutical forms of quinine and Artesunate. (Table 3)

Following the intake of Sulfadoxine-purimethamine by 7 pregnant women and the intake of quinine by 5 pregnant women, side effects such as dizziness, tinnitus, nausea and vomiting were reported. (Table 2).


 

 

Table 2 : Number of times the Sulfadoxine-Pyrimethamine has been taken depending on the age of pregnancy. 

Number of doses of Sulfadoxine-Pyrimethamine

Pregnancy age in trimester

1er (n=33)

2ème (n=95)

3ème (n=48)

1

30 (90,91%)

52 (54,74%)

0   

2

0

15 (15,79%)

29 (60,42%)

3

0

0

6 (12,5%)

TOTAL

30 (90,91%)

67 (70,53%)

35 (72,92%)

 

Table 3: Antimalarial prescribed for curative treatment of uncomplicated malaria according to age of pregnancy and compliance with Mali's NMCP guidelines.

Prescribed antimalarial 

Pregnancy age in trimester (n=46)

Total 

1er

2ème

3ème

n (%)

Artemether-lumefantrine (Tablet)

3 (NC)

15 (C)

12 (C)

30 (65,22)

Quinine (Tablet)     

2 (C) 

(NC)

5 (NC)

10 (21,74)

Quinine (Injectable)     

0

(NC)

1 (NC)

2 (4,35)

Artesunate (Injectable)     

0

(NC)

0

4 (8,69)

NC: not compliant, C: compliant 


 

All prescribed molecules according to the FDA risk category 

A total of 506 drugs distributed among 14 molecules, including 5 fixed combinations, were identified out of 178 prescriptions containing an antimalarial drug. 35 (6.92%) drugs were unclassified by FDA risk category. Category C was the most prescribed and included 232 (45,85%) drugs; category B included 74 (14,62%) drugs and 165 (32,61%) drugs for category A. (Table 4 and 5).


 

 

Table 4: Frequency distribution of the medicines prescribed and FDA risk category

Drug name

Frequency 

Percent

FDA risk category

Iron - Folic acid

161 

31,82

A

Vitamin C

0,79

A

Paracetamol

53 

10,47

B

Clotrimazole

7

1,38

B

Erythromycin

0,79

B

Metronidazole

10 

1,98

B

Artemether-lumefantrine

30

5,93

C

Sulfadoxine-pyrimethamine

132

26,09

C

Hyoscine-butylbromide

30 

5,93

C

Domperidone

28 

5,53

C

Quinine

12

2,37

C

Phloroglucinol-Trimethylphloroglucinol

29 

5,73

Unclassified

Artesunate

4

0,79

Unclassified

Metopimazine

2  

0,40

Unclassified

Total

506

100,00

 

Table 5 : FDA risk category and percent 

FDA risk category

Frequency n (%)

FDA Categories are defined

A

165 (32,61)

Adequate clinical studies have shown no risk to fetus in any trimester

B

74 (14,62)

Animal studies have not shown adverse effect on the fetus and there are inadequate clinical studies

C

232 (45,85)

Animal studies have shown adverse effects, no adequate clinical studies. May be useful in pregnancy despite potential risks.

D

0

There is evidence of risk to human fetus, but potential benefits may be acceptable despite potential risks.

X

0

Animal/human studies show foetal abnormalities. Risks involved clearly outweigh benefits.

Unclassified

35 (6,92)

 

Total

506 (100)

 

 


 

DISCUSSION

This study assessed compliance with the national malaria control program guidelines in pregnant women. The frequency of prescription of antimalarials was 85%. This percentage is higher than the 38% obtained by Eze et al.,11. This difference is explained by the fact that this study was conducted in community health centers while a university hospital was part of their study site. The majority of the pregnant women (58.43%) were between 21 and 30 years of age. The mean age was 24.16±5.83 years with extremes ranging from 13 to 37 years. This result is similar to that of Alemu BK.et al.,12 with 26.5 years as the mean age of the gestating females and the age range of 25 and 34 years was in majority. The majority of pregnant women were in the second trimester with 53.98% in contrast to the study of  Alemu et al.,12 where 63.2% of pregnant women were in the third trimester.

Among the 178 prescriptions given to 176 pregnant women, 132 (74.16%) were for preventive treatment with sulfadoxine purimethamine and 46 (25.84%) for curative treatment. The prevalence of 62.4% in pregnant women reported by Idowu et al.,13 is higher. Indeed, malaria chemoprophylaxis is known to reduce parasite levels during pregnancy.14 This would explain the low prevalence of malaria in pregnant women. 

16.85% of the drugs were prescribed in international non-proprietary names. However, the value obtained (43%) by Eze et al.,11 was higher. This means that prescribers were not fully complying with the WHO recommendation that drugs should be prescribed using their international non-proprietary names.15 This very low prescription of generic names leads to an increase in the direct and indirect cost of medicines due to the unavailability of non-branded medicines at the community health center.

75% of the 176 pregnant women received pyrimethamine sulfadoxine. This is higher than the 36% reported in the 2011 Mali Health Information and Management System survey.16 This difference is explained by the low attendance of health centers in several localities. In addition, the 20.3% obtained by Eze et al.,11 is much lower because their study concerned all prescriptions. 90.91% of women in the first trimester received a dose of sulfadoxine-pyrimethamine, which confirms the inconsistency or lack of clarity of Mali's guidelines on malaria in pregnancy compared to the WHO recommendations that sulfadoxine-pyrimethamine be administered under direct observation as early as possible in the second trimester of pregnancy and at each prenatal visit at least one month apart.16,17 Of those in the second trimester, 54.74% received a single dose of sulfadoxine-pyrimethamine and 15.79% received two doses. 60.42% of those in the third trimester received two doses and 12.5% received three doses. These results show that second and third trimester pregnant women did not receive even one dose of sulfadoxine-pyrimethamine. They are clearly below the WHO target of at least three doses during pregnancy.18

Regarding the treatment of uncomplicated malaria, of the 46 antimalarial drugs prescribed 65.22% was artemether-lumefantrine (Tablet), 21.74% was quinine (Tablet), artesunate (Injectable) in third position with 8.69% and Quinine (Injectable) with 4.35%.  These values are higher than those of Luz et al.,19 who found a prescription frequency of 16.2% for artemeter-lumefantrine, 10.8% for quinine sulphate and 1% for artesunate.This difference could be explained by the application of therapeutic regimens prescribed according to the type of plasmodium in their study  

Treatment of uncomplicated malaria was 63.04% compliant with Mali's NMCP guidelines and 36.96% non-compliant. 

The non-compliances concerned 3 prescriptions of Artemether-lumefantrine (Tablet) in the first trimester, 3 and 5 prescriptions of quinine (Tablet) respectively in the second and third trimester and at the end 2 and 4 non-compliances respectively for the prescription of injectable pharmaceutical forms of quinine and Artesunate which are reserved for the treatment of severe malaria by the guidelines of the NMCP of Mali and WHO.8,9

The most prescribed drugs were in category C of the FDA drug classification for fetal risk, followed by those in category A. Animal studies have shown adverse effects with category C drugs, no adequate clinical studies. These drugs such as Artemether-lumefantrine, Sulfadoxine-pyrimethamine, Quinine can be used according to the age of the pregnancy and thus minimize the potential risks.5,11 Phloroglucinol-trimethylphloroglucinol, artesunate and metopimazine have not been classified by the FDA as a risk category. Other studies have shown that these molecules are probably safe.7,20

CONCLUSION 

This study showed a great non compliance with the Mali's NMCP guidelines in the prescription of antimalarial drugs during the treatment of uncomplicated malaria to the detriment of pregnant women and their fetus. Chemoprophylaxis with sulfadoxine-pyrimethamine should be prohibited in the first trimester. We suggest improving the Mali's NMCP guidelines for chemoprophylaxis.

ACKNOWLEDGMENT

The authors acknowledge the team of the seven health centers of commune VI of district of Bamako, Mali. We are grateful to many colleagues at the Malaria Research and Training Center for provided critical reviews of the manuscript. 

COMPETING INTERESTS

The authors declare that they have no competing interests.

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