The use of sulfadoxine-pyrimethamine (SP) as an intermittent preventive treatment (IPT) against malaria during pregnancy has become a policy in most sub-Sahara African countries and crucially depends on the efficacy of SP. This study sets out to evaluate the effectiveness of the SP given to the pregnant women in some selected health facilities in the Central Region of Ghana to prevent maternal malaria in pregnant women. A total of 543 pregnant women recruited from 7 selected health centres in Central Region of Ghana participated in the study. Parasite density of
Over 50 million pregnant women a year are exposed to malaria resulting in 2 500–10 000 maternal deaths annually [
The 2014 WHO policy update for intermittent preventive treatment in pregnancy (IPTp) recommends that doses should be delivered at each antenatal care visit after the first trimester, with a minimum of three doses received during each pregnancy [
Following the implementation of IPTp-SP, clinical and parasitological parameters of pregnant women attending ANC at Agogo Hospital in Ghana improved [
The study was carried out in 7 health centres in 6 selected towns in the Central Region of Ghana. The Central Region is located at the southern part of Ghana. It is bordered by the Ashanti and Eastern regions to the north, Western region to the west, Greater Accra region to the east, and the Atlantic Ocean to the south. The Central Region is situated within latitudes 6°15N and 5°N and longitudes 2°15W and 45°E. The region is partitioned into 13 districts (Figure
Map of Central Region of Ghana showing districts.
The study was carried out on pregnant women who had reported their routine monthly antenatal visit at the antenatal clinics of seven randomly selected health facilities in Central Region of Ghana. The selected facilities included Cape Coast Metropolitan Hospital, Ewim Urban Health Centre at Cape Coast, St. Francis Xavier Hospital at Assin Foso, Twifo Praso Government Hospital, Elmina Urban Health Centre, Saltpond District Hospital, and Abura Dunkwa District Hospital.
Ethical approval was obtained from the University of Cape Coast Institutional Review Committee. Approval was also sought from the Central Regional Directorate of the Ghana Health Service before commencement of this research. The rationale of the study was explained to the subjects with the assistance of the midwives. Voluntary participation was emphasized and ensured. Participant anonymity was also ensured. Written informed consent from each consenting pregnant woman was sought before sample collection.
Participants were randomly recruited from pregnant women who had reported their routine monthly antenatal visit at the antenatal clinics of seven randomly selected health facilities in Central Region of Ghana. Blood was collected from participants upon their next antenatal visit from the day of recruitment. This was to ensure that blood collection was done at least a week after the consumption of SP by the pregnant women. The number of SP doses each participant has consumed was recorded. Participants were, thus, categorized as no-SP dose, one-SP dose, two-SP dose, and three-SP dose groups depending on the number of SP doses they had consumed at the point of sample collection.
Five millilitres (5 mL) of blood sample was collected from each participant into tubes containing EDTA by trained and licensed medical laboratory technologists in the various health facilities. All blood samples collected were stored on ice and transported to the Parasitology Research Laboratory of the Department of Biomedical and Forensic Sciences, University of Cape Coast
Giemsa-stained thick blood films were prepared and the slides were observed under the light microscope using ×100 objective lens [
The haemoglobin level of each sample collected was estimated using a Cell Dyn 1800 automated blood analyzer. A participant was considered anaemic if his/her haemoglobin level was below 11 g/dL.
Three SP drugs were sampled for this study between October and November 2009. For the purpose of confidentiality, the original names and batch numbers of the drugs have been withheld. The drugs were coded as Drugs I, II, and III. Drug I is locally manufactured and given to pregnant women at the antenatal care clinics as prophylaxis. Drug II is also locally manufactured and sold on the open market in pharmacies and licensed chemical shops. Drug III is an imported product commonly found in pharmacies and licensed chemical shops. Drug I was obtained from antenatal clinics in Cape Coast, Saltpond, Elmina, Twifo Praso, Assin Foso, and Abura Dunkwa, while Drugs II and III were obtained from pharmacies and licensed chemical shops in these same areas through mystery buying. All three drugs sampled for this study had more than a year to expire. The manufacturing and expiry dates for the Drugs I were September 2007–September 2011 and those for both Drugs II and III were April 2008–April 2012. The health facilities and retail shops stored the drugs in well ventilated rooms at room temperature and kept them away from sunlight. After sampling, the drugs were stored in their various packages at room temperature until drug analysis was carried out at the laboratory of Ghana Standard Authority in February 2010.
In assessing the quality of the SP, the chemical or biological assay and the dissolution methods were employed. Reference standard solution of SP was prepared by dissolving approximately 0.5 g (500 mg) of sulfadoxine and 0.025 g (25 mg) of pyrimethamine in 10 mL methanol and diluted with mobile phase to 100 mL. Five replicate injections of a system suitability preparation (standard solution) were chromatographed and the peak areas were recorded [
Twenty tablets of each brand of SP drug were weighed and the average weight was determined. The 20 tablets of each brand were powdered separately with mortar and pestle. An accurately weighed amount of the finely ground powder, equivalent to 0.5 g sulfadoxine and 0.025 g pyrimethamine of each sample, was dissolved in 10 mL of methanol with the aid of an ultrasonic bath. It was then diluted with mobile phase to 100 mL, mixed, and filtered [
Tablet dissolution was performed in the ERWEKA DT 600 dissolution apparatus using 6 tablets of each product. Dissolution of the antimalarial products was carried out using 1 litre of 0.01 M pH phosphate buffer solution (sodium hydroxide and potassium dihydrogen orthophosphate, Fisher Scientific) and heated to a temperature of 37°C, with a rotor speed of 75 revolutions per minute (rpm). The 6 tablets were introduced into the dissolution vessels and dissolution was carried for 30 minutes [
The data collected were recorded into a precoded case record forms. Thereafter, the data were transferred to Statistical Package for the Social Sciences (SPSS) version 10 for analysis. Descriptive statistics such as means and standard deviations were used to summarize quantitative variables, while categorical variables were summarized with proportions. The student
A total of 543 pregnant women were recruited into the programme. The ages of the participants ranged from 16 to 44 of which the majority 444 (82%) of the women were between the ages of 18 and 34 years. The pregnancies were from 5 to 9 months. The women who were pregnant for the first time constituted 32% (172), whilst 68% (371) of them have had between 1 and 9 pregnancies. About 77% of the subjects were employed.
Malaria parasites were found in the peripheral blood of pregnant women who had taken SP and those who had not taken. Of the 543 pregnant women, 304 (56.0%) had taken Drug I (SP). Those who had not taken SP were 239 (44.0%). A total of 63 pregnant women out of the 543 (11.6%) had malaria parasites in their blood. Out of the 63 infected pregnant women, 34 (54.0%) had taken SP and 29 (46.0%) had not taken SP (Table
IPTp-SP compliance and haemoglobin level against malaria in pregnant women.
Category | Malaria status |
|
|
---|---|---|---|
Infected | Noninfected | ||
|
|
||
IPTp-SP compliance |
|
||
Yes | 34 (54.0%) | 270 (56.3%) | |
No | 29 (46.0%) | 210 (43.7%) | |
Total | 63 (100%) | 480 (100%) | |
Haemoglobin level |
|
||
Low | 49 (77.8%) | 350 (72.9%) | |
Normal | 14 (22.2%) | 130 (27.1%) | |
63 (100%) | 480 (100%) |
The haemoglobin levels of the pregnant women were generally low. As many as 399 (73.5%) of the pregnant women had low haemoglobin, whilst 144 (26.5%) had normal haemoglobin. Forty-nine pregnant women representing 77.8% of the infected pregnant women had low haemoglobin (below 11 g/dL), whilst 72.9% of the uninfected pregnant women also had low haemoglobin (Table
There was relatively greater parasite density in the multigravidae than in the primigravidae. There were 33.9% (184) and 66.1% (359) primigravidae and multigravidae, respectively. The infected primigravidae and multigravidae were 25 (39.7%) and 38 (60.3%), respectively. Forty-five infected pregnant women had parasite densities within 1–999 parasites/
Comparison of malaria parasite density between primigravidae and multigravidae.
Category | Gravidity |
|
|
---|---|---|---|
Primigravida | Multigravida | ||
|
|
||
Malaria status |
|
||
Infected | 25 (13.6%) | 38 (10.6%) | |
Noninfected | 159 (86.4%) | 321 (89.4%) | |
Total | 184 (100%) | 359 (100%) | |
Parasite density |
|
||
0 | 159 (86.4%) | 321 (89.4%) | |
1–999 | 16 (8.7%) | 29 (8.1%) | |
1000–9999 | 9 (4.9%) | 9 (2.5%) | |
|
0 (0%) | 0 (0%) | |
Total | 184 (100%) | 359 (100%) |
Drug I and Drug III passed the drug assay test in that the average percentage composition of both sulfadoxine and pyrimethamine in these drugs fell within the 90.0%–110.0% range. Drug II failed the assay test because the average percent composition of pyrimethamine in it was below 90.0 percent (Table
Calculated weight in milligram and percentage composition of sulfadoxine and pyrimethamine in Drugs I, II, and III.
Weight of sulfadoxine | Percentage composition | Weight of pyrimethamine | Percentage composition | |
---|---|---|---|---|
Drug I | Per tablet (mg) | (%) | Per tablet (mg) | (%) |
1 | 485.72 | 97.14 | 21.88 | 87.52 |
2 | 490.36 | 98.07 | 23.92 | 95.68 |
3 | 489.52 | 97.90 | 23.78 | 95.12 |
Average | 97.71 | 92.76 | ||
Drug II | ||||
1 | 485.31 | 97.06 | 18.39 | 73.56 |
2 | 485.88 | 97.18 | 18.89 | 75.56 |
3 | 485.62 | 97.90 | 19.16 | 76.64 |
Average | 97.12 | 75.24 | ||
Drug III | ||||
1 | 497.76 | 99.55 | 22.51 | 90.04 |
2 | 498.00 | 99.60 | 23.72 | 94.80 |
3 | 498.76 | 99.75 | 22.85 | 91.40 |
Average | 99.63 | 92.12 |
(mg): milligram; (%): percentage.
Recorded peak responses of five replicate injections and calculated percentage dissolution of sulfadoxine and pyrimethamine in Drugs I and III.
Average peak area of sulfadoxine (mV) | Percentage of sulfadoxine dissolved (%) | Average peak area of pyrimethamine (mV) | Percentage of pyrimethamine dissolved (%) | |
---|---|---|---|---|
Drug I | ||||
1 | 6892774 | 59.42 | 90182 | 20.20 |
2 | 7076779 | 61.00 | 114852 | 25.74 |
3 | 6991092 | 60.27 | 90667 | 20.31 |
4 | 7017232 | 60.49 | 105682 | 23.67 |
5 | 6981546 | 60.18 | 110563 | 24.76 |
6 | 6889575 | 59.39 | 115472 | 25.86 |
Drug III | ||||
1 | 10898130 | 93.94 | 358382.5 | 80.27 |
2 | 10516241 | 90.65 | 347357 | 77.80 |
3 | 10790608 | 93.02 | 305035 | 68.32 |
4 | 10811924 | 93.20 | 314093.5 | 70.35 |
5 | 10679338 | 92.06 | 298327.6 | 66.82 |
6 | 10592611 | 91.31 | 306223.3 | 68.59 |
(mV): millivolts.
All participants were eligible to take SP; however, only 56% had used IPTp-SP. This rather low compliance to IPTp-SP has been explained to be due to late first ANC clinic enrolment [
Generally, the pregnant women were anaemic. Anaemia is one of the most important consequences of malaria infection during pregnancy. Anaemia during pregnancy can cause low birth weight and low birth haemoglobin in the infant. This consequently may lead to increased morbidity for the infant [
In Ghana, the government provides free antenatal care. Pregnant women are given malaria prophylaxis in the form of SP tablets (Drug I) obtained from a particular pharmaceutical firm. SP from other sources are sold in pharmaceutical shops. Drug I and Drug III passed the drug assay test, implying that they contain the right quantities of the active ingredients, sulfadoxine and pyrimethamine. However, only Drug III passed the drug dissolution test. The test for dissolution determines the amount of active ingredient that is released and available for absorption. Poor manufacturing practices, poor storage of a product, and the use of incorrect excipients will lead to poor dissolution profiles [
Drug I, being used in IPTp-SP in Ghana, is of low quality and thus may be ineffective in prevention and treatment of malaria in pregnancy.
The authors declare that there is no conflict of interests regarding the publication of this paper.