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Background: Malaria in pregnancy is associated with many negative outcomes for the woman, foetus and neonate.
Intermittent preventive treatment during pregnancy (IPTp) using three doses of sulfadoxine/pyrimethamine (SP),
insecticide-treated mosquito nets (ITNs) and indoor residual spray (IRS), constitute the main strategies used
to prevent malaria. The aim of this study is to evaluate the effectiveness of these strategies for the reduction of
malaria prevalence in pregnant women. Methods: A questionnaire on socio-demographic information, history of malaria during current pregnancy
and prevention strategies used was administered to 450 consecutive patients admitted into labour wards at three
local clinics. From the antenatal cards, information was collected on the last menstrual period, date of each dose of SP
taken, gravidity, and HIV status. A blood slide to detect Plasmodium was then collected from each woman after consent. Results: Of the participants in the study, 2.4% had a positive blood slide at term and 15.8% reported malaria
during pregnancy. All the participants took at least one dose of SP with 87.6% completing the stipulated three doses.
The mean gestational ages for each dose were 22.1 (SD 4.6), 29.1 (SD 4.4) and 34.4 (SD 3.9) weeks for the first,
second and third dose respectively. With regard to ITNs, 79.5% had one, but only 74.1% used it regularly. IRS was
completed in all three of the clinics’ catchment areas. Only 23.4% used commercial insecticide. Conclusion: The measured prevalence of malaria at term in Ndola was remarkably low, although the
self-reported rate during pregnancy was still high. The national targets for accessing IPTp were exceeded,
although the timing of each dose needs to be improved. Access to ITNs was high, but usage needs to increase.
Malaria infection due to Plasmodium falciparum still causes significant morbidity and mortality in
countries with limited resources that are situated in endemic zones. It is still a global health problem,
with most of the disease burden carried by children younger than 5 years of age and pregnant
women.1 It is estimated that up to 90% of global cases of malaria occur in
sub-Saharan Africa.1,2 Although there are four species causing malaria, most complications are due to the P. falciparum
species.1,2,3In pregnancy, malaria poses a risk to the mother, the foetus and the neonate. In areas of
stable malaria where adult women have considerable acquired immunity, P. falciparum infection during pregnancy
does not typically develop into a symptomatic febrile disease, but rather
leads to maternal anaemia and placental malaria
infection, particularly in the primigravidae and the
secundigravidae.1,2,3,4 On the other hand, pregnant women who are
HIV-positive are particularly vulnerable
to malaria.5,6,7,8 P. falciparum is associated with an increased risk of
maternal anaemia and mortality. It is also accompanied by an increased risk of prematurity. Placental malaria can lead to cord anaemia, intrauterine growth retardation, low birth weight (LBW), and possibly intrauterine death.
Neonatal malaria is also possible and leads to an increased risk of infant
mortality.1,9,10 All of these complications can be avoided by cost-effective prevention of malaria in pregnancy, as well as
early detection and effective treatment of patients. Zambia is a southern African country where malaria is endemic and still constitutes a major public health problem.
The Zambian government has designated malaria control as one of its priorities, as demonstrated in the National Health
Strategic Plan 2006-2010.11 It is estimated that in Zambia, 3.4 million cases of malaria occur every year,
translating into 308 infections per 1000 persons each year and that sulfadoxine/pyrimethamine (SP) total treatment failure
has risen from 14.5% in 2003 to 37.0% in 2004.5 The HIV prevalence in Zambia is 16.0% amongst adults aged 15-49 years,
while amongst pregnant women attending antenatal care, the prevalence is 19.0%.12 Currently, efforts to control malaria in Zambia are being escalated and coordinated under the Roll Back
Malaria (RBM) initiative. Under this initiative, the Zambian government, in collaboration with other partners,
has come up with four strategies, namely (1) use of insecticide-treated mosquito nets (ITNs), (2) indoor residual
spray (IRS) in all houses, with pyrethroids and dichlorodiphenyltrichloroethane (DDT), (3) use of intermittent preventive
treatment of malaria in pregnancy (IPTp) and (4) prompt, effective case management. IPTp was introduced in 2003 and requires three doses of an SP combination that are given to pregnant
women at the gestational ages of 16, 20 and 24 weeks during their antenatal care visits.13 Though
studies elsewhere advise monthly SP for HIV-positive pregnant women,14,15 a 2007 Zambian study concluded
that in zones of meso-endemic malaria transmission,
this was not more efficacious than the standard regimen.5 The use of SP in pregnancy as IPTp has been demonstrated to be safe, however, its concomitant use with co-trimoxazole or
with high-dose folic acid is not advisable.16The implication of this is crucial for HIV-positive women who are
on co-trimoxazole prophylaxis. At the antenatal visits, ITNs are also distributed at a very subsidised price of $1.00 per net and health talks about the
effects of malaria on pregnancy are communicated. IRS spraying at home is provided through the District Health Management Team (DHMT). The Ministry of Health recommends that pregnant women diagnosed with malaria be treated with quinine only in the first
trimester, or if the malaria is severe. In the second and third trimesters, SP should be prescribed. The treatment should
commence within 24 hours of the onset of symptoms.11,13 Although the Zambian malaria control programme in pregnant women was implemented in 2003, its success has not been widely
studied. The aim of this study was to evaluate the effectiveness of strategies employed to prevent malaria in pregnant women
in Ndola, Zambia and, if possible, to make recommendations on how prevention can be improved.
The specific objectives were: • To determine the proportion of pregnant women who have access to and complete the recommended three-dose course of IPTp. • To determine the gestational age at which each dose of IPTp is taken. • To determine the prevalence of maternal parasitemia at term in pregnant women taking SP/IPTp. • To determine the proportion of pregnant women who sleep under ITNs regularly. • To describe the provision of IRS and other non-official strategies used by pregnant women to prevent malaria. • To determine what type of medication is prescribed to pregnant women when they contract malaria.
The study was approved by the Human Research Ethics Committee, Stellenbosch University, South Africa and the Ethics Committee,
Tropical Disease Research Centre, Zambia.
A cross-sectional study evaluated the effect of the RBM prevention strategy on the prevalence of malaria in pregnancy
within the maternity ward.
Settings
The study was conducted in three health clinics in the suburb of Ndola between January and April 2009. Ndola is one of
the urban centres in the Copperbelt province of Zambia, in southern Africa. These three clinics provide health care to
approximately 96 000 people. In all three clinics women give birth routinely and the strategies for malaria prevention
in pregnancy follow the national programme. This includes sleeping under an ITNs, receiving three doses of SP and yearly
IRS with pyrethroids and dichlorodiphenyltrichloroethane (DDT), which is carried out by the Ndola DHMT. Every woman attending antenatal classes is educated on HIV and prevention of mother-to-child transmission.
Zambia uses the opt-out strategy when it comes to HIV testing in pregnant women. The HIV status is then coded on
the antenatal card and on the under-5 card of the child after birth.
Sample size
Taking into consideration that in the chosen three clinics, the total average number of deliveries is 7000 per annum and the
expected malaria prevalence at delivery is 13.6% without IPTp and 6.3% after IPTp.17 For the purpose of the study a
minimum sample size of 350 was calculated using Cochrane's cross-section survey sample size calculation.
Enrolment
Participants who had given informed consent and were at least 28 weeks pregnant and 18 years or older, were
enrolled consecutively as they came into the maternity ward. We excluded those with (1) a history of splenectomy,
(2) sickle cell disease, (3) allergy to sulfadoxine/pyrimethamine and (4) those that came to the maternity ward without
the antenatal cards. Enrolment into the study ceased once 450 patients had consented.
Questionnaire procedures
The purpose of the study and its requirements were explained to the patients prior to obtaining written, informed
consent from each participant. Enrolled women were given a questionnaire by the local midwife to collect (1) socio-demographic
information, (2) history of malaria during the current pregnancy, (3) any anti-malarial treatment and (4) malaria prevention
strategies used. From each participant's antenatal card, information was collected (1) on the last menstrual period, (2)
date at which each dose of IPTp was taken,
(3) gravidity and (4) HIV status.
Laboratory procedures
A drop of blood was collected using a fingerprick sample, and a blood slide was prepared and air-dried. The slides were stained with Giemsa
stain and then examined at the Tropical Disease Research Centre twice a week by a laboratory technician. The number of parasites per 200
white blood cells determined the parasite count and a slide was only considered negative after 100 oil-immersion fields were examined
and no parasite found to be
present.
Out of the 450 participants (150 from each clinic), 11 (2.4%) blood slides tested positive for malaria parasite and
439 (97.6%) tested negative. Their characteristics are shown in Table 1. Information about the gravidity of five participants was absent. Of the 445 for whom gravidity information was available,
122 (27.4%) were either primigravidae or secundigravidae. This represents the group of pregnant women who are at a higher
risk for adverse outcomes. Out of the 445 participants who revealed their HIV status, 89 (20.0%) were HIV-positive. Of these, 15 (16.9%) were either
primigravidae or secundigravidae. This means that 15 women out of the 445 were both HIV-positive and either primigravidae
or secundigravidae, representing 3.4%. Of the 450 participants, all had taken at least one dose of SP (100.0%), and 394 (87.6%) had completed the course of all
three doses. Overall, 99.1% of participants took two or three doses of IPTp. The mean gestational ages for each dose were 22.1 (SD 4.6), 29.1 (SD 4.4) and 34.4 (SD 3.9) weeks for the first, second
and third doses respectively. Only 18 participants (4.1%) took the first dose at 16 weeks, 3 (0.7%) took the second dose at
20 weeks and 1 (0.3%) took the third dose at 24 weeks, as recommended in the national guidelines. In addition, 14.9% of the
women who took three doses of IPTp received their last dose after 38 weeks of gestation. We found that 448 participants owned ITNs; of these, only 356 (79.5%) actually used them. The results also show that
332 women (73.8%) used their ITNs regularly (four times a week or more). Information collected about the use of commercial insecticide showed that 105 respondents (23.4%) had used it. Only 35
(7.8%) used it regularly; this means that the majority of our participants (92.3%) either used it occasionally, or not at all.
More importantly, 76 (72.4%) women out of the 105 still used ITNs regularly. Only five participants (1.1%) applied any mosquito repellents. Although only 2.4% of women were positive for malaria when tested (Table 1), 15.8% reported that they had malaria during
their pregnancy and received treatment, as shown in Table 2. Almost two-thirds of women who suffered from malaria were treated with SP, while only a third (36.6%) received quinine. Out of the 11 women who had a positive slide, 5 were HIV-positive, representing 45.5% of the positive slides. Of the 89
HIV-positive participants, these 5 suggest a prevalence of 5.6%, which is more than double the baseline value. The DHMT confirmed that IRS spraying had been performed throughout the catchment areas of all three clinics during the previous year.
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Table 1: Characteristics of enrolled women participants
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Table 2: Self-reported malaria and treatment received
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Main findings of the study
Overall, the RBM programme was implemented effectively, with 87.6% of pregnant women receiving three doses of SP, 79.5% owning an
ITNs and households in all areas being offered IRS. The timing of the three doses of SP was not aligned with the guidelines and only
74.1% used their ITNs regularly. Only a small number of women supplemented the official strategies with the use of their own
commercial insecticides and repellents. The prevalence of malaria in the maternity ward was low at 2.4%, whilst the self-reported
prevalence during pregnancy was 15.8%.
Comparison to previous studies
The prevalence of malaria in this study is significantly lower than the 6.3% found in Mozambique (with two doses of SP as
the prevention strategy).17The difference can be explained by the fact that in the Zambian situation, many other
strategies are simultaneously implemented, such as IRS and ITNs, as part of the Integrated Vector Control Programme,
in conjunction with the prompt treatment of infected individuals. Although it was found that 15.8% of participants reported having suffered from malaria during their current pregnancy,
many people suffering from any febrile illness in an endemic region like Zambia would call it malaria and a large number
will self-medicate.18 In addition, most pregnant women who present at their local clinic with fever are likely
to be told that they are suffering from malaria and receive treatment with anti-malarial medication. Many health care workers
still prescribe anti-malarial treatment, even when the malaria test is negative.18 Nonetheless, this percentage
is similar to the 15.7% malaria parasitemia found in Burkina Faso.4 In this case, the study was done in a more rural area,
the prevention strategy did not include regular IRS, and the IPTp progamme had only been running for 1 year. On the other hand,
the fact that malaria in pregnancy is usually asymptomatic means that many pregnant women with no fever do not seek medical advice,
even if they may have malaria. The true prevalence of malaria in pregnancy, therefore, can only be fully assessed through placental biopsy. Although the levels of total treatment resistance to SP have increased over the past few years, its effectiveness as an
intermittent preventive treatment is still high.14It is also possible that the use of IPTp as an integrated
part of a larger strategy including other measures, such as ITNs, increases the effectiveness. The Zambian Ministry of Health (MoH) and the World Health Organization (WHO) recommend quinine as the drug of choice during
the first trimester and in severe malaria in pregnancy, while SP can be prescribed in the second and third
trimesters.1,13
However, with the current SP resistance level in Zambia,19 cost-effectiveness studies should be conducted with a view
to prescribing quinine throughout pregnancy. The WHO actually recommends that in areas of combined resistance to chloroquine and SP,
quinine should be the first-line drug, even in second and third trimester.1 In addition, studies should be done, locally,
to assess the possible use of artemisinin and artemisinin combination therapies (ACT). Currently, Zambia does not
recommend prescription of ACT during pregnancy, as there is no evidence base to show its safety. There is emerging data
showing that artesunate and ACT are safe and efficacious in pregnancy.20 Further studies are
required to evaluate
alternatives to SP in the light of increasing resistance. The use of IPTp met the goal of the Zambian MoH to ensure access to IPTp for at least 80% of women by December 2008.
The level exceeds the findings of the Zambia National Malaria Survey in 2006, which recorded that 85.9% of urban women
accessed any IPTp and only 71.2% took all three recommended doses. On average, the first dose was received 6 weeks later than recommended; the second dose was 7 weeks after the first,
and the third dose 5 weeks after the second; instead of the recommended 4-week interval. This late delivery certainly
increases the time that pregnant women spend at risk. In addition, there are suggestions that the late delivery of the
first dose of IPTp could be related to the subsequent late delivery of the other following doses, or lead to an incomplete
IPTp schedule.21 Infection in early or late pregnancy has been associated with more negative effects on the
pregnancy outcome22 and this fact should be the basis for advocating that the first dose of IPTp be on time. The use of ITNs is not far below the target of 80% of pregnant women accessing ITNs by December 2008, as stated in the
National Health Strategic Plan 2006-2010.11 Though the document is silent about the target
concerning the use
of these nets, we would want to believe that the intention of the document was to achieve a comparable target.
This means that the current usage rate (74.1%) is well below the expected rate. Nonetheless, there has been tremendous
improvement when compared to 18% of urban women who slept under an ITNs in 2006.23 Application of insect-repellent ointments or lotion is not a practice that is commonly embraced by the population.
However, there is evidence to show that insect repellent in addition to ITNs provides greater protection, especially
in areas where mosquitoes feed in the early evening, and between dusk and bedtime.24 In countries
with restricted economic power, this might not be a cost-effective programme, but one which is particularly advocated
for tourists and those who can afford it. However, more studies are needed to clarify their safety profile in pregnancy.
Limitations
The exact prevalence of malaria during the whole of pregnancy could not be determined by this cross-sectional study within the
maternity ward. These women were also likely to have frequented the same clinics for their antenatal visits and would most likely
have been educated about the risk factors related to pregnancy in general and malaria in particular. Therefore they were more likely
to have received IPTp and to use ITNs. The results, therefore, for the whole community of pregnant women, which includes those giving
birth at home, those not attending the clinic and those in rural areas, are likely to be worse. The number of women refusing
to participate in the study was not recorded by the research assistants and the uptake of IRS per household was not confirmed
in the questionnaire. The questionnaire could have attempted to verify the gestational age of reported malaria and use of
diagnostic tests, although this would still have been subject to a potential reporting and recall bias.
Recommendations
Further studies should attempt to determine the rates of malaria throughout pregnancy and to assess if the self-reported rate of 15.8%
is correct. There is a need to improve the gestational age at which the first dose of IPT is delivered, as well as the follow-up doses.
This can be achieved through education of health care providers and community sensitisation by health talks given during antenatal
classes. Although access to ITNs has improved dramatically, attention must now be given to the usage rate. There is a need for
more educational messages to pregnant women about the dangers of malaria, the emphasis on taking IPT on time, and always sleeping under
ITNs, especially if one is HIV-positive. The correct treatment of malaria in pregnancy as well as the risks of over-prescription of
anti-malaria drugs needs to be emphasised to health care workers, during continuing medical education sessions. More research needs
to be conducted to evaluate the situation in rural areas and amongst those women who give birth at home with the help of traditional
birth attendants.
The aim of this study was to evaluate the effectiveness of strategies employed to prevent malaria in pregnant women in Ndola,
Zambia, and if possible to make recommendations on how prevention can be improved. The study evaluated 450 consecutive pregnant
women admitted into maternity wards at three local clinics. Overall, the Rolling Back Malaria programme was implemented effectively,
with 87.6% of pregnant women receiving three doses of SP, 79.5% owning an ITNs and households in all areas being offered IRS. T
he timing of the three doses of SP was not aligned with the guidelines and only 74.1% used their ITNs regularly. Only a small
number of women supplemented the official strategies with the use of their own commercial insecticides and repellents.
The prevalence of malaria in the maternity ward was low at 2.4%, whilst the self-reported prevalence during pregnancy was 15.8%.
The results show that the programme is on target for use of IPTp, although improvements can be made on the timing of SP doses and the
actual usage of the ITNs.Â
The authors sincerely thank the midwives in all three clinics for their assistance in administering
the questionnaire to the participants and collecting the blood slides, the Provincial Health Director of the
Copperbelt Province and the Director of Ndola DHMT for their support. We also thank Mr Malunga at the Tropical
Disease Research Centre for the reading of the peripheral smears and the Director, Dr Mulenga.
1. World Health Organization. A strategic framework for malaria prevention and control during pregnancy in the African region. Brazzaville: WHO Regional Office for Africa; 2004. 2. Steketee RW, Nahlen BL, Paris ME, Mendez C. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg. 2001;64(1)28-35. 3. Newman RD, Parise ME, Slutsker L, Nahlen B, Steketee RW. Safety, efficacy, and determinants of effectiveness of antimalarial drugs during pregnancy: Implications for prevention programmes in Plasmodium falciparum-endemic sub-Saharan Africa. Trop Med Int Health. 2003;8(6):488-506. 4. Sirima SB, Cotee AH, Konate A, et al. Malaria prevention during pregnancy: assessing the disease burden one year after implementing a program of intermittent preventive treatment in Koupela district, Burkina Faso. Am J Trop Med Hyg. 2006;75(2):205-211. 5. Hamer HD, Mwanakasale V, Macleod W, et al. Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-seropositive pregnant Zambian women. J Infect Dis. 2007;196(11):1585-1594. 6. Van Eijk AM, Ayisi JG, Ter Kuile FO, et al. HIV increases the risk of malaria in women of all gravidities in Kisumu, Kenya. AIDS. 2003;17(4):595-603. 8. Ter kuile FO, Parise ME, Verhoeff FH, et al. The burden of co-infection with Human Immuno-Deficiency Virus type1 and malaria in pregnant women in sub-Saharan Africa. Am J Trop Med Hyg. 2004;71(suppl 2):41-54. 8. Idemyor V, Pharm D. Human Immuno-deficiency Virus (HIV) and malaria interaction in sub-Saharan Africa: the collision of two titans. HIV Clin Trials. 2007;8(4):246-253. 9. Rogerson SJ, Chaluluka E, Kanjala M, Mkundika P, Mhango C, Molineux ME. Intermittent sulfadoxine-pyrimethamine in pregnancy: Effectiveness against malaria morbidity in Blantyre, Malawi, in 1997-99. Trans R Soc Trop Med Hyg. 2000;94(5):549-553. 10. Ramharter M, Schuster K, Bouyou-akotet MK, et al. Malaria in pregnancy before and after the implementation of a national IPTp program in Gabon. Am J Trop Med Hyg. 2007;77(3):418-422. 11. Ministry of Health. National Health Strategic Plan 2006-2010. Lusaka: Ministry of Health; 2005. 12. Ministry of Health. National scale-up plan for prevention of mother-to-child transmission of HIV and paediatric HIV care services 2007-2010. Lusaka: Directorate of Public Health and Research; 2007. 13. Ministry of Health. Integrated technical guidelines for frontline health workers. 3rd ed. Lusaka: Ministry of Health; 2009. 14. Ter Kuile FO, Van Eijk AM, Filler SJ. Effect of sulfadoxine-pyrimethamine resistance on the efficacy of intermittent preventive therapy for malaria control during pregnancy: a systematic review. JAMA. 2007;297(23):2603-2616. 15. Filler SJ, Kazembe P, Thigpen M, et al. Randomized trial of 2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-positive and HIV-negative pregnant women in Malawi. J Infect Dis. 2006;194(3):286-293. 16. Peters PJ, Thigpen MC, Parise ME, Newman RD. Safety and toxicity of sulfadoxine/pyrimethamine: implications for malaria prevention in pregnancy using intermittent preventive treatment. Drug Saf. 2007;30(6):481-501. 17. Challis K, Osman NB, Cotiro M, Nordahl G, Dgedge M, Bergstrom S. Impact of a double dose of sulphadoxine-purimethamine to reduce prevalence of pregnancy malaria in southern Mozambique. Trop Med Int Health. 2004;9(10):1066-1073. 18. Ministry of Health. National Malaria Control Action Plan 2009. Lusaka: Ministry of Health; 2009. 19. Mkulama MA, Chishimba S, Sikalima J, Rouse P, Thuma PE, Mharakurwa S. Escalating Plasmodium falciparum antifolate drug resistance mutations in Macha, rural Zambia. Malar J. 2008;7:87. 20. McGready R, Tan SO, Ashley EA, et al. Randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated Plasmodium falciparum treatment in pregnancy. PLoS Medicine. 2008;5(12):253. 21. Anders K, Marchant T, Chombo P, Mapunda P, Reyburn H. Timing of intermittent preventive treatment for malaria during pregnancy and the implication of current policy on early uptake in north-east Tanzania. Malaria Journal. 2008;7:79-86. 22. Cottrell G, Mary J, Barro D, Cot M. The importance of the period of malarial infection during pregnancy on birth weight in tropical Africa. Am J Trop Med Hyg. 2000;76(5):849-854. 23. Ministry of Health. Zambia National Malaria Indicator Survey 2006. Lusaka: Ministry of Health; 2006. 24. Hill N, Lenglet A, Arnez A, Carneiro I. Plant-based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: Double blind randomised placebo controlled clinical trial in Bolivian Amazon. BMJ. 2007;335(7628):1023.
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