Malaria in pregnancy: Access to effective interventions in Africa

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1 International Journal of Gynecology and Obstetrics (2006) 94, REGIONAL AND NATIONAL PERSPECTIVES Malaria in pregnancy: Access to effective interventions in Africa J.E. Yartey * Department of Making Pregnancy Safer, World Health Organization, Geneva, Switzerland KEYWORDS Malaria; Pregnancy; Prevention; Intermittent preventive treatment (IPT); Insecticide-treated nets (ITNs) Abstract Malaria infection during pregnancy (MIP) poses substantial risks to the mother, her fetus and the newborn. Consequences of MIP include severe anemia, placental parasitemia and intrauterine growth retardation, which contribute to low birth weight, a principal cause of infant mortality in the African region. Effective interventions for the prevention and control of MIP include Intermittent preventive treatment (IPT), Insecticide treated nets (ITNs), and case management, and are being deployed by countries. The global political and fiscal environment is favorable with increasing resources to support the scale-up of interventions. What is needed at country level is strong collaboration among malaria and reproductive health programs and partners, to maximize the use of available resources for scaling-up to achieve the Millennium Development Goals. Equally important is the need for continuous advocacy at all levels to keep malaria high on the global agenda and maintain the current global commitment and momentum. D 2006 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction Approximately 90% of all malaria illness and death in the world today occurs in sub-saharan Africa, where the most virulent species of the malaria parasite Plasmodium falciparum thrives [1]. Malaria exacts its greatest toll on pregnant women and children, killing an estimated 1 to 2 million children each year and causing illness in a further 300 to 500 million individuals. About 25 million pregnancies * Tel.: ; fax: address: yarteyj@who.int. that occur in malaria-endemic areas of Africa are at risk of malaria infection each year [2,3] Consequences of malaria during pregnancy Malaria infection during pregnancy poses substantial risks to the mother, her fetus and the neonate (Fig. 1). The consequences of malaria during pregnancy differ according to the intensity of malaria transmission, level of antimalarial immunity acquired by the mother prior to pregnancy, and the efficacy of these immune responses during the pregnancy [4]. Although two distinct epidemiologic /$ - see front matter D 2006 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi: /j.ijgo

2 Malaria in pregnancy: Access to effective interventions in Africa 365 Figure 1 Adverse consequences of malaria during pregnancy. settings are recognized (low versus moderate to high transmission areas), in reality, the intensity of transmission and immunity in pregnant women occur on a continuum, and may vary within a specific country. In areas of high or moderate (stable) malaria transmission, P. falciparum infection during pregnancy is often asymptomatic due to a high level of acquired immunity. In these areas, primigravidas and, to a lesser extent, secundigravidas are at highest risk of malaria infection, and the principal effects of infection are maternal anemia and placental parasitemia [4,5]. Although anemia during pregnancy may have multiple causes (inadequate nutrition, hemoglobinopathies, hookworm, HIV and other infections), the contribution of malaria to anemia among pregnant women in the Africa region is substantial [6]. Severe maternal anemia increases the motherts risk of death and is estimated to cause as many as 10,000 maternal deaths in Africa each year [7]. The effects on the fetus are intrauterine growth retardation due to impaired fetal nutrition, which contributes to low birth weight (LBW), which is the single greatest risk factor for neonatal and infant mortality [4,5,8]. Consequently, in areas with stable malaria transmission, malaria contributes to approximately 2 15% of maternal anemia, 8 36% of prematurity, 13 70% of intrauterine growth retardation and 8 14% of LBW. Maternal malaria infection accounts for almost 30% of all the causes of LBW that can be prevented during pregnancy and 3 8% of all infant deaths [1,2]. The adverse consequences of P. falciparum malaria during pregnancy for the pregnant woman, the fetus and the newborn are shown in Fig. 1. In areas of low or unstable malaria transmission, women of reproductive age have relatively little or no acquired immunity to malaria. In these areas, all pregnant women, regardless of the number of previous pregnancies, are at similar risk of the adverse consequences of malaria, including severe illness and death as a direct result of severe malaria or malaria-related severe anemia [9,10]. In addition, malaria infection in the mother can result in other adverse pregnancy outcomes such as spontaneous abortion, stillbirths, prematurity and LBW, as well as congenital infection [9,11,12] Effects of infections with other malaria species The effect of malaria during pregnancy is best understood for P. falciparum infection. Adverse consequences due to the other three parasites that cause malaria in humans (P. vivax, P. malariae and P. ovale), all of which are less common in the Africa region, and occur primarily in areas of low or unstable transmission such as Asia and Latin America, are less clear. Studies among non-immune pregnant women have reported that P. vivax infection during pregnancy is associated with maternal anemia and LBW but to a lesser extent than is P. falciparum [13]. Further studies are needed to better examine the effects of P. vivax and other malaria species infections during pregnancy Malaria and HIV: interactions and consequences Apart from the co-endemicity of malaria and HIV in the Africa region, a synergistic interaction between the two major infectious diseases in the Africa region presents a significant concern with major public health implications. Evidence of a synergistic

3 366 interaction between the two diseases keeps mounting. A meta-analysis of studies on co-infection in pregnancy has shown that HIV infection impairs the efficacy of immune responses during pregnancy and diminishes a pregnant womants ability to control P. falciparum infections [14]. Hence, the prevalence and intensity of malaria infection during pregnancy is higher in women who are HIV-infected [15,16]. HIV-1 infection also increases susceptibility to new malarial infections. Kamya et al. (2006) observed a N 6-fold increased risk of new malarial infections associated with HIV infection in Uganda [17]. HIV infection also increases the risk of malaria-associated adverse pregnancy outcomes [18]. It is not yet clear how placental malaria affects the vertical transmission of HIV from mother-to-child (MTCT). Ongoing studies have yielded conflicting results with some suggesting increased transmission [19] and others, a protective effect of placental malaria on MTCT of HIV [20]. These mixed observations may reflect a complex interaction between placental malaria immune responses and stimulation of HIV replication. Although the consequences of MIP depend on the number of pregnancies in general, in the presence of HIV infection, the consequences of malaria during pregnancy have been shown to be independent of the number of pregnancies [21]. Recent studies also suggest that placental malaria might be a strong risk factor for malaria infection during infancy [22]. These diverse but important observations buttress the need for co-programming for malaria and HIV in the Africa region, to maximize the effective use of available resources for malaria and HIV control. 2. WHO strategy for the prevention and control of malaria during pregnancy Although the serious consequences of malaria infection during pregnancy are well known, strategies to mitigate its impact have not been effective in the past. Previously, the World Health Organization (WHO) recommended that pregnant women in malaria-endemic areas receive full antimalarial treatment on their first contact with antenatal care services followed by weekly chemoprophylaxis (i.e., frequent, regular use of an antimalarial drug given at less than a therapeutic dose) [23]. The drug most commonly used for chemoprophylaxis was chloroquine (CQ). The effectiveness of this strategy was limited by two factors: (i) poor compliance with a weekly regimen throughout pregnancy and (ii) increasing resistance of P. falciparum to CQ [24]. Due to the high level of P. falciparum resistance to CQ in most areas of Africa, J.E. Yartey weekly chemoprophylaxis with chloroquine (CQ) is no longer recommended for the prevention and control of malaria during pregnancy in areas of stable malaria transmission. WHO currently recommends a three-pronged approach to the prevention and control of malaria during pregnancy in areas of stable transmission [1]. The package of interventions consist of: (i) intermittent preventive treatment (IPT) of asymptomatic pregnant women, (ii) use of insecticide-treated bednets (ITNs) and (iii) prompt and effective case management of malaria illness and anemia Intermittent preventive treatment (IPT) IPT is the administration of full treatment doses of an effective, preferably one-dose, antimalarial for the prevention of malaria at predefined intervals. WHO recommends that all pregnant women in areas of stable malaria transmission should receive at least two doses of IPT after quickening (first noted movement of the fetus) during regularly/ routinely scheduled antenatal clinic visits [1]. WHO recommends a schedule of four antenatal clinic visits, with three visits after quickening [25]. The delivery of IPT with each scheduled visit after quickening will assure that a high proportion of women receive at least two doses. IPT doses should not be given more frequently than monthly [1]. Currently, the most effective drug for IPT is sulfadoxine pyrimethamine (SP) because of its safety in pregnancy, effectiveness in reproductive-age women and feasibility for use in programs, since it can be delivered as a single-dose treatment under observation by a health worker. IPT with SP has been shown to be effective in reducing the risk of malaria during pregnancy and associated adverse pregnancy outcomes including maternal anemia, placental parasitemia and the incidence of low birth weight [26,27]. Current scientific evidence suggests that at least two doses of IPT with SP are required to achieve optimal benefit in most women. Some studies in HIV-infected pregnant women have demonstrated that monthly dosing of IPT, with most women receiving three to four doses, is necessary to achieve optimal benefit [27]. In settings with HIV prevalence in pregnant women greater than 10%, it might be more cost-effective to treat all women with a three-dose regimen than to screen for HIV and provide this regimen only to HIV-infected women [1]. There is no evidence that receiving more than three doses of IPT with SP during

4 Malaria in pregnancy: Access to effective interventions in Africa 367 pregnancy offers additional benefit or increases the risk of adverse drug reactions. In response to concerns about the effectiveness of IPT with SP in areas with increasing P. falciparum resistance to SP, research is ongoing to assess the safety, efficacy and program feasibility of other antimalarial drugs for use in IPT Use of insecticide-treated nets (ITNs) ITNs reduce human-vector contact by killing or repelling vector mosquitoes, with a documented effect in reducing malaria-related illness and death and improved pregnancy outcomes [28]. Studies in Africa have demonstrated that wide-scale use of ITNs can reduce all-cause mortality in children by about 20% and the number of clinical malaria episodes in the same age group by as much as 50% [29 31]. Studies in intense malaria transmission areas in western Kenya also demonstrate that women who were protected by ITNs gave birth to approximately 25% fewer babies who were either small for gestational age or born prematurely than those not protected by ITNs [32]. In Asia and Latin America (areas with low malaria transmission), the use of ITNs also significantly reduced the number of clinical episodes due to both P. falciparum and P. vivax. When community coverage is high, ITNs not only protect those who sleep under them, but also protect those in the same dwelling (household effect) and the community as a whole (community effect) [33]. ITNs should be provided to pregnant women as early in pregnancy as possible and their use should be encouraged throughout pregnancy and during the postpartum period [1]. ITNs can be provided either through antenatal clinics or other outlets in the public and private sectors (e.g., effective community-based mechanisms, commercial vendors). Distribution of ITNs through antenatal care or other outlets should rely on local opportunities and strategies and should seek to achieve high levels of coverage. A critical concern is the rate of retreatment. Long-lasting insecticidal nets (LLINs) have been developed in response to low retreatment rates of conventional ITNs. These are pre-treated nets that require no further retreatment during their expected lifespan of 4 5 years. Use of LLINs reduces both human exposure (most of the insecticide is hidden in the net and not bioavailable) and the risk of environmental contamination. At about US$5 each, LLINs are more cost-effective than conventionally treated nets [34]. Efforts are being made to scale-up production capacity to meet demand, and the Roll Back Malaria (RBM) Partnership is facilitating technology transfer and stimulating local production of LLINs in Africa Other vector control options Indoor residual spraying (IRS) is another vector control option that involves the application of a liquid insecticide, which dries up to leave a residue with long-lasting insecticidal effect on indoor resting places of the vector. Insects absorb a lethal dose when they come in contact with the surface [34]. IRS also has an agitating and repellent effect on mosquitoes, with the added benefit of reducing the number of mosquitoes entering indoor spaces. IRS is most effective in areas of unstable transmission, areas with marked seasonal transmission peaks and disease outbreaks, and in highland areas. If implemented just before the transmission period or seasonal peaks, it may disrupt vector population dynamics and shorten the transmission period or even suppress epidemic outbreaks entirely. The effectiveness of IRS depends on coverage in the community and level of acceptance. IRS may have benefits similar to those obtained with ITNs and LLINs for pregnant women and may be a relevant alternative in the few settings where IRS is routinely supported. However, ITNs are as effective as IRS in reducing transmission in many settings, as long as high coverage is ensured. Hence, a decision to use IRS must be supported by a good understanding of the local conditions and community dynamics, and the appropriateness of this intervention [34,35]. WHO recommends 12 insecticides for IRS, including DDT [35], and supports the continued use of DDT for disease vector control under the Stockholm Convention on Persistent Organic Pollutants [36,37] Effective case management of malaria illness and anemia Effective case management of malaria illness for all pregnant women in malarious areas must be assured [1]. Treatment of malaria during pregnancy aims at completely eliminating the infection. Quinine is the drug of choice for treatment of malaria in the first trimester of pregnancy and severe malaria throughout pregnancy. The recommended antimalarial drugs for treatment of uncomplicated malaria are CQ in CQ-sensitive areas and sulfadoxine pyrimethamine (SP) in areas with CQ resistance. Quinine may also be used as an alternative in areas where both CQ and SP are not effective. A WHO meeting to review the limited data on use of artemisinin compounds in pregnancy concluded that these drugs appear to be safe for use in the second and third trimesters of

5 368 pregnancy and during lactation [38]. However, additional information will be needed before these are recommended for use routinely. Other antimalarial drugs are under investigation for use in pregnancy. The following drugs are not to be used during pregnancy: halofantrine, tetracycline, doxycycline and primaquine. Anemia poses appreciable risk during pregnancy even when asymptomatic [39]. P. falciparum parasitemia in the placenta could contribute to maternal anemia even in the absence of peripheral parasitemia. Hence, pregnant women with severe anemia in malaria-endemic areas must be treated presumptively with an effective antimalarial drug, whether or not peripheral parasitemia is present and with or without a history of fever. Pregnant women should be screened for anemia and those with moderate to severe anemia should be managed according to national reproductive health guidelines. Pregnant women should also be given iron supplementation for anemia as part of routine antenatal care [25]. In settings with low transmission intensity or where different Plasmodium species co-exist and pregnant women have little or no malarial immunity, emphasis should be placed on prompt effective treatment of malaria illness [1]. In some settings, chemoprophylaxis may be considered, but its programmatic limitations should be fully recognized [23,24]. There is need for further studies to determine the safety and cost-effectiveness of specific preventive approaches (e.g., IPT and ITNs) in such low transmission settings Cost-effectiveness of MIP interventions Malaria prevention during pregnancy using IPT and ITNs is highly cost-effective. IPT with SP is estimated to cost $12 to $21 per disability-adjusted life year prevented, which is a very favorable cost compared to the benefits [40]. ITN use by children has been shown to be very cost-effective in several settings, and is similar to most childhood vaccines [41 43]. The cost-effectiveness of ITN use by pregnant women is likely to be similar to that for children. The antenatal prevention package (of IPT and ITNs) is expected to be even more costeffective than either intervention alone, given its programmatic feasibility. 3. Program opportunities J.E. Yartey Interventions for the control of malaria during pregnancy should be delivered within a comprehensive package of antenatal care services and should be responsive to the range of malaria epidemiologic settings and antenatal care conditions that exist in the country. In sub-saharan Africa, an average of more than 70% of women attend antenatal clinics at least once during pregnancy and a significant proportion often make three or more visits [44]. This high utilization of antenatal care by women in the Africa region provides a unique opportunity for the delivery of interventions for the prevention and control of malaria, along with other interventions for improving pregnancy outcomes. Thus, in settings with moderate to high antenatal clinic attendance, every effort should be made to strengthen the care provided. Extension of anti-malaria services beyond the clinic setting should only occur if: (1) they can be specifically targeted to women not visiting antenatal clinics; (2) they can be part of a larger package of antenatal care as provided in the clinic setting; and (3) these efforts could be conducted in a manner that does not undermine service delivery in the clinics. The diverse but important observation on interactions between malaria [14] and HIV buttress the need for co-programming for malaria and HIV in the Africa region, to maximize the effective use of current available resources and global political will for malaria and HIV control. They also support the need for concurrent integration of malaria and HIV interventions into routine maternal and child health programs. Thus, preventive antimalarial measures such as the use of insecticide-treated bed nets and chemotherapy should be essential components of HIV programs in malaria endemic areas with long-term benefits for both mother and child. 4. Global initiatives related to the control of malaria during pregnancy In 1998, the World Health Organization (WHO), United Nations Children s Fund (UNICEF), the United Nations Development Program (UNDP) and the World Bank (WB) established the Roll Back Malaria (RBM) Partnership with an aim of halving the malaria burden by The RBM Partnership has expanded rapidly since its launch and now consists of a wide range of partners, including malaria-endemic countries, bilateral and multilateral development partners, the private sector, nongovernmental and community based organizations, as well as foundations and research and academic organizations. The core strategy of the RMB initiative is to forge partnerships that work together to coordinate activities, avoid duplication, and opti-

6 Malaria in pregnancy: Access to effective interventions in Africa 369 mize resources for scaling-up and improving access to malaria prevention and control interventions. The United Nations Millennium Declaration in 2000, to which 189 member countries agreed on eight Millennium Development Goals (MDGs) and pledged their commitment to achieving these goals by the year Two of these MDGs (4 and 5) focus on maternal and child health and aim at reducing maternal mortality ratio by 3/4 and under-five mortality by 2/3 of rates in Goal 6 focuses on malaria, HIV and other infectious diseases, and aims at halting/reversing the incidence of malaria by the year Core strategies for achieving these goals include: promotion of skilled care at birth (goals 4 and 5), and use of effective malaria prevention and treatment interventions among populations living in malaria-risk areas (goal 6). However, in malaria endemic areas, where malaria contributes significantly to maternal and child morbidity and mortality, control of malaria during pregnancy is also critical to the achievement of MDGs 4 and 5. In 2000, African Heads of State from 44 malaria endemic countries meeting in Abuja, Nigeria for the Roll Back Malaria summit, committed to ensuring that 60% of pregnant women in malariaendemic areas have access to effective prevention (IPT, ITNs) and treatment interventions for malaria by the end of This commitment from African leaders, known as the Abuja Declaration, and the goals set have facilitated the adoption and implementation of the WHO recommended three-prong strategy for the prevention and control of malaria during pregnancy in areas of stable transmission, and contributes to the realization of the RBM goal of halving the malaria burden by Status of implementation in Africa As at October 2005, 29 countries in sub-saharan Africa had adopted IPT as policy, with implementation at various stages in 21 countries. However, large-scale implementation had been achieved in only eight countries. The remaining malaria endemic countries in the region were considering changes in their policies in the light of the new WHO recommendations (Fig. 2). Twenty-five countries in the region also have ITN policies and several have ITN strategies, although ITN availability and utilization in countries is very low. Since 2002, several countries have initiated ITN distribution at no cost or highly subsidized to children under 5 years of age and pregnant women. As a result, there has been a substantial increase in ITN coverage in these countries, according to household surveys conducted over time that measured Figure 2 Status of IPT implementation and adoption/october 2005.

7 370 ITN use by children and/or household ownership of ITNs [45]. Estimates of net use (treated and untreated) show a great deal of disparity across sub-saharan Africa, but typically reveal that 10% to 30% of the population uses untreated nets with a much lower percentage using ITNs [46,47]. Although several countries distribute ITNs during immunization and other health campaigns, very few countries have routine distribution of ITNs targeted at pregnant women in antenatal care settings. 6. Challenges and priority actions for scaling-up 6.1. Alternative drugs for IPT and case management One of the key challenges to the continued effectiveness and success of IPT is the increasing P. falciparum resistance to sulfadoxine pyrimethamine (SP). Although P. falciparum resistance to SP in children is increasing rapidly in sub-saharan Africa, SP efficacy may persist longer in reproductive-age women because of their acquired immunity. Equally challenging is the availability of appropriate drugs for malaria case management in pregnant women. As P. falciparum resistance to chloroquine and sulfadoxine pyrimethamine increases, there is need to identify alternative drugs that are safe and effective for pregnant women. Research is ongoing to identify safe, effective and affordable alternatives for case management and intermittent preventive treatment of pregnant women ITN distribution Distribution of ITNs through broutineq antenatal care (ANC) is desirable but logistically challenging. Although a routine distribution system would reach most women who receive antenatal care, such a distribution mechanism would require additional inputs such as facilities for net storage, distribution and administrative systems, and incorporation into ANC training, supervision and logistics management schedules. Also, although a large proportion of women make at least one ANC visit during pregnancy, these ANC visits often occur at a late stage in pregnancy and may not yield the full benefit from the investment in an ITN at that stage. The cost of ITNs is also a major barrier to achieving high coverage and utilization rates. Given the effectiveness of ITNs in reducing malaria infection at the community level, it has been recommended that ITNs should be considered as a public good and provided at no cost to high risk populations such as pregnant women and children through routine health systems, and sustained financially by governments and donors in the same way as other ANC and childhood services and vaccines are provided [48]. Reducing taxes and tariffs to facilitate procurement, manufacture and distribution of insecticide-treated materials, and support for the expansion of the commercial market is likely to create an enabling environment for ITN utilization. Establishing public private partnerships between national malaria control programs and the commercial/private sector to support scale-up to improve net use and impact Weak health systems J.E. Yartey IPT delivery and case management are often constrained by lack of drugs and supplies and availability of qualified staff that can effectively manage cases of malaria during pregnancy. With the introduction of artemisinin-based combination theraples (ACTs), case management in pregnancy requires logistics for diagnosis and monitoring of complications. In general, laboratory services in most countries of the region are weak and incapable of adequately supporting malaria diagnosis and case management. In most situations, laboratory services, including tests for malaria parasites, hemoglobin and blood sugar levels, can only be accessed in urban health facilities and referral hospitals. Referral systems that are needed for cases of severe malaria are either non-existent or poor, leaving many women to die from complications of malaria at peripheral levels. Underlying determinants of poor referral systems include human resource constraints, poor supervision and lack of communication, transportation and supporting infrastructure. As is characteristic of most national health systems in the region, Health Management Information Systems (HMIS) are weak and characterized by incompleteness, inaccuracies, lack of standardization, poor flow and lack of analysis, and utilization of data for local planning and management purposes. The health systems, in general, are constrained by inadequate human resources with only 40 50% of pregnant women in the region accessing skilled care at birth, which makes monitoring of critical demographic markers such as birth weight very difficult. Effective implementation of malaria control interventions depends on the availability, skills and motivation of health pro-

8 Malaria in pregnancy: Access to effective interventions in Africa 371 viders, and their interactions with the community. Strengthening health systems in the Africa region is critical to the successful delivery of malaria interventions to pregnant women and their children. Community mobilization and participation in the planning and implementation of malaria control activities should be supported as an integral part of an effective district health system Collaboration between malaria control and reproductive health programs The success of the WHO Malaria Infection During Pregnancy strategy largely depends on collaboration between national malaria control and reproductive health programs. To foster collaboration between malaria control and reproductive health programs, the WHO Roll Back Malaria (RBM) department has established strong collaboration with Making Pregnancy Safer (MPS) and with key Partners to foster this relationship at all levels. Due to the high burden of malaria-associated anemia among pregnant women in Africa, malaria control has become an integral component of the Making Pregnancy Safer strategy at country level. Antenatal clinics offer an excellent platform for reaching women and their families with a comprehensive set of interventions, as many women in the Africa region access antenatal care during pregnancy [44]. Delivery of malaria interventions as part of an antenatal care package requires strong collaboration between malaria and reproductive health programs in order to ensure that pregnant women receive the comprehensive care they need in a holistic manner. It is also becoming increasingly clear that the effectiveness of these interventions in the region requires concurrent prevention and control of HIV infection in pregnant women, which is feasible within the antenatal care setting. Co-programming for Malaria and HIV with concurrent delivery of the necessary interventions within maternal and newborn health services, effectively supported by strong health systems, is imperative to the achievement of the Millenium Development Goals. Successful collaboration between programs must recognize the service delivery role of reproductive health programs with technical guidance from malaria and HIV control programs, and should include collaborative arrangements for the procurement of drugs and supplies, and joint training, supervision, monitoring and evaluation Partnerships and donor support A considerable number of public private partnerships have recently been formed and are actively engaged in the RBM Partnership to support the implementation and scaling-up of interventions to address the huge burden of malaria in the region. These include major funding initiatives such as the Global Fund for AIDS, TB and Malaria (GFATM), the World Bank Malaria Booster Program, US Presidential Malaria Initiative (PMI), the Malaria Vaccine Initiative (MVI) supported in part by the Bill and Melinda Gates Foundation, and other efforts supported by international organizations, pharmaceutical companies, research institutions, donor agencies, community-based groups and national governments working together in greater concert to effectively roll back malaria. In spite of these efforts, malaria control presents a paradox. On the one hand, several prevention and treatment interventions that are both effective and relatively inexpensive are available. On the other hand, the situation is worsening in many countries of Africa as a result of increasing drug resistance, conflict and associated epidemic situations, and increasing impoverishment, with effective interventions reaching only a small proportion of the population in need. Paradoxically, malaria itself has rendered the affected regions so impoverished that even lowcost interventions cannot be sustainably financed from national resources alone. Donor assistance, on a much larger scale will be necessary to support effective scale-up of interventions for the prevention and control of malaria during pregnancy in the Africa region [49]. 7. Conclusion Effective interventions that are safe for the prevention and control of malaria during pregnancy exist and are ready to be deployed on a largescale at national level. Several countries in the Africa region have adopted these policies and are in the process of developing related tools and scaling-up these interventions at national level. The global political and fiscal environment is favorable, even though donor assistance on a much larger scale will be necessary to support effective scale-up of interventions for the prevention and control of malaria. What is needed at the country level is strong collaboration among programs and partners to maximize the use of

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