Global Call to Action to scale-up coverage of intermittent preventive treatment of malaria in pregnancy: seminar report

In 2014, a global ‘Call to Action’ seminar for the scale-up of intermittent preventive treatment of malaria in pregnancy was held during the 63rd Annual Meeting of the American Society of Tropical Medicine and Hygiene. This report summarizes the presentations and main discussion points from the meeting.


Purpose of the meeting
Administration of IPTp with sulphadoxine-pyrimethamine (SP) as part of routine antenatal care (ANC) is one of three key interventions recommended by the World Health Organization (WHO) for the control of malaria in pregnancy in areas of stable malaria transmission. The other two interventions are the provision of insecticidetreated nets and effective case management. Coverage has remained unacceptably low in countries with an IPTp policy. The aim of this seminar was to convene key stakeholders to review barriers to the scale-up of IPTp and to develop an action plan to increase coverage rapidly. This report summarizes central issues presented and discussed during the Call to Action seminar relating to the scale-up of IPTp. Key issues raised at the seminar have been used to outline a set of recommended actions as part of a Global Call to Action which aims to increase national and international coverage to rapid effect.
Pedro Alonso, the newly appointed Director of the WHO Global Malaria Programme (GMP), strongly voiced his support for increasing the coverage of IPTp and pledged that he would make the scale-up of IPTp a priority for GMP. Reinforcing this point, he said that until better and more cost-effective tools are available for the prevention of malaria in pregnancy, GMP will drive the scale-up for IPTp coverage. "Intermittent preventive therapy for pregnancy is a life-saving tool which will be a main priority for the WHO Global Malaria Programme team moving forward." (Pedro Alonso, Director of the Global Malaria Programme, World Health Organization)

Status of IPTp coverage in sub-Saharan Africa
Current coverage estimates of IPTp and insecticidetreated nets (ITNs) in sub-Saharan Africa were presented by Anna Maria van Eijk (Liverpool School of Tropical  Medicine, UK) for the period between 2003 and 2014 based on previously published data [1,2], highlighting an alarming lack of IPTp scale-up. Although coverage for IPTp increased from less than 5 % in 2003 to above 20 % in 2010, no further progress has been made with average coverage rates that have since stagnated between 22 % and 24 %. Overall, IPTp coverage estimates remain far below global targets set by the RBM Partnership of 80 % by 2010, and 100 % (universal coverage) by 2015. Although six countries (The Gambia, Ghana, Malawi, Sao Tomé and Principe, Senegal and Zambia) reached the original 60 % coverage target for 2005, the combined estimate for all countries with an IPTp policy was 24 % in 2013 (Fig. 1). It is of particular concern that the latest estimates for 2014 indicate that coverage is falling in some countries. Progress for ITN coverage is comparatively better but still unacceptably low at 38 % overall. Production of 'rolling coverage estimates' are essential to track overall progress as well as to estimate the uptake and impact of the revised WHO recommendation for IPTp [3]. WHO updated the IPTp policy recommendation in September 2012, increasing the regimen from at least two doses of SP to the provision of a dose of IPTp-SP given at every ANC visit beginning as early as possible in the 2nd trimester throughout pregnancy and at least one month apart, ideally administered as directly observed therapy [3]. Measuring the impact of the policy update will require national household surveys to include data on two, three, and more than three doses of IPTp.

Factors affecting antenatal care delivery of IPTp
Examples from observational studies in Mali and Kenya presented by Jayne Webster (LSHTM, UK) showed that IPTp delivered by direct observation at antenatal care (ANC) facilities was low and ineffective. Despite different operating contexts across countries in terms of IPTp policy on timing of doses and HIV prevalence, the same intermediate steps appeared to impede receiving any SP, and receiving SP by direct observation. SP stock-outs were not an issue when surveys were conducted. Interestingly, surveys revealed high variability across health facilities within the same district and highlighted the need to monitor and to intervene at the facility level to overcome barriers to IPTp, as well as to make distinctions between issues that are driven by individual providers and, separately, those related to facilities. Surveys employed mixed-methods to identify ineffective processes and their predictors for the delivery of IPTp with qualitative analysis offering deeper insights into certain practices as summarized in Table 1. These surveys enabled an in-depth assessment of the ANC processes that are required to deliver IPTp as well as to quantify the major barriers to its provision. Moreover, evidence from mixed-methods is needed to inform policymakers and programme managers on the most appropriate interventions that can improve the uptake of IPTp as well as other ANC interventions.
Harry Tagbor   found over 80 % of pregnant women to have received at least two doses of IPTp while 71 % of women made more than four ANC visits during their pregnancies. The number of ANC visits was significantly associated with greater IPTp dosing. This study further highlighted the importance of making every ANC visit count as an opportunity to deliver IPTp, and also the need to address bottlenecks at the local district and health facility levels.
The need for improved communication and messaging around the benefit of IPTp was illustrated by Matthew Chico (LSHTM, UK) from the findings of a qualitative investigation carried out in Tanzania in 2013 into the barriers to IPTp [4]. Knowledge of IPTp and an understanding of the difference between prevention and treatment of malaria among pregnant women in the study area was low. Many women reported that SP had undesirable side effects, including the misconception that IPTp negatively prolonged pregnancy, thereby increasing the risk to maternal health at delivery. It is possible that scientific evidence of IPTp protection against pre-term birth has been misinterpreted by pregnant women so that SP use in pregnancy is viewed as something undesirable or unsafe. Such beliefs and lack of awareness of malaria prevention interventions have potentially significant implications on the uptake of IPTp and should be addressed through appropriate behaviour change communication strategies. The same study showed strong demand in Tanzania from national policymakers, district-level healthcare providers and pregnant women at ANC facilities for holistic approaches that protect against MiP and curable sexually transmitted and reproductive tract infections in pregnancy.

Cost-effectiveness of IPTp with SP
Findings from cost-effectiveness analyses of IPTp with SP (IPTp-SP) were presented by Elisa Sicuri (Barcelona  Centre for International Health Research, Spain) who showed that two doses of IPTp-SP was highly costeffective and that three or more doses of IPTp-SP was more cost-effective than two doses. The first analysis estimated the cost-effectiveness of IPTp-SP from a randomized placebo-controlled trial of IPTp-SP in the context of ITN use and moderate SP resistance in Mozambique [5]. This trial found that two doses of Even assuming a reduction in SP efficacy to 15 % in clinical case management and a reduction in neonatal deaths averted from 11 to 4.5 per 1,000 women taking the prevention, IPTp-SP remained cost-effective. The study concluded that two doses of IPTp-SP is a highly cost-effective intervention both in terms of prevention of maternal clinical malaria and reduction in neonatal mortality in this context (Table 2). Furthermore, provision of IPTp with a more efficacious drug than SP, even if more expensive, may still remain a cost-effective public health measure to prevent malaria in pregnancy, particularly in HIV-infected pregnant women [6]. The second costeffectiveness study was based on the meta-analysis of IPTp with three or more IPTp doses of SP versus two doses across a range of African settings [7]. The meta-analysis found that three or more doses of IPTp-SP was associated with increased birth weight and decreased risk of low birth weight, placental malaria and maternal parasitaemia compared to the standard two-dose regimen. Analysis showed that three or more doses of IPTp-SP were more cost-effective compared to two doses of IPTp-SP. This finding remained robust even if the underlying population level risk of low birth weight changes or if only HIVnegative women were considered. An update of this costeffectiveness analysis has since been published [8].
However, the results might not be generalizable to areas with lower malarial transmission and/or with very high levels of malaria parasite resistance to SP [9].

Strengthening health systems and the antenatal care platform
Kate Mitchell (Harvard School of Public Health/Maternal Health Task Force, USA) described the current shift in the delivery of ANC. The ANC platform is a key point of entry into the formal health system and presents a unique opportunity to reach the majority of pregnant women. Although ANC attendance is relatively high, even in low income countries, further efforts need to focus on the quality of care and service delivery. A recent study has drawn attention to the enormous gap between coverage as measured by attendance and coverage with specific ANC interventions [10]. Several recent studies stressed other challenges with and barriers to accessing ANC such as hidden costs (transportation, time off work, purchase of drugs on the private market when there were stock outs at health facilities); cultural factors influencing timing of pregnancy disclosure and healthcare workers negative attitudes exhibited towards women who present at ANC facilities [11]. Findings from a recent secondary analysis of the original focused ANC trials showed an increase in perinatal mortality which is of great concern and needs to be further researched [12]. Although the original WHO-sponsored focused ANC trial did not include sites from sub-Saharan Africa, the WHO is working with numerous partners to revise ANC guidelines through technical consultations that have included mapping of ANC guidelines worldwide and defining a new womencentred approach to ANC delivery. Revision of ANC guidelines will need to consider ways to increase healthcare worker adherence to delivery of IPTp and to yield better uptake among women. This is a critical time to revisit antenatal care policy and consider the following issues: harmonization of policies, guidelines, and recommendations; draw on lessons learned from slow IPTp uptake; review the role of community health workers to increase uptake of both ANC and IPTp; ensure a women-centred approach is adopted; tap into funding streams which support integration of maternal and newborn health.
Beyond the ANC platform, Elaine Roman (JHPEIGO, USA) discussed the need to target shortcomings in the following components of the health system to improve coverage of IPTp and key interventions: better integration of policies and guidelines between Reproductive Health and National Control Malaria Programmes; focus on healthcare worker capacity development both preand in-service training; quality assurance through support supervision; community engagement for early ANC Moving forward, strengthening ANC and components of the health system that are based on specific country contexts will be necessary to scale up IPTp coverage and have lasting health benefit for both mother and newborn.
A summary of the key issues and recommendations for scale-up of IPTp-SP discussed by seminar participants following the presentations is provided below. A comprehensive list of recommended actions by stakeholder group is presented in a companion paper [15]. acid which has been shown to decrease SP efficacy. The pharmaceutical industry needs to align with ANC programmes to manufacture and to register low-dose folic acid. 4.3. To investigate anti-malarial drugs that could replace SP and be given safely in the first trimester of pregnancy. 5. What are we calling private health care providers to do? 5.1. The importance of private healthcare providers is often overlooked. However, their importance in health service provision is growing in low and middle-income countries (up to 50 % in certain areas). Private healthcare providers, including facilities operated by non-governmental organizations and faith-based organizations, should be included in IPTp training, supervision and supported with an uninterrupted supply of quality SP.