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A decade after the Global Malaria Eradication Program, El Salvador had the highest burden of malaria in Mesoamerica, with approximately 20% due to Plasmodium falciparum. A resurgence of malaria in the 1970s led El Salvador to alter its national malaria control strategy. By 1995, El Salvador recorded its last autochthonous P. falciparum case with fewer than 20 Plasmodium vivax cases annually since 2011. By contrast, its immediate neighbors continue to have the highest incidences of malaria in the region. We reviewed and evaluated the policies and interventions implemented by the Salvadoran National Malaria Program that likely contributed to this progress toward malaria elimination. Decentralization of the malaria program, early regional stratification by risk, and data-driven stratum-specific actions resulted in the timely and targeted allocation of resources for vector control, surveillance, case detection, and treatment. Weekly reporting by health workers and volunteer collaborators-distributed throughout the country by strata and informed via the national surveillance system-enabled local malaria teams to provide rapid, adaptive, and focalized program actions. Sustained investments in surveillance and response have led to a dramatic reduction in local transmission, with most current malaria cases in El Salvador due to importation from neighboring countries. Additional support for systematic elimination efforts in neighboring countries would benefit the region and may be needed for El Salvador to achieve and maintain malaria elimination. El Salvador's experience provides a relevant case study that can guide the application of similar strategies in other countries committed to malaria elimination.

On October 16, 2014, a woman aged 48 years traveled from Monrovia, Liberia, to the Kayah region of Rivercess County, a remote, resource-poor, and sparsely populated region of Liberia, and died on October 21 with symptoms compatible with Ebola virus disease (Ebola). She was buried in accordance with local tradition, which included grooming, touching, and kissing the body by family and other community members while it was being prepared for burial. During October 24-November 12, eight persons with probable and 13 with confirmed Ebola epidemiologically linked to the deceased woman had onset of symptoms. Nineteen of the 21 persons lived in five nearby villages in Kayah region; two, both with probable cases, lived in neighboring Grand Bassa County (Figure). Four of the confirmed cases in Kayah were linked by time and location, although the source case could not be determined because the patients had more than one exposure.

The Malaria Policy Advisory Committee to the World Health Organization met for the first time from 31 January to 2 February 2012 in Geneva, Switzerland. This article provides a summary of the discussions, conclusions and recommendations from that meeting, as part of the newly launched Malaria Journal thematic series “WHO Malaria Policy Advisory Committee: Reports and Recommendations”. Summaries are provided, referencing the relevant background documents, for the meeting sessions on global malaria control, drug resistance and containment, rapid diagnostic test procurement criteria, larviciding, classification of countries for elimination, estimating malaria cases and deaths, and seasonal malaria chemoprevention. Policy statements, position statements, and guidelines that will arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization member states by the World Health Organization Global Malaria Programme.

The Malaria Policy Advisory Committee to the World Health Organization held its fourth meeting in Geneva, Switzerland from 11 to 13 September, 2013. This article provides a summary of the discussions, conclusions and recommendations from that meeting. Meeting sessions included: recommendations for achieving universal coverage of long-lasting insecticide-treated nets; guidance on estimating the longevity of insecticide-treated nets; improving capacity in entomology and vector control; a review of the latest evidence on intermittent preventive treatment in pregnancy; improving dissemination of Malaria Policy Advisory Committee guidance; updates on the development of the global technical strategy for malaria control and elimination (2016–2025) and the global strategy for control and elimination of Plasmodium vivax; updates from the drug resistance and containment technical expert group, the evidence review group on malaria burden estimation, a consultation on malaria case management indicators, and the constitution of the surveillance, monitoring and evaluation technical expert group; subnational elimination criteria; and consideration for future evidence review groups, including diagnosis in low transmission settings and testing for Glucose-6-Phosphate Dehydrogenase Deficiency. Policy statements, position statements and guidelines that arise from the Malaria Policy Advisory Committee meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed. This paper considers tools (both those available and others that may be required) to achieve and maintain malaria elimination. New diagnostics are needed to direct treatment and detect transmission potential; new drugs and vaccines to overcome existing resistance and protect against clinical and severe disease, as well as block transmission and prevent relapses; and new vector control measures to overcome insecticide resistance and more powerfully interrupt transmission. It is also essential that strategies for combining new and existing approaches are developed for different settings to maximise their longevity and effectiveness in areas with continuing transmission and receptivity. For areas where local elimination has been recently achieved, understanding which measures are needed to maintain elimination is necessary to prevent rebound and the reestablishment of transmission. This becomes increasingly important as more countries move towards elimination., David Kaslow and colleagues examine the progress in reasearch for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication and propose a research agenda.

Mary Hamel and colleagues in the RTS,S Clinical Trials Partnership report updated safety and efficacy results from an ongoing Phase 3 trial, including calculations of vaccine impact (malaria cases prevented). Please see later in the article for the Editors' Summary, Background A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission. Methods and Findings 6,537 infants aged 6–12 wk and 8,923 children aged 5–17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p, Editors' Summary Background Every year, more than 200 million cases of malaria occur worldwide, and more than 600,000 people, mainly children living in sub-Saharan Africa, die from this parasitic disease. Malaria parasites are transmitted to people through the bites of infected night-flying mosquitoes and cause fever that needs to be treated promptly with anti-malarial drugs to prevent anemia (a reduction in red blood cell numbers) and life-threatening organ damage. Malaria transmission can be prevented by using long-lasting insecticides sprayed on the indoor walls of homes to kill the mosquitoes that spread the malaria parasite or by sleeping under insecticide-treated nets to avoid mosquito bites and further reduce mosquito numbers. Widespread use of these preventative measures, together with the introduction of artemisinin combination therapy (an effective anti-malarial treatment), has reduced the global burden of malaria by 45% in all age groups, and by 51% among young children, since 2000. Why Was This Study Done? Unfortunately, the emergence of insecticide and drug resistance is threatening this advance in malaria control. Moreover, additional interventions—specifically, effective malaria vaccines—will be needed to eliminate malaria in the large areas of Africa where malaria transmission remains high. Currently, there is no licensed malaria vaccine, but RTS,S/AS01, the most advanced malaria vaccine candidate, is undergoing phase 3 clinical trials (the last stage of testing before licensing) in infants and children in seven African countries. The RTS,S Clinical Trials Partnership reported encouraging results on the efficacy and safety of RTS,S/AS01 during 12 months of follow-up in 2011 and 2012. Here, researchers report on the 18-month efficacy and safety of RTS,S/AS01. Vaccine efficacy (VE) is the reduction in the incidence of a disease (the number of new cases that occur in a population in a given period) among trial participants who receive the vaccine compared to the incidence among participants who do not receive the vaccine. What Did the Researchers Do and Find? The researchers randomly assigned 6,537 infants aged 6–12 weeks and 8,923 children aged 5–17 months to receive three doses of RTS,S/AS01 or a control vaccine. During 18 months of follow-up, there were 0.69 episodes of clinical malaria (a high temperature and parasites in the blood) per person-year among the children who received all the planned doses of RTS,S/AS01 (the “per protocol” population) and 1.17 episodes per person-year among the control children—a VE against clinical malaria in the per-protocol population of 46%. A similar VE was seen in an intention-to-treat analysis that included all the enrolled children, regardless of whether they received all of the planned vaccine doses; intention-to-treat analyses reflect the real-life situation—in which children sometimes miss vaccine doses—better than per-protocol analyses. In intention-to-treat analyses, the VE among children against severe malaria (fever, parasites in the blood, and symptoms such as anemia) and hospitalization for malaria was 34% and 41%, respectively. Among infants, the VE against clinical malaria was 27% in both per-protocol and intention-to-treat analyses; the vaccine showed no protection against severe malaria or hospitalization. In both infants and children, VE waned with time since vaccination. Across all the study sites, RTS,S/AS01 averted an average of 829 and 449 cases of clinical malaria per 1,000 children and infants vaccinated, respectively. Finally, the serious adverse event meningitis (inflammation of the tissues lining the brain and spinal cord) occurred more frequently in trial participants given RTS,S/AS01 than in those given the control vaccine, but the incidence of other serious adverse events was similar in both groups of participants. What Do These Findings Mean? These and other findings show that, during 18 months of follow-up, vaccination of children and young infants with RTS,S/AS01 prevented many cases of clinical and severe malaria and that the impact of vaccination was highest in regions with the highest incidence of malaria. They indicate, as in the earlier analysis, that the VE against clinical and severe malaria is higher in children than in young infants and suggest that protection wanes over time. Whether or not the vaccine played a causal role in the observed cases of meningitis cannot be determined from these results, and the occurrence of meningitis will be followed closely during the remainder of the trial. Other study limitations (for example, variations in the clinical characteristics of participants from one center to another) may also affect the accuracy of these findings and their interpretation. However, by showing that even a modest VE can avert a substantial number of malaria cases, these findings suggest that vaccination with RTS,S/AS01 could have a major public health impact in sub-Saharan Africa. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001685. Information is available from the World Health Organization on all aspects of malaria (in several languages), including malaria immunization; the World Malaria Report 2013 provides details of the current global malaria situation; the World Health Organization also provides information on its Global Immunization Vision and Strategy (in English and French) The US Centers for Disease Control and Prevention provides information on malaria, including a selection of personal stories about malaria Information is available from the Roll Back Malaria Partnership on the global control of malaria and on the Global Malaria Action Plan (in English and French); its website includes a fact sheet about malaria in Africa The latest results from the phase 3 trial of RTS,S are available on the website of the PATH Malaria Vaccine Initiative, a global program of the international nonprofit organization PATH that aims to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world MedlinePlus provides links to additional information on malaria and on immunization (in English and Spanish)

The Malaria Policy Advisory Committee to the World Health Organization met in Geneva, Switzerland from 13 to 15 March, 2013. This article provides a summary of the discussions, conclusions and recommendations from that meeting. Meeting sessions included: a review of the efficacy of artemisinin-based combination therapy in Guyana and Suriname; the outcomes from a consultation on non-malaria febrile illness; the outcomes from the second meeting of the Evidence Review Group on malaria burden estimation; an update on the review of the WHO Guidelines for the Treatment of Malaria; an update regarding progress on the constitution of the vector control Technical Expert Group; updates on the RTS, S/AS01 vaccine and the malaria vaccine technology roadmap; financing and resource allocation for malaria control; malaria surveillance and the need for a surveillance, monitoring and evaluation Technical Expert Group; criteria and classification related to malaria elimination; the next meeting of the Evidence Review Group on Intermittent Preventive Treatment in pregnancy; an update on the soon-to-be launched Elimination Scenario Planning Tool; and an update on the process for the Global Technical Strategy for Malaria Control and Elimination (2016–2025). Policy statements, position statements, and guidelines that arise from the MPAC meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

The Malaria Eradication Research Agenda (malERA) Consultative Group on Monitoring, Evaluation, and Surveillance present a research and development agenda for the tools required to monitor and evaluate progress toward malaria eradication., Monitoring, evaluation, and surveillance measure how well public health programs operate over time and achieve their goals. As countries approach malaria elimination, these activities will need to shift from measuring reductions in morbidity and mortality, to detecting infections (with or without symptoms) and measuring transmission. Thus, the monitoring and evaluation and surveillance research and development agenda needs to develop the tools and strategies that will replace passive surveillance of morbidity with active and prompt detection of infection, including confirmation of interruption of transmission by detecting present and past infections, particularly in mobile populations. The capacity to assess trends and respond without delay will need to be developed, so that surveillance itself becomes an intervention. Research is also needed to develop sensitive field tests that can detect low levels of parasitaemia, together with strategies for their implementation. Other areas to explore include the rigorous evaluation of the utility of more detailed maps of disease and infection incidence and prevalence, the development of new maps to inform programmatic responses and the use of surveillance technologies based on cell phone or real-time internet Web-based reporting. Because any new strategies for monitoring and evaluation and surveillance for eradication have major implications for program implementation, research is also needed to test systems of delivery for acceptability, feasibility, efficiency, cost-effectiveness, and community engagement. Finally, there is a clear need to systematically review the information from past elimination efforts for malaria and other infectious diseases.

Objectives: Sulfadoxine-pyrimethamine (SP) is an antimalarial drug that acts on the folate metabolism of the malaria parasite. We investigated whether folate (FA) supplementation in a high or a low dose affects the efficacy of SP for the treatment of uncomplicated malaria in pregnant women.\ud \ud Design: This was a randomized, placebo-controlled, double-blind trial.\ud \ud Setting: The trial was carried out at three hospitals in western Kenya.\ud \ud Participants: The participants were 488 pregnant women presenting at their first antenatal visit with uncomplicated malaria parasitaemia (density of >= 500 parasites/mu l), a haemoglobin level higher than 7 g/dl, a gestational age between 17 and 34 weeks, and no history of antimalarial or FA use, or sulfa allergy. A total of 415 women completed the study.\ud \ud Interventions: All participants received SP and iron supplementation. They were randomized to the following arms: FA 5 mg, FA 0.4 mg, or FA placebo. After 14 days, all participants continued with FA 5 mg daily as per national guidelines. Participants were followed at days 2, 3, 7, 14, 21, and 28 or until treatment failure.\ud Outcome Measures: The outcomes were SP failure rate and change in haemoglobin at day 14.\ud Results: The proportion of treatment failure at day 14 was 13.9% (19/137) in the placebo group, 14.5% (20/138) in the FA 0.4 mg arm (adjusted hazard ratio [AHR], 1.07; 98.7% confidence interval [CI], 0.48 to 2.37; p = 0.8), and 27.1% (38/140) in the FA 5 mg arm (AHR, 2.19; 98.7% CI, 1.09 to 4.40; p = 0.005). The haemoglobin levels at day 14 were not different relative to placebo (mean difference for FA 5 mg, 0.17 g/dl; 98.7% CI, -0.19 to 0.52; and for FA 0.4 mg, 0.14 g/dl; 98.7% CI, -0.21 to 0.49).\ud \ud Conclusions: Concomitant use of 5 mg FA supplementation compromises the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. Countries that use SP for treatment or prevention of malaria in pregnancy need to evaluate their antenatal policy on timing or dose of FA supplementation.