The American Journal of Tropical Medicine and Hygiene - Volume 77, Issue 6_Suppl, December 2007

Severe malaria is clinically similar to other severe febrile illnesses. However, in endemic areas, parasitological confirmation of parasitemia is often unavailable or unreliable. False-positive malaria microscopy is common. The most important consequence of treating only for malaria when no parasitemia exists is failure to address other life-threatening conditions. Invasive bacterial infections are detected in up to one third of children with clinical features of severe malaria but a slide with results negative for malaria. Even among genuinely parasitized children, severe illness is not always due to malaria in endemic areas. We believe that routine use of parenteral antibiotics among children with a slide that indicates malaria and life-threatening disease is warranted because invasive bacterial infections are likely to be under-ascertained and are associated with increased mortality. Published data on co-morbidity with HIV infection and malnutrition are reviewed. A structured approach to assessment and care is essential, and is largely independent of underlying etiology.

All-cause childhood mortality (ACCM) has been recommended as an indicator for evaluating the impact of malaria control efforts in parts of Africa where the malaria burden is high and vital registration systems are weak. As ACCM is not malaria-specific, we explored the relationship between ACCM and malaria mortality. First, we show that if malaria mortality is reduced by 50% in populations exposed to high-intensity malaria transmission, ACCM is predicted to decrease by ≈ 17% (plausible values range from 12% to 25%). Second, if malaria interventions are scaled-up from very low (2%) to reasonably high coverage levels (70%), epidemiologic models predict that ACCM would decrease by ≈ 17% or 18% (precision estimate: 15–19%). These results suggest that if malaria interventions are scaled-up to reach or exceed 70% coverage, it is plausible that a goal of reducing malaria mortality by 50% could be achieved. It is also likely that a pair of “typical”-size mortality surveys could detect this ACCM change as being statistically significant. Although existing models have important limitations, they could be improved by incorporating empirical results during scale-up of multiple interventions and by adding precision estimates and sensitivity analyses.

In two cross-sectional surveys carried out in the rural health district of Boromo, Burkina Faso, malaria infection was evaluated in 295 pregnant women in May 2003 and 288 pregnant women in December 2003. Malaria prevalence, all P. falciparum infection, was higher in December (32.2%) than in May (11.9%) (P < 0.0001). In both surveys primigravidae had a significantly higher risk of infection than multigravidae (P < 0.0001). Such risk decreased significantly and progressively with gestational age, the highest risk being during the first trimester. Women who had not attended the antenatal clinic had also a significantly higher risk of malaria infection. Despite the high antenatal clinic attendance and the use (or misuse) of chloroquine chemoprophylaxis, malaria remains an important problem for pregnant women living in the rural district of Boromo. This requires a major effort by the health authorities to guarantee all pregnant women have access to and use preventive measures.

Eritrea has a successful malaria control program, but it is still susceptible to devastating malaria epidemics. Monthly data on clinical malaria cases from 242 health facilities in 58 subzobas (districts) of Eritrea from 1996 to 2003 were used in a novel stratification process using principal component analysis and nonhierarchical clustering to define five areas with distinct malaria intensity and seasonality patterns, to guide future interventions and development of an epidemic early warning system. Relationships between monthly clinical malaria incidence by subzoba and monthly climate data from several sources, and with seasonal climate forecasts, were investigated. Remotely sensed climate data were averaged over the same subzoba geographic administrative units as the malaria cases. Although correlation was good between malaria anomalies and actual rainfall from ground stations (lagged by 2 months), the stations did not have sufficiently even coverage to be widely useful. Satellite derived rainfall from the Climate Prediction Center Merged Analysis of Precipitation was correlated with malaria incidence anomalies, with a lead time of 2–3 months. NDVI anomalies were highly correlated with malaria incidence anomalies, particularly in the semi-arid north of the country and along the northern Red Sea coast, which is a highly epidemic-prone area. Eritrea has 2 distinct rainy seasons in different parts of the country. The seasonal forecasting skill from Global Circulation Models for the June/July/August season was low except for the Eastern border. For the coastal October/November/December season, forecasting skill was good only during the 1997–1998 El Niño event. For epidemic control, shorter-range warning based on remotely sensed rainfall estimates and an enhanced epidemic early-detection system based on data derived for this study are needed.

In India, nine Anopheline vectors are involved in transmitting malaria in diverse geo-ecological paradigms. About 2 million confirmed malaria cases and 1,000 deaths are reported annually, although 15 million cases and 20,000 deaths are estimated by WHO South East Asia Regional Office. India contributes 77% of the total malaria in Southeast Asia. Multi-organ involvement/dysfunction is reported in both Plasmodium falciparum and P. vivax cases. Most of the malaria burden is borne by economically productive ages. The states inhabited by ethnic tribes are entrenched with stable malaria, particularly P. falciparum with growing drug resistance. The profound impact of complicated malaria in pregnancy includes anemia, abortions, low birth weight in neonates, still births, and maternal mortality. Retrospective analysis of burden of malaria showed that disability adjusted life years lost due to malaria were 1.86 million years. Cost–benefit analysis suggests that each Rupee invested by the National Malaria Control Program pays a rich dividend of 19.7 Rupees.

Plasmodium vivax threatens almost 40% of the world’s population, resulting in 132–391 million clinical infections each year. Most of these cases originate from Southeast Asia and the Western Pacific, although a significant number also occurs in Africa and South America. Although often regarded as causing a benign and self-limiting infection, there is increasing evidence that the overall burden, economic impact, and severity of disease from P. vivax have been underestimated. Malaria control strategies have had limited success and are confounded by the lack of access to reliable diagnosis, emergence of multidrug resistant isolates, the parasite’s ability to transmit early in the course of disease and relapse from dormant liver stages at varying time intervals after the initial infection. Progress in reducing the burden of disease will require improved access to reliable diagnosis and effective treatment of both blood-stage and latent parasites, and more detailed characterization of the epidemiology, morbidity, and economic impact of vivax malaria. Without these, vivax malaria will continue to be neglected by ministries of health, policy makers, researchers, and funding bodies.

Human co-infection with Plasmodium falciparum and helminths is ubiquitous throughout Africa, although its public health significance remains a topic for which there are many unknowns. In this review, we adopted an empirical approach to studying the geography and epidemiology of co-infection and associations between patterns of co-infection and hemoglobin in different age groups. Analysis highlights the extensive geographic overlap between P. falciparum and the major human helminth infections in Africa, with the population at coincident risk of infection greatest for hookworm. Age infection profiles indicate that school-age children are at the highest risk of co-infection, and re-analysis of existing data suggests that co-infection with P. falciparum and hookworm has an additive impact on hemoglobin, exacerbating anemia-related malarial disease burden. We suggest that both school-age children and pregnant women—groups which have the highest risk of anemia—would benefit from an integrated approach to malaria and helminth control.

In Tanzania, malaria remains one of the major causes of illness and death. The disease causes major obstacles to social and economic development. The extent of the problem is greatest among children less than five years of age and pregnant women. Malaria has been estimated to cost Tanzania more than US$ 240 million every year in lost gross domestic product, although it can be controlled for a fraction of that sum. Tanzania has actively participated in malaria research and in developing most control tools. However, the use of such tools and scaling up of effective interventions has been a major challenge. Major system constraints include inadequate human, financial, material resources, as well as an inefficient health care system. With an increasing burden with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), there has been a shift in the use of resources whereby more prioritization is given to interventions for HIV/AIDS than for malaria. The country is faced with several challenges including diagnosis, treatment, and control measures. Districts are faced with the inability to generate reliable information needed to make decisions to inform policy and lack skills for priority setting and planning. Budget allocation is not done according to evidence-based priorities, thus leading to stagnation over time. In this report, we present some success stories and discuss the challenges facing scaling up of interventions and propose priority areas to solving the problems.

In Tanzania malaria is the leading cause of morbidity and mortality, especially in children under 5 years. The disease ranks number one in both outpatient and inpatient statistics. The socio-economic impact of malaria is so high that it contributes highly to poverty and underdevelopment. Efforts made during the past century to combat and control malaria have not been successful. The prospects of achieving the Abuja declaration targets are uncertain within the remaining period of time. Currently, the Ministry of Health through a 5-year strategic plan advocates four main approaches in the fight against the disease. These include improved case management, vector control using insecticide treated mosquito nets, prevention and control of malaria in pregnancy and epidemic preparedness, prevention and control. However, these strategies face various challenges including inadequate human, financial, and material resources; inefficiency in the healthcare system that is incapable of providing quality health services and access to prompt diagnosis and treatment; lack of an effective disease surveillance system; and an inefficient health education communication mechanism. Tanzania is at the crossroads and is challenged with the need to introduce a new antimalarial treatment regimen and the reintroduction of DDT for indoor residual spray. Unless malaria control strategy adopts an integrated approach its success is far from being realized. This article reviews the current malaria control strategies and its challenges in Tanzania and proposes new strategies.

The absolute necessity for rational therapy in the face of rampant drug resistance places increasing importance on the accuracy of malaria diagnosis. Giemsa microscopy and rapid diagnostic tests (RDTs) represent the two diagnostics most likely to have the largest impact on malaria control today. These two methods, each with characteristic strengths and limitations, together represent the best hope for accurate diagnosis as a key component of successful malaria control. This review addresses the quality issues with current malaria diagnostics and presents data from recent rapid diagnostic test trials. Reduction of malaria morbidity and drug resistance intensity plus the associated economic loss of these two factors require urgent scaling up of the quality of parasite-based diagnostic methods. An investment in anti-malarial drug development or malaria vaccine development should be accompanied by a parallel commitment to improve diagnostic tools and their availability to people living in malarious areas.

The introduction of artemisinin-based combination therapy in sub-Saharan Africa has prompted calls for increased use of parasitologic diagnosis for malaria. We evaluated the cost-effectiveness of rapid diagnostic tests (RDTs) in comparison to microscopy in guiding treatment of non-severe febrile illness at varying levels of malaria endemicity using data on test accuracy and costs collected as part of a Tanzanian trial. If prescribers complied with current guidelines, microscopy would give rise to lower average costs per patient correctly treated than RDTs in areas of both high and low transmission. RDT introduction would result in an additional 2.3% and 9.4% of patients correctly treated, at an incremental cost of $25 and $7 in the low and high transmission settings, respectively. Cost-effectiveness would be worse if prescribers do not comply with test results. The cost of this additional benefit may be higher than many countries can afford without external assistance or lower RDT prices.

This paper estimates the number of people at risk of contracting malaria in Africa using GIS methods and the disease’s epidemiologic characteristics. It then estimates yearly costs of covering the population at risk with the package of interventions (differing by level of malaria endemicity and differing for rural and urban populations) for malaria as recommended by the UN Millennium Project. These projected costs are calculated assuming a ramp-up of coverage to full coverage by 2008, and then projected out through 2015 to give a year-by-year cost of meeting the Millennium Development Goal for reducing the burden of malaria by 75%. We conclude that the cost of comprehensive malaria control for Africa is US$3.0 billion per year on average, or around US$4.02 per African at risk.

Malaria is endemic in about 90 countries of the world, half of which are in Africa. Little is known about the demographic impact of the disease, however. This article uses demographic methods to examine the impact of mortality from malaria on overall mortality in a hyperendemic rural African setting. Using longitudinal demographic surveillance data from northern Ghana and applying multiple decrement and associated single-decrement life-table methods, we estimate the total number of person-years that would have been saved had malaria been eliminated from the population in 1995, given the age- and cause-specific mortality conditions of the period and gains in life expectancy that are implied. Results suggest that as many as one third of deaths in this population are attributable to malaria, depending on the age group under consideration, and that life expectancy at birth would likely increase by more than six years if malaria were eliminated as a cause of death.

Reduced sensitivity of Plasmodium falciparum to formerly recommended cheap and well-known antimalarial drugs places an increasing burden on malaria control programs and national health systems in endemic countries. The high costs of the new artemisinin-based combination treatments underline the use of rational and updated malaria treatment policies, but defining and updating such policies requires a sufficient volume of high-quality drug-resistance data collected at national and regional levels. Three main tools are used for drug resistance monitoring, including therapeutic efficacy tests, in vitro tests, and analyses of molecular markers. Data obtained with the therapeutic efficacy test conducted according to the standard protocol of the World Health Organization are most useful for updating national treatment policies, while the in vitro test and molecular markers can provide important additional information about changing patterns of resistance. However, some of the tests are technically demanding, and thus there is a need for more resources for training and capacity building in endemic countries to be able to adequately respond to the challenge of drug resistance.

As chloroquine and sulfadoxine-pyrimethamine (SP) are replaced by more effective artemisinin-based combination therapies (ACTs), strategies for monitoring (and, if possible, deterring) drug-resistant malaria must be updated and optimized. In vitro methods for measuring resistance will be critical for confirming and characterizing resistance to ACTs. Molecular markers are useful for tracking the emergence and dissemination of resistance and guiding treatment policy where resistance is low or moderate. Genomic approaches may help identify molecular markers for resistance to artemisinins and their partner drugs. Studies of reported ACT treatment failure should include assessing factors other than resistance that affect efficacy, including pharmacokinetics. Longitudinal clinical trials are particularly useful for comparing the benefits and risks of repeated treatment in high transmission settings. The malaria research and control community should not fail to exploit this opportunity to apply the lessons of the last 50 years to extend the useful therapeutic lives of ACTs.

Artemisinin-based combination treatments (ACTs) are now generally accepted as the best treatments for uncomplicated falciparum malaria. They are rapidly and reliably effective. Efficacy is determined by the drug partnering the artemisinin derivative and, for artesunate–mefloquine, artemether–lumefantrine, and dihydroartemisinin–piperaquine, this usually exceeds 95%. Artesunate–sulfadoxine–pyrimethamine and artesunate–amodiaquine are effective in some areas, but in other areas resistance to the partner precludes their use. There is still uncertainty over the safety of artemisinin derivatives in the first trimester of pregnancy, when they should not be used unless there are no effective alternatives. Otherwise, except for occasional hypersensitivity reactions, the artemisinin derivatives are safe and remarkably well tolerated. The adverse effect profiles of the artemisinin-based combination treatments are determined by the partner drug. Most malaria endemic countries have now adopted artemisinin-based combination treatments as first-line treatment of falciparum malaria, but in most of these only a minority of the patients that need artemisinin-based combination treatments actually receive them.

Parasite resistance to conventional antimalarial medicines has led, in recent years, to a dramatic shift in malaria treatment. Sixty-seven countries with endemic Plasmodium falciparum malaria, 41 of them in Africa, have recently adopted the highly effective artemisinin-based combination therapies (ACTs). In 2005, 31.3 million ACT treatment courses were procured globally for public sector use, 25.5 million of them in Africa. However, in the 39 countries, and in particular the 21 African countries in which ACTs are being deployed, access to these medicines is still unacceptably low. After a period of market instability, the global manufacturing capacity for ACTs is now sufficient to meet the demand. However, increased and sustained financing will be necessary to extend the current levels of ACT coverage. Artemisinins as monotherapies are widely available in the private sector of 47 endemic countries, and their consumption will, if unabated, promote resistance to artemisinins and compromise the effectiveness of ACTs.

Despite considerable efforts by multiple governmental and nongovernmental organizations to increase access to artemisinin-based combination therapies (ACTs), these life-saving antimalarial drugs remain largely unaffordable to the most vulnerable populations. The cost of artemisinin derivatives, ACTs’ crucial active ingredients, contributes significantly to the high price of these therapies. With a grant from the Bill and Melinda Gates Foundation, a partnership between Amyris Biotechnologies, the Institute for OneWorld Health, and the University of California, Berkeley is using synthetic biology to help reduce the cost of artemisinin. This article presents a description of the technological platform the partnership—called the Artemisinin Project—is developing to manufacture a low-cost, semi-synthetic artemisinin through a fermentation process. By making life-saving ACTs affordable to the people who most need them, the Artemisinin Project hopes to show that the power of biotechnology can be harnessed to provide solutions to global health problems.

Medicine sellers are widely used for fever and malaria treatment in sub-Saharan Africa, but concerns surround the appropriateness of drugs and information provided. Because there is increasing interest in improving their services, we reviewed the literature on their characteristics and interventions to improve their malaria-related practices. Sixteen interventions were identified, involving a mixture of training/capacity building, demand generation, quality assurance, and creating an enabling environment. Although evidence is insufficient to prove which approaches are superior, tentative conclusions were possible. Interventions increased rates of appropriate treatment, and medicine sellers were willing to participate. Features of successful interventions included a comprehensive situation analysis of the legal and market environment; buy-in from medicine sellers, community members and government; use of a combination of approaches; and maintenance of training and supervision. Interventions must be adapted to include artemisinin-based combination therapies, and their sustainability and potential to operate at a national level should be further explored.

In 2004, the Institute of Medicine concluded that a global high-level subsidy was the best way to make effective antimalarial drugs—currently, artemisinin-combination therapies (ACTs)—widely available at affordable prices and at the same time substantially delay the emergence and spread of artemisinin-resistant strains of falciparum malaria. The subsidy would be available to manufacturers of all ACTs meeting pre-specified efficacy, safety, and quality criteria. Buyers would pay very low prices, allowing drugs to flow through existing channels, with the aim of reaching consumers at a similar price to chloroquine, the most frequently used (although no longer effective) malaria drug. Unsubsidized artemisinin monotherapies would be more expensive than subsidized ACTs (co-formulations), thereby largely eliminating their use through market forces. Conditions favoring the emergence of artemisinin-resistant malaria would be greatly reduced. The global high-level subsidy is a powerful idea that is moving from economic concept to pragmatic reality.

A review of the main elements determining strategic choices for the large-scale distribution of insecticide-treated nets (ITNs) clearly shows the need for multiple strategies. Mass distributions of free nets provide a unique opportunity to achieve quickly high coverage rates. However, there is also a need for additional approaches to 1) provide continuous provision of ITNs for newly pregnant women and their babies and 2) provide protection for the rest of the population. Targeted subsidies will continue to be an important tool to achieve the first objective, either through direct distribution of ITNs or through vouchers. To achieve objective 2, a strong and competitive commercial sector for ITNs seems to be a good option. It is clear that “one size doesn’t fit all,” and more experience needs to be gathered and shared. With planning and good promotion campaigns, these strategies can co-exist and re-enforce each other.

Seven years ago, the removal of taxes and tariffs on insecticide treated nets (ITNs) was considered one of the easiest resolutions for most countries to implement among the targets agreed upon at the African Summit on Roll Back Malaria in Abuja, Nigeria, on April 25, 2000. However, seven years later, 24 of the 39 Abuja signatories continue to impose taxes and tariffs on this life-saving tool. Taxes and tariffs significantly increase the price of an insecticide treated net, reduce affordability, and discourage the commercial sector from importing insecticide treated net products. Consequently, Roll Back Malaria partners are engaged in advocacy efforts to remove taxes and tariffs on insecticide treated nets in malaria-endemic countries of Africa. This viewpoint summarizes key obstacles to the removal of taxes and tariffs that have been identified through a review of country situations. To achieve the goal of producing and supplying more than 160 million insecticide treated nets needed to reach the revised Roll Back Malaria Partnership targets by 2010, tax and tariff reforms are urgently needed. Such reforms must be accompanied by country-specific systems to protect the poor (e.g., through voucher systems for vulnerable groups and other forms of targeted subsidies).

Genetic modification (GM) of mosquitoes (which renders them genetically modified organisms, GMOs) offers opportunities for controlling malaria. Transgenic strains of mosquitoes have been developed and evaluation of these to 1) replace or suppress wild vector populations and 2) reduce transmission and deliver public health gains are an imminent prospect. The transition of this approach from confined laboratory settings to open field trials in disease-endemic countries (DECs) is a staged process that aims to maximize the likelihood of epidemiologic benefits while minimizing potential pitfalls during implementation. Unlike conventional approaches to vector control, application of GM mosquitoes will face contrasting expectations of multiple stakeholders, the management of which will prove critical to safeguard support and avoid antagonism, so that potential public health benefits can be fully evaluated. Inclusion of key stakeholders in decision-making processes, transfer of problem-ownership to DECs, and increased support from the wider malaria research community are important prerequisites for this. It is argued that the many developments in this field require coordination by an international entity to serve as a guiding coalition to stimulate collaborative research and facilitate stakeholder involvement. Contemporary developments in the field of modern biotechnology, and in particular GM, requires competencies beyond the field of biology, and the future of transgenic mosquitoes will hinge on the ability to govern the process of their introduction in societies in which perceived risks may outweigh rational and responsible involvement.

A total of 255 bednets were collected 38 months after distribution in Lawra District of northwest Ghana to examine their physical condition and residual insecticide levels. Physical condition varied from nearly pristine to highly damaged. In 50 selected nets, 2023 holes ≥ 0.5 cm and 31 holes ≥ 10 cm were counted. The incidence of holes increases toward the bottom edge of the net. Seam failures were found in 50% of the nets. Repairs, mostly sewn, were evident in 64% of the nets. Using a combination of bromine x-ray fluorescence (XRF) spectrometry, high-pressure liquid chromatography, and cone bioassays, it was determined that 14.9% of the nets had retained full insecticidal strength. These results highlight the value of real-world data on bednet longevity to guide decisions regarding mosquito control strategies, bednet purchasing, frequency of bednet replacement, and product development.

In 2006, the World Health Organization issued a position statement promoting the use of indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) for malaria vector control in epidemic and endemic areas. Other international organizations concurred because of the great burden of malaria and the relative ineffectiveness of current treatment and control strategies. Although the Stockholm Convention of 2001 targeted DDT as 1 of 12 persistent organic pollutants for phase-out and eventual elimination, it allowed a provision for its continued indoor use for disease vector control. Although DDT is a low-cost antimalarial tool, the possible adverse human health and environmental effects of exposure through IRS must be carefully weighed against the benefits to malaria control. This article discusses the controversy surrounding the use of DDT for IRS; its effective implementation in Africa; recommendations for deployment today, and training, monitoring, and research needs for effective and sustainable implementation. We consider the costs and cost effectiveness of IRS with DDT, alternative insecticides to DDT, and the importance of integrated vector control if toxicity, resistance, and other issues restrict its use.

At six sites in western Kenya, we explored the presence of Anopheles immature stages in treeholes. An. gambiae larvae were found in 19 species, 13 of which are exotic. The most common exotic species were Delonix regia, Jacaranda mimosipholia, and Eucalyptus citrodora. In Kisumu city, longitudinal assessments of 10 flamboyant trees showed repeated presence of An. gambiae s.s. in treeholes with water. Production of Anopheles larvae did not correlate with habitat volume but with habitat height, showing a strong but statistically insignificant negative correlation. During a dry season, eggs recovered by rinsing dry treeholes hatched into 2.5 ± 3.06 An. gambiae and 7.9 ± 8.2 Aedes larvae. In cage experiments, An. gambiae s.s. laid more eggs in water originating from treeholes than in distilled or lake water, implying preference for ovipositing in this habitat. Our findings indicate that treeholes represent a hitherto unrecognized habitat for malaria vectors, which needs further studies.

Malaria has been the greatest scourge of humankind for many millennia, and as a consequence has had more impact than any other pathogen in shaping the human genome. The sequencing of the human genome provides a new opportunity to determine the genetic traits that confer resistance to infection or disease. The identification of these traits can reveal immune responses, or host–parasite interactions, which may be useful for designing vaccines or new drugs. Similarly, the parasite genome sequence is being exploited to accelerate the development of new antimalarial interventions, for example by identifying parasite metabolic pathways that may be targeted by drugs. The malaria parasites are well known for their ability to undergo antigenic variation, and in parallel to cause a diverse array of disease syndromes, including the severe syndromes that commonly cause death. Genome-based technologies are being harnessed to relate gene and protein expression levels, or genetic variation, to the parasite forms that are targets of protective immunity. Well-conducted clinical studies are required to relate host or parasite diversity with disease. However, genomics studies of human populations raise important ethical issues, such as the disposition of data related to disease susceptibility or paternity, and the ability of communities to understand the nature of the research.

The past few years have witnessed the appearance of public-private partnerships and a significant increase of resources devoted to the development of malaria vaccines. Lessons have been learned on different approaches to the clinical development plan for a vaccine candidate, including different clinical trial phases and endpoints and methods to conduct them. Improved understanding of mechanisms underlying naturally acquired immunity, definitions of surrogate markers of protection, including improved in vitro assays and animal models, and strengthened capacity in malaria-endemic countries to conduct clinical trials would accelerate the development of malaria vaccines. We are closer to having a first-generation vaccine being registered. The impact of this vaccine and subsequent products will need to be evaluated under program conditions in the context of comprehensive malaria control activities. Deployment of a safe and effective malaria vaccine administered in early childhood could become a major public health tool, particularly in sub-Saharan Africa.

The African Malaria Network Trust (AMANET), whose mission is to promote capacity strengthening of African malaria research institutions, was founded in 2002 and is currently focusing on malaria vaccine development. AMANET has trained over 900 African malaria researchers at workshops relevant to clinical trials of candidate malaria vaccines that will meet scientific, ethical, and international Good Clinical Practice standards. African centers selected for developing malaria vaccines initially undergo a needs assessment, followed by filling gaps in short- and long-term training, provision of essential equipment, and infrastructure improvement. Four centers from different malaria ecoepidemiologic settings are being strengthened; two of these have been approved for carrying out malaria vaccine trials. Researchers from prospective trial sites are mentored at northern institutions undertaking Phase 1a and/or 2a trials; five researchers are undergoing doctoral training. AMANET has sponsored one successful Phase 1b trial; three more are underway. Expert site audits will precede launch of phase 2b trials. Several lessons have been learned: the building of comprehensive capacity, essential for undertaking internationally acceptable trials including their sponsorship, is complex and costly. AMANET has spent over US$ 1 million on capacity strengthening of its leading trial center. Despite the high costs, development of three other sites is underway and there are plans to develop two more sites. To succeed, genuine north–south collaboration based on mutual trust and sharing of available information and responsibilities has been essential. AMANET as a sponsor has assumed roles usually reserved for the pharmaceutical industry, yet is operating where regulatory authorities are generally weak or wanting.

GlaxoSmithKline Biologicals (GSK) is committed to the development of a safe and effective malaria vaccine. Its research program in this field was initiated in 1984 and has been continuously active to this day, making it unparalleled within the vaccine industry. Although it works in partnerships with several leading organizations from the public sector, this effort has required GSK to invest major financial and human resource commitments, and its partners rely heavily on the company’s global infrastructure and expertise in research, advanced clinical development, regulatory, large-scale manufacturing, and commercialization. Through GSK’s pioneering business model and working in partnership with global vaccine funding agencies, the company is committed to seeing that, once approved, a safe and effective malaria vaccine will be available to everyone that needs it.

Malaria is a major public health problem; about half of the world’s populations live under exposure. The problem is increasing in magnitude and complexity because it is entwined with low socio-economic status, which makes African women and children particularly vulnerable. Combating malaria therefore requires concerted international efforts with an emphasis on Africa. The Multilateral Initiative on Malaria (MIM) was founded in 1997 to meet that need through strengthening research capacity in Africa, increasing international cooperation and communication, and utilization of research findings to inform malaria prevention, treatment, and control. The review undertaken in 2002 showed that through improved communication and science-focused institutional networks, MIM had brought African scientists together, opened up communication among malaria stakeholders, and provided Internet access to literature. The achievements were made through four autonomous constituents including the coordinating Secretariat being hosted for the first time in Africa by the African Malaria Network Trust (AMANET) for the period 2006–2010. The other constituents are the MIM TDR providing funding for peer-reviewed research; MIMCom facilitating Internet connectivity, access to medical literature, and communication between scientists inside and outside of Africa; and MR4 providing scientists access to research tools, standardized reagents, and protocols. Future plans will mostly consolidate the gains made under the MIM Strategic Plan for the period 2003–2005.

Until recent years, public interest and political investment in malaria prevention, control, and research have been stagnant. The global malaria agenda is now experiencing an unprecedented time of public and political will and momentum. At the heart of this favorable period lies a nascent, but increasingly sophisticated, global advocacy effort that has contributed to new and expanded malaria funding, programs, and technology. This paper reviews the elements of malaria’s rise to political and public prominence, tracks the increase in funding and policy commitments to malaria over the past decade, and comments on an evolving policymaking progress, increasing transparency and accountability in program governance, and the impact of philanthropic investments in malaria advocacy. In addition, the principles of sound advocacy are described along with the mechanisms that will underlie sustained pro-political momentum for malaria research, resources, and results.

“Today, we have begun to write the final chapter in the history of malaria. We have raised hopes and expectations of our people—we must not let them down. We cannot afford to let them down.”

—His Excellency Olusegan Obasanjo, President of Nigeria, Abuja Summit 2000

The Global Fund to Fight AIDS, Tuberculosis, and Malaria was established in 2002 to fund substantial scaling-up coverage of proven and effective interventions to reduce infection, illness, and deaths in those communities most at risk. As of December 2006 the Global Fund has committed $2.6 billion over 5 years to support malaria prevention and control in 85 countries. The Global Fund has worked closely with Roll Back Malaria partners to develop consensus on a set of outcome and impact indicators that have been incorporated into malaria grant agreements. Although the Global Fund has recommended that 5–10% of grant funds be invested in improving the capacity of the national monitoring and evaluation systems, an average of only 3.9% is invested in these systems. Several countries are already demonstrating reductions in the malaria burden. To sustain the scale-up in funding to support malaria interventions, countries must ensure that resources are used now to show robust, systematic, and regular measurement of impact on the burden of malaria.