Malaria Eradication Campaign Research Articles

Selecting an anti-malarial clinical candidate from two potent dihydroisoquinolones

BackgroundThe ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. The process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles is described.MethodsThe compounds were tested to define their physicochemical properties including kinetic and thermodynamic solubility, partition coefficient, permeability, ionization constant, and binding to plasma proteins. Metabolic stability was assessed in both microsomes and hepatocytes derived from mice, rats, dogs, and humans. Cytochrome P450 inhibition was assessed using recombinant human cytochrome enzymes. The pharmacokinetic profiles of single intravenous or oral doses were investigated in mice, rats, and dogs.ResultsAlthough both compounds displayed similar physicochemical properties, SJ733 was more permeable but metabolically less stable than SJ311 in vitro. Single dose PK studies of SJ733 in mice, rats, and dogs demonstrated appreciable oral bioavailability (60–100%), whereas SJ311 had lower oral bioavailability (mice 23%, rats 40%) and higher renal clearance (10–30 fold higher than SJ733 in rats and dogs), suggesting less favorable exposure in humans. SJ311 also displayed a narrower range of dose-proportional exposure, with plasma exposure flattening at doses above 200 mg/kg.ConclusionSJ733 was chosen as the candidate based on a more favorable dose proportionality of exposure and stronger expectation of the ability to justify a strong therapeutic index to regulators.

"Debordering" public health: the changing patterns of health border in modern Europe.

According to David Fidler, the governance of infectious diseases evolved from the mid-nineteenth to the twenty-first century as a series of institutional arrangements: the International Sanitary Regulations (non-interference and disease control at borders), the World Health Organization vertical programs (malaria and smallpox eradication campaigns), and a post-Westphalian regime standing beyond state-centrism and national interest. But can international public health be reduced to such a Westphalian image? We scrutinize three strategies that brought health borders into prominence: pre-empting weak states (eastern Mediterranean in the nineteenth century); preventing the spread of disease through nation-building (Macedonian public health system in the 1920s); and debordering the fight against epidemics (1920-1921 Russian-Polish war and the Warsaw 1922 Sanitary Conference).

Thomas J.Bollyky, Plagues and the Paradox of Progress: Why the World is Getting Healthier in Worrisome Ways. Cambridge, MA: The MIT Press. 280 p. $27.95.

Currently, Niger's GDP per capita is $393; in 1980 it was $419. Today, students in Niger average 5 years of schooling, the lowest in the world, and just $71 is spent on the average Nigerien's health each year. The government is weak and corrupt, the country has the world's second lowest Human Development Index, and it is surrounded by regions experiencing violent insurgences. Yet, compared to 25 years ago, its life expectancy of 61 is 14 years higher and its infant mortality rate more than 60 percent lower. Over the past decade, the death rate from HIV/AIDS has dropped over 60 percent, malnutrition by 35 percent, malaria by 27 percent, and diarrheal disease by 48 percent. Bollyky, the Director of Global Health at the Council of Foreign Relations, uses Niger's statistics to illustrate that control over infectious disease and child mortality no longer depends on state capacity or income level, factors that were central to the control of infectious disease in now developed countries. This disconnect, while a notable accomplishment, worries Bollyky. Millions of infants and children, that formerly would have died, have survived as global vaccination campaigns have virtually eradicated smallpox and measles. The global distribution of mosquito netting and oral rehydration kits has significantly reduced the incidence of malaria and diarrheal diseases. These survivors have matured, and many now find themselves living impoverished lives in countries with underdeveloped health care systems that lack the capability to deal with unprecedented increases in noncommunicable diseases. They flee, in large numbers, to rapidly growing cities with poor infrastructures and few productive jobs. For Bollyky, whether the recent remarkable control of infectious disease will end with tragedy or triumph is yet to be determined. Bollyky argues his case using historical and disease-specific narratives. Chapter 1 covers the history of infectious disease from premodern time, when more advanced countries tended to be more disease-ridden, to the modern era when wealth and public health advances reversed that relationship. Chapter 2 traces the 1950s smallpox and malaria eradication campaigns to their colonial and military roots, noting that these top-down technology-driven strategies, while producing dramatic results, required few fundamental changes in governments or economies. Chapter 3 looks at the recent control of childhood disease; effective vaccines for measles, mumps, and rubella were only developed in the 1960s. The ensuing dramatic declines in childhood diseases occurred very quickly and produced age structures with distinct “youth bulges.” Bollyky contrasts the success that China has had in securing its demographic dividend with Kenya's much more limited success. Chapter 4 examines the story of tuberculosis, cholera, and other intestinal diseases, ones that in the past had made cities dangerous places in which to live. These diseases can now be “frugally” controlled, but the result has been the explosive growth of “poor world cities,” such as Dhaka, where population growth has outpaced gains in access to clean water, adequate sanitation, and schools. Chapter 5 assesses the very recent international health campaigns that have targeted the diseases common to the world's poorest and most ecologically challenged countries: meningitis and other neglected infectious and parasitic diseases. Success here has produced growing cohorts of young adults for whom emigration seems to hold the only key to a positive future. Today less than 20 percent of the total death and disability in South Asia is caused by infectious diseases, and it is less than 44 percent in sub-Saharan Africa. By 2040, Bangladesh's health burden will look like that of the contemporary United States, dominated by cancer, heart disease, and other noncommunicable diseases. Bollyky contends that what will be needed to deal with this new health burden is much more than just a revamped health care system. What will be needed is freer trade, more rapid economic growth, a more inclusive educational system, and better governance.

Endoperoxide-8-aminoquinoline hybrids as dual-stage antimalarial agents with enhanced metabolic stability

Hybrid compounds may play a critical role in the context of the malaria eradication agenda, which will benefit from therapeutic tools active against the symptomatic erythrocytic stage of Plasmodium infection, and also capable of eliminating liver stage parasites. To address the need for efficient multistage antiplasmodial compounds, a small library of 1,2,4,5-tetraoxane-8- aminoquinoline hybrids, with the metabolically labile C-5 position of the 8-aminoquinoline moiety blocked with aryl groups, was synthesized and screened for antiplasmodial activity and metabolic stability. The hybrid compounds inhibited development of intra-erythrocytic forms of the multidrug-resistant Plasmodium falciparum W2 strain, with EC50 values in the nM range, and with low cytotoxicity against mammalian cells. The compounds also inhibited the development of P. berghei liver stage parasites, with the most potent compounds displaying EC50 values in the low μM range. SAR analysis revealed that unbranched linkers between the endoperoxide and 8-aminoquinoline pharmacophores are most beneficial for dual antiplasmodial activity. Importantly, hybrids were significantly more potent than a 1:1 mixture of 8-aminoquinoline-tetraoxane, highlighting the superiority of the hybrid approach over the combination therapy. Furthermore, aryl substituents at C-5 of the 8-aminoquinoline moiety improve the compounds' metabolic stability when compared with their primaquine (i.e. C-5 unsubstituted) counterparts. Overall, this study reveals that blocking the quinoline C-5 position does not result in loss of dual-stage antimalarial activity, and that tetraoxane-8- aminoquinoline hybrids are an attractive approach to achieve elimination of exo- and intraerythrocytic parasites, thus with the potential to be used in malaria eradication campaigns.

Fighting Fire with Aid: Development Assistance as Counterinsurency Tool - Evidence for Colombia

I study the causal effect of the foreign aid for development assistance —implemented by the U.S. Agency for International Development (USAID)— on the intensity of municipality-level armed conflict in Colombia, for the period 2009-2013. To address potential endogeneity biases, I use a Bartik-like instrument which exploits the spatial persistence of aid from USAID in Colombia. Specifically, I instrument foreign aid with the interaction between the United States GDP and municipality-level intent-to-treat indicators for the Malaria Eradication Campaigns (circa 1957). The results point out that foreign aid reduces the insurgency associated with left-wing guerrillas, especially FARC. However, foreign aid does not affect the violence associated with criminal gangs from right-wing paramilitary origins (BACRIM). I provide both quantitative and anecdotic evidence on two potential mechanisms behind my results: (i) Development programs raise the opportunity cost of fighting and; (ii) foreign aid improves the trust, and the information flows between civilians and the government. Finally, I provide empirical evidence that casts doubt on two alternative channels whose predictions cannot be reconciled with the results: (i) that foreign aid increases the potentially- looted rents by the insurgents and; (ii) that development programs rise targeted assassinations committed by insurgents to sabotage and reestablish bargaining power.

Blood Diseases in the Backyard: Mexican “indígenas” as a Population of Cognition in the Mid-1960s

This paper aims to widen the history of blood disease research beyond sickle cell anemia, situating it at the intersection of US racial politics and public health, and international malaria eradication campaigns in the Third World. It focuses on studies of G6PD deficiencies in the Mixtecos of the Mexican Pacific coast, and the Lacandones of the Mayan region in Chiapas. Two medical geneticists, Ruben Lisker and James E. Bowman, developed research projects that engaged these populations, looking for answers to evolutionary, biomedical, and genetics questions. Their practices and the context of knowledge production about these indigenous groups—how they were made objects of inquiry and intervention (Populations of Cognition)—are in full view in both cases.1

Anopheline Reproductive Biology: Impacts on Vectorial Capacity and Potential Avenues for Malaria Control.

Vectorial capacity is a mathematical approximation of the efficiency of vector-borne disease transmission, measured as the number of new infections disseminated per case per day by an insect vector. Multiple elements of mosquito biology govern their vectorial capacity, including survival, population densities, feeding preferences, and vector competence. Intriguingly, biological pathways essential to mosquito reproductive fitness directly or indirectly influence a number of these elements. Here, we explore this complex interaction, focusing on how the interplay between mating and blood feeding in female Anopheles not only shapes their reproductive success but also influences their ability to sustain Plasmodium parasite development. Central to malaria transmission, mosquito reproductive biology has recently become the focus of research strategies aimed at malaria control, and we discuss promising new methods based on the manipulation of key reproductive steps. In light of widespread resistance to all public health-approved insecticides targeting mosquito reproduction may prove crucial to the success of malaria-eradication campaigns.

The Molecular Basis of Evolution and Disease: A Cold War Alliance

This paper extends previous arguments against the assumption that the study of variation at the molecular level was instigated with a view to solving an internal conflict between the balance and classical schools of population genetics. It does so by focusing on the intersection of basic research in protein chemistry and the molecular approach to disease with the enactment of global health campaigns during the Cold War period. The paper connects advances in research on protein structure and function as reflected in Christian Anfinsen's The molecular basis of evolution, with a political reading of Emilé Zuckerkandl and Linus Pauling's identification of molecular disease and evolution. Beyond atomic fallout, these advances constituted a rationale for the promotion of genetic surveys of human populations in the Third World, in connection with international health programs. Light is shed not only on the experimental roots of the molecular challenge but on the broader geopolitical context where the rising role of biomedicine and public health (particularly the malaria eradication campaigns) had an impact on evolutionary biology.

Net Loss? Agrochemicals and Insecticide Resistance in the Fight against Malaria.

Net Loss? Agrochemicals and Insecticide Resistance in the Fight against Malaria.

Routine in vitro culture of P. falciparum gametocytes to evaluate novel transmission-blocking interventions.

The prevention of parasite transmission from the human host to the mosquito has been recognized as a vital tool for malaria eradication campaigns. However, transmission-blocking antimalarial drug and/or vaccine discovery and development is currently hampered by the expense and difficulty of producing mature Plasmodium falciparum gametocytes in vitro-the parasite stage responsible for mosquito infection. Current protocols for P. falciparum gametocyte culture usually require complex parasite synchronization and addition of stimulating and/or inhibitory factors, and they may not have demonstrated the essential property of mosquito infectivity. This protocol details all the steps required for reliable P. falciparum gametocyte production and highlights common factors that influence culture success. The protocol can be completed in 15 d, and particular emphasis is placed upon operating a gametocyte culture facility on a continuous cycle. In addition, we show how functionally viable gametocytes can be used to evaluate transmission-blocking drugs both in a field setting and at high throughput (HTP) for drug discovery.

The Long Struggle Against Malaria in Tropical Africa by James L. A. Webb, Jr. (review)

Reviewed by: The Long Struggle Against Malaria in Tropical Africa by James L. A. Webb, Jr. Brian Greenwood James L. A. Webb, Jr. The Long Struggle Against Malaria in Tropical Africa. New York: Cambridge University Press, 2014. xxi + 219 pp. Ill. $99.00 (978-1-107-05257-4). There is a new enthusiasm for the eradication of malaria, initiated by Bill and Melinda Gates at a Malaria Forum held in Seattle in October 2007, and the Bill and Melinda Gates Foundation now directs a substantial proportion of its resources for malaria research and control toward achieving this objective. It is hard to argue against the notion that getting rid of all human malaria parasites (eradication) must be the ultimate goal for malaria control for otherwise the parasite will almost inevitably bounce back with devastating consequences. However, it is salutatory to be reminded from time to time how difficult it will be to achieve eradication. Frank Snowden has documented the challenges faced in achieving elimination of malaria in Italy,1 a program of sustained effort that took over fifty years. In this new book, James L. A. Webb, Jr., describes how parallel efforts undertaken in tropical Africa have yet to achieve similar success. The first two chapters of this book discuss the little that is known about malaria in tropical Africa before the arrival of the Europeans and the devastating effects of the infection on the latter, especially on the coast of West Africa, “the white man’s grave.” Although some of the early European travellers took quinine, it was not until Ronald Ross’s discovery of the mode of transmission of malaria in 1897 that better targeted control programs could be attempted. Ross visited Freetown in 1899 and initiated a program of mosquito control that was temporarily successful but, like many subsequent programs, it was not sustained. In chapter 3, Webb describes the many malaria control programs that were undertaken in tropical Africa from the time of Ross’s visit up to the start of the first malaria eradication campaign in 1955. Many of these, which used chemoprevention and/or mosquito control, were at least partially successful, but a key message that emerges from the history of this period is the lack of continuity in effort; temporary success was often achieved but almost invariable followed by declining interest and a return to the status quo or even worse. It was recognized from early on that a successful malaria control program in children, which saved many young lives, might impair the immunity that they acquired as a result of by repeated infections, rendering them susceptible to severe disease in later life if a control program was wound up, as was so often the case. The risk of achieving protection in early childhood at the cost of increasing susceptibility to severe disease in later life, sometimes termed “rebound malaria,” was hotly debated at a famous malaria conference held in Kampala, Uganda, in 1950, and it is an issue that is still very relevant today as vaccines and other effective interventions are developed. The story of why the first malaria eradication failed has been well told previously,2 and, sensibly, Webb does not go over this ground again in any detail. [End Page 169] The second half of the book deals with the years of neglect of malaria from the end of the eradication programme in 1969 until a re-awakening of interest in the infection around 1997. I would like to have learnt more about the author’s thoughts on why malaria was so neglected during this period and what was responsible for the resurgence of interest around 1997 after a 30-year gap. Chapter 6 deals, rather briefly, with some of the recent encouraging developments in malaria control, including success in developing new drugs, insecticides, and vaccines, tools that are needed urgently in the face of increasing threats from drug and insecticide resistance. An area that could have been given more attention is that of funding for malaria control and how and why this has varied so much over time. Recent success in malaria control in Africa has been achieved largely through an increase in funding, allowing scaling up of tools...

Luciferase-Based, High-Throughput Assay for Screening and Profiling Transmission-Blocking Compounds against Plasmodium falciparum Gametocytes.

The discovery of new antimalarial drugs able to target both the asexual and gametocyte stages ofPlasmodium falciparumis critical to the success of the malaria eradication campaign. We have developed and validated a robust, rapid, and cost-effective high-throughput reporter gene assay to identify compounds active against late-stage (stage IV and V) gametocytes. The assay, which is suitable for testing compound activity at incubation times up to 72 h, demonstrates excellent quality and reproducibility, with averageZ' values of 0.85 ± 0.01. We used the assay to screen more than 10,000 compounds from three chemically diverse libraries. The screening outcomes highlighted the opportunity to use collections of compounds with known activity against the asexual stages of the parasites as a starting point for gametocytocidal activity detection in order to maximize the chances of identifying gametocytocidal compounds. This assay extends the capabilities of our previously reported luciferase assay, which tested compounds against early-stage gametocytes, and opens possibilities to profile the activities of gametocytocidal compounds over the entire course of gametocytogenesis.

Malaria eradication and economic outcomes in sub-Saharan Africa: Evidence from Uganda

This study evaluates the economic consequences of a 1959–1960 malaria eradication campaign in southwestern Uganda. The effort constitutes a rare, large-scale, and well-documented attempt to eliminate malaria in sub-Saharan Africa and produced an immediate disease reduction. We use this quasi-experimental health shock to identify long-term changes in educational and economic outcomes. Comparing the treatment district to a similar synthetic control, we find malaria eradication raised educational attainment by about a half year for both males and females, increased primary school completion among females and generated an almost 40% rise in the likelihood of male wage employment.

Long-lasting insecticidal nets to prevent visceral leishmaniasis in the Indian subcontinent; methodological lessons learned from a cluster randomised controlled trial.

Long-lasting insecticidal nets to prevent visceral leishmaniasis in the Indian subcontinent; methodological lessons learned from a cluster randomised controlled trial.

The Long Struggle against Malaria in Tropical Africa by James L. A. Webb Jr.

Reviewed by: The Long Struggle against Malaria in Tropical Africa by James L. A. Webb Jr. Urmi Engineer The Long Struggle against Malaria in Tropical Africa. By james l. a. webb jr. New York: Cambridge University Press, 2014. 219 pp. $94.95 (cloth); $72.00 (ebook). James L. A. Webb’s The Long Struggle against Malaria in Tropical Africa is an interdisciplinary historical study of the successes and failures of twentieth-century efforts to control malaria in tropical Africa. The book is a critical contribution to the study of world history and the growing literature on histories of disease, ecology, and global health, as well as the emergent subfield of historical epidemiology, of which Webb is a pioneer. Historical epidemiology brings a historical perspective to the study of contemporary disease challenges, which can be used to evaluate the strengths and limitations of current practices (p. xi). This book [End Page 655] serves as a sequel to and elaboration of arguments that Webb presented in Humanity’s Burden: A Global History of Malaria, which detailed the complex ecological history of humans and malarial parasites.9 The Long Struggle against Malaria in Tropical Africa begins with an introduction to the history of malaria, which lays the groundwork for understanding the author’s critical arguments about acquired immunity and the severe consequences of lapses in malaria control policy, a core theme that Webb reiterates throughout the text. Gaps in malaria control efforts enabled the resurgence of malaria and caused impacts that were more devastating to adult African populations than prior outbreaks, since they were not exposed to malaria as children and did not acquire immunity. The first two chapters, “European Vulnerability” and “African Immunity,” outline European and African experiences with malaria in the early twentieth century. Chapter 1 discusses the history of European efforts to avoid malaria, which included the use of quinine, residential segregation, and mosquito control. Chapter 2 focuses on African responses to malaria and outlines indigenous strategies for treating malarial symptoms and repelling mosquitoes, including burning smoky fires, applying plant ointments, and using mosquito traps. These chapters also demonstrate how European settlement, agricultural development, and urban growth resulted in new patterns of malaria transmission in rural highlands and lowlands in tropical East Africa. Chapter 3 focuses on the postwar global malaria eradication campaign (1950–1965) led by the World Health Organization (WHO) and elucidates the consequences of the closure of WHO pilot projects. The WHO campaign operated by spraying synthetic insecticides and administering synthetic antimalarial drugs. The success of eradication campaigns in the United States, Mexico, Italy, Greece, Corsica, Venezuela, Ceylon, and elsewhere led to optimism among global public health policymakers. Webb argues that these campaigns ultimately failed in tropical Africa due to the development of resistance to insecticides among mosquitoes and the lack of cooperation with African populations in malarial zones. Further, the loss of acquired immunities among local populations eventually enabled the resurgence of malaria, with higher mortality and morbidity rates among African adults than ever before. The book’s discussion of African responses to public health programs raises questions about the necessity and motivations of early eradication [End Page 656] campaigns. During the colonial period, European states were primarily concerned with protecting nonimmune Europeans from malaria; however by the World War II era, they became increasingly interested in eradicating the disease in African environments. Cultural perceptions of the seriousness of malaria shaped African and European ideas about the necessity of antimalarial campaigns, as most African adults saw malaria as “an annoyance, an unpleasant reality of life like the seasonal flu, rather than a problem to be tacked with scarce resources” (p. 94). Chapter 4, entitled “Positive Turbulence,” focuses on responses to malaria among new independent African governments between 1965 and 1980. Webb argues that resistance to WHO campaigns was political as well as ecological; new African governments expressed ideological resistance to colonial models of public health administration, and parasites and mosquitoes developed genetic resistance to antimalarials and insecticides. However, African states did facilitate the distribution of chloroquine, which was generally accepted among Africans and led to a general decline of malaria in sub-Saharan Africa. Despite the promise of chloroquine, “serious trouble lay ahead,” as chloroquine resistance...

Indigenous populations in Mexico: Medical anthropology in the work of Ruben Lisker in the 1960s

Ruben Lisker's research on the genetic hematological traits of Mexican indigenous populations illustrates the intersection of international health policies and the local modernizing nationalism of the Mexican post-revolution period. Lisker's surveys of blood group types, and of G6PD (glucose-6-phosphodehydrogenase) and hemoglobin variants in indigenous populations, incorporated linguistic criteria in the sampling methods, and historical and cultural anthropological accounts in the interpretation of results. In doing so, Lisker heavily relied on the discourse and the infrastructure created by the indigenista program and its institutions. Simultaneously, Lisker's research was thoroughly supported by international and bilateral agencies and programs, including the malaria eradication campaign of the 1950s and 1960s. As a member of the scientific elite he was able to make original contributions to the postwar field of human population genetics. His systematic research illustrates the complex entanglement of local and international contexts that explains the co-construction of global knowledge on human variation after WWII.11James V. Neel stated his position in the context of his contribution to the Wenner-Gren Symposium at Burg Wartenstein, Austria, that took place in August 9–18, 1969 on The Ongoing Evolution of Latin American Populations (Neel, 1971, p. 563). Victor McKusick's Opening Comments on the 5th International Congress of Human Genetics, that took place in Mexico City 1976 (Armendares & Lisker, 1977, p. 133).

Long-Term Health Effects of Malaria Exposure around Birth: Evidence from Colonial Taiwan

In the early twentieth century, the Japanese colonial government initiated an island-wide malaria eradication campaign in Taiwan, resulting in not only a rapid decline in malaria across time but also elimination of disparity across regions. Exploiting variations in malaria deaths caused by the campaign, we estimate causal effects of malaria exposure around birth on the health of elderly born in the colonial period. To mitigate potential biases caused by measurement errors and omitted confounders, we employ climatic factors to instrument for malaria deaths. Our findings suggest that people who were exposed to a high malaria risk around birth tend to have a higher likelihood of cardiovascular diseases and worse cognitive functions at old age.

Malaria in South Africa: 110 years of learning to control the disease

In Africa today, the drive towards controlling malaria is comparable with efforts made in the 1950s and 1960s during the World Health Organization's Global Malaria Eradication Campaign. Unlike the Eradication Campaign that 'covered' the globe but excluded Africa, the current endeavours focus on Africa, but not to the exclusion of the rest of the tropical and sub-tropical world. Major donor agencies are partnering with African governments in an attempt to curb transmission of malaria parasites, and in some countries on the edges of the distribution of malaria, there is talk of eliminating the disease. South Africa is at the very southernmost fringe of malaria distribution on the African continent and has a long history of intense malaria control activities. This article looks at what South Africa has achieved in the past and where it needs to go in the future, not only to maintain the status quo, but hopefully to eliminate transmission of the disease within its borders.

A Second Chance to Tackle African Malaria Vector Mosquitoes that Avoid Houses and Don't Take Drugs

Sometimes history gives us a second chance by repeating itself. The timely and lucid modeling analysis presented by Phillip Eckhoff in this issue1 reminds us all that the challenges and opportunities faced by the malaria control community today remain remarkably similar to those of our predecessors who undertook the Global Malaria Eradication Campaign (GMEP). The anti-malarial drugs we use in 2013 are relatively new to the front lines but they are still overwhelmingly used in the same way for reactive clinical management of symptomatic cases.2 Long-lasting insecticidal nets (LLINs) now offer a proven alternative to indoor residual spraying (IRS) as the front-line vector control tool of the GMEP era but both approaches target mosquitoes within the same indoor environment and evidence that combining the two yields incremental benefits remains mixed.3–7 Although efficacious vaccines against malaria now exist and their expected impacts are simulated here,1 the protection they confer is partial and may wane8 as naturally acquired immunity fades9 and/or naturally acquired skin stage infections induce immunotolerance of pre-erythrocytic stages.10 Therefore, the fundamental properties, applications, and limitations of “off-the-shelf” intervention options available to control program managers today have not dramatically changed since the heyday of GMEP optimism half a century ago.11 And neither have the most fundamental knowledge gaps we face. The white arrows in Figure 1 crudely illustrate the impacts of intervention strategies we have reasonable experience and understanding of (suppression of high transmission with LLINs or IRS and elimination of sparse residual human parasite reservoirs with drugs), whereas the dark arrows illustrate those we urgently need to develop and learn about through trial and error (long-term resistance management, programmatic-scale vector control outdoors or at source, elimination of mosquito-to-human transmission during the dry season with vaccines, novel vector control tools, or chemoprophylaxis).

Genetic Surveillance Detects Both Clonal and Epidemic Transmission of Malaria following Enhanced Intervention in Senegal

Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified a growing frequency of infections caused by genetically identical parasite strains, coincident with increased deployment of malaria control interventions and decreased malaria deaths. Parasite genotypes in some cases persisted clonally across dry seasons. The increase in frequency of genetically identical parasite strains corresponded with decrease in the probability of multiple infections. Further, these observations support evidence of both clonal and epidemic population structures. These data provide the first evidence of a temporal correlation between the appearance of identical parasite types and increased malaria control efforts in Africa, which here included distribution of insecticide treated nets (ITNs), use of rapid diagnostic tests (RDTs) for malaria detection, and deployment of artemisinin combination therapy (ACT). Our results imply that genetic surveillance can be used to evaluate the effectiveness of disease control strategies and assist a rational global malaria eradication campaign.