Overview of malaria control in the Americas

The malaria endemic countries of the Americas have adopted in 1992 the WHO Global Malaria Control Strategy whose difficulties of implementation have been compounded to a major reform in the health sector, as the countries adjust to conform to financial scarcity and new economic policies. Most countries of the Region have reoriented its control program from eradication of malaria to the elimination of malaria mortality and morbidity. The Region has advanced towards these objectives having already reduced its mortality by 60% and is now in the final stages of applying new tools to control transmission and rapidly advance to reduce the incidence of malaria in the Americas.     

Some lessons for the future from the Global Malaria Eradication Programme (1955-1969)

Encouraged by the early success of using dichloro-diphenyl-trichloroethane (DDT) against malaria, the World Health Organization (WHO) embarked on the Global Malaria Eradication Program (GMEP) in 1955. Fourteen years later, the campaign was discontinued when it was recognised that eradication was not achievable with the available means in many areas, although the long-term goal remained unchanged. During the GMEP, malaria was permanently eliminated from many regions. In other areas, however, substantial gains were lost in resurgences, sometimes of epidemic proportions. During the 1970s and 1980s, because of economic and financial crises, international support for malaria control declined rapidly, but in the past decade, following increasing demands from endemic countries and promising results from scaling up of control activities, interest in malaria elimination and the long-term goal of eradication has received international political and financial support. In 2007, there was a renewed call for malaria eradication and a consultative process to define a research and development agenda for malaria eradication (malERA) was established. Lessons learned from the GMEP (1955-1969) highlight the fact that no single strategy can be applicable everywhere and that a long-term commitment with a flexible strategy that includes community involvement, integration with health systems, and the development of agile surveillance systems is needed.     

Getting ready for malaria elimination: a check list of critical issues to consider

In recent years, a renewed interest in malaria elimination and eradication has emerged and seems to be rooting in the minds of the scientific community, public health specialists, funding bodies, policy makers and politicians. Malaria eradication will certainly benefit from improved and innovative tools; notwithstanding novel knowledge in fields ranging from basic science to mathematical modelling and health systems research. However, the elimination of malaria also encompasses a broad range of essential aspects that countries and other actors need to consider when thinking of embarking on such an adventure, including the implementation of innovative strategies, the ability to incorporate the most up-to-date evidence into policy, the integration of malaria into the broader health agenda, the strengthening of surveillance and health systems, capacity building, funding, advocacy and, very importantly, research. While in some cases this enthusiasm is clearly justified, some countries are still a long way from realistically advancing towards elimination. This paper attempts to provide guidance on all the necessary issues that should be considered when initiating a malaria elimination program.     

Dealing with malaria in the last 60 years. A personal experience

Dealing with malaria in the last 60 years is seen by the author in the perspective of his own experience. His malaria work, which began in 1941, covered the study of the habits of the mosquitoes dwelling in the savanna country of Eastern Colombia and the effect on malaria transmission of the newly introduced DDT residual spraying. The success of the campaign he later directed in Sarawak and Brunei contributed to the launching by WHO of its global malaria eradication campaign. Further successful work in Uganda showed the possibility of effective control and even eradication in highland country but left unsolved the problem of how to interrupt transmission of holoendemic malaria in Africa. The author's work with WHO in the Middle East showed to what extent social and economic conditions could influence the course of a malaria campaign. This was also the experience in America, both in Colombia in the author's early work and later in Mexico during an evaluation of the national malaria programme. Development of insecticide resistance was also encountered in his career and the refractoriness of the European vectors was also observed in his work as a malariologist.     

Should the use of DDT be revived for malaria vector control?

Indoor residual spraying with DDT was the principle method by which malaria transmission was eradicated or greatly reduced in many countries between the late 1940s and 1970s. Since then, decreasing use of DDT has been associated with a resurgence of malaria in India, Sri Lanka, former Soviet Central Asia, Zanzibar, Venezuela and several other Latin American countries. In India and Zanzibar, DDT resistance in vectors, as well as a decline in spray coverage, are probable causes of reduced effectiveness of DDT in recent decades. In southern Europe, eradication of malaria transmission was achieved by DDT spraying in the 1940s and 50s and eradication has been sustained by adequate treatment of imported human malaria cases. In the highlands of Madagascar and South Africa, recent reversion to DDT spraying has been successful in stemming resurgences of malaria. Continued use of DDT for vector control, but not for agriculture, is approved by the Stockholm Convention on Persistent Organic Pollutants. DDE residues in breast milk have been associated with DDT anti-malaria spraying in South Africa, but it is not known whether this is harmful. A claimed association of DDE residues with breast cancer have not been substantiated. There is a recent report of association of DDE residues with probability of premature birth; the possible relevance of this to anti-malarial use of DDT should be investigated. In Colombia, testing of the DDT stockpile for suspensibility, DDT resistance in Anopheles darlingi and investigation of the present affordability of widespread spraying with DDT, compared with alternative chemicals, are recommended.     

Epidemiology in the strategies for malaria control

A rapid overview is presented of the evolution of the main orientations of malaria control, since the discovery of mosquito transmission. Stated control objectives appear to have oscillated between expectations to eradicate the vector, or at least the disease, and more modest approaches to minimise the effects of the infection. High optimism was raised when a new control measure, or new combination of existing measures, appeared to be highly effective and was expected to have universal applicability. The implementation of large scale campaigns eventually found the limits of applicability of the proposed strategy and the exaggerated expectations soon gave way to disillusion and, eventually, to a revival of research. The longest and most impacting period of exaggerated expectations was the global malaria eradication campaign of the 1950s and 1960s, which completely disregarded the study of local epidemiology, considering that all it was needed was to know if an area was "malarious" or not. Research was practically abandoned and, even when reinstated after the recognised failure of the campaign, it has retained an almost exclusive orientation towards the development of control tools, drugs or eventually vaccines. One of the earliest victims of the eradication campaign was the study of epidemic malaria and its determinants in different epidemic prone areas. In spite of an extremely long period of disillusion, lasting for almost two decades, the reality of the malaria problem led WHO and member countries to agree on a global strategy of control, aiming at a realistic use of existing tools, to at least reduce or prevent mortality. An essential element of this strategy is the prevention or control of malaria epidemics and the selective use of vector control, both of which have to be based on a solid knowledge of local epidemiology, the study of which has to rejoin the path abandoned fifty years ago.     

A sticky situation: the unexpected stability of malaria elimination

Malaria eradication involves eliminating malaria from every country where transmission occurs. Current theory suggests that the post-elimination challenges of remaining malaria-free by stopping transmission from imported malaria will have onerous operational and financial requirements. Although resurgent malaria has occurred in a majority of countries that tried but failed to eliminate malaria, a review of resurgence in countries that successfully eliminated finds only four such failures out of 50 successful programmes. Data documenting malaria importation and onwards transmission in these countries suggests malaria transmission potential has declined by more than 50-fold (i.e. more than 98%) since before elimination. These outcomes suggest that elimination is a surprisingly stable state. Elimination''s ‘stickiness’ must be explained either by eliminating countries starting off qualitatively different from non-eliminating countries or becoming different once elimination was achieved. Countries that successfully eliminated were wealthier and had lower baseline endemicity than those that were unsuccessful, but our analysis shows that those same variables were at best incomplete predictors of the patterns of resurgence. Stability is reinforced by the loss of immunity to disease and by the health system''s increasing capacity to control malaria transmission after elimination through routine treatment of cases with antimalarial drugs supplemented by malaria outbreak control. Human travel patterns reinforce these patterns; as malaria recedes, fewer people carry malaria from remote endemic areas to remote areas where transmission potential remains high. Establishment of an international resource with backup capacity to control large outbreaks can make elimination stickier, increase the incentives for countries to eliminate, and ensure steady progress towards global eradication. Although available evidence supports malaria elimination''s stickiness at moderate-to-low transmission in areas with well-developed health systems, it is not yet clear if such patterns will hold in all areas. The sticky endpoint changes the projected costs of maintaining elimination and makes it substantially more attractive for countries acting alone, and it makes spatially progressive elimination a sensible strategy for a malaria eradication endgame.     

Is vaccine the magic bullet for malaria elimination? A reality check

Malaria remains a major health burden especially for the developing countries. Despite concerted efforts at using the current control tools, such as bed nets, anti malarial drugs and vector control measures, the disease is accountable for close to a million deaths annually. Vaccines have been proposed as a necessary addition to the armamentarium that could work towards elimination and eventual eradication of malaria in view of their historical significance in combating infectious diseases. However, because malaria vaccines would work differently depending on the targeted parasite stage, this review addresses the potential impact various malaria vaccine types could have on transmission. Further, because of the wide variation in the epidemiology of malaria across the endemic regions, this paper proposes that the ideal approach to malaria control ought to be tailor-made depending on the specific context. Finally, it suggests that although it is highly desirable to anticipate and aim for malaria elimination and eventual eradication, many affected regions should prioritize reduction of mortality and morbidity before aspiring for elimination.     

Internationalism and nationalism: the Rockefeller Foundation, public health, and malaria in Italy, 1923-1951

The Rockefeller Foundation's support of malaria control and public health in Italy over three decades, the 1920s, 1930s and 1940s, was one of the foundation's most successful collaborations in its history. Nearly one-sixth of the funds the Rockefeller Foundation allocated for malaria programs was spent in Italy in those years. Outstanding research, a new and important institution, and decided improvements in public health were historically-significant results. The three most important episodes of this American-Italian relationship were the operations of the Stazione Sperimentale per la Lotta Antimalarica, the founding of the Istituto Superiore di Sanità, and the campaign to eradicate mosquitoes in Sardinia. In each of these episodes there was a tension between the international aspects and national aspects of the partnership that to some degree limited its success.     

Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?

Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication.     

Strengthening of the clinical research capacity for malaria: a shared responsibility

Malaria remains a major health burden especially for the developing countries. Despite concerted efforts at using the current control tools, such as bed nets, anti malarial drugs and vector control measures, the disease is accountable for close to a million deaths annually. Vaccines have been proposed as a necessary addition to the armamentarium that could work towards elimination and eventual eradication of malaria in view of their historical significance in combating infectious diseases. However, because malaria vaccines would work differently depending on the targeted parasite stage, this review addresses the potential impact various malaria vaccine types could have on transmission. Further, because of the wide variation in the epidemiology of malaria across the endemic regions, this paper proposes that the ideal approach to malaria control ought to be tailor-made depending on the specific context. Finally, it suggests that although it is highly desirable to anticipate and aim for malaria elimination and eventual eradication, many affected regions should prioritize reduction of mortality and morbidity before aspiring for elimination.

     

A research agenda for malaria eradication: drugs

Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or "attack" phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission.     

Epidemiological considerations for malaria reduction by transmission blocking vaccination

Outside of the temperate regions, malaria transmission continues throughout much of the world in a distribution which is not very different to that of one hundred years ago. However, with the notable exception of Africa sub Sahara, the morbidity and mortality due to malaria has generally been reduced to very low levels by comparison with earlier times. In a broad sense the malaria problem today falls into two distinct compartments, 1) how to deal with the remaining problem of malaria in the affected areas outside of sub Saharan Africa and 2) how to manage the, currently, much greater problem of malaria-related morbidity and mortality in Africa sub Sahara. Malaria control campaigns of the past have always placed great emphasis on reducing malaria inoculation rates in the affected populations. This may seem entirely logical, and is, indeed, an absolute requirement where eradication of malaria from an endemic area is the goal. There can, nevertheless, be dangers as well as benefits associated with reducing malaria inoculation rates in previously endemic populations. I discuss here the epidemiological issues which should be taken into account in this respect. I then examine the role that vaccination to reduce malaria inoculation rates in endemic populations--malaria transmission blocking vaccination--could play in malaria control.     

Malaria eradication in Calabria, residual anopheles and transmission risk]

The paper is from a presentation at the meeting "La malaria in Calabria" (Cosenza, Italy, May 3, 1997) held to celebrate the half centenary of the antimalaria campaign (1947-1952) that eradicated the infection from the region. While Plasmodium falciparum had already disappeared in 1950, P. vivax persisted and the last autochtonous case was documented on the river Esaro in 1955. From the records of that time, it is clear that malaria eradication was achieved in the presence of important vector densities, as shown by larval surveys. Indoor DDT spraying, acting through the insecticide irritant effect, mainly avoided the house resting by the vector and forced the exposure of the mosquito to the outdoor environment where the lower mean temperatures eventually proved instrumental in destabilizing the parasite's life cycle. It is stressed that insecticide resistance never arised in the Anopheles vector populations of Calabria, in spite of at least ten years of continuous indoor spraying with an excellent overall coverage. This is expected in the absence of important selection pressures at the larval breeding sites and whenever the impact of the house spraying on the vector is due mainly to the insecticide irritant effect rather than to a direct imagocidal effect.     

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.     

Epidemiology and control of malaria in Colombia

Malaria is currently one of the most serious public health problems in Colombia with an endemic/epidemic transmission pattern that has maintained endemic levels and an average of 105,000 annual clinical cases being reported over the last five years. Plasmodium vivax accounts for approximately 70% of reported cases with the remainder attributed almost exclusively to Plasmodium falciparum. A limited number of severe and complicated cases have resulted in mortality, which is a downward trend that has been maintained over the last few years. More than 90% of the malaria cases in Colombia are confined to 70 municipalities (about 7% of the total municipalities of Colombia), with high predominance (85%) in rural areas. The purpose of this paper is to review the progress of malaria-eradication activities and control measures over the past century within the eco-epidemiologic context of malaria transmission together with official consolidated morbidity and mortality reports. This review may contribute to the formulation of new antimalarial strategies and policies intended to achieve malaria elimination/eradication in Colombia and in the region.     

The role of research in viral disease eradication and elimination programs: lessons for malaria eradication

By examining the role research has played in eradication or regional elimination initiatives for three viral diseases--smallpox, poliomyelitis, and measles--we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios.     

Malaria control: achievements, problems and strategies

Even if history has not always been the Magistra vitae, Cicero expected it to be, it should provide, as Baas said, a mirror in which to observe and compare the past and present in order to draw therefrom well-grounded conclusions for the future. Based on this belief, this paper aims to provide an overview of the foundations and development of malaria control policies during the XX century. It presents an analysis of the conflicting tendencies which shaped the development of these policies and which appear to have oscillated between calls for frontal attack in an all-out campaign and calls for sustainable gains, even if slow. It discusses the various approaches to the control of malaria, their achievements and their limitations, not only to serve as a background to understand better the foundations of current policies, but also to prevent that simplistic generalisations may again lead to exaggerated expectations and disillusion. The first part of the paper is devoted to the development of malaria control during the first half of the century, characterised by the ups and downs in the reliance on mosquito control as the control measure applicable everywhere. The proliferation of "man-made-malaria", which accompanied the push for economic development in most of the endemic countries, spurred the need for control interventions and, while great successes were obtained in many specific projects, the general campaigns proposed by the enthusiasts of vector control faced increasing difficulties in their practical implementation in the field. Important events, which may be considered representative of this period are, on the campaign approach, the success of Gorgas in the Panama Canal, but also the failure of the Mian Mir project in India; while on the developmental approach, the Italian and Dutch schools of malariology, the Tennessee Valley and the development of malaria sanitation, included the so called species sanitation. The projection of these developments to a global scale was steered by the Malaria Commission of the League of Nations and greatly supported by the Rockefeller Foundation. Perhaps the most important contribution of this period was the development of malaria epidemiology, including the study of the genesis of epidemics and their possible forecasting and prevention. Although the great effectiveness of DDT was perhaps the main determinant for proposing the global eradication of the disease in the 1950s, it was the confidence in the epidemiological knowledge and the prestige of malariology, which gave credibility to the proposal at the political level. The second part deals with the global malaria eradication campaign of the 1950s and 1960s. It recognises the enormous impact of the eradication effort in the consolidation of the control successes of the first half of the century, as well as its influence in the development of planning of health programmes. Nevertheless, it also stresses the negative influence that the failure to achieve its utopian expectations had on the general disappointment and slow progress of malaria control, which characterised the last third of the century. The paper then analyses the evolution of malaria control funding, which often appears out of tune with political statements. The fourth part is devoted to the search for realistic approaches to malaria control, leading to the adoption of the global malaria control strategy in Amsterdam in 1992, and the challenge, at the end of the century, to rally forces commensurate with the magnitude of the problem, while aiming at realistic objectives. After discussing the conflicting views on the relations between malaria and socio-economic development and the desirable integration of malaria control into sustainable development, the paper ends with some considerations on the perspectives of malaria control, as seen by the author in early 1998, just before the launching of the current Roll Back Malaria initiative by WHO.     

Malaria eradication: the Taiwan experience

In November 1965, the World Health Organization (WHO) certified Taiwan as an area where malaria had been eradicated. Malaria eradication in Taiwan resulted from government initiatives and involvement, careful planning and organization, the development of basic health structure and community support, as well as the cooperation and assistance of international agencies. The Japanese colonial government of Taiwan had contributed to the antimalarial efforts through the establishment of a rudimentary health infrastructure and introduction of measures to combat malaria and other diseases during their occupation of the island from 1895 to 1945. The Chinese government regained control of the island after Japan's surrender in 1945, and with the support of the Rockefeller Foundation, established a research institute to investigate the malaria problem. Political instability in 1949, however, caused the Foundation to end its support. After the Nationalist government moved to Taiwan, it continued antimalarial efforts which received the support of WHO and other international agencies. While Taiwan followed closely WHO's guidelines and plan of attack, the development of the program illustrates the importance of local factors in shaping its actual implementation and eventual success. Malaria eradication in Taiwan went through the following phases: preparatory (1946-1951); attack (1952-1957); consolidation (1958-1964); and maintenance (after 1965).     

Spatio-temporal incidence of malaria patients in Incheon Metropolitan City

Malaria, a globally significant mosquito-borne infectious disease, re-emerged in the Republic of Korea, and manifested annually in regions close to the demilitarized zone. Notably, Incheon Metropolitan City has witnessed an alarming upswing in malaria infections in recent years, drawing attention to this public health issue. This research was conducted to catch spatio-temporal and ecological landscape encompassing malaria patients and mosquito vectors in Incheon over the past decade. The top two incidences of malaria cases were found in Ganghwa-gun and Seo-gu, an occurrence potentially attributed to their geographic proximity to North Korea. Furthermore, the incidence of malaria infections displayed a seasonal pattern commencing in March, reaching its peak between June and August, and decreasing to a minimum in November. A correlation was noted between prevalence of malaria cases and number of mosquito breeding sites, such as ponds and rice fields within the region. Collectively, these research outcomes underlined the importance of systematically and holistically advocating mosquito elimination measures to enhance the efficacy of malaria eradication policies. These measures encompass the establishment of a robust mosquito outbreak surveillance system, targeted control of vector mosquitoes, residual pesticide spray, management of mosquito breeding sites, and adoption of repellents during outdoor activities.