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.     

A research agenda for malaria eradication: cross-cutting issues for eradication

Discipline-specific Malaria Eradication Research Agenda (malERA) Consultative Groups have recognized several cross-cutting issues that must be addressed to prevent repetition of some of the mistakes of past malaria elimination campaigns in future programs. Integrated research is required to develop a decision-making framework for the switch from malaria control to elimination. Similarly, a strong economic case is needed for the very long-term financial support that is essential for elimination. Another cross-cutting priority is the development of improved measures of intensity of transmission, especially at low and nonrandom levels. Because sustained malaria elimination is dependent on a functioning health system, a further key cross-cutting research question is to determine how inputs for malaria can strengthen health systems, information systems, and overall health outcomes. Implementation of elimination programs must also be accompanied by capacity building and training to allow the assessment of the impact of new combinations of interventions, new roles for different individuals, and the operational research that is needed to facilitate program expansion. Finally, because community engagement, knowledge management, communication, political, and multisectoral support are critical but poorly understood success factors for malaria elimination, integrated research into these issues is vital.     

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.     

Molecular surveillance and temporal monitoring of malaria parasites in focal Vietnamese provinces

In the past decade substantial reduction in malaria morbidity and mortality has been observed through well-implemented case management and vector control strategies. India has also achieved a significant reduction in malaria burden in 2018 and has committed to eliminate malaria by 2030. The Mandla Malaria Elimination Demonstration Project (MEDP) was started in 2017 in 1233 villages of District Mandla to demonstrate malaria elimination in a tribal district with hard-to-reach areas was possible using active and passive surveillance, case management, vector control, and targeted information, education and communication campaigns. An operational plan was developed to strengthen the existing surveillance and malaria elimination systems, through fortnightly active case detection to ensure that all cases including those that are introduced into the communities are rapidly identified and treated promptly. The plan also focused on the reduction of human-mosquito contact through the use of Long-Lasting Insecticial Nets (LLINs) and Indoor Residual Spray (IRS). The operational plan was modified in view of the present COVID-19 pandemic by creating systems of assistance for the local administration for COVID-related work while ensuring the operational integrity of malaria elimination efforts. The use of MEDP study design and operational plan, with its built-in management control systems, has yielded significant (91%) reduction of indigenous cases of malaria during the period from June 2017 to May 2020. The malaria positivity rate was 0.33% in 2017–18, 0.13% in 2018–19, and 0.06% in 2019–20. Mass screening revealed 0.18% malaria positivity in September–October 2018, followed by 0.06% in June 2019, and 0.03% in December 2019, and these were mostly asymptomatic cases in the community. The project has been able to sustain the gains of the past three years during the ongoing COVID-19 pandemic. This paper provides the study design and the operational plan for malaria elimination in a high-burden district of Central India, which presented difficulties of hard to reach areas, forest malaria, and complex epidemiology of urban and rural malaria. The lessons learned could be used for malaria elimination efforts in rest of the country and other parts of South Asia with comparable demography and epidemiology.     

Serologic markers in relation to parasite exposure history help to estimate transmission dynamics of Plasmodium vivax

Plasmodium vivax infection has been gaining attention because of its re-emergence in several parts of the world. Southeastern Turkey is one of the places in which persistent focal malaria caused exclusively by P. vivax parasites occurs. Although control and elimination studies have been underway for many years, no detailed study has been conducted to understand the mechanisms underlying the ineffective control of malaria in this region. Here, for the first time, using serologic markers we try to extract as much information as possible in this region to get a glimpse of P. vivax transmission. We conducted a sero-immunological study, evaluating antibody responses of individuals living in Sanliurfa to four different P. vivax antigens; three blood-stage antigens (PvMSP1₁₉, PvAMA1-ecto, and PvSERA4) and one pre-erythrocytic stage antigen (PvCSP). The results suggest that a prior history of malaria infection and age can be determining factors for the levels and sustainability of naturally acquired antibodies. Significantly higher antibody responses to all the studied antigens were observed in blood smear-negative individuals with a prior history of malaria infection. Moreover, these individuals were significantly older than blood smear-negative individuals with no prior history of infection. These data from an area of sole P. vivax-endemic region may have important implications for the global malaria control/elimination programs and vaccine design.     

HIV: evolution of a pandemic.

Although the prevalence of AIDS is still relatively low in many countries in Asia and the Pacific Rim, the rate of HIV transmission in this region continues to rise inexorably and will surpass that of sub-Saharan Africa by 1997. The challenge of mobilizing governments and communities to counter this largely invisible threat was the theme of the Third International Conference on AIDS in Asia and the Pacific, held in Chiang Mai, Thailand, in September 1995. Thailand has led the way with bold and far-reaching HIV prevention programs. Nevertheless, the long-term consequences of existing HIV infection in Thailand and elsewhere in Asia will be severe. Moreover, these repercussions will be felt globally as productivity is undermined, health care costs soar and purchasing power weakens. Supporting programs for HIV prevention and care abroad is thus an urgent matter of economic and political self-interest as well as a humanitarian imperative.     

Components and Public Health Impact of Population Growth in the Arab World

The Arab world, which consists of the 22 member states of the Arab League, is undergoing a rapid transition in demographics, including fertility, mortality, and migration. Comprising a distinctive geographic region spread across West Asia and North East Africa and unified by the Arabic language, these states share common values and characteristics despite having diverse economic and political conditions. The demographic lag (high fertility and low mortality) that characterizes the Arab world is unique, but the present trend of declining fertility, combined with the relatively low mortality, brings about significant changes in its population size. This research aimed to: (i) assess the population growth in the Arab world over 3 time periods, (ii) explore its components, and (iii) understand its public health impact. Data from the International Data Base (IDB) of the U.S. Census Bureau for 3 time periods (1992, 2002, and 2012) in 21 countries of the Arab world were analyzed by dividing them into four geographic sectors, namely, the Gulf Cooperation Council (GCC), West Asia, Maghreb, and the Nile Valley African Horn. The population of the Arab world has grown considerably due to both natural growth and migration. The immigration is pronounced, especially into resource-intensive GCC nations, not only from East Asian and Central African countries but also from resource-thrifty (limited-resource) Arab nations. The migrations within, as well as outside, the Arab world reveal an interesting demographic phenomenon that requires further research: migration flows and trends. However, the transformations in public health statistics related to mortality—the impact of demographic changes—depict a new era in the Arab world.     

Safety of insecticide-treated mosquito nets for infants and their mothers: randomized controlled community trial in Burkina Faso

The Asia Pacific Malaria Elimination Network (APMEN) is a collaboration of 18 country partners committed to eliminating malaria from within their borders. Over the past 5 years, APMEN has helped to build the knowledge, tools and in-country technical expertise required to attain this goal. At its inaugural meeting in Brisbane in 2009, Plasmodium vivax infections were identified across the region as a common threat to this ambitious programme; the APMEN Vivax Working Group was established to tackle specifically this issue. The Working Group developed a four-stage strategy to identify knowledge gaps, build regional consensus on shared priorities, generate evidence and change practice to optimize malaria elimination activities. This case study describes the issues faced and the solutions found in developing this robust strategic partnership between national programmes and research partners within the Working Group. The success of the approach adopted by the group may facilitate similar applications in other regions seeking to deploy evidence-based policy and practice.     

A historical perspective on malaria control in Brazil

Malaria has always been an important public health problem in Brazil. The early history of Brazilian malaria and its control was powered by colonisation by Europeans and the forced relocation of Africans as slaves. Internal migration brought malaria to many regions in Brazil where, given suitableAnopheles mosquito vectors, it thrived. Almost from the start, officials recognised the problem malaria presented to economic development, but early control efforts were hampered by still developing public health control and ignorance of the underlying biology and ecology of malaria. Multiple regional and national malaria control efforts have been attempted with varying success. At present, the Amazon Basin accounts for 99% of Brazil’s reported malaria cases with regional increases in incidence often associated with large scale public works or migration. Here, we provide an exhaustive summary of primary literature in English, Spanish and Portuguese regarding Brazilian malaria control. Our goal was not to interpret the history of Brazilian malaria control from a particular political or theoretical perspective, but rather to provide a straightforward, chronological narrative of the events that have transpired in Brazil over the past 200 years and identify common themes.     

Estimation of Plasmodium falciparum transmission using multiepitope chimeric antigen in the postelimination phase in Yunnan,China

BackgroundThe continuous monitoring of malaria transmission intensity is still required to maintain elimination status after reaching the malaria elimination stage. In this study, serological surveillance with multiepitope artificial antigen was used to assess the transmission of Plasmodium falciparum in Yunnan, China, where malaria elimination has just been achieved, to provide data to support malaria control in the postelimination period.MethodsSamples were collected in three border counties and one inland county in Yunnan Province in 2016 using a stratified whole-group sampling method. Fingerstick blood was collected from all participants, and antibodies to Malaria Random Constructed Antigen-1 (M. RCAg-1) were detected by indirect ELISA. The transmission intensity of P. falciparum malaria was estimated using a catalytic conversion model based on the maximum likelihood of generating a community seroconversion rate (SCR).ResultsA total of 5566 samples were collected. There was no statistically significant difference in antibody level between the inland county and the nonendemic area, but the antibody level in border counties was significantly higher than those in the inland county and the nonendemic control area. No seropositive cases were found in Yanjin County, and the seropositivity rate increased with age in the three border counties. The highest intensity of P. falciparum malaria transmission was in Zhenkang County (SCR = 0.0030, CI: 0.0029, 0.0031), followed by Gengma County (SCR = 0.0013, CI: 0.0012, 0.0015) and Yingjiang County (SCR = 0.00088, CI: 0.00083, 0.00090).ConclusionThe transmission intensity of P. falciparum malaria in Yunnan Province has obviously decreased in recent years, but for the border areas where malaria has just been eliminated, the transmission intensity will not immediately drop to zero, and it still needs to be monitored for a period of time to maintain malaria elimination status.     

Regional Personality Differences in Great Britain

Recent investigations indicate that personality traits are unevenly distributed geographically, with some traits being more prevalent in certain places than in others. The geographical distributions of personality traits are associated with a range of important political, economic, social, and health outcomes. The majority of research on this subject has focused on the geographical distributions and macro-level correlates of personality across nations or regions of the United States. The aim of the present investigation was to replicate and extend that past work by examining regional personality differences in Great Britain. Using a sample of nearly 400,000 British residents, we mapped the geographical distributions of the Big Five Personality traits across 380 Local Authority Districts and examined the associations with important political, economic, social, and health outcomes. The results revealed distinct geographical clusters, with neighboring regions displaying similar personality characteristics, and robust associations with the macro-level outcome variables. Overall, the patterns of results were similar to findings from past research.     

Cryptic erythrocytic infections in Plasmodium vivax,another challenge to its elimination

Human malaria caused by Plasmodium vivax infection (vivax malaria) is a major global health issue. It is the most geographically widespread form of the disease, accounting for 7 million annual clinical cases, the majority of cases in America and Asia and an estimation of over 2.5 billion people living under risk of infection. The general perception towards vivax malaria has shifted recently, following a series of reports, from being viewed as a benign infection to the recognition of its potential for more severe manifestations including fatal cases. However, the underlying pathogenic mechanisms of vivax malaria remain largely unresolved. Asymptomatic carriers of malaria parasites are a major challenge for malaria elimination. In the case of P. vivax, it has been widely accepted that the only source of cryptic parasites is hypnozoite dormant stages. Here, we will review new evidence indicating that cryptic erythrocytic niches outside the liver, in particular in the spleen and bone marrow, can represent a major source of asymptomatic infections. The origin of such parasites is being controversial and many key gaps in the knowledge of such infections remain unanswered. Yet, as parasites in these niches seem to be sheltered from immune response and antimalarial drugs, research on this area should be reinforced if elimination of malaria is to be achieved. Last, we will glimpse into the role of reticulocyte-derived exosomes, extracellular vesicles of endocytic origin, as intercellular communicators likely involved in the formation of such cryptic erythrocytic infections.     

Land use change in Asia and the ecological consequences

Viewed within a historical context, Asia has experienced dramatic land transformations, and currently more than 50% of Asian land area is under agriculture. The consequences of this transformation are manifold. Southeast Asia has the highest deforestation rate of any major tropical region. Many of the world’s large rivers and lakes in Asia have been heavily degraded. About 11 of 19 world megacities with more than 10 million inhabitants are in Asia. These land use activities have resulted in substantial negative ecological consequences, including increased anthropogenic CO₂ emissions, deteriorated air and water quality, alteration of regional climate, an increase of disease and a loss of biodiversity. Although land use occurs at the local level, it has the potential to cause ecological impact across local, regional and global scales. Reducing the negative environmental impacts of land use change while maintaining economic viability and social acceptability is an major challenge for most developing countries in Asia.     

Land use change and carbon cycle in arid and semi-arid lands of East and Central Asia

Dramatic changes in land use have occurred in arid and semi-arid landsof Asia during the 20th century. Grassland conversion into croplands and ecosystem degradation is widespread due to the high growth rate of human population and political reforms of pastoral systems. Rangeland degradation made many parts of this region vulnerable to environmental and political changes. The collapse of the livestock sector in some states of central Asia, expansion of livestock inChina and intensive degradation of grasslands in China are examples of the responses of pastoral systems to these changes over the past decades. Carbon dynamics in this region is highly variable in space and time. Land use/cover changes with widespread reduction of forest and grasslands increased carbon emission from the region.     

Land use change and carbon cycle in arid and semi-arid lands of East and Central Asia

Dramatic changes in land use have occurred in arid and semi-arid lands of Asia duringthe 20th century. Grassland conversion into croplands and ecosystem degradation is widespreaddue to the high growth rate of human population and political reforms of pastoral systems. Rangeland degradation made many parts of this region vulnerable to environmental and political changes. The collapse of the livestock sector in some states of central Asia, expansion of livestockin China and intensive degradation of grasslands in China are examples of the responses of pastoral systems to these changes over the past decades. Carbon dynamics in this region is highly variable in space and time. Land use/cover changes with widespread reduction of forest and grasslands increased carbon emission from the region.     

Epidemiology and Clinical Burden of Malaria in the War-Torn Area,Orakzai Agency in Pakistan

Background

Military conflict has been a major challenge in the detection and control of emerging infectious diseases such as malaria. It poses issues associated with enhancing emergence and transmission of infectious diseases by destroying infrastructure and collapsing healthcare systems. The Orakzai agency in Pakistan has witnessed a series of intense violence and destruction. Military conflicts and instability in Afghanistan have resulted in the migration of refugees into the area and possible introduction of many infectious disease epidemics. Due to the ongoing violence and Talibanization, it has been a challenge to conduct an epidemiological study.

Methodology/Principal Findings

All patients were sampled within the transmission season. After a detailed clinical investigation of patients, data were recorded. Baseline venous blood samples were taken for microscopy and nested polymerase chain reaction (nPCR) analysis. Plasmodium species were detected using nested PCR (nPCR) and amplification of the small subunit ribosomal ribonucleic acid (ssrRNA) genes using the primer pairs. We report a clinical assessment of the epidemic situation of malaria caused by Plasmodium vivax (86.5%) and Plasmodium falciparum (11.79%) infections with analysis of complications in patients such as decompensated shock (41%), anemia (8.98%), hypoglycaemia (7.3%), multiple convulsions (6.7%), hyperpyrexia (6.17%), jaundice (5%), and hyperparasitaemia (4.49%).

Conclusions/Significance

This overlooked distribution of P. vivax should be considered by malaria control strategy makers in the world and by the Government of Pakistan. In our study, children were the most susceptible population to malaria infection while they were the least expected to use satisfactory prevention strategies in such a war-torn deprived region. Local health authorities should initiate malaria awareness programs in schools and malaria-related education should be further promoted at the local level reaching out to both children and parents.     

A Country on the Verge of Malaria Elimination – The Kingdom of Saudi Arabia

Significant headway has been made in the global fight against malaria in the past decade and as more countries enter the elimination phase, attention is now focused on identifying effective strategies to shrink the malaria map. Saudi Arabia experienced an outbreak of malaria in 1998, but is now on the brink of malaria elimination, with just 82 autochthonous cases reported in 2012. A review of published and grey literature was performed to identify the control strategies that have contributed to this achievement. The number of autochthonous malaria cases in Saudi Arabia decreased by 99.8% between 1998 and 2012. The initial steep decline in malaria cases coincided with a rapid scaling up of vector control measures. Incidence continued to be reported at low levels (between 0.01 and 0.1 per 1,000 of the population) until the adoption of artesunate plus sulfadoxine-pyrimethamine as first line treatment and the establishment of a regional partnership for a malaria-free Arabian Peninsula, both of which occurred in 2007. Since 2007, incidence has decreased by nearly an order of magnitude. Malaria incidence is now very low, but a high proportion of imported cases, continued potential for autochthonous transmission, and an increased proportion of cases attributable to Plasmodium vivax all present challenges to Saudi Arabia as they work toward elimination by 2015.     

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.     

Geographically separate increases in the frequency of the derived ADH1B*47His allele in eastern and western Asia

The ADH1B Arg47His polymorphism has been convincingly associated with alcoholism in numerous studies of several populations in Asia and Europe. In a review of literature from the past 30 years, we have identified studies that report allele frequencies of this polymorphism for 131 population samples from many different parts of the world. The derived ADH1B*47His allele reaches high frequencies only in western and eastern Asia. To pursue this pattern, we report here new frequency data for 37 populations. Most of our data are from South and Southeast Asia and confirm that there is a low frequency of this allele in the region between eastern and western Asia. The distribution suggests that the derived allele increased in frequency independently in western and eastern Asia after humans had spread across Eurasia.