Transmission immunity in malaria: reflections on the underlying immune mechanisms during natural infections and following artificial immunization

Malaria transmission-blocking immunity has been studied in natural malaria infections in man, during infections in animals and following artificial immunization of animals with sexual stage malaria parasites. Effective immunity, which prevents infectivity of a malarial infection to mosquitoes, has been observed under all of these circumstances. Two general types of effector mechanism have been identified. One is an antibody mediated mechanism which acts against the extracellular sexual stages of the parasite within the midgut of a blood feeding mosquito. The other is a cytokine mediated mechanism which inactivates the gametocytes of the parasites while in the circulation of the vertebrate host. Both effects have been observed during natural infections and following artificial immunization. The basis of induction of transmission-blocking immunity, including the nature of the memory for such immunity, however, may be very different in different host/parasite systems and during natural infection of following artificial immunization. Following artificial immunization a strong immune memory for transmission blocking immunity has been observed in animal systems. By contrast, following natural infections in man immune memory for transmission blocking immunity has been found to be weak and short lived if it occurs at all. It is suggested that the immunogens which induce natural transmission blocking immunity may be CD4+ independent

Trends in malaria research in 11 Asian Pacific countries: an analysis of peer-reviewed publications over two decades

Background: Quantitative data are lacking on published malaria research. The purpose of the study is to characterize trends in malaria-related literature from 1990 to 2009 in 11 Asian-Pacific countries that are committed to malaria elimination as a national goal. Methods. A systematic search was conducted for articles published from January 1990 to December 2009 in PubMed/MEDLINE using terms for malaria and 11 target countries (Bhutan, China, North Korea, Indonesia, Malaysia, Philippines, Solomon Islands, South Korea, Sri Lanka, Thailand and Vanuatu). The references were collated and categorized according to subject, Plasmodium species, and whether they contained original or derivative data. Results: 2,700 articles published between 1990 and 2009 related to malaria in the target countries. The annual output of malaria-related papers increased linearly whereas the overall biomedical output from these countries grew exponentially. The percentage of malaria-related publications was nearly 3% (111/3741) of all biomedical publications in 1992 and decreased to less than 1% (118/12171; p < 0.001) in 2009. Thailand had the highest absolute output of malaria-related papers (n = 1211), followed by China (n = 609) and Indonesia (n = 346). Solomon Islands and Vanuatu had lower absolute numbers of publications, but both countries had the highest number of publications per capita (1.3 and 2.5 papers/1,000 population). The largest percentage of papers concerned the epidemiology and control of malaria (53%) followed by studies of drugs and drug resistance (47%). There was an increase in the proportion of articles relating to epidemiology, entomology, biology, molecular biology, pathophysiology and diagnostics from the first to the second decade, whereas the percentage of papers on drugs, clinical aspects of malaria, immunology, and social sciences decreased. Conclusions: The proportion of malaria-related publications out of the overall biomedical output from the 11 target Asian-Pacific countries is decreasing. The discovery and evaluation of new, safe and effective drugs and vaccines is paramount. In addition the elimination of malaria will require operational research to implement and scale up interventions

Malaria transmission-blocking vaccines—how can their development be supported?

Malaria is a disease of poor countries. The development of malaria vaccines requires considerable investment, for which there is little commercial interest, particularly for transmission-blocking vaccines that have the public health objective of protecting communities from the spread of malaria rather than protecting individuals from the disease. Here, Carter et al. summarize the report of a committee of experts on the relevance and prospects for these vaccines

Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation

<p>Abstract</p> <p>Background</p> <p>Paroxysms are recurrent febrile episodes, characteristic of <it>Plasmodium vivax </it>infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes <it>in vitro </it>in the presence of parasite and host factors released during paroxysms.</p> <p>Methods</p> <p>Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms.</p> <p>Results</p> <p>Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute <it>P. vivax </it>infections was neutralized by immune sera raised against schizont extracts of either <it>P. vivax </it>or <it>Plasmodium falciparum</it>. However, immune sera against <it>P. vivax </it>were more effective than that against <it>P. falciparum </it>indicating that the parasite activity involved may be antigenically at least partially parasite species-specific.</p> <p>Conclusion</p> <p>Leukocyte aggregation was identified as associated with paroxysms in <it>P. vivax </it>infections. This phenomenon is mediated by plasma factors including host-derived cytokines and lipids of putative parasite origin. The characteristics of the phospholipid fraction in paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing GPI moieties described by others. The more active cholesterol/triglyceride(s), however, represent a novel malarial toxin, which is a new class of biologically active lipid associated with the paroxysm of <it>P. vivax </it>malaria.</p

A Research Agenda to Underpin Malaria Eradication

Pedro Alonso and colleagues introduce the Malaria Eradication Research Agenda (malERA) initiative and the set of articles published in this PLoS Medicine Supplement that distill the research questions key to malaria eradication

Spatial targeting of interventions against malaria

Malaria transmission is strongly associated with location. This association has two main features. First, the disease is focused around specific mosquito breeding sites and can normally be transmitted only within certain distances from them: in Africa these are typically between a few hundred metres and a kilometre and rarely exceed 2-3 kilometres. Second, there is a marked clustering of persons with malaria parasites and clinical symptoms at particular sites, usually households. In localities of low endemicity the level of malaria risk or case incidence may vary widely between households because the specific characteristics of houses and their locations affect contact between humans and vectors. Where endemicity is high, differences in human/vector contact rates between different households may have less effect on malaria case incidences. This is because superinfection and exposure-acquired immunity blur the proportional relationship between inoculation rates and case incidences. Accurate information on the distribution of malaria on the ground permits interventions to be targeted towards the foci of transmission and the locations and households of high malaria risk within them. Such targeting greatly increases the effectiveness of control measures. On the other hand, the inadvertent exclusion of these locations causes potentially effective control measures to fail. The computerized mapping and management of location data in geographical information systems should greatly assist the targeting of interventions against malaria at the focal and household levels, leading to improved effectiveness and cost-effectiveness of control

Initial response to SARS-CoV-2 (COVID-19) outbreak in Sri Lanka; views of public health specialists through an International Health Regulations lens.

The COVID-19 pandemic affected Sri Lanka despite having developed an International Health Regulations (IHR) steering committee in 2016 and a national action plan for health security following the Joint External Evaluation in 2018. Many steps were taken to improve the disaster management skills of healthcare workers even before the COVID-19 outbreak. We interviewed seven public health specialists to obtain their views on the country's response to the pandemic. A thematic analysis was conducted, leading to the emergence of three major themes and seven subthemes. The major themes included health security preparedness; COVID-19 management; and effects of COVID-19. The subthemes were; preparedness prior to pandemic and gaps in the preparedness (under health security preparedness); dual burden for the curative sector, strategies to reduce transmission and barriers to managing COVID-19 (under COVID-19 management) and negative and positive effects of COVID-19 (under effects of COVID-19). When COVID-19 reached Sri Lanka, healthcare workers, border control authorities and those involved with infectious disease control were overwhelmed by the magnitude of the pandemic. Healthcare workers' hesitation to work amidst the pandemic due to fear of infection and possible transmission of infection to their families was a major issue; the demand for personal protective equipment by health workers when stocks were low was also a contributory factor. Lockdowns with curfew and quarantine at government regulated centers were implemented as necessary. Perceptions of the public including permitting healthcare workers to perform field public health services, logistical barriers and lack of human resources were a few of the barriers that were expressed. Some persons did not declare their symptoms, fearing that they would have to be quarantined. The pandemic severely affected the economy and Sri Lanka relied on donations and loans to overcome the situation. Pandemic also brought about innovative methods to maintain and upgrade health service provision. Individuals with non-communicable diseases received their regular medications through the post which reduced their risk of being infected by visiting hospitals. Improvement of laboratory services and quarantine services, a reduction of acute respiratory infections and diarrhoeal diseases, improved intersectoral coordination and public philanthropic response were other positive effects

From malaria control to eradication: The WHO perspective.

Efforts to control malaria have been boosted in the past few years with increased international funding and greater political commitment. Consequently, the reported malaria burden is being reduced in a number of countries throughout the world, including in some countries in tropical Africa where the burden of malaria is greatest. These achievements have raised new hopes of eradicating malaria. This paper summarizes the outcomes of a World Health Organization's expert meeting on the feasibility of such a goal. Given the hindsight and experience of the Global Malaria Eradication Programme of the 1950s and 1960s, and current knowledge of the effectiveness of antimalarial tools and interventions, it would be feasible to effectively control malaria in all parts of the world and greatly reduce the enormous morbidity and mortality of malaria. It would also be entirely feasible to eliminate malaria from countries and regions where the intensity of transmission is low to moderate, and where health systems are strong. Elimination of malaria requires a re-orientation of control activity, moving away from a population-based coverage of interventions, to one based on a programme of effective surveillance and response. Sustained efforts will be required to prevent the resurgence of malaria from where it is eliminated. Eliminating malaria from countries where the intensity of transmission is high and stable such as in tropical Africa will require more potent tools and stronger health systems than are available today. When such countries have effectively reduced the burden of malaria, the achievements will need to be consolidated before a programme re-orientation towards malaria elimination is contemplated. Malaria control and elimination are under the constant threat of the parasite and vector mosquito developing resistance to medicines and insecticides, which are the cornerstones of current antimalarial interventions. The prospects of malaria eradication, therefore, rest heavily on the outcomes of research and development for new and improved tools. Malaria control and elimination are complementary objectives in the global fight against malaria