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Mosquito Malaria Research Papers

Malaria has been curse to human life since ancient times. Our understanding about this deadly pathogen has increased yet we are not able to eradicate malaria successfully. The death toll increment on a regular basis and emergence of evolved new parasite raised the concern tremendously.
Malaria Control and Elimination journal is a peer reviewed and open access, critique and fully exemplified journal which aim to scaffold underlying and enforced aspects of malaria research in equatorial and other arena. This open access journal will provide researchers, scholars and academicians with a forum for publication of research advances, in the form of original articles, review articles, case reports, short communications, etc.
Malaria Control and Elimination is using Editorial Manager System for quality review process. Editorial Manager system is an online manuscript submission, review and tracking system. Review processing is performed by the editorial board members of Malaria Control and Elimination or outside experts; at least two independent reviewers approval followed by editor approval is required for acceptance of any citable manuscript. Authors may submit manuscripts and track their progress through the system, hopefully to publication. Reviewers can download manuscripts and submit their opinions to the editor. Editors can manage the whole submission/review/revise/publish process.
Extensive global research and on growing understanding about malaria requires a common podium for exchange of information among the authors and the readers.
Malaria Control and Elimination journal offers excellent scope for exchanging such information. This journal considers articles in the areas of medicine for malaria, malaria control, cerebral malaria, malaria vaccines, antimalarial, neonatal malaria, malaria parasites,etc.  advances in discovery, development and implementation of drugs, vaccines and mosquito control measures and any other related aspects for elimination of malaria which will regularly involve multi-disciplinary collaborations with laboratories and public education.

Malaria fever

Malaria is a serious infectious disease spread by certain mosquitoes. It is most common in tropical climates. It is characterized by recurrent symptoms of chills, fever, and an enlarged spleen. The disease can be treated with medication, but it often recurs.

Related Journals for Malaria fever

Malaria Journal, Malaria Research & Treatment, Journal of Food: Microbiology, Safety & Hygiene, Journal of Food & Industrial Microbiology, Journal of Microbial & Biochemical Technology, Journal of Plant Pathology & Microbiology, Malaria Journal, Journal of Malaria Research United States.

Chloroquine-resistant

Chloroquine has long been used in the treatment or prevention of malaria. After the malaria parasite Plasmodium falciparum started to develop widespread resistance to it, new potential uses of this cheap and widely available drug have been investigated. Chloroquine can be used for preventing malaria from Plasmodium vivax, P. ovale, and P. malariae.

Related journals for Chloroquine-resistant

Malaria Vaccine, Malaria Vaccine & Review, Emerging Infectious Diseases, Cerebral Malaria, Recurrent Malaria.

Vector of malaria

The mosquito has been described as the most dangerous vector in the world and the mosquito-borne disease with the greatest detrimental impact is undoubtedly malaria. There are about 3,500 mosquito species and those that transmit malaria all belong to a sub-set called the Anopheles. Approximately 40 Anopheles species are able to transmit malaria well enough to cause significant human illness and death.

Related journals for Vector of malaria 

Malaria Research,Current Malaria Research, Vector Malaria, Air Diseases, Food Microbiology.

Malarial genetic resistance

Genetic resistance to malaria is an inherited change in the genome of an organism that confers a selective survival advantage due to conferring or increasing resistance to disease. In malaria, an infection of the erythrocytes (red blood cells), the genetic change is an alteration of the hemoglobin molecule or cellular proteins or enzymes of erythrocytes that inhibits invasion by or replication of Plasmodia, the microorganisms that cause the disease.

Related journals for Malarial genetic resistance 

Preventing Malaria, Current Research on Malaria, Biochemistry and Molecular Biology, Biochemistry and Analytical Biochemistry, Genetics .

Cerebral malaria

Cerebral malaria forms part of the spectrum of severe malaria, with a case fatality rate ranging from 15% in adults in southeast Asia to 8.5% in children in Africa. Cerebral malaria is the most severe neurological complication of infection with Plasmodium falciparum.

Related journals for Cerebral malaria 

Current Research on Malaria, Current Malaria Research, Neurology and Neurophysiology, Neuroinfectious Diseases.

Malaria in pregnant women

Malaria infection during pregnancy is a significant public health problem with substantial risks for the pregnant woman, her fetus, and the newborn child. Malaria-associated maternal illness and low birth weight is mostly the result of Plasmodium falciparum infection and occurs predominantly in Africa. The symptoms and complications of malaria in pregnancy vary according to malaria transmission intensity in the given geographical area, and the individual’s level of acquired immunity.

Related journals for Malaria in pregnant women 

Preventing Malaria, Current Research on Malaria, Immunology, Emerging Infectious Diseases, Bacteriology.

Malaria parasites

Malaria parasites are micro-organisms that belong to the genus Plasmodium. There are more than 100 species of Plasmodium, which can infect many animal species such as reptiles, birds, and various mammals. Four species of Plasmodium have long been recognized to infect humans in nature. In addition there is one species that naturally infects macaques which has recently been recognized to be a cause of zoonotic malaria in humans.

Related journals for Malaria parasites

Malaria Information, Current Malaria Research, Air Borne Diseases, Emerging Infectious Diseses, Food Pathology.

Recurrent malaria

Recur­rent malaria is a perplexing clinical problem and limited scien­tific data is available on its diag­nostic approach, and manage­ment. Symptoms of malaria can recur after varying symptom-free periods. Depending upon the cause, recurrence can be classified as either recrudescence, relapse, or reinfection. Recrudescence is when symptoms return after a symptom-free period. It is caused by parasites surviving in the blood as a result of inadequate or ineffective treatment.

Related journals for Recurrent malaria 

Malaria Information, Current Malaria Research, Vector Malaria, Air Borne Malaria, Genetics, Immunology.

Diagnosis of malaria

Early and accurate diagnosis of malaria is essential for effective disease management and malaria surveillance. High-quality malaria diagnosis is important in all settings as misdiagnosis can result in significant morbidity and mortality.

Related journals for Diagnosis of malaria 

Preventing Malaria, Current Research on Malaria, Current Malaria Research, Malaria Journal United Kingdom, Bacteriology and Parasitology.

 

Neonatal Malaria

Neonatal malaria was thought to be uncommon, even in malaria endemic areas. Neonates with febrile illness or related symptoms are often presumed to have neonatal septicaemia and examination of blood films for malaria parasites is rarely included in the initial work-up of these babies.

Related journals for Neonatal Malaria

Malaria Research, Malaria Vaccine & Review, Emerging Infectious Diseases, Cerebral Malaria, Recurrent Malaria.

 

Malaria prophylaxis

Malaria prophylaxis is the preventive treatment of malaria. Several malaria vaccines are under development. The ABCD of malaria prophylaxis: Awareness of the risk of malaria, Bites - reducing likelihood of bites from anopheline mosquitoes, Chemoprophylaxis, Diagnosis and prompt treatment to prevent complications.

Related journals for Malaria prophylaxis 

Malaria Research, Emerging Infectious Diseases, Vector Parasites .

 

Malaria vaccines

Malaria vaccines are an area of intensive research. Emergence of artemisinin and multi-drug resistant strains of especially P. falciparum are driving research. Current approaches are focusing on recombinant protein and attenuated whole organism vaccines. Various vaccines have reached the state of clinical trials; most demonstrated insufficient immunogenicity.

Related journals for Malaria vaccines

Malaria Vaccine, Malaria Vaccine & Review, Advanced Techniques in Biology and Medicine, Clinical Trials, Emerging Infectious Diseases.

 

Antimalarial

Antimalarial drugs are used for the treatment and prevention of malaria infection. A drug directed against malaria. Most antimalarial drugs target the erythrocytic stage of malaria infection, which is the phase of infection that causes symptomatic illness. The extent of preerythrocytic (hepatic stage) activity for most antimalarial drugs is not well characterized.

Related journals for Antimalarial

Malaria Prevention, Preventing Malaria, Current Research on Malaria, Emerging Infectious Diseases, Cerebral Malaria, Recurrent Malaria, Malaria World, Communicable Disesse .

 

Malaria pills

Malaria is a very serious disease, and its presence in many regions of the world is well known. So if you are traveling to an area where malaria is present, it is important to reduce the risk of infection by taking medicine before you travel, while you are in the area, and after you return home. Malaria is usually a preventable infection. There are good drugs to prevent malaria. During malaria treatment, doctor may do daily blood smears to follow the course of the infection. Most medicines for malaria are ones you take by mouth.

Related journals for Malaria pills

Journal of malaria, Journal of Malaria Research, Medical and Veterinary Entomology, Applied Entomology.

 

Plasmodium malariae

Plasmodium malariae is a parasitic protozoa that causes malaria in humans. It is one of several species of Plasmodium parasites that infect humans including Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that produced by P. falciparum or P. vivax. It causes fevers that recur at approximately three-day intervals (a quartan fever), longer than the two-day (tertian) intervals of the other malarial parasites, hence its alternate names quartan fever and quartan malaria.

Related journals for Plasmodium malariae

Malaria Journal, Journal of Malaria Research, Malaria Parasites, Recurrent Malaria, Malaria Vaccines.

 

Malaria Control

New strategies for malaria prevention and control are emphasizing ‘integrated vector management’. This approach reinforces linkages between health and environment, optimizing benefits to both. Integrated vector management is a dynamic and still-evolving field. IVM strategies are designed to achieve the greatest disease-control benefit in the most cost-effective manner, while minimizing negative impacts on ecosystems and adverse side-effects on public health.

Related journals for Malaria Control

Malaria Prevention, Preventing Malaria, Malaria Control and Elimination, Vector Parasites,Air Borne Diseases.

 

Congenital malaria

Congenital malaria is defined as malarial parasites demonstrated in the peripheral smear of the newborn from twenty four hours to seven days of life. Clinically apparent congenital malaria is rare in areas in which malaria is endemic and levels of maternal antibody are high. The most common clinical features of congenital malaria are fever, anaemia and splenomegaly. Other signs and symptoms include hepatosplenomegaly, jaundice, regurgitation, loose stools, and poor feeding.

Related journals for Congenital malaria

Current Research on Malaria, Malaria Research & Treatment, Emerging Infectious Diseases, Cerebral malaria, Recurrent malaria, epidemiology, malaria relapse.

 

Malaria parasite life cycle

The malaria parasite develops both in humans and in the female Anopheles mosquitoes. The size and genetic complexity of the parasite mean that each infection presents thousands of antigens (proteins) to the human immune system. The parasite also changes through several life stages even while in the human host, presenting different antigens at different stages of its life cycle.

Related journals for Malaria parasite life cycle

Journal of Malaria Research, Malaria Research & Treatment Impact Factor, Malaria Parasites, Pathogenesis,  Epidemiology.

 

Malaria relapse

Relapse has a specific meaning in regards to malaria and refers to the reactivation of the infection via hypnozoites. Relapse is when symptoms reappear after the parasites have been eliminated from blood but persist as dormant hypnozoites in liver cells. Relapse commonly occurs between 8–24 weeks and is commonly seen with P. vivax and P. ovale infections.P. vivax malaria cases intemperate areas often involve overwintering by hypnozoites, with relapses beginning the year after the mosquito bite.

Related journals for Malaria relapse

Malaria Information, Malaria Prevention, Biochemistry of Analytical Biology, Biochemistry of Medicine, Malaria Journal United Kingdom, Journal of Malaria Research United States.

 

Malaria management

Malaria continues to be a major health problem in many parts of the world. Delay in treatment, especially of cases caused by P. falciparum the species of the parasite that is the main cause of the severe forms of the disease – may result in rapid deterioration in the patient’s condition, and in the development of life-threatening complications. Recognizing and promptly treating uncomplicated malaria is therefore of vital importance.

Related journals for Malaria management

Journal on Malaria, Malaria Research, Malaria World, Emerging Infectious Diseases, Control and Elimination, Malaria Journal United Kingdom, Journal of Malaria Research United States.

Epidemiology malaria

Malaria is transmitted via the bite of a female Anopheles spp mosquito, which occurs mainly between dusk and dawn. Other comparatively rare mechanisms for transmission include congenitally acquired disease, blood transfusion, sharing of contaminated needles, and organ transplantation.

Related journals for Epidemiology malaria

Preventing Malaria, Current Research on Malaria, Epidemiology, Applied Entomology, Malaria Journal United Kingdom, Journal of Malaria Research United States.

Zoonotic malaria

Malaria is caused by the protozoan parasite Plasmodium. Human malaria is caused by four different species of Plasmodium: P. falciparum, P. malariae, P. ovale and P. vivax. Humans occasionally become infected with Plasmodium species that normally infect animals, such as P. knowlesi. As yet, there are no reports of human-mosquitohuman transmission of such “zoonotic” forms of malaria.

Related journals for Zoonotic malaria

Malaria Research & Treatment Impact Factor, Malaria Vaccine, Biology and Medicine, Vector Parasites, Contol and Elimination, Malaria Journal United Kingdom, Journal of Malaria Research United States.

 

Placental malaria

Placental malaria is recognized as a common complication of malaria in pregnancy in areas of stable transmission, is particularly frequent and severe in primigravidae. Many hypotheses, based on a systemic or local failure of the immunological response to malaria.

Related jounals for Placental malaria 

Malaria Information, Current Research on Malaria, Clinical Trials, Clinics in Mother and Child Care, Malaria Journal United Kingdom, Journal of Malaria Research United States.

 

Malaria transmission

The malaria parasite typically is transmitted to people by mosquitoes belonging to the genus Anopheles. In rare cases, a person may contract malaria through contaminated blood. Malaria also may be transmitted from a mother to her fetus before or during delivery ("congenital" malaria). Because the malaria parasite is found in red blood cells, malaria can also be transmitted through blood transfusion, organ transplant, or the shared use of needles or syringes contaminated with blood.

Related journals for Malaria transmission 

Current Malaria Research, Tropical Medicine and Surgery , Malaria Journal United Kingdom, Journal of Malaria Research United States.

 

Malaria Endemicity

Endemicity (or disease intensity) is a measure of disease prevalence in a particular region and prevalence is the proportion of people infected at a given point in time. We predict the prevalence of malaria parasites at different locations to provide estimates of endemicity.The vast majority of malaria disease and death occurs within these areas and the level of endemicity within these areas is of particular interest to groups involved in malaria control. Information about areas of unstable malaria transmission is important for regions that are close to malaria elimination and it is more appropriate to measure disease incidence.

Related journals for Malaria Endemicity

Journal of Malaria, Journal of Malaria Research, Malaria Journal United Kingdom, Journal of Malaria Research United States, emerging infectious diseases , control and elimination .

 

Sporozoite

A female Anopheles mosquito carrying malaria-causing parasites feeds on a human and injects the parasites in the form of sporozoites into the bloodstream. The sporozoites travel to the liver and invade liver cells. The sporozoites are transmitted via the saliva of a feeding mosquito to the human bloodstream.

Related journals for Sporozoite

Journal of Malaria, Journal of Malaria Research, Malaria Journal United Kingdom, Journal of Malaria Research United States, occupational medicines and health affairs .

 

Pathogenesis of malaria

All of the pathology of malaria is due to parasites multiplying in erythrocytes. The primary attack of malaria begins with headache, fever, anorexia, malaise, and myalgia. This is followed by paroxysms of chills, fever, and profuse sweating. There may be nausea, vomiting, and diarrhea. Such symptoms are not unusual for an infectious disease and it is for this reason that malaria is frequently called “The Great Imitator.” Then, depending on the species, the paroxysms tend to assume a characteristic periodicity. In P. vivax, P. ovale and P. falciparum the periodicity is 48hr and for P. malariae the periodicity is 72 hours.

Related journals for Pathogenesis of malaria

Preventing Malaria, Current Research on Malaria, Malaria journal United Kingdom, malaria parasites, recurrent malaria .

 

Febrile malaria

Acute febrile disease in the tropics and sub-tropics has often been considered to be due to malaria and treated as such. As accurate diagnosis for malaria, based on rapid diagnostic tests, is rolled out across malaria-endemic regions, it is becoming increasingly apparent that most fevers are due to other causes. By ‘acute febrile syndrome’ in this context we mean causes of acute fever and related symptoms that are similar to malaria. These are usually due to infection, resulting from a wide variety of pathogens.

Related journals for Febrile malaria

Malaria Information, Current Malaria Research, Biology and Medicine, Malaria Vaccines, Malaria World.

 

Malaria vector surveillance

Vector control is a fundamental element of the existing global strategy to fight malaria. Vector control interventions have a proven track record of successfully reducing or interrupting disease transmission, particularly in areas that are highly prone to malaria. Indoor residual spraying and long-lasting insecticidal nets are the two core, broadly applicable malaria vector control measures. This section covers both core and supplementary vector control methods and discusses the action that is required to prevent and manage the increasing challenge of malaria vector resistance to insecticides.

Related journals for Malaria vector surveillance

Malaria Journal, Journal of Malaria Research United States, epidemiology .

Malaria, mosquitoes and the legacy of Ronald Ross

Robert E Sinden a

This section looks back to some ground-breaking contributions to public health, reproducing them in their original form and adding a commentary on their significance from a modern-day perspective. Robert E Sinden reviews Ronald Ross’s pivotal work on the malaria parasite and comments on the potential for malaria vector research and control.

In 1895, Ronald Ross was based in Sekunderabad, India, where he embarked on his quest to determine whether mosquitoes transmitted malaria parasites of man. For two years his studies were clouded by observations on what we now know to be insusceptible mosquito species. He nonetheless observed “flagellation” of Plasmodium in the bloodmeal of these insects, the true nature of which was revealed by McCallum in 1897.1 Ross’s later work also benefited from the numerous observations on insects infected by other parasites (including helminths, fungi and gregarines) he made in this early phase of his quest for the malaria vector. Eventually in July 1897 he reared 20 adult “brown” mosquitoes from collected larvae. Following identification of a volunteer (Husein Khan) infected with crescents of malignant tertian malaria and the expenditure of 8 annas (one anna per blood-fed mosquito!), Ross embarked on a four-day study of the resultant engorged insects. This “compact” study was written up and submitted for publication.

Imagine today sending an article to a leading medical journal in which you describe observations on novel objects found on the midguts of just two “brown” mosquitoes, obtained from larvae of natural origin, that you had previously fed on a naturally infected patient – with no appropriate controls and no replicates! What hope would it have of getting past the editor and reviewers? Thankfully, Ronald Ross’s paper was more fortunate: it was published by the British Medical Journal on 18 December 1897.2 His conclusions were understandably modest. “To sum up: The [putative malarial] cells appear to be very exceptional; they have as yet been found only in a single species of mosquito fed on malarial blood; they seem to grow between the fourth and fifth day; and they contain the characteristic pigment of the parasite of malaria.” So begins one of the most influential stories for malaria research and control.

Recognizing the relative simplicity of the research tools available to Ross, the observations made by him and his collaborators using simple brightfield microscopy were exceptional. He had just eight “brown” mosquitoes that had fed on the patient with P. falciparum gametocytes in his blood. Four mosquitoes were killed immediately to examine the fabulous process of exflagellation (male gamete production), so critical to the discovery of the bloodstages of the parasite by Laveran seventeen years earlier.3 One mosquito was dissected on the second day to no advantage and two on the fourth day, of which one had twelve “substantial cells”. The description of these cells, the malarial oocysts (formed through the developmental progression: gametocyte-gamete-zygote-ookinete-oocyst) is unmistakeable. The characteristic round/oval shape, the diameter (10–16 microns), the sharp line of the oocyst wall and the nature and distribution of the malarial pigment were reported with precision. The presence of pigment was critical in Ross’s eyes, but even this, his defining character, was nonetheless cautiously considered as potentially being a mosquito-derived product of bloodmeal digestion. On the fifth day he dissected the last mosquito and noted 21 cells with the same visual properties, but larger (he estimated the diameter to be about 20 microns). Few today would complain about oocyst intensities and prevalences such as this. There were, however, no controls, such as mosquitoes from the same source fed on a crescent/gametocyte-negative volunteer. In this regard Ross excuses himself, stating “I have not yet succeeded in obtaining any more of the species of mosquito referred to,” and felt it was adequate to describe results from other mosquito species (including a genus Aedes now known to be refractory to infection by P. falciparum) fed on different volunteers. While hardly conforming to the concept of a controlled and replicated study, Ross commendably obtained, and reported fully, a second opinion on the nature of the preparations from Surgeon-Major John Smyth, whose comments are very detailed. The formaldehyde-fixed specimens were then considered to be of such potential importance that they were shipped from Sekunderabad to the United Kingdom to be observed by Manson, Sutton and Thin. Their observations and reviews are also reported in the publication. Manson and Sutton enthusiastically endorsed the views expressed by Ross, and the drawings Manson commissioned unquestionably illustrate oocysts that are either undergoing sporoblast formation before sporozoite budding or possibly degenerating (should the “pebbled” appearance indicate vacuolation). In contrast, Thin sets about a thorough dismemberment of the interpretations of his four colleagues, concluding through logical argument (but with no evidence) that they were describing midgut epithelial cells in which pigment had been phagocytosed from the gut lumen. He then diplomatically apologizes for his unsupportive interpretation!

What can we learn from this seminal publication that is relevant to today’s research environment? First, the importance of seizing the opportunity. Second – and related – persistence: Ross recounts that, before the reported successful experiment, work in the preceding two years examining about a thousand brindled, grey and white mosquitoes had failed to reveal any relevant data. Third, the power and importance of careful observation combined with exact and objective recording. Finally, the benefit of sharing data before publication so as to put forward conflicting interpretations of the results. Notwithstanding these commendable attributes, nobody today would have condemned the editor if he had had rejected such a speculative, uncontrolled and unreplicated study.

Irrespective of the perceived inadequacies of the study design, it is difficult to overstate the importance of Ross’s paper: the award of a Nobel Prize hardly does justice to the subsequent impact of his conclusions. The biological significance of the paper lies in three areas: basic research; malaria transmission/epidemiology, and the identification of what is perhaps the most vulnerable stage in the parasite life-cycle for effective intervention. The last was very quickly recognized (inevitably in the military–political context) and resulted in the rapid adoption of environmental vector control campaigns (personal protection and house screening to prevent contact with the adult mosquito, and water management to destroy larval breeding sites). These were followed in the 1930s by the introduction of effective insecticides including the “wonder compound” DDT which, together with the new antimalarial drug chloroquine, formed the foundation of the ill-fated but very successful global control campaign of the 1950s and 1960s.

It was immediately clear from these early control campaigns that attacking mosquito vectors of malaria can be one of the most effective ways to reduce the transmission of disease in endemic areas. Research today is identifying an ever-wider range of potential intervention technologies and targets to achieve this objective. In addition to continued refinements of established environmental management and insecticide programmes, a major step forward has been made through the design of effective and environmentally friendly insecticide-treated bednets. New concepts for the reduction of mosquito populations by biological control have been introduced. Variants of this theme include the use of larvivorous predators (Gambusia and Tilapia), pathogens, e.g. bacteria (Bacillus thuringiensis israelensis), fungi (Beauveria) and viruses (Bacculovirus). Most recently it has been suggested that genetic control of vector populations may be possible. Methods proposed include the introduction of lethal homing endonucleases,4 the disruption of the olfactory mechanisms that guide the potential vector to the human host,5 introduction of cytoplasmic incompatibility induced by the endosymbiont Wolbachia,6 or genetic dominant-lethal technologies.7 Only time and objective study will reveal which, if any, of these approaches will prove to have the appropriate combination of efficacy and practicality to reduce vector populations.

It matters not whether we block the dissemination of Plasmodium through endemic populations by killing the vector or the parasite within the vector, the impact upon malaria transmission is comparable. In this regard, the exciting basic studies now under way on the biology of the Plasmodium in Anopheles, of vector–parasite interactions, and on the mosquito innate immune system have already given us insights into yet more methods by which to modulate parasite dissemination. The question as to whether any mosquito gene that confers refractoriness to Plasmodium can be driven into the vector populations remains a challenging and interesting area for investigation. Recognizing the evolutionary forces that have driven the current global distribution and genetic structures of parasite, human and mosquito populations, we must be aware that, just as the fitness cost to the human host in being genetically resistant to Plasmodium (e.g. sickle cell anaemia) has driven a balanced polymorphism (stable resistance–gene frequency), the cost to the vector of being refractory to Plasmodium may itself be a constraining influence on the future introduction of refractory genes by genetic manipulation technologies.

Notwithstanding the caveats expressed above, intervention in the vector – but targeted directly at the parasite – is one of the more rational approaches to attack parasite populations. Transmission-blocking vaccines are the exemplar intervention of this type. The reasons for this optimism are founded on the precarious nature of the transmission. Of the thousands of parasites (gametocytes) that might be ingested by the female mosquito, just a handful survive to form the oocysts (as described by Ross in his paper), and this in a small fraction of the vector population. Similarly, the parasite passes through another constraint as it returns, in the form of sporozoites, from the vector to the human host. Although military analogy suggests that such bottlenecks are invariably the best targets for attack, we must further recognize that exposing one’s chosen intervention strategy to 109 parasite genomes per host (e.g. bloodstage infections) as opposed to 5–50 genomes per host (e.g. the oocyst) is more likely to lead to the rapid selection of resistant mutations. Second, vaccine efficacy is critically influenced by the exposure time of the parasite to the effector mechanism8; in the case of current transmission-blocking vaccine targets such as Pv25 and 289 this exposure time is 24 hours, as opposed to a few minutes per cycle for vaccines targeting the surface of the bloodstage merozoite. Third, problems that can hinder the development of some bloodstage/sporozoite vaccine include antigenic polymorphism and antigenic diversity, two molecular mechanisms that are logically considered to have evolved in the parasite to overcome the adaptive immune systems of the vertebrate hosts. The mosquito, on current evidence, does not have an adaptive immune system, and it is interesting to note that those molecules expressed de novo on the surface of the malarial ookinete in the mosquito midgut are comparatively non-polymorphic10,11 and do not undergo antigenic variation, thus rendering them relatively stable global targets for any vaccine. It is encouraging to record the early human trials of pv25 suggest that these vaccines, first described in avian and rodent models, successfully induced 30% blockade of transmission.9

An area that for many years has not received the attention it deserves is that of drugs that can target the stages of the parasite responsible for transmission, and which have a realistic possibility of being exposed to effective drug concentrations (if delivered from the human host), i.e. the gametocyte, zygote and ookinete. While it is now known that the gametocyte arrests in the cell cycle with increasing maturity, and is therefore less susceptible than the schizogonic blood stages to many antimetabolites, it is now appreciated that drugs targeting energy metabolism, such as artemesinin and Malarone, can reduce transmission to the vector.12 Recent proteomic studies further suggest that energy metabolism is upregulated in the ookinete which might render this stage more sensitive to such inhibitors.13 In view of the high cost of antimalarial drug development, it is a source of constant concern that all potential antimalarials are not routinely screened for their potential to suppress (or indeed enhance!) mosquito infection. Had it been recognized that chloroquine can enhance the infectivity of the drug-insensitive mature gametocytes,14 it might have been administered differently and might perhaps still be of use today.

Without detracting from the outstanding individual and global efforts made, we have waited far too long to capitalize effectively on the seminal observation made by Ross 110 years ago. The fact that malaria remains as serious a world problem today as it was when Ross and Laveran made their insightful contributions reflects not only the scale and complexity of the interacting populations of Plasmodium, mosquitoes and human hosts, but also our financial and political priorities, and perhaps the competitive as opposed to collegiate manner in which research can be supported and conducted. Notwithstanding the most earnest and sustained endeavours of numerous private, national and international agencies, governmental and scientific attitudes must change if the potential for malaria control revealed by the studies of Ross, Manson and their Italian contemporaries is ever to be achieved. The parasite will inexorably evolve, our priorities and attitudes must evolve faster. ■


References

  • WG McCallum. On the flagellated form of the malarial parasite. Lancet 1897; 2: 1240-1.
  • R Ross. On some peculiar pigmented cells found in two mosquitoes fed on malarial blood. BMJ 1897; 18: 1786-8.
  • A Laveran. Note sur un nouveau parasite trouvé dans le sang de plusieurs malades atteints de fièvre palustres. Bull Acad Med 1880; 9: 1235-6.
  • A Burt. Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Pro.Biol Sci 2003; 270: 921-8.
  • LJ Zweibel, W Takken. Olfactory regulation of mosquito-host interactions. Insect Biochem Mol Biol 2004; 34: 645-52.
  • SJ Sinkins, F Gould. Gene drive systems for insect disease vectors. Nat Rev Genet 2006; 7: 427-35.
  • DD Thomas, CA Donnelly, RJ Wood, LS Alphey. Insect population control using a dominant, repressible, lethal genetic system. Science 2000; 287: 2474-6.
  • RM Anderson, RM May, S Gupta. Non-linear phenomena in host-parasite interactions. Parasitology 1989; 99: S59-79.
  • EM Malkin, AP Durbin, DJ Diemert, J Sattabongkot, Y Wu, K Miura, et al., et al. Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria. Vaccine 2005; 23: 3131-8.
  • DC Kaslow, IA Quakyi, DB Keister. Minimal variation in a candidate from the sexual stage of Plasmodium falciparum.Mol Biochem Parasitol 1989; 32: 101-4.
  • JS Richards, NJ MacDonald, DP Eisen. Limited polymorphism in Plasmodium falciparum ookinete surface antigen, von Willebrand factor A domain-related protein from clinical isolates. Malar J 2006; 5: 55-.
  • GA Butcher. Antimalarial drugs and the mosquito transmission of Plasmodium. Int J Parasitol 1997; 27: 975-87.
  • N Hall, M Karras, JD Raine, JM Carlton, TW Kooij, M Berriman, et al., et al. A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science 2005; 307: 82-6.
  • B Hogh, A Gamage Mendis, GA Butcher, R Thompson, K Begtrup, C Mendis, et al., et al. The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria species to the mosquito vector. Am J Trop Med Hyg 1998; 58: 176-82.

Affiliations

  • Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College, London SW7 2AZ, England.

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