Parasitic diseases are among the Third World's three great killers, along with tuberculosis and Aids. In the annals of public health history, no disease occupies as special a place as malaria. Between 1900 and 2000, up to 300 million people died of the disease accounting for ~5% of all recorded deaths. Even though significant strides have been made in malaria control over the last 20 years, resource-limited nations in Sub-Saharan Africa, Amazonia and Southeast Asia remain significantly affected. In 2019, over 220 million malaria cases were estimated with approximately 400 000 individuals dying of the disease, mainly in Sub-Saharan Africa.
Malaria is caused by a single-celled parasite, Plasmodium. The parasite spreads to humans and other animals through the bites of infected female mosquitoes.
The life cycle of the parasite was discovered in the 1880s by Dr Alphonse Laveran and with it, the role of female mosquitos in the spread of the disease. Disease transmission mostly depends on how well the mosquitos fare. It is more intense where the climate is favourable to the insects, where the mosquitos’ lifespan is longer and where they prefer to bite humans rather than other animals. The long lifespan and strong human-biting habit of the African vector species is the main reason why approximately 90% of the world's malaria cases are in Africa.
As the plasmodium spreads and reproduces in the body it causes symptoms including fever, tiredness, vomiting, and headaches. In severe cases, the parasites can cause yellow skin, seizures, coma, or death. Control measures against the disease are aimed at both the mosquito vector and the parasite inside its host.
The plasmodium parasite
Research on anti-malarial drugs
Research on vaccines
The plasmodium parasite
There are more than 200 species of parasites in the Plasmodium genus. Each species has a different life cycle and history. Humans are infected by only five of these, Plasmodium falciparum, P. vivax, P. malariae, P. knowlesi and P. ovale. The most important of these is P. falciparum, which is responsible for at least one million deaths worldwide each year, the majority being among African children. Reptiles, birds and other mammals can also fall sick to the diseasebut it is caused by different parasites in each case.
Malaria parasites are transmitted from person to person through Anopheles mosquitoes. When a mosquito bites, blood containing the parasites is taken into the mosquito's gut. Over a period of 10 or more days, the parasites undergo a complex development, the mature parasite eventually coming to reside in the mosquito's salivary glands, ready for transmission to a new person when it bites again. In the next human host, the parasite first infects the liver, undergoes rapid replication in this site for at least five days, and then infects red blood cells. It is in the blood that the parasites causes the most serious symptoms of malaria, including cerebral malaria initiated by parasitised blood cells blocking blood capillaries in the brain.
The parasite readily undergoes mutation during its rapid growth in humans, allowing it to develop strains resistant to antimalarial drugs. In addition, it undergoes genetic recombination during the mosquito phase of its life-cycle, thereby producing strains with novel combinations of genes. These genetic processes present major obstacles to control measures based on drugs or future vaccines.
Research into the biology of malaria has relied largely on animal models, especially on species of Plasmodium affecting rodents. A culture system is available for the blood forms of P. falciparum, which has greatly assisted the testing of drugs and vaccines against these stages of this species. However, no culture methods are available for the stages of the parasite in the liver, or for any of the other human malaria species. Animal models remain necessary to study these stages of the disease.
For a long time, the only way to prevent Malaria was to focus on the mosquitos. The mosquito kills more people than any other creature in the world. Even today, almost one million people a year die from mosquito-borne disease.Killing mosquitoes is, therefore, an obvious, and deceptively simple way of keeping some major diseases at bay.
Control of the insect vectors helps keep the disease in check. Destroying mosquito populations or reducing insect bites by measures such as using effective mosquito nets at night have also proven effective in reducing malaria transmission.
The use of insecticides, particularly DDT, has been responsible for the eradication of malaria in many countries, and this approach is still of primary importance. Mass-spraying of insecticides is still used to counter the outbreak of mosquito-borne disease, but its effects are not limited to the enemy and many other insects, including bees, butterflies, and other pollinators, are severely affected, so more targeted measures are sought.
Insecticide-treated bed nets, produced from the late 1980s, are deemed responsible for two-thirds of the seven million lives saved from malaria between 2000 and 2015, mainly in Africa. They are seen as a cornerstone of malaria prevention and control efforts.
However, mosquitoes are becoming resistant to insecticides, whether mass-sprayed or added to mosquito nets. Due to genetic changes over time, female Anopheles mosquitoes become resistant to many forms of treatments. This causes scientists to constantly be on the hunt for new and better preventative measures and treatments.
More effective interventions against mosquito-borne diseases are needed and these will rely more and more on knowledge of local mosquito species and their host-seeking behaviour as well as a deeper understanding of the conditions that increase or decrease risk of infection. Good timing of interventions can make a big difference. Ideally mosquito populations should be reduced before they trigger an outbreak of disease.
- GM mosquitoes
Mosquitoes have been genetically modified to limit their reproduction and spread but also that of the disease.
Genetically modified mosquitoes have been successfully used in parts of Brazil, the Cayman Islands, Panama, and India to control Ae. aegypti mosquitoes. Since 2019, over one billion GM mosquitoes have been released. When genetically modified mosquitoes stop being released into an area, the Ae. aegypti mosquito population slowly returns to normal levels, so control requires regular release of modified mosquitos.
One of great advantage is that genetically modified mosquitoes will only work to reduce numbers of the target mosquito species (eg Ae. aegypti), not other types of mosquitoes, leaving ecosystems intact.
Genetically modified mosquitos
Producing genetically modified mosquitos is a laborious process. Pieces of DNA are injected into mosquito embryos at a very particular developmental stage in the egg and at a very precise location. This is a very delicate micro-injection procedure that is technically demanding.
Although the success rate is quite good, 1,000 or so eggs need to be injected to get about 100 fully grown adults. These are then bred to see which one can transmit the gene of interest to a next generation. 10,000 or so individuals in the next generation might need to be screened to find the one. Scientists often use fluorescent tags attached to the gene of interest to identify the mosquitoes that carry it – a very useful visual cue to differentiate them from others in the field
- limiting population spread
Although it is only female mosquitoes that bite, often, only the nectar-feeding males will be targeted and modified.When they are released in the wild, they produced offsprings that are not viable. If enough wild females mate with these modified males, the target population declines pretty dramatically, sometimes by up to 90%.
Several large-scale experiments in using genetically modified mosquitoes to control populations are being run in different locations around the world. There are two main approaches :
- In the first, sterile male mosquitos are mass produced and released into the wild. These sterile males mate with wild females who then lay sterile eggs which will not hatch. This approach has been shown to reduce wild populations by as much as 90% in trials with Aedes aegypt.
- The second approach is to introduce a gene that, if inherited, results in the death of the female, but not the male. Genetically modified males are mass produced and released. Only male offspring from matings between the modified males and wild females survive. They go on to breed, further spreading the female-killing gene and reducing the overall mosquito population.
This technique has many advantages. For one thing, it is extremely species specific.
It doesn’t do anything that insecticides or other mosquito control methods aren’t already doing, but it is much more precise. Only the species of interest is affected. The released males only mate with females of the same species and nothing else. It is also quite effective. The released mosquitoes go out and look for females, which are neutralised even in relatively inaccessible hiding places, where the female is safe from chemical insecticides.
Genetically modifying mosquitoes it is a very specific and efficient targeted technique. The possibility of a really precise targeted species-specific control is quite hard to achieve by other methods. Moreover, it has a very significant environmental benefit as other insect populations don’t have to die in order to control one species of mosquito. Plus, this targeted technique can be used to control invasive species in ecologically vulnerable settings. This is incredibly valuable for conservation biology and biodiversity
- limiting disease spread
Genetic manipulation can be used for population suppression, but researchers are also seeking other approaches to population modification. The objective is to make mosquitoes less able to transmit the disease and make it a heritable trait that could spread through a target population.
The mosquitoes would still be filling their ecological niche - and still be biting people - but they wouldn’t be transmitting diseases, or at least not nearly as well.
“It would be a bit like going around vaccinating mosquitoes. It would be the same outcome. The mosquitoes would still be there, and they’d still be biting people and doing their thing, but they wouldn't be transmitting disease, “ Professor Luke Alphey, an arthropod geneticist at The Pirbright Institute, told UAR.
But for that kind of approach, scientists first need to understand more about why some mosquitoes carry diseases and some don’t.
In recent years, mosquitoes have been genetically modified to render them - and their offspring - ineffective at transmitting malaria. Genes that stop Plasmodium moving from the mosquito's gut to its salivary glands have been inserted successfully into mosquitoes. This is a promising novel approach to malaria control, although it can obviously be effective only if the inserted gene manages to persist in the wild mosquito population2.
- understanding mosquito biology
Genetically modifying mosquitoes allows researchers to learn more about mosquito biology, how a pathogen infects and spreads in the insect, how the mosquito interacts with the pathogen but also its food source (humans) in hopes to find a way to limit or, even better, stop the spread of the disease.
Research on antimalarial drugs
After scientists found in 1968 that African penguins can be infected with Avian malaria, much in hte same way as humans, they became an important model of research. Thanks to the studies done on the African penguins, scientists were able to better understand the effects of chloroquine, a popular anti-malarial drug discovered in 1950.
Chloroquine prevents the growth of the Plasmodium parasite in red blood cells. It is the first-choice drug to take against malaria because it is safe for both pregnant women and children. With the help from owl monkeys, scientists have been able to study chloroquine and its relation to P. falciparum – the parasite species that causes the most dangerous strain of malaria in humans.
Along with chloroquine, scientists were able to discover the effects of primaquine. Primaquine is the only drug proven to prevent a relapse of malaria and is used if chloroquine has no affect against a specific strain of malaria; but it is not safe for pregnant women and those with a deficiency of glucose-6-phosphate dehydrogenase (G6PD) - an enzyme deficiency most commonly found in males. Along with penguins, scientists were able to study subacute toxicity of primaquine in dogs, monkeys, and rats.
After administrating chloroquine and primaquine into the malaria-infected penguins, researchers discovered the mortality rate reduced from 50% to 10-15%. From these studies, researchers have been able to develop various medications containing chloroquine as an active ingredient to fight against different strains of malaria in humans. Unfortunately, over the years, the Plasmodium parasite has developed a resistance towards chloroquine, but it is still used in combination with other anti-malarial drugs to fight against this disease.
New safe and effective drugs are desperately needed. The parasite has become resistant to most of the drugs used to treat it, the only exception being the most recently developed drug artemisinine and its derivatives3.
The majority of drugs available aim to halt the fast-replicating stages of the parasite in the blood. However, this is not the only phase that an be targeted by drugs. The parasite initially infects only a few liver cells and can stay dormant there for a long time before it resurfaces, causing global symptoms to arise once mode. This stage could be the perfect target for drugs and vaccines but unfortunately only a few drugs kill the liver forms.
Ideally, researchers are looking for drugs that target biochemical pathways unique to the parasite, and that aren’t present in the host. These could be any of its unique features including vood vacuoles or apicoplasts present in its cells. A promising new drug, fosmidomycin, is notably known to affect an enzyme pathway in the apicoplast4 and could be interesting in that regards. A new antibiotic, azithromycin, has also shown some effect in mice and monkeys, and has been successfully trialled as a malaria prophylaxis in humans5. Moreover, an antibiotic called triclosan, used in mouthwashes, anti-acne preparations and deodorants, could be an effective treatment. It completely clears the parasite from infected mice6 by blocking a parasitic enzyme called Fab I. New antimalarial drugs may target the gene that produces this enzyme.
In 2012, a professor of veterinary medicine discovered that a herd of goats were able to produce a protein (P. falciparum) in their milk that could aid in preventative measures against malaria. Today, this discovery is still under research, but scientists hope to formulate a drinkable cure in years to come.
Equally, in 2015, after a study done on mice, a drug called AB-1 was found to cure malaria infections without any of the harmful side effects that were commonly found in drugs used against malaria. The next phase for AB-1 is human clinical trials.
Research on Vaccines
There is a long history of attempts to develop vaccines against malaria. Three types of vaccine have been envisaged:
– anti-infection vaccines, which target the infective stages of the parasite, the sporozoites, injected by mosquitoes
– anti-disease vaccines, targeted principally against the blood forms responsible for this disease's pathogenicity
– transmission-blocking vaccines, aimed at preventing the development of the parasite in its mosquito host.
It has taken a lot of time for a malaria vaccine to come to fruition because there are thousands of genes in malaria - compared to around a dozen in the coronavirus for example - , and a very high immune response is needed to fight off the disease. It is a real technical challenge, which has meant that most vaccines developed until recently have either failed or have only shown a low protective capacity.
Numerous early studies in humans and in rodent models have provided information of fundamental importance on potential immune protective mechanisms. Individual proteins have been shown to be at least partially protective in vaccination tests in both human and animal trials6.
More information on the mouse models for unravelling immunology of blood stage malaria :https://www.mdpi.com/2076-393X/10/9/1525
- the RTS, S vaccine
Progress has notably been made using an antigenic protein of the sporozoite, the CSP protein, first demonstrated to be highly immunogenic in a rodent model over 20 years ago. The RTS, S vaccine took over 30 years of extensive research in which animal models have been significant contributors leading to this recent discovery. A human vaccine based on this work, denoted RTS,S, has given encouraging results in field trials in African countries by providing partial protection of humans from infection7. During clinical trials, RTS, S was able to prevent 4 in 10 malaria cases. Although this does not give 100% protection against malaria, it is clear that for this step closer to that aim we can thank animal research.
In 2019, the World Health Organization (WHO) announced that the RTS, S vaccine would be given to approximately 360,000 children up to two years of age in three African countries: Malawi, Ghana, and Kenya. Whilst the recent pilot implementation of the RTS,S malaria vaccine is indeed a remarkable feat, highly effective vaccines against malaria remain elusive.
- Vaccines that target the parasite
Similarly, there are now numerous vaccine trials being undertaken based on different antigens present in the blood stages of the disease. All of these were originally examined for their immunogenic potential in animal models.
For instance, non-human primates helped researchers discover in 2017 that combining an existing malaria vaccine with the protein RON2L would result in a more nullifying antibody and protect against more malaria strains. Studies continue to build upon this discovery, primarily experimenting RON2L with new vaccines. Vaccines consisting of combinations of target proteins have also completely protected mice from malaria, and human trials have been started8.
One of the ideas is to generate the antigenic properties of the vaccines in milk. A cheap vaccine purified from the milk of genetically modified mice has protected monkeys against malaria. Only one of five immunised animals contracted the disease, compared with six out of seven unvaccinated monkeys. The mice were engineered to carry the gene for a surface protein from P. falciparum. The gene was designed to be switched on by cells lining mouse mammary glands, so the protein would be secreted into the milk. The same team also modified goats to produce the protein in their milk, raising the prospect that one herd of goats could produce enough vaccine for the whole of Africa. The next step will be to find out whether the vaccine produced in goats' milk also protects monkeys10
- Vaccines that target toxins
Research is also being done on a different type of vaccine, which targets a toxin released by the parasite. Mice inoculated with the toxin GPI were protected against many of the signs of malaria, and did not die from the disease. The findings demonstrate the potential of synthetic GPI in anti-toxic vaccines, and suggests that GPI is responsible for some symptoms of malaria in humans9.
- transmission blocking vaccines
A study on mice in 2018 showed that a combination of transmission- blocking vaccines (TBVs) and pre-erythrocytic vaccines (PEVs) significantly reduced malaria infections by 91%. TBV prevented the mosquito from transferring the parasite while PEV focused on protecting the liver. This discovery helped scientists learn the possibility and power of combining two malaria fighting vaccines and provides a foundation for more discoveries in years to come.
- the most effective vaccine to date
In 2021, a vaccine developed by the University of Oxford proved to be 77% effective in early trials. The vaccine is a low-dose protein-based vaccine (R21) that targets the first part of the malarial parasite life cycle in the human, the sporozoite, by aiming at a protein secreted by the sporozoite called Circumsporoite . When trialled in 450 children in Burkina Faso, the vaccine was found to be safe, and showed "high-level efficacy" over 12 months of follow-up.Despite the many vaccines trialled over the years, this is the first to meet the required target. Before then, the most effective malaria vaccine had only shown 55% efficacy in trials on African children. Larger trials in nearly 5,000 children between the ages of five months and three years are currently be carried out across four African countries to confirm the findings. The researchers say this vaccine could have a major public health impact.
- the difficulties of finding the right vaccine
In experimental work that would not be possible in humans, scientists have produced some disturbing evidence that vaccines may well lead to the evolution of more aggressive malaria parasites, unless every parasite is eliminated (this is the same principle as antibiotic resistance in bacteria). They found that parasites that survived in immunised mice were more virulent than those which developed in mice that had not been immunised11. Clearly, the search for a fully effective safe vaccine against this parasite will continue to be a long and difficult undertaking.
History of animal research
There have been several reasons to favour the use of animal models to study malaria. First, models allow investigation into the progress of the disease, which is more difficult in humans. It also permits studies of organs to which the parasite sequesters, such as the spleen, lungs and brain. The use of non-lethal parasites in mice has identified the role of adaptive and innate immunity in mediating clearance and survival from infection. Studies in mice with different species and strains of parasite have also identified how the parasite mediates disease. Finally, these studies have led to the development of novel vaccine approaches .
Historically and due to the practical and ethical difficulties of working with human malaria infections, research into malaria parasite biology has been extensively facilitated by animal models. These have ranged from birds, bats, non-human primates, rodents and more recently humanized mice and complex three-dimensional ex vivo organoids. Animals have been used to study disease pathogenesis, host immune responses and their (dys)regulation and further disease processes such as transmission. Moreover, animal models remain at the forefront of pre-clinical evaluations of antimalarial drugs (drug efficacy, mode of action, mode of resistance) and vaccines.
In the past, researchers first used birds to study the malaria parasite and develop medications, such as chloroquine. In 1968, scientists discovered Avian malaria in African penguins which they suspected the penguins may have acquired during their migration season. Being exposed to the Plasmodium parasite was shown to be extremely fatal for the African penguin. Since malaria was shown to affect birds the same way as it does humans, the African penguin became a fitting animal model for research. Thanks to the studies done on the African penguins, scientists were able to better understand the effects of chloroquine, a popular anti-malarial drug discovered in 1950 and primaquine. Along with penguins, scientists were able to study subacute toxicity of primaquine in dogs, monkeys, and rats. With the help from owl monkeys, scientists have been able to study chloroquine and its relation to P. falciparum – the parasite species that causes the most dangerous strain of malaria in humans.
Better knowledge of the parasites led to the discovery of new drugs and sent researchers on a vaccine quest. For example, antibodies created to fight the blood stages of infection could be transferred from one person to another, conferring some protection. But malaria is such a complex parasite that it proved harder to defeat than many had first hoped.
“Unfortunately, the energy put into the vaccine research didn’t live up to expectations. The field didn’t move nearly as fast as I believed it could,” Jacob Baum, Professor of Cell Biology and Infectious Diseases at Imperial College Londontold UAR.
Today, in vitro models, monkeys and rodents play a key role in the discovery and development of anti-malarial drugs and vaccines. Advances in animal research have enabled scientists to model human malarial symptoms much more closely in mice. It is now possible, thanks to work in mass genetics to humanise mouse models. In immune-deficient models, it is possible to generate a chimeric liver, with human and mouse liver cells, which human malaria parasites are capable of infecting.
For more information on animal models of different stages of the disease : https://www.cambridge.org/core/journals/parasitology/article/current-status-of-experimental-models-for-the-study-of-malaria/DC3AA116BE55820193043159D48CC1FC
- Rodent malaria
The rodent malaria model has been absolutely essential for research. In order to develop a new vaccine candidate or target you have to test it in a living, breathing system. Mouse models have several advantages for immunological studies including the availability of inbred and congenic strains with defined major histocompatibility complex haplotypes, well-defined natural mutants defective in components of the immune system and specific gene-targeted mouse strains. All of our understanding of the biology of the liver stages, how the parasite gets from the skin to the liver or it doesn’t, how it interacts with the immune system, how it emerges from the liver, has all been entirely dependent on the rodent malaria model. There are huge areas of our understanding that couldn’t have been filled without the rodent malaria model.
Malaria parasites that infect rodents (mice and rats) have been extensively used to study and model human disease in vivo. Four species of rodent malaria parasites (RMPs i.e. P. berghei, P. yoelii, P. chabaudi, P. vinckei) that were originally isolated on various occasions in Central African thicket rats have been at the centre of these studies. These parasite species share a highly conserved chromosomal gene synteny with the human infecting P. falciparum with, however, subtle differences in stage-specific morphologies, duration of life cycle and host cell preferences.
Nevertheless, the basic biology of rodent- and human-infectious Plasmodium is fundamentally conserved. This has allowed for their use in studying several aspects of malaria parasite development, host–pathogen interactions, drug efficacy evaluations and vaccine studies which would otherwise be inaccessible with P. falciparum in vitro. Furthermore, rodent malaria parasites offer numerous advantages among which include their ease of handling in rodents, experimental tractability of all life cycle stages under lab conditions as well as the availability of a wide array of genetic manipulation systems.
Still, these rodent parasites are divergent from their human equivalents. Even though they can provide crucial insights into the conserved elements of parasite biology, the finer molecular details might be different from their human counterparts due to the unique aspects of their hosts. The use of these models should therefore be pertinently tailored to the biological question under study through direct comparison to human parasites.
For more information on what we’ve learnt on malaria from mouse models : https://onlinelibrary.wiley.com/doi/full/10.1002/eji.200939552
- Non human primate malaria
For decades, NHPs have also proved invaluable to studying malaria disease pathogenesis as well as fundamental aspects of parasite biology. Crucially, P. cynomolgi and P. vivax hypnozoites (dormant liver stages) were first discovered in NHPs, specifically in rhesus macaques for the former and in Chimpanzees for the latter.
NHPs have thus been instrumental for understanding the biology of this parasite. Over 40 P. vivax strains that are able to infect NHPs, specifically New World monkeys of the Aotus and Saimiri species have been archived by the CDC. By infecting splenectomized NHPs (to minimize splenic clearance of infected red blood cells) through mosquito bites or intravenous injection of purified sporozoites, chronic relapsing P. vivax malaria can be reproduced in these models.
Unlike P. vivax which is mostly restricted to New World monkeys, P. cynomolgi strains that infect larger Old World monkeys (macaques) have been successfully adapted providing, in the absence of long-term in vitro culture, the only means to generate sufficient amounts of parasite material for downstream analyses. P. cynomolgi remains the main model of understanding P. vivax biology among which include evaluating the efficacy of antimalarial drugs with potential activity in difficult to eliminate hypnozoite stages. Other NHP infecting malaria parasites include P. coatneyi and P. knowlesi.
- Avian malaria
Before the discovery of the first rodent malaria parasites in 1949, avian malaria parasites were the experimentalspecies of choice for studying malaria parasite biology as they were discovered at almost the same time as P. falciparum. Avian malaria parasites comprise of an unknown number of species (>55) belonging to two genera, Plasmodium and Haemoproteus.
Despite conserved life cycle features with other Plasmodium, avian malaria parasites have a slightly different life cycle. They display a low host specificity across bird species as well as a marked variation in developmental patterns in various hosts. Avian malaria parasites also appear to produce dormant parasite forms both in the liver and bloodcycles as opposed to other Plasmodium such as P. vivax which produce the same only during the liver stage.
After the discovery of RMPs, experimental malaria almost, entirely, switched to rodents. However, in recent years, avian malaria parasites have re-emerged as appropriate models to studying malaria parasite ecology and evolution mostly due to their rich genetic and phenotypic diversities. Complete genomes for P. relictum and P. gallinaceum have now been published. Avian malaria parasites have also played some vital historical role not just in understanding parasite ecology and evolution but also technology development. In fact, the first genetic transformation of a malaria parasite was achieved in P. gallinaceum.
- in vitro liver platform
To replace animal models, there has been a push, in the last five years, to develop an entirely invitro liver platforms. Work is still ongoing to perfect the system and follow the full liver development all the way through to the parasites being able to emmerge and then go into blood cells culture, although that’s on the horizon.The platform is expected to become available within the next 5 to 10 years.
- experimenting on humans
There is also something unique about malaria research: humans - under very strictly regulated conditions - can be infected with malaria experimentally because it is possible to cure them. This means that a human model of the disease can be used in some cases instead of animals, which is an extremely powerful tool, especially when trying to find a vaccine.
“A lot of research is moving in that direction. So if you have an experimental strategy and you can show it’s safe you can actually quite quickly move to human trials, having done the groundwork in rodent malaria models. But there are obvious limitations,” Prof Baum told UAR.
Animal research & human cerebral malaria
In 2010 there were a number of publications discussing the relevance of rodent models for the study of human cerebral malaria (HCM). These were prompted by an initial discussion paper from Professor Nick White and colleagues in which the suggestion was made that the Plasmodium berghei ANKA (PbA) mouse model of experimental cerebral malaria (ECM) did not replicate the pathophysiology of cerebral disease in humans. This has resulted in some polarisation of the research community on this topic and an occasionally uncritical application of some of the perceived conclusions of this initial paper to other areas of malaria research using rodent animal models.
In light of the recent controversies over the role of animal models for research into the development of new treatments for severe malaria, particularly cerebral disease, a group of scientists came together to discuss the relative merits of a range of animal models and their overlap with the complex clinical syndromes of human disease. The driving force behind this was the desire to ensure better translation of experimental findings into effective treatments for severe malaria.
For more information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271056/
Questioning the relevance of animal research : https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-10-23
Contributions of animal models : https://www.sciencedirect.com/science/article/abs/pii/S1286457902015411
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Last edited: 27 April 2023 08:32