Bio-larvicides

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QUESTION

Why is there no mention here of all the work being done on biolarvicides – the low cost solution for malaria control?

ANSWER

Actually, we had a question a while ago about the ECOWAS program in West Africa, which centers around the use of biolarvicides. A link to that question, and the answer, is provided here: http://www.malaria.com/questions/ecowas-malaria.

The most common form of biolarvicides are those using various microbes, notably Bacillus species, which target mosquito larvae but are harmless to other non-target organisms. A recent study in the Gambia showed very high success rates in killing Anopheles gambiae larvae, when a microbial larvicide using Bacillus thuringiensis var. israelensis strain AM65-52 was applied weekly. Some practitioners are concerned about the amount of effort and man-power a weekly application of larvicide might require, plus the training necessary for correct identification of habitat, but the study in the Gambia seemed to show good compliance once personnel were suitable trained. A link to the study, which is freely available via the Malaria Journal, is available here: http://www.malariajournal.com/content/6/1/76.

 

Researchers Discover Proteins in Mosquitoes that Help Fight Malaria Infection

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Researchers have discovered the function of a series proteins within the mosquito that transduce a signal that enables the mosquito to fight off infection from the parasite that causes malaria in humans. Together, these proteins are known as immune deficiency (Imd) pathway signal transducing factors, are analogous to an electrical circuit. As each factor is switched on or off it triggers or inhibits the next, finally leading to the launch of an immune response against the malaria parasite.

The latest study, conducted at the Johns Hopkins Malaria Research Institute, builds upon earlier work of the research team, in which they found that silencing one gene of this circuit, Caspar, activated Rel2, an Imd pathway transcription factor of the Anopheles gambiae mosquito. The activation of Rel2 turns on the effectors TEP1, APL1 and FBN9 that kill malaria-causing parasites in the mosquito’s gut. More significantly, this study discovered the Imd pathway signal transducing factors and effectors that will mediate a successful reduction of parasite infection at their early ookinete stage, as well as in the later oocyst stage when the levels of infection were similar to those found in nature.

“Identifying and understanding how all of the players work is crucial for manipulating the Imd pathway as an invention to control malaria. We now know which genes can be manipulated through genetic engineering to create a malaria resistant mosquito” said George Dimopoulos PhD, professor in the Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health.

To conduct the study, Dimopoulos’s team used a RNA interference method to “knock down” the genes of the Imd pathway. As the components were inactivated, the researchers could observe how the mosquito’s resistance to parasite infection would change.

“Imagine a string of Christmas lights or other circuit that will not work when parts aren’t aligned in the right sequence. That is how we are working with the mosquito’s immune system,” explained Dimopolous. “We manipulate the molecular components of the mosquito’s immune system to identify the parts necessary to kill the malaria parasites.”

Malaria kills more than 800,000 people worldwide each year. Many are children.

The authors of “Anopheles Imd pathway factors and effectors in infection intensity-dependent anti-Plasmodium action” are Lindsey S. Garver, Ana C. Bahia, Suchismita Das, Jayme A. Souza-Neo, Jessica Shiao, Yuemei Dong and George Dimopoulos.

The research was funded by the Johns Hopkins Malaria Research Institute and was published June 7, 2012 in the journal PLoS Pathogens.

Source: Johns Hopkins Bloomberg School of Public Health

Malaria Mosquito

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QUESTION

Which mosquito causes malaria?

ANSWER

Malaria mosquito vector map CDC

Map of the main global mosquito vectors of malaria (image courtesy of CDC)

It is important to note that mosquitoes do not CAUSE malaria—the disease itself is caused by microscopic, single-celled animals called Plasmodium. These Plasmodium parasites live and reproduce inside the mosquito, and when the mosquito bites a person, the parasites are transferred into that person’s blood via the mosquito’s saliva. If another mosquito bites a person with malaria, they will pick up the parasites from the person’s blood, and the cycle continues.

Malaria parasites are simply transmitted by mosquitoes, and specifically of the genus Anopheles, of which a variety of different species are capable of transmitting it to humans. In Africa, the species most responsible for transmission is An. gambiae, which actually consists of a group of very similar and closely related species; the group as a whole is known as the An. gambiae species complex. An. funestus is also a wide-spread and important vector species in Africa. Below is a map, courtesy of the CDC, which shows the distribution of some of the main malaria vector mosquitoes worldwide.

How does malaria spread?

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QUESTION:

How does malaria spread?

ANSWER:

Malaria is a vector-borne disease; this means that it has to be spread through a “vector” species, which in this case are female mosquitoes of the genus Anopheles. The female mosquito needs to feed on blood in order to produce eggs; most species lay eggs every 2-3 days, which means each female mosquito needs to take very regular blood meals.

Around 20 species of Anopheles mosquito have been implicated in the transmission of malaria; some species are better than others at acting as a vector. The most important group in Africa is the Anopheles gambiae complex; these mosquitoes are also relatively long-lived, which is important for transmission since it means that whole portions of the malaria parasite’s life cycle can be completed inside the vector mosquito.

When the female mosquito takes a blood meal, she inserts her slender mouth part (called a ‘proboscis’) into a tiny cut she makes uses specialized slicing parts of her mouth. She probes until she finds a small surface blood vessel, from which she feeds. The proboscis contains two narrow tubes – one delivers her own saliva into the wound (containing chemicals to stop the blood coagulating as well as a slight pain-killer, to stop you feeling the bite) while the other sucks up blood.

The mosquito’s saliva also contains the malaria parasite; this is how the parasite is delivered into the human body. Similarly, the parasite passes back into the mosquito through the blood she ingests, once the human portion of the life cycle has been completed. As mosquitoes pass between human to human, and indeed also between other animals, they spread the malaria parasite through the delivery of saliva and the uptake of blood.

Mosquitos Make Proteins to Handle Heat Spike of Hot Blood Meals

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Mosquitoes make proteins to help them handle the stressful spike in body temperature that’s prompted by their hot blood meals, a new study has found.

The mosquito’s eating pattern is inherently risky: Taking a blood meal involves finding warm-blooded hosts, avoiding detection, penetrating tough skin and evading any host immune response, not to mention the slap of a human hand.

Until now, the stress of the hot blood meal itself has been overlooked, researchers say.

Scientists have determined in female mosquitoes that the insects protect themselves from the stress of the change in body temperature during and after a meal by producing heat shock proteins. These proteins protect the integrity of other proteins and enzymes, in turn helping the mosquitoes digest the blood meal and maintain their ability to produce eggs.

Tests in two other types of mosquitoes and in bed bugs showed that these insects undergo a similar response after a blood meal.

“These heat shock proteins are really important in a lot of stress responses. Our own bodies make these proteins when we have a fever,” said David Denlinger, professor of evolution, ecology and organismal biology at Ohio State University and senior author of the study. “It’s one of those things that, in retrospect, seems obvious – that blood meals might cause a stress like that. But it hadn’t been pursued before.”

The research appears this week in the online early edition of the Proceedings of the National Academy of Sciences.

Denlinger and colleagues conducted experiments in the Aedes aegypti mosquito, which is a carrier of yellow fever.

The researchers placed sensors on female mosquitoes and observed that upon taking in a blood meal on a chicken, the insects’ body temperatures increased from 22 to 32 degrees Celsius (71.6 to 89.6 Fahrenheit) within one minute – among the most rapid body temperature increases ever recorded in a cold-blooded animal. After the feeding, their body temperatures decreased to room temperature within a few minutes.

In response to that blood feeding, the mosquitoes’ level of Hsp70 – heat shock protein 70 – increased nearly eightfold within one hour and remained at least twice as high as usual for 12 hours. The increase in these proteins was most pronounced in the midgut area.

Denlinger and colleagues tested potential triggers for this protein increase by injecting the mosquitoes with a saline solution at two temperatures: 37 degrees Celsius (98.6 degrees Fahrenheit) and room temperature. Only the warmer saline generated an increase in Hsp70, suggesting that the elevation in temperature associated with the meal, rather than the subsequent increase in body volume, is what causes the generation of those proteins.

Sometimes, mosquitoes feed on cold-blooded amphibians, which should not cause the same amount of stress. To test that theory, the researchers also gave mosquitoes a feeding opportunity on cooler blood, which failed to generate an increase in heat shock proteins.

And what happens if this protein is not produced? The researchers manipulated the mosquitoes’ RNA to figure that out.

When the scientists knocked down expression of the gene that encodes the heat shock protein, the amount of Hsp70 production was reduced by 75 percent. Under those circumstances, mosquitoes still ate a normal blood meal. But blood protein levels remained elevated for a longer period of time, suggesting that digestion of those proteins was impaired. In addition, egg production decreased by 25 percent when the heat shock protein was suppressed.

Heat shock proteins help maintain the three-dimensional integrity of enzymes and proteins when temperatures rise suddenly, and can target damaged proteins and enzymes for elimination, Denlinger said. “We think that in this case, they are important to maintaining the integrity of some critical enzymes and proteins involved in digestive processes. When we knock out those proteins, it impairs digestion a bit and as a result the mosquitoes don’t lay as many eggs,” he said.

The researchers observed similar body temperature increases and elevations in Hsp70 levels in three other insects: Culex pipiens and Anopheles gambiae, mosquitoes that are carriers of West Nile virus and malaria, respectively, and Cimex lectularius, the bed bug. Though new knowledge about the genetics of these insects, especially the mosquitoes, might someday inform attempts to kill them as a method of disease control, Denlinger said the primary contribution of this research is better understanding of how mosquitoes protect themselves in this novel way.

This work was supported by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases and the National Science Foundation.

Co-authors include Joshua Benoit, a former Ohio State graduate student who is now a postdoctoral researcher at Yale University, and Giancarlo Lopez-Martinez, Kevin Patrick, Zachary Phillips and Tyler Krause of Ohio State’s Departments of Entomology and Evolution, Ecology and Organismal Biology. Lopez-Martinez is now at the University of Florida.

Source: Proceedings of the National Academy of Sciences, Ohio State University

Malaria Mosquitoes Reveal Pathogen Defense Strategies

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In analyzing malaria mosquitoes in sub-Saharan Africa, a Cornell-led team of researchers finds evidence of two very different evolutionary paths in the immune systems of neighboring mosquito groups.

Genes in animal immune systems may evolve in one of two main ways in the constant fight against pathogens: They may evolve diverse forms of genes (alleles) to fight a wide variety of pathogens, or when only a few pathogens dominate, they may evolve one or a few alleles that specialize against common infections. The Cornell researchers have found evidence of both these adaptive strategies occurring in the same immune-defense genes in different subpopulations of the human malaria vector mosquito, Anopheles gambiae.

via PhysOrg.com.

APL1 Malaria Resistance Genes of Anopheles Gambiae

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Immune defense genes are sometimes highly variable in host populations, reflecting selective pressure to combat diverse pathogens. In other instances, where there are only a few dominant pathogens, natural selection may favor only one or a few defense alleles. Here, we show that both adaptive strategies can occur in the same genes under different circumstances.

We examined diversity in the APL1 genes of the human malaria vector mosquito Anophleles gambiae, which play a role in defense against malaria parasites. We found that the APL1 genes are exceptionally polymorphic, being 10-fold more diverse than typical A. gambiae genes.
[Read more…]

Evolution of Malaria-Transmitting Mosquitoes

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Researchers have found that the major malaria-transmitting mosquito species, Anopheles gambiae, is evolving into two separate species with different traits, a development that could both complicate malaria control efforts and potentially require new disease prevention methods.

A. gambiae is the most common vector of human malaria in sub-Saharan Africa, where rates of the disease are highest. The researchers compared the genomes of two emerging species, dubbed M and S. Given that M and S appear to be physically indistinguishable and interbreed often, they were unexpectedly different at the DNA level. They also were found to behave differently and thrive in different habitats. For example, in the absence of predators, S mosquitoes out-competed M mosquitoes, but the outcome was reversed when predators were present.

As these two emerging species of mosquito evolve to develop new traits and behaviors, changes in disease transmission could result, the authors say. This could complicate malaria control efforts, which currently are based on the mosquitoes’ patterns of behavior and vulnerability to insecticides.

Future research will further investigate these emerging species, exploring how they compete with one another in various habitats and the molecular basis of their evolution. The results will be used to refine existing malaria interventions and inform the development of new disease prevention strategies.

Their findings were published in back-to-back articles in the October 22, 2010 issue of the journal Science.

Articles
DE Neafsey et al. Complex gene-flow boundaries among vector mosquito populations. Science. DOI: 10.1126/science.1193036 (2010).

MKN Lawniczak et al. Widespread divergence between incipient Anopheles gambiae species revealed by whole genome sequences. Science. DOI: 10.1126/science.1195755 (2010).

Source: NIH