Vaccine for malaria? Differences with yellow fever?

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QUESTION

Is there a vaccine to prevent malaria?
What is the difference between yellow fever and malaria?

ANSWER

In answer to your first question, no, there is not currently a vaccine available to prevent malaria. The best current candidate, the RTS,S vaccine which was developed by GlaxoSmithKline, is currently undergoing Phase III clinical trials in Africa. Although preliminary results showed up to a 50% rate of protection against malaria in some age groups, the trials will not conclude until 2014 and so full results will not be known until after that date.

As for your second question, while yellow fever and malaria are both transmitted by mosquitoes, they share few other similarities. Yellow fever is caused by a virus, for example, whereas malaria is caused by a single-celled parasite of the genus Plasmodium. The group of organisms that Plasmodium belongs to is often called “Protista” (the exact grouping and classification constantly changes!), and they more generally belong, based on cell type, to the Eukaryotes, an enormous group of organisms which also includes all mammals and even humans! Viruses, on the other hand, are tiny pieces of genetic material wrapped in a protein coating, and can hardly be described as alive in a conventional sense.

While both yellow fever and malaria are transmitted by mosquitoes, yellow fever is transmitted by the genus Aedes, whereas malaria is exclusively transmitted by the genus Anopheles (at least in humans, and all other mammals for that matter).While spraying inside households may reduce the prevalence of  both types of mosquitoes, Aedes mosquitoes tend to feed during the day, so sleeping under an insecticide-treated bednet is less protective against yellow fever than it is against malaria. Also, a vaccine is available for yellow fever (and has been available for over 50 years), whereas as I describe above, no such vaccine yet exists for malaria.

Finally, while superficially the symptoms of yellow fever and malaria may seem similar (fever, nausea, aches), other manifestations of the disease can be very different. Yellow fever is technically considered a hemorrhagic disease, since it can cause increased tendency to bleed in patients. Also, in some patients, the initial symptoms are followed by an acute liver phase, causing jaundice which can turn the patient yellow (and hence the name). Malaria can also affect the liver, and cause ild jaundice, but usually not to the extent of yellow fever.  Once a patient has been diagnosed with yellow fever, there is no specific treatment, and the patient is merely treated based on symptoms, to ease their discomfort. Vaccination is the mainstay of control of this disease, and has been very successful in many places; the total number of worldwide cases is estimated by the World Health Organization to be around 300,000, with 20,000 deaths, mainly in Africa.

The burden of malaria is also mainly felt in Africa, though the number of cases and deaths is vastly higher – globally, there are approximately 200 million cases of malaria in 2010, with almost 700,000 deaths. Along with the general symptoms of fever and nausea, the most dangerous manifestation of malaria is when it causes cerebral symptoms; this is usually only caused by Plasmodium falciparum malaria, and can lead to impaired consciousness, coma and even death. Also in contrast to yellow fever,  the mainstay of control is a combination of prevention (mostly with vector control, i.e. using bednets, indoor residual spraying and destruction of breeding habitats and larvae) and treatment (using a variety of medications).

Mosquito Types

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QUESTION

How many types of mosquito are there?

ANSWER

There are over 3,500 species of mosquito! However, most of these do not transmit any diseases to humans. Mosquitoes are usually divided into two sub-families, the Anophelinae and the Culicinae. The latter group consists of about 40 genera, including Culex and Aedes, which contain some species that transmit diseases to humans (such as yellow fever, dengue fever and West Nile). The former contains the genus Anopheles, which are the mosquitoes that transmit malaria. There are about 460 described species of Anopheles mosquito, of which about 100 can transmit malaria, though the vast bulk of transmission is usually limited to about 30 species.

US Army Doctor William Crawford Gorgas: Sent to Panama to fight Malaria

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QUESTION

What was the doctor’s name who was sent to Panama to fight Malaria when Panama Canal was being built?

ANSWER

I believe the person you are referring to is Dr. William Crawford Gorgas. Dr Gorgas was the chief sanitary officer for the Panama Canal project and had gained experience in controlling vector borne diseases while working in Havana, Cuba, where yellow fever was a problem.

It had also been shown a few years earlier, in 1898, that mosquitoes carried malaria as well. In Panama, Dr Gorgas focused his efforts on controlling mosquitoes, through drainage of standing water, adding larvicide and oil to remaining water and hand-collection of adult mosquitoes. In addition, Dr Gorgas screened all government buildings and workers’ quarters to prevent mosquitoes from entering, and gave workers prophylactic quinine. He was assisted in these endeavours by Dr Joseph Augustin LePrince and Dr Samuel Taylor Darling; together, their efforts led to the elimination of yellow fever from the canal zone and a great decrease in the number of malaria cases, though malaria continued to be a problem throughout the construction of the Panama Canal.

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