Will the sun soon be setting on dangerous mosquito populations?
Could that once-monthly beef-flavored pill you give your dog to kill fleas and ticks save thousands of human lives in Zika virus- and malaria-infected areas of the world?
That’s the hypothesis examined in a 2018 publication “Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases”, published by Miglianico, et al., in PNAS.
Vector-Borne Diseases Under Siege
Mosquito-transmitted diseases, such as malaria and Zika virus, and sand fly-transmitted leishmaniasis are major causes of mortality in sub-tropical regions. Although with a lower mortality incidence, mosquito-borne West Nile virus has spread in temperate regions such as Europe and the United States. Continue reading
Life cycle of the Malaria parasite.
A paper published in on August 8 in ChemBioChem
has identified a number of small molecule kinase inhibitors that may have potential as antimalarial drugs. The authors, Derbyshire et al
from Duke University, used a panel of human kinase inhibitors to screen for activity against malaria parasites. Using a high-throughput screening approach, they were able to identify several potential drug targets among the kinases of Plasmodium sp.
,—most of which were effective against the parasite during both it’s blood-borne and liver-based life cycle stages.
Liver and blood-stage malaria parasites have different gene expression profiles and infect different host cells. The authors exploited these differences to try to specifically identify compounds that were active against the parasite while it was still in the liver, the idea being that any drug-based prevention strategy needs to be effective against the parasites in the liver in order to eradicate infection.
The authors screened a library of over 1300 kinase inhibitors that included several compounds already being used in clinical trials for anti-cancer activity. Initial screening was performed in human liver-derived HepG2 cells infected with Plasmodium berghei expressing a luciferase reporter. Compounds that decreased parasite load by more than 95% were further characterized in dose-response experiments, and promising hits were tested in using luminescent and fluorescent cell based assays to identify compounds that were not toxic to liver cells. Continue reading
My family and I just returned from a week-long camping trip along the North Shore of Lake Superior in Minnesota. It is beautiful country, filled with lakes, rivers, ponds—and mosquitoes, lots and lots of mosquitoes. We went prepared for the worse. We had a screen tent, head nets and tubes and tubes of insect repellent because in this area of the world, mosquitoes are a flying, buzzing, picnic-ruining, itch-inducing pest. In the US, though, a pest is really all they are. In other areas of the world they are a flying, buzzing, disease-carrying, deadly menace.
Image courtesy of James Gathany and the CDC
Mosquitos act as vectors for many diseases including malaria, Dengue fever, Yellow fever, encephalitis, West Nile Virus and chikungunya virus. Many of these diseases are deadly; in fact, mosquitoes are responsible for more human deaths than any other animal (~725,000 deaths annually). Although most of these diseases have a long and infamous history, two of them, West Nile virus (first identified in 1932) and chikungunya virus (first identified in 1950), are relative new comers on the world health stage. Continue reading
Image courtesy of James Gathany and the CDC
Mosquitos: They are the scourge of summer activities—the annoying buzzing noise as they fly around our ears and the pain, itching and swelling associated with their bites. Worst of all, certain species of mosquitoes can transmit diseases such as West Nile virus, Dengue fever and malaria. Defense mechanisms such as mosquito repellent, covering my head with netting and wearing heavy clothing are often insufficient against the swarm of hungry insects. It’s enough to make me want to stay indoors.
Those people who cannot escape these pests have a higher risk of being bitten and contracting a disease such as malaria, which killed an estimated 627,000 people in 2012, mostly in Africa and southeast Asia (1). A common step in malaria reduction programs in high-risk areas is reducing the number of Anopheles gambiae mosquitoes, which act as the host for malaria-causing parasites. This often involves massive amounts of insecticides, including limited amounts of the much maligned but very effective insecticide dichlorodiphenyltrichloroethane (DDT). Due to these programs, the World Health Organization (WHO) estimates that between 2000 and 2012, malaria mortality rates decreased by 42% worldwide, including a 48% decrease in children under 5 years of age. Clearly these programs are saving lives, but wouldn’t it be nice to achieve the same thing with fewer pesticides?
A recent report in Nature Communications makes me hopeful that we can.
Although it is more than 200 years since Jenner’s pioneering work on vaccination, there are still many infectious diseases that resist the development of effective vaccines. Somewhat shockingly, despite years of research effort, there are still no highly effective vaccines against human parasitic diseases. Malaria, the most problematic of these, kills more than half a million people each year—many of these infants and children, qualifying the mosquito that transmits the parasite as one of the most dangerous creatures on earth. Not surprisingly then, recent hopeful news of an anti-malaria vaccine that appears to protect against the disease has been greeted with enthusiasm.
The search for an effective anti-malaria vaccine has been fraught with difficulty due to the complex life cycle of the parasite (Plasmodium falciparum and other Plasmoduim species), compounded by its propensity to change its surface composition and develop resistance to various treatment efforts. The parasite thus presents an ever-changing target for treatment efforts. In the absence of an effective vaccine, anti-malarial efforts have been dependent on drug treatment (also liable to development of resistance), eradication programs, and preventive measures such as insecticide-laced mosquito netting. Continue reading
For many of us mosquitoes are an itchy aggravation. They come in the evenings in the warmer months. They disrupt hikes, camping trips and picnics, leaving behind itching reminders that have us reaching for antihistamines and no-itch creams. For people in some areas of the world however, mosquitoes are more than just a pest with an itchy calling card, they are a deadly menace. Mosquitoes of the genus Anopheles can carry Plasmodium, the parasitic micro-organism that causes malaria.
According to the World Health Organization, there were an estimated 243 million cases of malaria worldwide in 2008. Most of these cases were in Africa, followed by South-East Asia and the Eastern Mediterranean (1). In that year, malaria caused an estimated 863,000 deaths, and tragically, the majority of these deaths were in children younger than five. Continue reading