Research Ideas

Now Jean-Paul Paluzzi, a PhD candidate in biology at the University of Toronto Mississauga, believes that manipulating physiology to prevent the insects from leaving their messy calling card represents the best hope for stopping the transmission of the illness, known as Chagas’ disease.

“This is a disease of the poor,” says Paluzzi, who has visited parts of the world affected by the illness. “The bugs are found in makeshift homes with mud walls and palm tree-like ceilings. Unfortunately, the people of Central and South America that this affects don’t have sufficient voice to get help. Given that there are roughly 15 to 19 million people that are infected-a substantial proportion of that area’s population-it’s a disease that’s been neglected.”

Chagas’ disease is one of the major health problems in South and Central America and is spread by reduvid bugs, also known as “kissing bugs” because of their fondness for lips. The disease they transmit is caused by Trypanosoma cruzi, a parasite that lives in their gut. In the initial acute stage, symptoms are relatively mild, but as the disease progresses over several years, serious chronic symptoms can appear, such as heart disease and malformation of the intestines. Without treatment, it can be fatal. Currently, insecticide sprays are used to control insect populations, and anti-parasitic drugs are somewhat successful at treating acute infections. Once the disease is chronic, it cannot be cured.

To make matters worse, kissing bugs are particularly “bloodthirsty”. In mosquitoes, which go through four distinct stages of development, only adult females feed on blood (and potentially transmit disease). This means that pest control methods need to target only one out of eight stages (when you include both sexes). But in kissing bugs, each sex feeds on blood through all fives stages of development. “So you have about a ten-fold greater chance of infection just because of the number of times that these insects have to feed,” says Paluzzi.

His research focuses on insect diuresis-more specifically, the genes and peptides that control how the kissing bug eliminates excess fluid in its gut after it gorges on blood. For the insect, the real prize in its meal is the red blood cells, while the water and salt is “excess baggage”. After they feed, the bugs are bloated and sluggish, and must jettison the waste so they can make their escape.

Here’s how it happens: when the kissing bug finds a snoozing victim and feeds, its levels of serotonin and diuretic hormones rise sharply, targeting the insect’s midgut and Malpighian tubules (the equivalent of kidneys), and triggering the release of waste. About four hours later, a peptide named CAP2b is released in the insect’s gut, abolishing the effect of the diuretic hormones.

Paluzzi has identified two genes (RhoprCAPA-alpha and RhoprCAPA-beta) that carry the chemical recipe for the peptides that stop diuresis. With that information, he hopes to create a peptide “agonist”-something that would enhance the activity of the CAP2B peptide and prevent the insect from leaving waste (and the parasite) on the wound. In theory, says Paluzzi, this might be an insecticide-like room spray or topical lotion that is biologically stable and has no effect on humans or other insects. Paluzzi is collaborating with a structural biochemist at the U.S. Food and Drug Administration in Texas, with the ultimate goal of creating a pest control solution, but he cautions that a market-ready product is many years away.

The truffle, found mainly in France but also in Spain and Italy, is known by its Latin name of Tuber melanosporum.

But to truffle fanatics in the southwestern French region of Perigord, the warty, golfball-sized fungus is known as the “black diamond.”

It can reach 1,000 euros a kilo (605 dollars a pound) at local farmers’ markets, and several times more at shops in Paris.

A tri-nation group led by geneticists at France’s National Institute for Agricultural Research (INRA) says that the truffle has a DNA signature pointing to its geographical origins.

Its genome comprises 125 million base pairs — the “rungs” on the double-helix genetic ladder — which encompass 7,500 genes, of which 6,000 are shared by other fungi.

The remaining 1,500 genes play a key role in the truffle’s development and its symbiosis, or linked growth, with the roots of a host tree, predominantly the oak.

In addition, the genome is studded with DNA telltales crafted by the nature of the soil and other local factors.

Ten of these markers will go to a “truffle databank,” covering some 50 areas in France, Italy and Spain where T. melanosporum is found.

“This database of genetic fingerprints will help identify the regional origin of harvested truffles and set up the means to certify these products and detect any frauds,” INRA said.

Truffle hunters in France use trained pigs or dogs to sniff out the delicacy, which is found buried just under the soil surface.

They are incensed by the incursion into the market of cheap rivals, especially Chinese truffles that are often passed off as “black diamonds.”

One of these Chinese species is sometimes seeded with extracts from the real T. melanosporum to boost a lacklustre aroma. Another is rarer but is so similar to T. melanosporum that, until now, the only sure way to distinguish the two is analysis by an expert.

Truffle associations are calling for the European Union (EU) to create a special appellation or origin to protect their national treasure.

The genome, which took five years to compile, is reported online by the British journal Nature.

More related research content: http://www.inqua2007.net.au/

Digital billboards change images every four to 10 seconds, flashing multiple messages from one or more advertisers on the same sign. Opponents such as John Regesnbogen of Scenic Missouri deride them as “television on a stick.”

Several communities have banned digital billboards outright, the most recent being Denver earlier this month. Other places have put a moratorium on them pending a federal study on whether they distract drivers. At least one other city and two states are studying moratoriums.

“The digital billboards are a distraction,” says Fred Wessels, an alderman in St. Louis, which just approved a one-year moratorium on such signs.

“If they weren’t distracting, they wouldn’t be doing their job,” says Max Ashburn, spokesman for Scenic America, a national nonprofit group that seeks to limit billboards.

Research on the issue is mixed. A Virginia Tech Transportation Institute study in 2007, financed by the billboard industry, found that they aren’t distracting. A review of studies completed last year for the American Association of State Highway and Transportation Officials, however, concluded that they “attract drivers’ eyes away from the road for extended, demonstrably unsafe periods of time.”

“There’s no doubt in my mind that they are not a driving distraction,” says Bryan Parker, an executive vice president for Clear Channel Outdoor, which owns about 400 digital billboards. He cites industry-sponsored studies of collisions before and after digital billboards were installed in Albuquerque, N.M.; Cleveland; and Rochester, Minn., that found no correlation.

“We’ve looked at that very carefully,” says Bill Ripp, vice president of Lamar Advertising, which owns 159,000 billboards, 1,150 of them digital. “We don’t want to cause any unsafe conditions for drivers.”

Digital billboards are a fast-growing segment of the outdoor advertising market. Since a federal rule against them was eased in 2007, the number of digital billboards has more than doubled to about 1,800 of 450,000 total billboards. At least 39 states allow them. They cost an average $200,000 to $300,000 apiece, according to the industry group Outdoor Advertising Association of America.

In 2007, the Federal Highway Administration relaxed a rule against digital billboards, saying they don’t violate the 1965 Highway Beautification Act’s ban on “intermittent,” “flashing” or “moving” lights. FHWA is researching the signs, using eye-trackers inside volunteers’ vehicles to determine whether drivers look at the billboards and for how long. The study is to be completed this summer.

There is little current data on whether greater distractions for drivers come from in-vehicle or external factors.

The Department of Transportation, which is leading a national push against texting while driving, says that 5,870 people were killed in distracted-driving crashes in 2008. The department has not determined how many of those deaths involved an electronic device, another distraction such as eating or tuning the radio, or something outside the vehicle such as a digital billboard.

The myth may come closer to reality this summer than at any time in decades in several states in the West and the Plains.

A federal survey of adult grasshoppers last fall indicated that parts of Wyoming, Montana, South Dakota, North Dakota, Nebraska and Idaho could face costly grasshopper infestations this summer.

Ranchers and farmers as well as federal and municipal pest control agencies are praying for well-timed cool and wet weather to stifle the young grasshoppers when they hatch around May and June.

In the meantime, they’re scrambling to line up the millions of dollars it will cost to battle an outbreak with aerial insecticide.

“They’re grass eaters,” said Tom Wright, a rancher near Newcastle in northeast Wyoming about 20 miles from the South Dakota border. “They’ll eat the leaves and leave the stem. And they will eat the stems finally.

“When they’re really thick, people say they’ll eat T-shirts on a line,” he said as he recalled a time in the mid-1980s when the grasshoppers were so thick that you couldn’t put your hand on the shady side of a fence post without squashing one.

Grasshoppers are found across the United States, but outbreaks of pest species are most common in the Plains and Western states. Different species range from a length of under an inch to more than 3 inches.

They provide some ecological benefits, serving as a food source for other animals. However, some pest species are capable of eating their body weight daily in vegetation and can waste up to six times more by dropping forage to the ground.

Making matters worse is the prevalence of migratory species in the latest surveys – insects that can fly 60 miles in a day.

The Wyoming acreage infested with 15 or more grasshoppers per square yard increased more than 10-fold from 2008 to 2.9 million acres last summer, according to federal surveys.

Regionwide, surveys predict at least 48 million acres of outbreak-level infestation this summer.

“In some states, we may see some of the most severe grasshopper outbreaks that we’ve seen in nearly 30 years,” said Charles Brown, the national grasshopper suppression program manager at the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service.

No government agency keeps a comprehensive tally of the economic damage from grasshoppers, but the cost of spray programs can exceed a million dollars for a single county.

Last summer, when an outbreak first surfaced in Wyoming, the voracious insects hurt hay production and prompted some ranchers to downsize their herds.

Wright didn’t sell any cattle because of grasshoppers, but his calves weighed 30 pounds lighter than normal last fall as a result of the insects eating up forage. The grass damage also forced the ranch to buy extra feed to help its cows through the winter, costing about $10,000, he said.

Paying to participate in a spray program could make sense if it was cheaper than the alternatives, he said.

“At the point that (grasshoppers) eat all the grass, you have to either sell all your cows, lease grass somewhere else or buy hay,” he said.

Grasshopper eggs tend to survive better in untilled soil, but that doesn’t stop the grown insects from hopping to cropland and eating crops such as corn, alfalfa, sunflowers, soybeans and sugar beets.

“In the past couple of years, we’ve had some crop damage by grasshoppers, especially alfalfa and soy beans,” said Dave Boxler, a research technologist in entomology for the University of Nebraska based in North Platte.

In Wyoming, Gov. Dave Freudenthal announced this month a $2.7 million plan to help local pest districts and to pay for spraying on state lands this summer. Freudenthal and the state’s congressional delegation have also urged the federal government to make more money available for treating federal rangeland.

Pest managers combat rangeland grasshoppers by using planes to spray alternating strips of land with an insecticide that kills the bugs in the nymphal stage, meaning it must be applied within a few weeks after eggs hatch.

Entomologist Scott Schell of the University of Wyoming said the insecticide, Dimilin 2L, has a very low toxicity level for mammals, reptiles and birds. It also has little effect on bees, he said.

Gail Mahnke, supervisor of the Niobrara County Weed and Pest Control District, said she expects grasshopper treatment in the eastern Wyoming county to run about $1.2 million this summer. That works out to a cost to landowners of about $1.65 a protected acre. The district plans to spend its $60,000 in emergency reserves on the project, she said.

Mahnke said she’s not sure what will happen if weather conditions unexpectedly kill off the grasshoppers.

“When you’re talking a $1.2 million deal just in this county, and getting it all set up and having all that money sitting here, and then those conditions just happen to hit perfect, what do you do?” she said.

The study — an observational analysis of the DART trial published by The Lancet in 2009 — was written by Dr A Sarah Walker, MRC Clinical Trials Unit, London, UK, and colleagues in Uganda, Zimbabwe and the UK.

Co-trimoxazole (trimethoprim-sulfamethoxazole) is a widely available, off-patent, low-cost antibiotic that is used in resource-limited settings to treat and prevent community-acquired infections. In HIV infection, it is highly effective for treatment of and prophylaxis against Pneumocystis jirovecii pneumonia, Toxoplasma gondii, Isospora belli, and bacterial infections; it also has antimalarial properties.

Results of clinical trials and observational studies in HIV-infected adults and children across Africa who are not taking anti-HIV treatment have shown that co-trimoxazole prophylaxis reduces mortality, morbidity, and hospital admissions, even in areas of high background bacterial resistance. WHO guidelines recommend that co-trimoxazole prophylaxis is given to all symptomatic adults with CD4 counts lower than 350 cells per ?L in resource-limited settings, and is continued when people start HIV treatment. However, these recommendations for continuing co-trimoxazole with anti-HIV treatment were based on extrapolation from US studies. There were no African data and concerns about limited benefit and the potential to compromise adherence led to variable use in low-income settings.

Participants in this new analysis were from the DART randomised trial of management strategies in HIV-infected, symptomatic, previously untreated Ugandan and Zimbabwean adults starting triple-drug ART with CD4 counts lower than 200 cells per ?L. Co-trimoxazole prophylaxis was not routinely used or randomly allocated, but was variably prescribed by clinicians. The authors estimated the effects of prophylaxis on clinical outcomes, CD4 cell count, and body-mass index (BMI).

The results covered 3179 participants who contributed 14 214 years of follow-up (8128 [57%] person-years on co-trimoxazole). Predictors of co-trimoxazole use were the most recent CD4 cell count, haemoglobin concentration, and BMI; and previous WHO stage 3 or 4 events on ART. Current prophylaxis reduced risk of death by 35% overall. Mortality risk reduction on ART was substantial to 12 weeks (59%), sustained from 12? weeks (44%), but not evident after 72 weeks. Variation in mortality reduction was not accounted for by time on co-trimoxazole, nor surprisingly by current CD4 cell count. Prophylaxis also reduced frequency of malaria by 26%, an effect that was maintained with time. Of note, no statistically significant effect of prophylaxis was observed on new WHO stage 4 events (eg opportunistic infections such as oesphageal candidiasis, cryptococcal disease, or extra-pulmonary tuberculosis), CD4 cell count, or BMI.

The authors say: “Since DART participants, who had advanced immunodeficiency and symptomatic disease, had similar characteristics to those of most patients starting ART in rollout programmes in Africa, our findings should be generalisable.”

Furthermore, the authors point out that mortality in patients accessing ART programmes in sub-Saharan Africa is very high in the first year on treatment, with 8% of patients dying, most in the first 3-4 months. Even when baseline immunodeficiency is allowed for, early mortality is several times higher in resource-limited settings than it is in high-income settings.

They conclude: “In DART, adherence was high, and concerns that initiation of both co-trimoxazole and ART together might lead to unacceptably high rates of toxic effects are not substantiated by our data. The mortality benefits, safety, and tolerability, together with the low cost and simplicity of implementation, suggest that co-trimoxazole prophylaxis [combined with anti-HIV treatment] is cost effective and has a substantial public health effect. Our results reinforce WHO guidelines and provide strong motivation for provision of co-trimoxazole prophylaxis for at least 72 weeks to all adults starting combination ART in Africa.”

They add: “Whether co-trimoxazole can be stopped after this 72 week period needs further investigation.”

In an accompanying Comment, Dr Xavier Anglaret, INSERM, U897, Universit? Victor Segalen Bordeaux, France, and Dr Serge Eholie, Service des Maladies Infectieuses et Tropicales, CHU de Treichville, Abidjan, Ivory Coast, say: “Why duration of combination ART (cART) is the key determinant of co-trimoxazole efficacy, independent of current CD4 cell count, is uncertain. However, the results of today’s study clearly suggest that in sub-Saharan Africa, starting on cART should not be a reason for not starting or for stopping co-trimoxazole, and that prophylaxis should be maintained for more than 1 year after starting cART. Furthermore, the findings of this study show that important practical questions about HIV management can be answered with cohort data, as long as the study meets standard research criteria. For countries with restricted resources to address such questions, large cohort studies, such as DART, need to be done.”