Interbreeding of two malaria mosquito species in the West African country of Mali has resulted in a "super mosquito" hybrid that's resistant to insecticide-treated bed nets. 
 
 "It's 'super' with respect to its ability to survive exposure to the insecticides on treated bed nets," said medical entomologist Gregory Lanzaro of UC Davis, who led the research team. 
 
 The research, published Jan. 6 in the Proceedings of the National Academy of Sciences, "provides convincing evidence indicating that a man-made change in the environment -- the introduction of insecticides -- has altered the evolutionary relationship between two species, in this case a breakdown in the reproductive isolation that separates them," said Lanzaro, who is director of the Vector Genetics Laboratory and professor in the Department of Pathology, Microbiology and Immunology in the School of Veterinary Medicine. 
 
 "What we provide in this new paper is an example of one unusual mechanism that has promoted the rapid evolution of insecticide resistance in one of the major malaria mosquito species." 
 
 Anopheles gambiae, a major malaria vector, is interbreeding with isolated pockets of another malaria mosquito, A. coluzzii. Entomologists initially considered them as the "M and S forms" of Anopheles gambiae. They are now recognized as separate species. 
 
 Interbreeding of two malaria mosquito species in the West African country of Mali has resulted in a "super mosquito" hybrid that's resistant to insecticide-treated bed nets. 
 
 "It's 'super' with respect to its ability to survive exposure to the insecticides on treated bed nets," said medical entomologist Gregory Lanzaro of UC Davis, who led the research team. 
 
 "What we provide in this new paper is an example of one unusual mechanism that has promoted the rapid evolution of insecticide resistance in one of the major malaria mosquito species." 
 
 Anopheles gambiae, a major malaria vector, is interbreeding with isolated pockets of another malaria mosquito, A. coluzzii. Entomologists initially considered them as the "M and S forms" of Anopheles gambiae. They are now recognized as separate species. 
 
 The insecticide resistance came as no surprise. "Growing resistance has been observed for some time," Lanzaro said. "Recently it has reached a level at some localities in Africa where it is resulting in the failure of the nets to provide meaningful control, and it is my opinion that this will increase." 
 
 Lanzaro credits insecticide-treated nets with saving many thousands, probably tens of thousands of lives in Mali alone. The World Health Organization's World Malaria Report indicates that deaths from malaria worldwide have decreased by 47 percent since 2000. Much of that is attributed to the insecticide-treated bed nets. However, it was just a matter of time for insecticide resistance to emerge, medical entomologists and epidemiologist agree. 
 
 Now there's "an urgent need to develop new and effective malaria vector control strategies," Lanzaro said. A number of new strategies are in development, including new insecticides, biological agents -- including mosquito-killing bacteria and fungi -- and genetic manipulation of mosquitoes aimed at either killing them or altering their ability to transmit the malaria parasite. 
 
 ### 
 
 First author on the paper is Laura Norris, a postdoctoral scholar in the UC Davis Department of Entomology and Nematology who was supported by a National Institutes of Health training grant awarded to Lanzaro. She has since accepted a position with the President's Malaria Initiative in Washington, D.C. 
 
 Other co-authors include, at UC Davis, Anthony Cornel, Yoosook Lee, Bradley Main and Travis Collier; and Abdrahamane Fofana of the Malaria Research and Training Center at the University of Bamako, Mali. Three grants from the National Institutes of Health funded the research. 
 
 Lanzaro has researched mosquitos in Mali for 24 years with Cornel, who is an associate professor in the UC Davis Department of Entomology and Nematology and headquartered at the UC Kearney Agriculture and Research Center, Parlier. Both are graduate student advisors in the department, training medical entomologists of tomorrow. ||||| Fact sheet on the World Malaria Report 2014 
 
 Malaria is an entirely preventable and treatable mosquito-borne illness. In 2014, 97 countries and territories had ongoing malaria transmission. 
 
 An estimated 3.3 billion people are at risk of malaria, of whom 1.2 billion are at high risk. In high-risk areas, more than one malaria case occurs per 1000 population. 
 
 Disease burden in 2013 
 
 There were an estimated 198 million cases of malaria worldwide (range 124–283 million) in 2013, and an estimated 584 000 deaths (range 367 000–755 000). 90% of all malaria deaths occur in Africa. 
 
 In 2013, an estimated 437 000 African children died before their fifth birthday due to malaria. Globally, the disease caused an estimated 453 000 under-five deaths in 2013. 
 
 Between 2000 and 2013, an expansion of malaria interventions helped to reduce malaria incidence by 30% globally, and by 34% in Africa. 
 
 During the same period, malaria mortality rates decreased by an estimated 47% worldwide and by 54% in Africa. In the under-five age group, mortality rates have declined by 53% globally, and by 58% in Africa. 
 
 New analysis reveals that the prevalence of malaria parasite infection (including both symptomatic and asymptomatic infections) has decreased significantly in Africa since 2000. The number of people infected fell from 173 million in 2000 to 128 million in 2013 – a reduction of 26%. This has occurred despite a 43% increase in the African population living in malaria transmission areas. 
 
 Trends in the scale-up of malaria interventions 
 
 During the past 10 years, coverage with vector control interventions increased substantially in Africa. In 2013, almost half of the population at risk in Africa (49%) had access to an insecticide-treated mosquito net, compared to 3% in 2004. 
 
 In 2014, an estimated 214 million long-lasting insecticidal nets (LLINs) were delivered to malaria-endemic countries in Africa, bringing the total number of LLINs delivered to that region since 2012 to 427 million. 
 
 In 2013, 124 million people were protected from malaria by indoor residual spraying around the world. In Africa, 55 million people, or 7% of the population at risk, lived in households that were regularly sprayed. 
 
 Access to rapid diagnostic tests (RDTs) and quality-assured artemisinin-based combination therapies (ACTs) has been increasing around the world. 
 
 The volume of RDT sales to the public and private sectors of endemic countries has increased from 46 million in 2008 to 319 million in 2013. 
 
 The number of patients tested by microscopic examination increased to 197 million in 2013, with India accounting for over 120 million slide examinations. 
 
 Globally, 392 million courses of ACTs were procured by endemic countries in 2013, up from 11 million in 2005. 
 
 In 2013, for the first time, the total number of diagnostic tests (RDTs and microscopy combined) provided in the public sector in Africa exceeded the total number of ACTs distributed. This indicates a prominent shift away from presumptive treatment and is thus an encouraging sign. 
 
 In Africa, the proportion of women who receive intermittent preventive treatment in pregnancy (IPTp) for malaria has been increasing over time, although the levels remain below national targets. An estimated 15 million of the 35 million pregnant women did not receive a single dose of IPTp in 2013. 
 
 Progress in adopting and rolling out preventive therapies for children has been even slower. As of 2013, only six of the 16 countries where WHO recommends preventive therapies for children under five have adopted the treatment as national policy. Only one country has adopted the recommended preventive therapy for infants, but has not yet started rolling out the programme. 
 
 Drug and insecticide resistance 
 
 Emerging parasite resistance to antimalarial medicines and mosquito resistance to insecticides, if left unaddressed, could render some of the current tools ineffective and trigger a rise in global malaria mortality. 
 
 In recent years, parasite resistance to artemisinin has been detected in five countries of the Greater Mekong subregion: Cambodia, the Lao People’s Democratic Republic, Myanmar, Thailand and Viet Nam. In areas along the Cambodia–Thailand border, P. falciparum has become resistant to most available antimalarial medicines, and multi-drug resistance is a major concern. 
 
 Between 2010 and 2013, 53 countries globally have reported mosquito resistance to at least one insecticide. Of these, 41 have reported resistance to two or more insecticide classes. The most commonly reported resistance is to pyrethroids, the most frequently used insecticide in malaria vector control. 
 
 Progress towards global targets 
 
 The malaria-specific Millennium Development Goal (MDG 6 target C: to have halted by 2015 and begun to reverse the incidence of malaria) has already been met. 
 
 In terms of country-level progress, a total of 64 countries are currently on track to reverse the incidence of malaria nationally by 2015. 
 
 Of these, 55 are on track to meet the World Health Assembly and Roll Back Malaria Partnership target of reducing malaria incidence by 75% by 2015. 
 
 Funding remains inadequate 
 
 International and domestic funding for malaria control and elimination totalled US$ 2.7 billion in 2013. Although this represents a threefold increase since 2005, it is still significantly below the US$ 5.1 billion that is required to achieve global targets for malaria control and elimination. ||||| This photo provided by the Centers for Disease Control and Prevention (CDC ) shows a feeding female Anopheles stephensi mosquito. (James Gathany/CDC via AP) 
 
 In the history of the world, few weapons have been more destructive than a tiny mosquito bearing a microscopic dose of malaria. 
 
 The disease is one of Earth’s oldest and deadliest. It may have infected the dinosaurs. It’s been found in the mummified remains of ancient Egyptians. It’s thought to have killed Genghis Khan. One Nobel Prize-winning scientist even went so far as to suggest that malaria may be responsible for half of all human deaths, ever. 
 
 And despite our fiercest efforts at treatment and eradication — bed nets, quinine pills, pesticides, vaccines — the illness persists in killing us, to the tune of roughly half a million deaths per year. 
 
 So scientists are trying a different tactic: Instead of treating the humans, why not treat the mosquitoes? 
 
 On Monday, researchers from the University of California’s Irvine and San Diego campuses reported in the Proceedings of the National Academy of Sciences that they’ve bred a strain of mutant bugs that could all but eliminate malaria from the world’s mosquito population. 
 
 The breakthrough relies on a controversial new gene-editing technique called CRISPR-Cas9, a sort of molecular cut-and-paste that allows scientists to snip out segments of a creature’s DNA and insert new ones. With CRISPR, the California researchers added a set of genes conferring malaria resistance to their mutant mosquitoes, as well as a powerful tool called a “gene drive” that guarantees that all of the mosquitoes’ descendants would inherit their resistance. 
 
 [Why we should all hope to get bitten by a GMO mosquito] 
 
 “Gene drives” work by manipulating the laws of genetics so that the desired genes are copied onto both of an offspring’s chromosomes when a mutant mates with a wild mosquito. Ordinarily, offspring get just half their traits from each parent — but with the mutant inserting its DNA into both chromosomes, mosquitoes with the gene drive were able to pass on the resistance to 99.5 percent of their offspring, the researchers say. 
 
 According to the New York Times, the gene drive has the potential to spread malaria resistance throughout a wild population in a matter of just 10 mosquito generations, or a single summer. 
 
 Kevin Esvelt, an evolutionary engineer at Harvard University who studies the technique in yeast and wasn’t involved in the mosquito study, called the research a “major advance.” 
 
 “This work suggests that we’re a hop, skip and jump away from actual gene drive candidates for eventual release,” he told the Associated Press, 
 
 For now, the mutant mosquitoes are being kept in a highly secure lab behind a series of locked doors. That’s because, alluring though the promise of eradicating malaria might be, neither science nor society has quite reached a consensus about when or how creatures with manipulated DNA should be released into the wild — or indeed, what will happen when they are. 
 
 “[Gene editing] is a little bit like geoengineering,” MIT researcher Feng Zhang told the New Yorker earlier this month. “Once you go down that path, it may not be so reversible.” 
 
 Zhang, a biological engineer, led the first team of researchers to employ the CRISPR-Cas9 editing technique on human cells. 
 
 The research out of California was led by UC-Irvine molecular biologist Anthony James and UC-San Diego biologists Ethan Bier and Valentino Gantz. 
 
 James specializes in engineering “anti-disease” mosquitoes, with which he hopes to halt the spread of disease without killing off the world’s bug population. For the PNAS paper, he developed a gene that spurs mosquitoes’ antibodies to attack the malaria parasite (which they acquire while biting infected humans), preventing them from passing the microbe to their offspring. He tested the new gene on the eggs of an Indian mosquito species Anopheles stephensi — that way, if the bugs somehow escaped, they’d find themselves on a foreign continent with an inhospitable climate and no one to mate. 
 
 Bier and Gantz contributed the second part of the potent anti-malaria package. The pair, which effectively introduced a gene drive into fruit flies earlier this year, teamed with James to plug the tool into A. stephensi DNA. They coupled the malaria resistance gene with one that makes mosquitoes’ eyes red, so they could measure whether the resistance gene was passed on. Nearly 100 percent of the offspring had red eyes — and, presumably, malaria resistance. 
 
 “This is a significant first step,” James said in a University of California press release. “We know the gene works. The mosquitoes we created are not the final brand, but we know this technology allows us to efficiently create large populations.” 
 
 James is a member of the National Academy of Sciences, which has convened a committee to review the ethical implication of gene editing and gene drive research. In the meantime, the scientists using CRISPR worry that an accident might undermine their technique before they have a chance to demonstrate its power. 
 
 “If anyone messes up and a gene drive gets out into the wild, there will be a huge media circus,” Esvelt told Nature earlier this month, before the release of the mosquito study. “The message will be that scientists cannot be trusted to deal with this technology, and we will be set back by years.” 
 
 In a study published last week, Esvelt and his colleagues at several Boston universities unveiled a gene drive “safeguard” that can override the initial mutation in yeast cells. 
 
 James told the New York Times that the UC researchers plan to move slowly and very carefully forward with their research. 
 
 “This is the kind of technology where the first trial has to be a success,” he said. 
 
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 Whole Foods Thanksgiving turkeys endure ‘horrific conditions’ at Calif. farm, activists say ||||| After 10 years of effort, a team led by scientists at Yale has finally decoded the genes of the tsetse fly, a bloodsucking scourge of Africa. 
 
 With that knowledge, they hope to find new ways to repel or kill the insects, whose bite transmits sleeping sickness, a parasitic disease that, like rabies, drives its victims mad before they lapse into a coma and die. The flies also carry nagana, which weakens or kills cattle and renders whole regions of Africa inhospitable to most livestock. 
 
 There are now fewer than 10,000 confirmed cases per year of sleeping sickness — formally known as human African trypanosomiasis — but the disease occurs in epidemics. As recently as 1998, the number of estimated cases was 300,000. Treatment is long and difficult, and without it, the disease is always fatal. 
 
 Sequencing the genome of Glossina morsitans, one of several tsetse species, took a decade, partly because tsetses have highly unusual biology — they are the only insects that nurse their young, among other traits — and partly because of global health politics. 
 
 Since mosquito-borne diseases are the major threat to Americans, and some of the diseases had bioterrorism potential, early federal grants for gene sequencing all went to mosquitoes, said Serap Aksoy, who ran the tsetse sequencing project from her lab at the Yale School of Public Health. 
 
 “Sleeping sickness is a neglected disease, an African disease,” she said, “so we didn’t get those funds.” 
 
 The sequencing of G. morsitans, a species found in dry savanna, was done for only $10 million, mostly from the World Health Organization, the Wellcome Trust, the Ambrose Monell Foundation, and with time donated by scientists in the United States, England, France, Japan and various African countries. 
 
 However, Dr. Aksoy added, now that the result is a genetic treasure trove and sequencing has become faster and cheaper, the National Institutes of Health will support sequencing of five more Glossina species. 
 
 The other challenge for researchers was the fly itself. 
 
 “Tsetse biology is just freaky,” said Leslie B. Vosshall, an insect neurobiologist at Rockefeller University. “This is an insect that breast-feeds its children.” 
 
 Dr. Aksoy’s project, she added, was “long overdue because tsetses are one of the most neglected insects with public health importance.” 
 
 While most flies lay hundreds of eggs in rotting fruit or carcasses, a tsetse mother gives birth to a single larva that weighs as much as she does. 
 
 Inside her uterus, it nurses on a milk gland, drinking proteins that do what different but similar proteins in human breast milk do, including blending fats with water, passing on hormones and making iron digestible. 
 
 “It’s an example of convergent evolution,” said Geoffrey Attardo, another Yale team leader and a co-author of the study, which was published Thursday by Science along with 11 companion papers in several PLOS journals. 
 
 At birth, the larva, resembling a squirming sack of milk, wriggles beneath the soil and spends up to a month there before hatching as a hungry adult. 
 
 “Other insects produce many progeny and hope a few survive,” Dr. Aksoy said. “With tsetse, the hatch rate is nearly 100 percent.” 
 
 That parsimonious reproduction caused problems, because sequencers need the bug equivalent of identical twin girls to be sure that all the DNA they are working on is uniform; they use females because male Y chromosomes are full of so-called junk DNA, which lacks the codes for making proteins. 
 
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 With most insects this is easy; a female mosquito might hatch 500 identical females after each blood meal. But tsetses produce fewer than 10 descendants in a life span, half of them male. 
 
 So all the sequencing — which involved 140 scientists — was done on 15 flies. Much of it, Dr. Aksoy said, relied on one mother and two daughters. 
 
 The researchers found several spots on the genome they hope will eventually lead to better insecticides or repellents. 
 
 For example, a gene called ladybird late, which also exists in fruit flies, controls milk production. When researchers disabled it in the lab, the larvae starved. 
 
 If a chemical that did the same thing could be found, the flies would die out. As long as it was safe for mammals, it could be sprayed on cows for the flies to pick up, Dr. Attardo said. 
 
 Another type of gene allows the flies to squeeze water droplets out of their immense blood meals, liquefy their milk and conserve water on hot days. Any disruption to that process could be fatal. Alternatively, tweaking gut or salivary gland genes could make the fly reject the parasites that cause sleeping sickness. 
 
 “The mosquito immune system has been manipulated to give it a stronger response against malaria parasites,” said George Dimopoulos, a mosquito expert at the Johns Hopkins Bloomberg School of Public Health who praised the tsetse study. “I don’t see any reason that can’t happen in the tsetse fly.” 
 
 Another possibility, said Dr. Vosshall, who studies insect olfactory genes, is that chemicals could be developed that block the fly’s ability to smell humans. 
 
 Among the many papers published on Thursday were histories of how five European powers fought sleeping sickness in their colonies. An epidemic that began in 1901 killed a third of the inhabitants of some fly-infested regions. By World War II, it was largely under control. 
 
 But the campaign against sleeping sickness may have had an unintended consequence: The widespread reuse of unsterilized syringes for vaccinations may have contributed to the spread of what in the 1980s became known as AIDS. ||||| We report that during a recent period of hybridization between two major African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii, an island of divergence on chromosome 2 introgressed from the A. gambiae into the A. coluzzii genome and its frequency subsequently increased. This introgression was coincident with the start of a major insecticide-treated bed net campaigns in Mali. These observations suggest that increased insecticide exposure acted as a selective force sufficient to drive introgression of an entire genomic island of divergence across the reproductive barrier separating these two species. This study provides a rare example of adaptive introgression in an animal species and elucidates the dynamics of how insecticide resistance evolved in A. coluzzii. 
 
 Abstract 
 
 Animal species adapt to changes in their environment, including man-made changes such as the introduction of insecticides, through selection for advantageous genes already present in populations or newly arisen through mutation. A possible alternative mechanism is the acquisition of adaptive genes from related species via a process known as adaptive introgression. Differing levels of insecticide resistance between two African malaria vectors, Anopheles coluzzii and Anopheles gambiae, have been attributed to assortative mating between the two species. In a previous study, we reported two bouts of hybridization observed in the town of Selinkenyi, Mali in 2002 and 2006. These hybridization events did not appear to be directly associated with insecticide-resistance genes. We demonstrate that during a brief breakdown in assortative mating in 2006, A. coluzzii inherited the entire A. gambiae-associated 2L divergence island, which includes a suite of insecticide-resistance alleles. In this case, introgression was coincident with the start of a major insecticide-treated bed net distribution campaign in Mali. This suggests that insecticide exposure altered the fitness landscape, favoring the survival of A. coluzzii/A. gambiae hybrids, and provided selection pressure that swept the 2L divergence island through A. coluzzii populations in Mali. We propose that the work described herein presents a unique description of the temporal dynamics of adaptive introgression in an animal species and represents a mechanism for the rapid evolution of insecticide resistance in this important vector of human malaria in Africa.
– For years, campaigns such as Nothing But Nets have been trying to control the scourge of malaria—a blood disease spread by mosquito bites—by sending insecticide-laced nets to hard-hit regions (mostly in Africa). But a University of California-Davis study has some bad news: Researchers have discovered a hybrid "super mosquito" that seems to be resistant to the treated nets. The study published in Proceedings of the National Academy of Sciences indicates that Anopheles coluzzii mosquitoes in Mali that cross-bred with the A. gambiae variety created the superinsect—"'super' with respect to its ability to survive exposure to the insecticides," says Gregory Lanzaro, the study's lead author, in a press release. Although he's not surprised insecticide resistance is rising, it's still worrisome: "It is resulting in the failure of the nets to provide meaningful control." There were about 584,000 deaths from malaria in 2013, 90% of them occurring in Africa, according to the World Health Organization; every 60 seconds a child there dies from the disease, Nothing But Nets adds. But inroads have been made: Intervention tactics, including insecticide-treated nets, helped cut the mortality rate 54% in Africa between 2000 and 2013, the WHO notes—and in 2013, 49% of all African residents at risk for the disease (up from a mere 3% in 2004) had access to insecticide-laced nets. This new finding could throw a wrench in that progress, and new preventative measures will need to be explored. (Another study: Pantyhose help reveal why mosquitoes prefer humans.)