Objectives:The objective of this trial was to investigate the safety and preliminary effectiveness of a daily dose of 300 mg of tenofovir disoproxil fumarate (TDF) versus placebo in preventing HIV infection in women.Design:This was a phase 2, randomized, double-blind, placebo-controlled trial.Setting:The study was conducted between June 2004 and March 2006 in Tema, Ghana; Douala, Cameroon; and Ibadan, Nigeria.Participants:We enrolled 936 HIV-negative women at high risk of HIV infection into this study.Intervention:Participants were randomized 1:1 to once daily use of 300 mg of TDF or placebo.Outcome measures:The primary safety endpoints were grade 2 or higher serum creatinine elevations (>2.0 mg/dl) for renal function, grade 3 or 4 aspartate aminotransferase or alanine aminotransferase elevations (>170 U/l) for hepatic function, and grade 3 or 4 phosphorus abnormalities (<1.5 mg/dl). The effectiveness endpoint was infection with HIV-1 or HIV-2.Results:Study participants contributed 428 person-years of laboratory testing to the primary safety analysis. No significant differences emerged between treatment groups in clinical or laboratory safety outcomes. Study participants contributed 476 person-years of HIV testing to the primary effectiveness analysis, during which time eight seroconversions occurred. Two were diagnosed in participants randomized to TDF (0.86 per 100 person-years) and six in participants receiving placebo (2.48 per 100 person-years), yielding a rate ratio of 0.35 (95% confidence interval = 0.03–1.93), which did not achieve statistical significance. Owing to premature closures of the Cameroon and Nigeria study sites, the planned person-years of follow-up and study power could not be achieved.Conclusion:Daily oral use of TDF in HIV-uninfected women was not associated with increased clinical or laboratory adverse events. Effectiveness could not be conclusively evaluated because of the small number of HIV infections observed during the study.

BackgroundThe New World screwworm, Cochliomyia hominivorax, is a devastating pest of livestock endemic to subtropical and tropical regions of the Western hemisphere. The larvae of this species feed on the tissue of living animals, including man, and can cause death if untreated. Over 60 years ago, the sterile insect technique (SIT) was developed with the aim of eradicating this pest, initially from Florida but subsequently from all of North and Central America. From the outset it was appreciated that SIT would be more efficient if only sterile males were released in the field, but this was not possible until now.ResultsHere, we report on the development and evaluation of the first sexing strains of C. hominivorax that produce only males when raised on diet without tetracycline. Transgenic lines have been developed that possess a tetracycline repressible female-lethal genetic system. Ten of these lines show high female lethality at the late larval/pupal stages and three of them present dominant female lethality. Most of the lines were comparable to the wild type parental strain in several fitness parameters that are relevant to mass rearing in a production facility. Further, three lines performed well in male mating success and male competition assays, suggesting they would be sexually competitive in the field. Consequently, one transgenic line has been selected by the New World Screwworm Program for evaluation under mass rearing conditions.ConclusionsWe conclude that the promising characteristics of the selected sexing strains may contribute to reduce production costs for the existing eradication program and provide more efficient population suppression, which should make a genetic control program more economical in regions were C. hominivorax remains endemic.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0296-8) contains supplementary material, which is available to authorized users.

New World screwworms, Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae: Chrysomyinae), are devastating pests of warm-blooded animals that cause significant economic damage to livestock. The successful campaign to eradicate screwworms from continental North America, led by the US Department of Agriculture and using the sterile insect technique, continues to receive research support that has resulted in improved technologies for all aspects of the program. The process and ingredients for mass-rearing screwworms is more efficient and sustainable, and there is now a standardized protocol for developing new strains used in mass rearing. Cryopreservation of screwworm embryos allows strains to be preserved and recovered if necessary and also reduces rearing requirements for backup and research strains. Sterile fly release procedures and equipment have been updated leading to optimized sterile fly release rates. Surveillance for screwworm infestations and outbreaks have incorporated new trap designs, habitat analysis, and molecular genetic techniques that enhance monitoring the progress of the program as well as early detection and response to outbreaks. Genetic analyses of screwworm populations across their current range have increased the understanding of genetic differentiation, which may aide in developing new strains and determining the geographic origin of screwworms causing outbreaks when they occur. The ability to release only sterile males, which has been a goal of the program for over 60 years, has recently been accomplished through the development of transgenic sexing strains. The strains carry a conditional female lethal gene and are comparable to the wild-type strain for several biological parameters that are important for mass production and performance in the field. The strains should improve efficiency of population suppression of the current and future eradication and prevention programs against screwworms. These research advances as well as future considerations are presented.

BackgroundBabesia are emerging health threats to humans and animals in the United States. A collaborative effort of multiple disciplines to attain optimal health for people, animals and our environment, otherwise known as the One Health concept, was taken during a research workshop held in April 2009 to identify gaps in scientific knowledge regarding babesioses. The impetus for this analysis was the increased risk for outbreaks of bovine babesiosis, also known as Texas cattle fever, associated with the re-infestation of the U.S. by cattle fever ticks.ResultsThe involvement of wildlife in the ecology of cattle fever ticks jeopardizes the ability of state and federal agencies to keep the national herd free of Texas cattle fever. Similarly, there has been a progressive increase in the number of cases of human babesiosis over the past 25 years due to an increase in the white-tailed deer population. Human babesiosis due to cattle-associated Babesia divergens and Babesia divergens-like organisms have begun to appear in residents of the United States. Research needs for human and bovine babesioses were identified and are presented herein.ConclusionsThe translation of this research is expected to provide veterinary and public health systems with the tools to mitigate the impact of bovine and human babesioses. However, economic, political, and social commitments are urgently required, including increased national funding for animal and human Babesia research, to prevent the re-establishment of cattle fever ticks and the increasing problem of human babesiosis in the United States.

Eradicating screwworm, Cochliomyia hominivorax (Coquerel), from continental North American via the sterile insect technique has provided huge economic benefit to livestock producers by eliminating screwworm myiasis. After confirmatory identification of fly samples from infested deer by the USDA National Veterinary Services Laboratory on September 30, 2016, an alert was issued that screwworm myiasis was discovered in the Florida Keys. Personnel from USDA Animal and Plant Health Inspection Service, Agricultural Research Service, the State of Florida, U.S. Fish and Wildlife Service and local officials responded to the outbreak focus on Big Pine Key. After witnessing infested Key deer (Odocoileus virginianus clavium Barboyr & Allen), screwworm adult sampling was initiated at 0930 h on October 5, 2016 using nets to collect flies arriving at putrid liver, with the first female collected within 1 h. Larval samples were collected from infested animals for DNA analyses and to develop a "Florida outbreak" colony to test mating compatibility with the mass-produced strain used for sterile fly releases. Ground release chambers for sterile screwworm releases were placed in favorable habitats based on satellite image analyses. Sterile pupae were first placed in the chambers on October 11, 2016. Further liver trapping showed that 13 Keys were infested. One case, presumably through animal movement, occurred near Homestead on the Florida mainland. Ultimately there were 35 sterile fly release stations, including 4 located around Homestead, but no further cases were identified. About 188 million sterile flies were released until successful eradication was declared on March 23, 2017. Containing the outbreak prevented economic losses to livestock producers and other wildlife on the mainland and kept eradication costs to a minimum.