Systemic insecticides (neonicotinoids and fipronil): trends, uses, mode of action and metabolites.

Since their discovery in the late 1980s, neonicotinoid pesticides have become the most widely used class of insecticides worldwide, with large-scale applications ranging from plant protection (crops, vegetables, fruits), veterinary products, and biocides to invertebrate pest control in fish farming. In this review, we address the phenyl-pyrazole fipronil together with neonicotinoids because of similarities in their toxicity, physicochemical profiles, and presence in the environment. Neonicotinoids and fipronil currently account for approximately one third of the world insecticide market; the annual world production of the archetype neonicotinoid, imidacloprid, was estimated to be ca. 20,000 tonnes active substance in 2010. There were several reasons for the initial success of neonicotinoids and fipronil: (1) there was no known pesticide resistance in target pests, mainly because of their recent development, (2) their physicochemical properties included many advantages over previous generations of insecticides (i.e., organophosphates, carbamates, pyrethroids, etc.), and (3) they shared an assumed reduced operator and consumer risk. Due to their systemic nature, they are taken up by the roots or leaves and translocated to all parts of the plant, which, in turn, makes them effectively toxic to herbivorous insects. The toxicity persists for a variable period of time-depending on the plant, its growth stage, and the amount of pesticide applied. A wide variety of applications are available, including the most common prophylactic non-Good Agricultural Practices (GAP) application by seed coating. As a result of their extensive use and physicochemical properties, these substances can be found in all environmental compartments including soil, water, and air. Neonicotinoids and fipronil operate by disrupting neural transmission in the central nervous system of invertebrates. Neonicotinoids mimic the action of neurotransmitters, while fipronil inhibits neuronal receptors. In doing so, they continuously stimulate neurons leading ultimately to death of target invertebrates. Like virtually all insecticides, they can also have lethal and sublethal impacts on non-target organisms, including insect predators and vertebrates. Furthermore, a range of synergistic effects with other stressors have been documented. Here, we review extensively their metabolic pathways, showing how they form both compound-specific and common metabolites which can themselves be toxic. These may result in prolonged toxicity. Considering their wide commercial expansion, mode of action, the systemic properties in plants, persistence and environmental fate, coupled with limited information about the toxicity profiles of these compounds and their metabolites, neonicotinoids and fipronil may entail significant risks to the environment. A global evaluation of the potential collateral effects of their use is therefore timely. The present paper and subsequent chapters in this review of the global literature explore these risks and show a growing body of evidence that persistent, low concentrations of these insecticides pose serious risks of undesirable environmental impacts.

Effects of neonicotinoids and fipronil on non-target invertebrates.

We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section "other invertebrates" review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.

Isolation of Kunjin virus from a patient with a naturally acquired infection.

OBJECTIVE: To describe the first isolation of Kunjin virus from a patient with a natural infection. CLINICAL FEATURES: A 48-year-old female egg collector presented with muscle weakness, fatigue and extreme lethargy three weeks after developing rigors, headache, photophobia and nausea. Kunjin virus was isolated from an acute phase serum sample. INTERVENTION AND OUTCOME: The patient made a partial recovery after treatment for 10 days with Catovit (Boehringer Ingelheim), one tablet twice a day, and then declined further medical contact. CONCLUSION: The isolation of Kunjin virus from this patient confirms previous serological observations which suggested that this mosquito-borne virus caused febrile episodes in humans accompanied, on occasion, by polyarthralgia or mild central nervous system signs and symptoms.

Clinical and subclinical Barmah Forest virus infection in Queensland.

Barmah Forest virus is a mosquito-borne agent (alphavirus) reported to cause both clinical and subclinical infections in New South Wales. This report describes 29 cases of clinical Barmah Forest virus infection diagnosed between July 1988 and March 1989 (21 from Queensland, six from New South Wales and two from Victoria) and provides evidence of extensive subclinical infection with this virus (0.23% of the population per annum) throughout Queensland. It also includes a description of the first isolation of Barmah Forest virus from a patient. Data obtained in the course of the study suggest that Barmah Forest virus infections may not be diagnosed correctly in many instances because of the similarity of the symptoms of this disease to those of epidemic polyarthritis and the small number of laboratories providing the necessary serological services.

Dengue in the northern region of Queensland, 1981-1982.

During the dengue epidemic in northern Queensland in 1981 and 1982, type I dengue was serologically confirmed in 196 patients (mean age, 32.2 years) from the Cairns district. The most common symptoms were fever (99%), headache (92%), rash (91%), myalgia (93%), skin itching (75%) and arthralgia (60%). Haemorrhagic manifestations were noted in 14 patients. Most only showed skin petechiae. One patient also had bleeding from the gastrointestinal and urinary tracts. No cases of shock were recorded. Leucopenia was present in 57% of patients. A discussion on the relevance of these findings to dengue haemorrhagic fever/dengue shock syndrome is included. A serological survey after the epidemic suggests that approximately 7% of the population have antibodies to dengue as a result of the recent epidemic.

Dengue fever. Reappearance in northern Queensland after 26 years.

During March, 1981, a number of cases of dengue fever occurred in Cairns and Townsville, northern Queensland. From October, 1981, an outbreak of the infection was recognized on Thursday Island and, by May 1982, an estimated 38% of residents had been infected. Isolated cases were reported from other towns in northern Queensland and from other islands in the Torres Strait. Clinical presentation varied from that of severe incapacitating illness lasting up to seven days to infections which were confirmed by serological tests, but were not associated with apparent illness. No deaths were reported. Entomological surveys indicated that the domestic breeding vector of dengue, Aedes aegypti, is widely distributed throughout Queensland - southwards to Dirranbandi and westwards to Mornington Island. In some localities, the indices of Ae. aegypti abundance are alarmingly high, but at least in some suburbs of Townsville, it has been effectively controlled.

Infection with Mycoplasma pneumoniae: clinical and serological data on 286 patients.

In a 14-month period from January, 1971, 286 patients, referred for investigation of a variety of illnesses, were found to have complement-fixing antibodies to Mycoplasma pneumoniae to a titre of 1:32 or greater. Clinical findings in these patients are presented in a form which relates them to different antibody levels. Patients with central nervous system disease are described in some detail and the occurence of rash, arthropathy and a variety of other syndromes is noted. The suggestion is made that low-titred M. pneumoniae antibody appears as an anamnestic response to infection with other agents.

Immunoglobulin M in Murray Valley encephalitis.

Twelve clinical cases of Murray Valley encephalitis are described, in which the sero-diagnosis was confirmed by the detection of Murray Valley encephalitis immunoglobulin M.