Survival and Fecundity of Anopheles stephensi and Anopheles albimanus Mosquitoes (Diptera: Culicidae) After Ingesting Bovine Blood Containing Various Veterinary Systemic Parasiticides.

Systemic parasiticides in livestock can control zoophilic malaria vectors that contribute to residual malaria transmission. Membrane feeding techniques were used to screen seven systemic parasiticidic drugs currently in veterinary use for livestock and dogs. Drugs were tested in two laboratory strains of zoophilic Anopheles - A. stephensi (South Asian vector) and A. albimanus (Central American vector). To assess the relative potentials of these drugs, the resultant LC-50 for each drug was compared with what is known about the pharmacokinetic of the drug. Drugs with LC-50 values below the reported maximum plasma concentration of treated animals were considered as showing the most promise for use in the field. Ivermectin and fipronil showed the greatest promise for use in cattle against A. stephensi. Fipronil showed the greatest promise for use in cattle against A. albimanus. Both fluralaner and afoxolaner were highly effective against both mosquito species but pharmacokinetic data for these drugs in cattle are lacking. Eprinomectin, moxidectin and abamectin showed marginal to no promise for either mosquito species. At sublethal doses, ivermectin, fipronil, and afoxolaner (but not fluralaner) significantly reduced the larval production of surviving A. stephensi and A. albimanus. Further testing of candidate systemic parasiticides, including their product formulations, in livestock against field-collected populations of Anopheles is the next logical step toward full implementation of this strategy to manage zoophilic vectors.

Oral susceptibility to ivermectin is over fifty times greater in a wild population of Anopheles albimanus mosquitoes from Belize than the STECLA laboratory reference strain of this mosquito.

BACKGROUND: The STECLA strain of Anopheles albimanus has been in continuous colony for many years and is the reference strain on which genomic studies for the species are based. Recently, the STECLA strain was demonstrated to be much less susceptible to ivermectin ingested in a blood meal (4-day LC50 of 1468 ng/ml) than all other Anopheles species tested to-date (LC50 values range from 7 to 56 ng/ml). The ability of An. albimanus to survive ingestion of ivermectin at concentrations far beyond that typically found in the blood of ivermectin-treated people or livestock (i.e., 30-70 ng/ml) could invalidate the use of ivermectin as a malaria vector control strategy in areas where An. albimanus is a primary vector. METHODS: To investigate this, host-seeking An. albimanus were captured in northern Belize and used in membrane feeding bioassays of ivermectin, employing the same methods as described earlier with the STECLA strain. RESULTS: Field-collected An. albimanus in Belize were 55 times more susceptible to ingested ivermectin than were the STECLA reference strain. Oral susceptibility to ivermectin in wild An. albimanus from Belize (4-day LC50 of 26 ng/ml) was equivalent to that of other Anopheles species tested. CONCLUSIONS: Contrary to initial assessments using a highly inbred strain of mosquito, laboratory studies using a field population indicate that ivermectin treatment of livestock could reduce An. albimanus populations in areas of Central America and the Caribbean where malaria transmission may occur. Toxicity screening of ivermectin and other systemic parasiticides for malaria control should examine wild populations of the vector species being targeted.

Fipronil and ivermectin treatment of cattle reduced the survival and ovarian development of field-collected Anopheles albimanus in a pilot trial conducted in northern Belize.

BACKGROUND: Most malaria vector control programmes rely on indoor residual spraying of insecticides and insecticide-treated bed nets. This is effective against vector species that feed indoors at night and rest inside the house afterwards. In Central America, malaria vectors have different behaviours and are typically exophagic (i.e., bite outdoors), exophilic (i.e., remain outdoors after feeding), and zoophagic (i.e., as likely to feed on non-humans as humans). Thus, malaria elimination in Central America may require additional tactics. This pilot study investigated whether commercially-available products used to treat livestock for ticks could also be used to kill and/or sterilize zoophagic malaria vectors that feed on treated cattle in Belize. METHODS: Cattle were treated with either a pour-on formulation of 1% fipronil (3 heifers) or injection of 1% ivemectin (1 heifer). Control heifers (n = 2) were left untreated. Field-collected Anopheles albimanus contained in screen-top cages were strapped onto cattle at 2, 5, 7, and 14 days after treatment. Mosquito mortality was monitored once a day for 4 successive days. Surviving mosquitoes were dissected to assess blood meal digestion and ovarian development. RESULTS: A total of 1078 female An. albimanus mosquitoes were fed and monitored for mortality. Both fipronil and ivermectin significantly reduced survivorship of An. albimanus for up to 7 days after treatment. By 14 days, efficacy had declined. The ivermectin treatment completely lost its effectiveness and even though the fipronil-treated heifers were still killing significantly more mosquitoes than the untreated heifers, the amount of mosquito killing had diminished greatly. Both treatments significantly reduced ovary development in mosquitoes fed on treated cattle for the duration of the 2-week trial. CONCLUSIONS: Treatment of cattle in northern Belize with topical fipronil and injectable ivermectin had significant lethal and sublethal effects on wild An. albimanus females. These results suggest that efforts towards eliminating residual transmission of malaria by zoophagic vectors in Central America may benefit by the judicious, targeted treatment of livestock with mosquitocidal compounds, such as fipronil or ivermectin.

Differential susceptibilities of Anopheles albimanus and Anopheles stephensi mosquitoes to ivermectin.

BACKGROUND: Vector control is a crucial element of anti-malaria campaigns and works best when there is a thorough knowledge of the biology and behaviour of the Anopheles vector species responsible for transmitting malaria within a given locale. With the push to eradicate malaria stronger than ever, there is a growing need to develop and deploy control strategies that exploit the behavioural attributes of local vector species. This is especially true in regions where the vectors are exophagic (i.e., prefer to bite outdoors), exophilic (i.e., prefer to remain outdoors), and zoophagic (i.e., as likely to feed on non-humans as humans). One promising strategy targeting vectors with these behavioural traits is the administration of avermectin-based endectocides, such as ivermectin, to humans and livestock. When ingested in a blood meal, ivermectin has been shown to reduce mosquito survivorship and fecundity in a number of Anopheles species. In this study, the relative toxicity of ivermectin was compared between two zoophagic, exophilic malaria vectors-Anopheles albimanus and Anopheles stephensi. RESULTS: Toxicity of ivermectin was assessed using membrane feedings, intrathoracic injections, and mosquito feedings on treated mice. When ingested in a blood meal, ivermectin was much less toxic to An. albimanus (4-day oral LC50 = 1468 ng/ml) than to An. stephensi (4-day oral LC50 = 7 ng/ml). However when injected into the haemocoel of An. albimanus, ivermectin was much more toxic (3-day parenteral LC50 = 188 ng/ml). Because the molecular targets of ivermectin (i.e., glutamate-gated chloride channels) reside outside the midgut in nerves and muscles, this suggests that ingested ivermectin was not readily absorbed across the midgut of An. albimanus. In contrast, ivermectin was considerably more toxic to An. stephensi when ingested (4-day oral LC50 = 7 ng/ml) than when injected (3-day parenteral LC50 = 49 ng/ml). This suggests that metabolic by-products from the digestion of ivermectin may play a role in the oral toxicity of ivermectin to An. stephensi. Blood meal digestion and subsequent oviposition rates were significantly hindered in both species by ingested ivermectin but only at concentrations at or above their respective oral LC50 concentrations. To test mosquitocidal activity of ivermectin in a live host system, two groups of three mice each received subcutaneous injections of either ivermectin (600 µg/kg BW) or saline (control). One day after injection, the ivermectin-treated mice (n = 3) exhibited significant mosquitocidal activity against both An. stephensi (85% mortality vs 0% in control-fed) and, to a lesser degree, An. albimanus (44% mortality vs 11% in control-fed). At 3 days, the mosquitocidal activity of ivermectin-treated mice waned and was effective only against An. stephensi (31% mortality vs 3% in control-fed). CONCLUSIONS: Ivermectin was not uniformly toxic to both Anopheles species. Previous studies indicate that ivermectin is a good choice of endectocide to use against malaria vectors in southeast Asia and Africa. However, these data suggest that ivermectin may not be the optimal endectocide to use in Central America or the Caribbean where An. albimanus is a major malaria vector species. If endectocides are to be used to help eradicate malaria, then additional efficacy data will be needed to define the activity of specific endectocides against the major malaria vector species of the world.