Long-lasting Formulation Research Articles

Impact of standard and long-lasting ivermectin formulations in cattle and buffalo on wild Anopheles survival on Sumba Island, Indonesia

The mosquito-lethal effect of commercially available standard and long-lasting ivermectin formulations were evaluated in cattle and buffalo against wild-caught Anopheles on Sumba Island, Indonesia. Cattle have substantially higher blood-level concentrations of ivermectin compared to buffalo after receiving similar doses, irrespective of formulation. In total, nine Anopheles species were captured to assess the mosquito-lethal effects of ivermectin with susceptibility ranked from lowest to highest: An. flavirostris < An. aconitus < An. annularis < An. tessellatus < An. maculatus < An. sundaicus < An. vagus < An. kochi < An. barbirostris. The duration of mosquito-lethal effect of long-lasting ivermectin was superior to standard ivermectin and in cattle it well exceeded the WHO criteria for new endectocides having a mortality hazard ratio greater than 4 through 30 days after administration. Buffalo may require higher doses of long-lasting ivermectin to achieve similar mosquito-lethal effects observed in cattle. Of the four hosts evaluated buffalo were the most attractive to Anopheles followed by cattle then horse and finally humans. This study demonstrates, for the first time, the superiority of a commercially available long-lasting ivermectin formulation for the potential deployment of mass ivermectin treatment of livestock as a vector control tool for malaria elimination in Southeast Asia.

Long-lasting residual efficacy of Actellic®300CS and Icon®10CS on different surfaces against Anopheles stephensi, an invasive malaria vector.

Anopheles stephensi, a malaria-transmitting mosquito species, has developed resistance to various insecticides such as DDT, Dieldrin, Malathion, and synthetic pyrethroids. To combat this issue, the World Health Organization (WHO) suggests using Actellic®300CS and Icon®10CS for Indoor Residual Spraying to tackle pyrethroid-resistant mosquitoes. The aim of this research project was to evaluate the susceptibility of An. stephensi to certain insecticides at the diagnostic concentration + intensity 5x diagnostic concentration (5XDC) assays in Iran and to study the lasting effectiveness of Actellic®300CS and Icon®10CS against this particular malaria vector. This study assessed the susceptibility of An. stephensi populations in southern Iran to various insecticides, including deltamethrin 0.05%, DDT 4%, malathion 5%, bendiocarb 0.1%, a synergist assay with PBO 4% combined with deltamethrin 0.05%, and an intensity assay using 5x the diagnostic concentration of deltamethrin (0.25%) and bendiocarb 0.5%. Laboratory cone bioassay tests were conducted to determine the residual effectiveness of Actellic®300 and Icon®10CS insecticides on different surfaces commonly found in households, such as cement, mud, plaster, and wood. The tests were carried out following the WHO test kits and standard testing protocols. The An. stephensi populations in Bandar Abbas were found to be susceptible to malathion 5% and deltamethrin 0.25% (5XDC), but exhibited resistance to DDT, standard concentration of deltamethrin, and both standard and intensity concentrations of bendiocarb. In laboratory cone bioassay tests, An. stephensi mortality rates when exposed to Actellic®300CS and Icon®10CS on different surfaces remained consistently more than 80%. Actellic®300CS achieved more than 80% mortality on all substrates for the entire 300-day post-spraying period. Conversely, Icon®10CS maintained mortality rates more than 80% on plaster and wood surfaces for 165 days and on mud and cement surfaces for 270 days post-spraying. Both Actellic®300CS and Icon®10CS demonstrated 100% mortality within 72 h of each test on all surfaces throughout the entire 300-day post-spraying period. The study shows the varying levels of resistance of An. stephensi Bandar Abbas population to different insecticides and demonstrates the consistent performance of Actellic®300CS in controlling these mosquitoes on various surfaces. The findings suggest that long-lasting CS formulations may be more effective for malaria vector control compared to the current options. Further research is needed to validate these findings in field settings and assess the impact of these insecticides on malaria transmission.

Preparation of a long-lasting tablet of spinosad microspheres and its residual insecticidal efficacy against the yellow fever mosquito, Aedes aegypti (Diptera: Culicidae) larvae.

In order to provide a long-lasting formulation for spinosad (SP) targeting larval stages of Aedes aegypti (Linnaeus) and others alike, a SP tablet was developed based on microspheres, using polylactic acid as inside coating material. The microspheres were encapsulated using polyethylene glycol and 1-hexadecanol to form a sustained-release SP tablet. Micromorphology, active ingredient loading, structure identification, photolysis resistance and biological activity were evaluated in this report. (i) The SP microspheres had an average particle size of 6.16 ± 2.28 μm, low adhesion and good dispersion as evaluated by scanning electron microscopy and morphology. (ii) The average active ingredient loading and encapsulation of SP microspheres were 32.80 ± 0.74% and 78.41 ± 2.22%, respectively. (iii) The chemical structure of encapsulated SP was confirmed by Fourier transform infrared and 1H-nuclear magnetic resonance. (iv) The photostability of the microspheres and the tablets were evaluated. The results showed that DT50 (time required to dissipate 50% of the mass originally present) of SP was 0.95 days in microspheres and 6.94 days in tablets. (v) The long-term insecticidal activity of SP tablets was investigated, and the tablet had a long-lasting activity against the mosquito larvae, showing 100% larval mortality for 63 days. The study provided a new long-lasting formulation of SP, which displayed good efficacy in the control of Ae. aegypti larvae. © 2024 Society of Chemical Industry.

Biotechnological Advancements in Streptokinase Production

This article offers a deep analysis of activating streptokinase which looks into the biotechnological challenges and future perspectives. One of the main problems associated with streptokinase is its short half-life, complex production process, and immunogenicity which hinders patients from getting a successful reperfusion. Yet, the development of biotechnology methods that would not face these drawbacks, such as the strategy of recombinant streptokinase production and enzyme engineering theories, is a promise. This paper aims to provide an overview of biotechnological breakthroughs in the production of streptokinase with a focus on discovering long-lasting formulations exhibiting less immunogenicity and in addition the economic viability and scalability of biotechnological production processes. This article also gives the comping image of known purification methods like chromatography, ultrafiltration, and I-A chromatography for the separation and purification of streptokinase. In addition, the author presents the advantage of such suitable production technologies as cell-free production systems and E. Coli system optimization, such as recombinant streptokinase synthesis in Yeast systems. Biotechnology is turning out to be a new area, having a future boom due to the rising innovation and demand that are associated with the prospects revealed by the market trends.

Rhizosphere Bacteria Biofertiliser Formulations Improve Lettuce Growth and Yield under Nursery and Field Conditions

Rhizosphere bacteria can provide multiple benefits to plants, including increased nutrient supply, pathogen/disease control, and abiotic stress tolerance, but results from pot trials do not always translate to field conditions. This study tested whether rhizosphere biocontrol bacteria can also provide plant growth promotion and how benefits can be provided at a commercial farm. Commercial lettuce seeds and plants were treated with rhizosphere biocontrol bacteria Bacillus velezensis UQ9000N, B. amyloliquefaciens 33YE, Brevibacillus laterosporus 4YE, and Pseudomonas azotoformans UQ4510An. 33YE increased the head diameter, plant height, and fresh weight of the Green Moon cultivar, while 33YE, UQ4510An, and UQ9000N increased the fresh and dry weight of Liston, a more heat-tolerant cultivar, via a single seed treatment or repeat root treatments under nursery and field conditions across different inoculation schedules and growth stages. Significant growth promotion was also demonstrated when inoculating field plants after transplanting (in particular for 33YE). Applications of these microbial biostimulants to lettuce seeds or plantlets potentially enable earlier transplanting and earlier harvests. Repeat inoculations using irrigation water and long-lasting formulations may further advance the benefits of these biostimulants as microbial biofertilisers for plant growth promotions in the field.

Evaluating the antimicrobial efficacy of long-lasting hand sanitizers on skin

The microbicidal efficacy of hand sanitizer formulations is usually measured through standardized quantitative suspension tests and fingerpad tests; these cannot evaluate long-lasting formulations or are impractical due to biological risks, high cost, or time required for testing. With increased numbers of long-lasting microbicidal activity claims of commercially available hand sanitizers, alternative testing strategies are required. To explore the use of a standardized ex-vivo pig skin model to reproducibly measure long-lasting efficacy of an alcohol-free hand sanitizer formulation. The microbicidal efficacy of an alcohol-free hand sanitizer was tested against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, and the enveloped virus SARS-CoV-2 with quantitative suspension tests (EN13727 and EN14476) with a contact time of 5min. The product was then tested over a 6h period using an ex-vivo pig skin model with a modified version of PAS 2424 to simulate the impact of skin abrasion. Quantitative suspension tests yielded a >5 log10 reduction for all organisms tested within a 5min contact time. Pig skin tests showed reduced but consistent efficacy at all time points and indicated no significant impact of abrasion on efficacy. The use of the ex-vivo pig skin model provides a potentially viable and convenient model system to test long-lasting hand sanitizer formulations, providing a path for sustainable hand sanitizer formulation claims of activity on skin.

Long-Acting Buprenorphine Formulations as a New Strategy for the Treatment of Opioid Use Disorder.

Long-acting buprenorphine formulations have been recently marketed for the Opioid Agonist Treatment (OAT) of opioid use disorder (OUD) associated with medical, social, and psychological support. Their duration of action ranges from one week up to 6 months. The non-medical use of opioids is increasing with a parallel rise in lethal overdoses. Methadone and buprenorphine are the standard treatment for opioid dependence. Methadone Maintenance Treatment (MMT) is widely recognized as one of the most effective ways of reducing the risks of overdose, crime, and transmission of HIV (Human Immunodeficiency Virus) in people who use opioids; however, its effectiveness has been hindered by low rates of uptake and retention in treatment. Furthermore, both methadone and buprenorphine are widely diverted and misused. Thus, a crucial aspect of treating OUD is facilitating patients' access to treatment while minimizing substance-related harm and improving quality of life. The newly developed long-acting buprenorphine formulations represent a significant change in the paradigm of OUD treatment, allowing an approach individualized to patients' needs. Strengths of this individualized approach are improved adherence (lack of peaks and troughs in blood concentrations) and a reduced stigma since the patient doesn't need to attend their clinic daily or nearly daily, thus facilitating social and occupational integrations as the quality of life. However, less frequent attendance at the clinic should not affect the patient-physician relationship. Therefore, teleconsulting or digital therapeutic services should be developed in parallel. In addition, diversion and intravenous misuse of buprenorphine are unlikely due to the characteristics of these formulations. These features make this approach of interest for treating OUD in particular settings, such as subjects staying or when released from prison or those receiving long-term residential treatment for OUD in the therapeutic communities. The long-lasting formulations of buprenorphine can positively impact the OUD treatment and suggest future medical and logistic developments to maximize their personalized management and impact.

Assessment of the impact of the biological larvicide VectoMax G: Combination of Bacillus thuringiensis and Lysinibacillus sphaericus on non-target aquatic organisms in Yaoundé-Cameroon

There has been a renewed interest for larviciding during the recent decade. Although biological larvicides are considered not to be harmful to non-target organisms, there is still not sufficient data on the effect of new long-lasting larvicide formulations such as VectoMax G combining Bacillus thuringiensis israelensis and Lysinibacullus sphaericus on the environment especially on non-target organisms. The present study aimed to assess the possible influence of VectoMax G on the diversity and abundance of the aquatic fauna cohabiting with mosquito larvae in breeding habitats during a larviciding trial in the city of Yaoundé.Twelve districts of the city of Yaoundé divided into 6 intervention and 6 control sites were chosen for the study. In each district 4 semi-permanent or permanent aquatic habitats were followed. VectoMax G application was done once every two weeks during 6 months and aquatic organisms were collected 48 h after each treatment. All collected organisms were brought to the laboratory for identification. Physico-chemical parameters were recorded as well.A high diversity of the zooplankton was recorded in the intervention areas with 28 species collected against 14 species in the control areas. Cladocerans were the most represented group in both sites while Ostracods were found only in control sites. A total of 19 macro-invertebrates species were recorded in the control areas vs 16 species in the intervention areas. Gasteropods were the most represented groups of macro-invertebrates. Vertebrates such as larvivorous fishes and amphibians larvae were also found in approximately similar densities in both sites.The study indicated no significant influence of larviciding with VectoMax G on the diversity and abundance of the non-target aquatic fauna in the city of Yaoundé.

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool

BackgroundDomesticated animals play a role in maintaining residual transmission of Plasmodium parasites of humans, by offering alternative blood meal sources for malaria vectors to survive on. However, the blood of animals treated with veterinary formulations of the anti-helminthic drug ivermectin can have an insecticidal effect on adult malaria vector mosquitoes. This study therefore assessed the effects of treating cattle with long-acting injectable formulations of ivermectin on the survival of an important malaria vector species, to determine whether it has potential as a complementary vector control measure.MethodsEight head of a local breed of cattle were randomly assigned to either one of two treatment arms (2 × 2 cattle injected with one of two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg), or one of two control arms (2 × 2 cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3–5-day-old Anopheles coluzzii mosquitoes through direct skin-feeding assays, from 1 to 210 days after treatment. The efficacy of each formulation was evaluated and compared using Cox proportional hazards survival models, Kaplan–Meier survival estimates, and log-logistic regression on cumulative mortality.ResultsBoth formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (hazard ratio > 1). The treatments significantly reduced mosquito survival, with average median survival time of 4–5 days post-feeding. The lethal concentrations to kill 50% of the Anopheles (LC50) before they became infectious (10 days after an infectious blood meal) were maintained for 210 days post-injection for both formulations.ConclusionsThis long-lasting formulation of ivermectin injected in cattle could complement insecticide-treated nets by suppressing field populations of zoophagic mosquitoes that are responsible, at least in part, for residual malaria transmission. The impact of this approach will of course depend on the field epidemiological context. Complementary studies will be necessary to characterize ivermectin withdrawal times and potential environmental toxicity.Graphical

Development of New Strategies for Malaria Chemoprophylaxis: From Monoclonal Antibodies to Long-Acting Injectable Drugs.

Drug discovery for malaria has traditionally focused on orally available drugs that kill the abundant, parasitic blood stage. Recently, there has also been an interest in injectable medicines, in the form of monoclonal antibodies (mAbs) with long-lasting plasma half-lives or long-lasting depot formulations of small molecules. These could act as prophylactic drugs, targeting the sporozoites and other earlier parasitic stages in the liver, when the parasites are less numerous, or as another intervention strategy targeting the formation of infectious gametocytes. Generally speaking, the development of mAbs is less risky (costly) than small-molecule drugs, and they have an excellent safety profile with few or no off-target effects. Therefore, populations who are the most vulnerable to malaria, i.e., pregnant women and young children would have access to such new treatments much faster than is presently the case for new antimalarials. An analysis of mAbs that were successfully developed for oncology illustrates some of the feasibility aspects, and their potential as affordable drugs in low- and middle-income countries.

Novel pyriproxyfen based treatment for Aedes breeding control through a long-lasting formulation: Laboratory and field trials in Western Maharashtra, India.

There is a need to evaluate novel techniques for dengue control in India. Several formulations of pyriproxyfen have been assessed for efficacy and duration of action. Pyriproxyfen is also used as a microencapsulated ready-to-use formulation against the Aedes vector. We evaluated a novel pyriproxyfen-based microencapsulated formulation. This slow-release, ready-to-use aqueous spray is a larvicidal formulation, and we assessed its efficacy and residual action through laboratory and semi-field trials against Aedes immature stages. The study was carried out as per the guidelines for laboratory and field/small-scale field testing of mosquito larvicides by the World Health Organization. The evaluation was conducted in laboratory and semi-field conditions from August to December 2018. We tested the novel formulation on three materials (plastic, ceramic, and enamel) in the laboratory for its action as an antilarval. Four containers of each kind were sprayed with the formulation and kept as replicates. Four controls were used in the laboratory trials - 120 larvae (third instar) were introduced in the replicates and the controls each. Readings were taken daily till complete adult emergence or larval and pupal mortality. In the semi-field trials, we applied this formulation to the inside of desert coolers and observed larvicidal and pupicidal activity over five months. Data is presented in numbers and percentages, along with mean and standard deviation. Adult emergence and Emergence Inhibition was calculated. There was 100% adult emergence inhibition amongst the exposed larvae in the treated containers in the laboratory trials. In the untreated controls, adult emergence ranged from 80-95% in all types of containers. In the semifield trials, Inhibition Emergence was 100% in the treated desert coolers during the five months of the study period. This advancement in insecticide formulation technology promises to make dengue control more effective and efficient.

Long-Term Evaluation of Poly(lactic acid) (PLA) Implants in a Horse: An Experimental Pilot Study.

In horses, there is an increasing interest in developing long-lasting drug formulations, with biopolymers as viable carrier alternatives in addition to their use as scaffolds, suture threads, screws, pins, and plates for orthopedic surgeries. This communication focuses on the prolonged biocompatibility and biodegradation of PLA, prepared by hot pressing at 180 °C. Six samples were implanted subcutaneously on the lateral surface of the neck of one horse. The polymers remained implanted for 24 to 57 weeks. Physical examination, plasma fibrinogen, and the mechanical nociceptive threshold (MNT) were performed. After 24, 28, 34, 38, and 57 weeks, the materials were removed for histochemical analysis using hematoxylin-eosin and scanning electron microscopy (SEM). There were no essential clinical changes. MNT decreased after the implantation procedure, returning to normal after 48 h. A foreign body response was observed by histopathologic evaluation up to 38 weeks. At 57 weeks, no polymer or fibrotic capsules were identified. SEM showed surface roughness suggesting a biodegradation process, with an increase in the median pore diameter. As in the histopathological evaluation, it was not possible to detect the polymer 57 weeks after implantation. PLA showed biocompatible degradation and these findings may contribute to future research in the biomedical area.

Antitrypanosomal Activity of Anthriscus Nemorosa Essential Oils and Combinations of Their Main Constituents.

This study aimed to investigate the susceptibility of Trypanosoma brucei to the Anthriscus nemorosa essential oils (EOs), isolated compounds from these oils, and artificial mixtures of the isolated compounds in their conventional and nanoencapsulated forms. The chemical composition of the essential oils from the aerial parts and roots of Anthriscus nemorosa, obtained from a wild population growing in central Italy, were analyzed by gas chromatography/mass spectrometry (GC/MS). In both cases, the predominant class of compounds was monoterpene hydrocarbons, which were more abundant in the EOs from the roots (81.5%) than the aerial parts (74.0%). The overall results of this work have shed light on the biological properties of A. nemorosa EO from aerial parts (EC50 = 1.17 μg/mL), farnesene (EC50 = 0.84 μg/mL), and artificial mixtures (Mix 3–5, EC50 in the range of 1.27 to 1.58 μg/mL) as relevant sources of antiprotozoal substances. Furthermore, the pool measurements of ADP (adenosine diphosphate) and NTPs (nucleoside triphosphates) in the cultivated bloodstream form of trypanosomes exposed to different concentrations of EOs showed a disturbed energy metabolism, as indicated by increased pools of ADP in comparison to ATP (adenosine triphosphate) and other NTPs. Ultimately, this study highlights the significant efficacy of A. nemorosa EO to develop long-lasting and effective antiprotozoal formulations, including nanoemulsions.

A long-lasting biological larvicide against the dengue vector mosquito Aedes albopictus.

Aedes albopictus is the primary vector of mosquito-borne diseases, including dengue and chikungunya, in China. The management of vector mosquitoes is the primary strategy for the control of such infectious diseases. The gravid Ae. albopictus prefers to skip-oviposit its eggs into different small water containers, and the management of these breeding places is critical for mosquito control. Bacillus thuringiensis subspecies Israelensis (Bti) is a useful biological larvicide, but the effective period of the currently available commercial product is relatively short. This study aimed to develop a long-lasting formulation of Bti to control the dengue vector mosquito Ae. albopictus. Water-soluble polyethylene glycols and water-insoluble hexadecanol were mixed with Bti to develop the long-lasting formulation Bti-BLOCK, based on the solid dispersion technique. The controlled release of Bti-BLOCK and its effect on Ae. albopictus were assayed in the laboratory and in the field. The results showed that Bti toxins were slowly released from Bti-BLOCK into the water and maintained at an effective dose for at least 6 months. Bti-BLOCK caused high mortality during the immature stage (>90%) and achieved full inhibition during pupation (100%). The efficacy lasted at least 12 weeks in the laboratory and 6 weeks in the field. Furthermore, we confirmed an 89% reduction in Ae. albopictus density and a reduction in the R0 of dengue to a low-risk level after 6 months of open-field interventions. We developed a long-lasting biological larvicide, Bti-BLOCK, which displayed very good efficacy in the control of the dengue vector mosquito Ae. albopictus.

Indoor spraying with chlorfenapyr (a pyrrole insecticide) provides residual control of pyrethroid-resistant malaria vectors in southern Benin

BackgroundNew classes of insecticides with novel modes of action, which can provide effective and prolonged control of insecticide-resistant malaria vector populations, are urgently needed for indoor residual spraying. Such insecticides can be included in a rotation plan to manage and prevent further development of resistance in mosquito vectors of malaria. Chlorfenapyr, a novel pyrrole insecticide with a unique mode of action, is being developed as a long-lasting IRS formulation.MethodsThe efficacy of several formulations of chlorfenapyr alone and as mixtures with alpha-cypermethrin were evaluated in an experimental hut trial against wild pyrethroid-resistant Anopheles gambiae sensu lato in Cové, Benin, in an attempt to identify the most effective and long-lasting formulations for IRS. The trial lasted 12 months. A comparison was made with alpha-cypermethrin and bendiocarb formulations. CDC bottle bioassays were performed to investigate cross-resistance to chlorfenapyr in the local vector population.ResultsMortality rates in World Health Organization (WHO) cylinder bioassays were < 5% with pyrethroids due to high levels of pyrethroid resistance, but > 95% with bendiocarb thus confirming susceptibility to carbamates in the vector population. CDC bottle bioassays showed no cross-resistance between pyrethroids and chlorfenapyr. Overall mortality of free-flying mosquitoes entering the experimental huts over the 12-month trial was 4% with alpha-cypermethrin and 12% with bendiocarb. The chlorfenapyr solo-formulations induced significantly higher levels of mortality (38–46%) compared to the bendiocarb (12% P < 0.001) and to the mixture formulations (18–22%, P < 0.05). The original Sylando 240SC formulation of chlorfenapyr was more efficacious than all other novel chlorfenapyr formulations tested. Bendiocarb induced > 80% mortality in the first month, but this declined sharply to < 20% by the third month while the mortality rates achieved with the chlorfenapyr formulations (38–46%) were persistent lasting 7–10 months. The mixtures induced significantly lower percentage mortality than chlorfenapyr-solo formulations. Wall cone bioassays only showed mortality rates that were consistent with chlorfenapyr IRS treated huts when the exposure time was increased to 2 h.ConclusionIndoor residual spraying with chlorfenapyr (Sylando® 240SC) provides moderate but prolonged control of pyrethroid-resistant malaria vectors compared to pyrethroid and bendiocarb IRS. Wall cone bioassays on chlorfenapyr-treated walls required longer exposure times of 2 h than the customary 30 min indicating that WHO guidelines on residual cone bioassays need to be more insecticide-specific.

PEGylated substance P augments therapeutic angiogenesis in diabetic critical limb ischemia

Substance P (SP) is a therapeutic peptide that has been widely used to induce angiogenesis and tissue regeneration. However, its therapeutic efficacy is often limited due to rapid degradation in vivo and a short half-life (˜1min) after systemic administration. In the present study, we chemically modified SP with polyethylene glycol (PEG) to generate long-lasting formulations with increased stability and extended retention time in vivo and evaluated their ability to enhance therapeutic angiogenesis. Compared to the unmodified SP, PEGylated SP (PEG-SP) exhibited significantly increased half-life in vivo (˜360-fold increase in normal mouse and ˜120-fold increase in diabetic mouse). Systemic injection of PEG-SP led to a marked increase in therapeutic efficacy and angiogenesis in diabetic hindlimb ischemia, as evident from the remarkable improvement in salvage of ischemic limb and recovery of blood perfusion in diabetic mice with limb ischemia. These formulations increased endogenous stem cell mobilization to the injured site and modulated the immune system to increase microvessel formation and reduce systemic inflammation. Importantly, PEGylation efficiently reduced the injection doses of SP while still maintaining its therapeutic efficacy. To conclude, our study demonstrated that PEG-SP formulations exhibited an improved in vivo pharmacokinetic profile with enhanced efficacy and clinically acceptable treatment regimens, thus acting as a potent therapeutic for diabetic ischemia and inflammation.

Systematic review of indoor residual spray efficacy and effectiveness against Plasmodium falciparum in Africa

Indoor residual spraying (IRS) is an important part of malaria control. There is a growing list of insecticide classes; pyrethroids remain the principal insecticide used in bednets but recently, novel non-pyrethroid IRS products, with contrasting impacts, have been introduced. There is an urgent need to better assess product efficacy to help decision makers choose effective and relevant tools for mosquito control. Here we use experimental hut trial data to characterise the entomological efficacy of widely-used, novel IRS insecticides. We quantify their impact against pyrethroid-resistant mosquitoes and use a Plasmodium falciparum transmission model to predict the public health impact of different IRS insecticides. We report that long-lasting IRS formulations substantially reduce malaria, though their benefit over cheaper, shorter-lived formulations depends on local factors including bednet use, seasonality, endemicity and pyrethroid resistance status of local mosquito populations. We provide a framework to help decision makers evaluate IRS product effectiveness.

Efficacy and persistence of long-lasting microbial larvicides against malaria vectors in western Kenya highlands

BackgroundChemical-based malaria vector control interventions are threatened by the development of insecticide resistance and changes in the behavior of the vectors, and thus require the development of alternative control methods. Bacterial-based larvicides have the potential to target both insecticide resistant and outdoor-biting mosquitoes and are safe to use in the environment. However, the currently available microbial larvicide formulations have a short duration of activity requiring frequent re-applications which increase the cost of control interventions. This study was designed to evaluate the efficacy and duration of activity of two long-lasting formulations of Bacillus thuringiensis var. israelensis (Bti) and Bacillus sphaericus (Bs) (LL3 and FourStar®) under field conditions in western Kenya highlands.MethodsThree sites were selected for this study in the highlands of western Kenya. In each site, one hundred anopheline larval habitats were selected and assigned to one of three arms: (i) LL3; (ii) FourStar®; and (iii) untreated control larval habitats. Four types of larval habitats were surveyed: abandoned gold mines, drainage canals, fish ponds and non-fish ponds. The habitats were sampled for mosquito larvae by using a standard dipping technique and collected larvae were recorded according to the larval stages of the different Anopheles species. The larvicides were applied at manufacturers’ recommended dosage of 1 briquette per 100 square feet. Both treatment and control habitats were sampled for mosquito larvae immediately before treatment (day 0), and then at 24 hours, 3 days and weekly post-treatment for 5 months.ResultsOverall larval density in treatment habitats was significantly reduced after application of the two microbial larvicides as compared to the control habitats. Post-intervention reduction in anopheline larval density by LL3 was 65, 71 and 84% for 1 day, 2 weeks and 4 weeks, respectively. FourStar® reduced anopheline larval density by 60, 66 and 80% for 1 day, 2 weeks and 4 weeks, respectively. Comparisons between the treatments reveal that LL3 and FourStar® were similar in efficacy. A higher reduction in Anopheles larval density was observed in the abandoned goldmines, while drainage canals had the lowest reduction.ConclusionsBoth LL3 and FourStar® long-lasting microbial larvicides were effective in reducing immature stages of An. gambiae complex and An. funestus group species, with significant reductions lasting for three months post-application.

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients

ABSTRACTIntroduction: Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company).Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i.e., basiliximab) in de novo kidney-transplant recipients. To achieve this, we searched for suitable articles through PubMed.Expert commentary: Phases-III and -IV studies comparing Advagraf®/Astagraf XL® to Prograf® in association with mycophenolate mofetil (more than 2,500 patients) have demonstrated overall similar results with regards to patient/graft survival, biopsy-proven acute-rejection rate, and renal function (p > 0.05). A randomized controlled study in maintenance kidney transplant patients has shown (using electronic monitoring) that, as compared to Prograf®, Advagraf® significantly improved adherence to medication. Other studies report that Advagraf®-treated patients receiving a mTOR-inhibitor agent (sirolimus or everolimus) instead of MMF: this was associated with good allograft outcome, and might also prevent late-onset cytomegalovirus infection. Advagraf®-based immunosuppression given to de novo kidney-transplant recipients, with or without an induction therapy, provided excellent results compared to Prograf®; it also increased patients’ adherence to treatment.

Targeting cattle for malaria elimination: marked reduction of Anopheles arabiensis survival for over six months using a slow-release ivermectin implant formulation

BackgroundMosquitoes that feed on animals can survive and mediate residual transmission of malaria even after most humans have been protected with insecticidal bednets or indoor residual sprays. Ivermectin is a widely-used drug for treating parasites of humans and animals that is also insecticidal, killing mosquitoes that feed on treated subjects. Mass administration of ivermectin to livestock could be particularly useful for tackling residual malaria transmission by zoophagic vectors that evade human-centred approaches. Ivermectin comes from a different chemical class to active ingredients currently used to treat bednets or spray houses, so it also has potential for mitigating against emergence of insecticide resistance. However, the duration of insecticidal activity obtained with ivermectin is critical to its effectiveness and affordability.ResultsA slow-release formulation for ivermectin was implanted into cattle, causing 40 weeks of increased mortality among Anopheles arabiensis that fed on them. For this zoophagic vector of residual malaria transmission across much of Africa, the proportion surviving three days after feeding (typical mean duration of a gonotrophic cycle in field populations) was approximately halved for 25 weeks.ConclusionsThis implantable ivermectin formulation delivers stable and sustained insecticidal activity for approximately 6 months. Residual malaria transmission by zoophagic vectors could be suppressed by targeting livestock with this long-lasting formulation, which would be impractical or unacceptable for mass treatment of human populations.