Bioefficacy and durability of Olyset® Plus, a permethrin and piperonyl butoxide-treated insecticidal net in a 3-year long trial in Kenya

Background Long-lasting insecticide nets (LLINs) are a core malaria intervention. LLINs should retain efficacy against mosquito vectors for a minimum of three years. Efficacy and durability of Olyset® Plus, a permethrin and piperonyl butoxide (PBO) treated LLIN, was evaluated versus permethrin treated Olyset® Net. In the absence of WHO guidelines of how to evaluate PBO nets, and considering the manufacturer’s product claim, Olyset® Plus was evaluated as a pyrethroid LLIN. Methods This was a household randomized controlled trial in a malaria endemic rice cultivation zone of Kirinyaga County, Kenya between 2014 and 2017. Cone bioassays and tunnel tests were done against Anopheles gambiae Kisumu. The chemical content, fabric integrity and LLIN survivorship were monitored. Comparisons between nets were tested for significance using the Chi-square test. Exact binomial distribution with 95% confidence intervals (95% CI) was used for percentages. The WHO efficacy criteria used were ≥ 95% knockdown and/or ≥ 80% mortality rate in cone bioassays and ≥ 80% mortality and/or ≥ 90% blood-feeding inhibition in tunnel tests. Results At 36 months, Olyset® Plus lost 52% permethrin and 87% PBO content; Olyset® Net lost 24% permethrin. Over 80% of Olyset® Plus and Olyset® Net passed the WHO efficacy criteria for LLINs up to 18 and 12 months, respectively. At month 36, 91.2% Olyset® Plus and 86.4% Olyset® Net survived, while 72% and 63% developed at least one hole. The proportionate Hole Index (pHI) values representing nets in good, serviceable and torn condition were 49.6%, 27.1% and 23.2%, respectively for Olyset® Plus, and 44.9%, 32.8% and 22.2%, respectively for Olyset® Net but were not significantly different. Conclusions Olyset® Plus retained efficacy above or close to the WHO efficacy criteria for about 2 years than Olyset® Net (1–1.5 years). Both nets did not meet the 3-year WHO efficacy criteria, and showed little attrition, comparable physical durability and survivorship, with 50% of Olyset® Plus having good and serviceable condition after 3 years. Better community education on appropriate use and upkeep of LLINs is essential to ensure effectiveness of LLIN based malaria interventions. Graphical Abstract

Blepharoplasty in Extensive Lower Eyelid Eversion of Severe III–IV Degree

Purpose. To analyze the efficacy of the lower eyelid eversions surgical treatment.Patients and Methods. We have analyzed the outcomes of treating patients with severe lower eyelid eversion during 2013–2019 — 153 patients, 156 operations. The patients were divided into 4 groups: atonic and paralytic eversion (109 eyes), traumatic tearing of the lower eyelid (8 eyes), cicatricial ectropion (28 eyes) and mechanical ectropion (in tumors) of the lower eyelid (11 eyes). The following surgeries were performed: duplicature surgery by Willer; by Kuhnt-Szymanowski; resection of the framework structure of the lower eyelid with fixation to the eyelid ligaments; implantation of various materials based on the orbital margin; sling to the eyelid ligaments; free skin plasty; local flaps; excision of tumors with one-stage reconstructive plastics.Results. Postoperatively the improvement was observed in all cases. The lower eyelid eversion was eliminated. There were no any complications. The efficacy criteria was the level of the eyelid margin height with regards to limbus, absence or reduction of lagophthalmus. “Good” result — symmetrical width of the eyelid fissure, absence of lagophthalmus was achieved in 100 % of cases in groups IA and II, in 28.12 % — in group IB, in 71.43 % — in group III, in 63.63 % — in group IV. “Satisfactory” result — the difference in the eyelid fissure width was 1.0–2.0 mm, absence or reduction of lagophthalmus was achieved in 65.62 % of cases in group IB, in 21.43 % — in group III, in 27.28 % — in group IV. “Unsatisfactory” result — the difference in the eyelid fissure width was more than 2.0 mm, the presence of lagophthalmus was achieved in 6.25 % of cases in group IB, in 7.14 % — in group III, in 3.33 % — in group IV.Conclusions. When operating the lower eyelid eversion it is possible to achieve good result. The pathogenically based combined methods of surgical treatment are the most effective. In case of traumatic tearing of the lower eyelid, we need to restore the lacrimal duct. In cicatricial ectropion it is possible to achieve engraftment of the skin graft, elimination of eversion and lagophthalmus. In mechanical eversion (due to eyelid tumors) it is necessary to perform radioexcision of the neoplasm with a single-stage reconstructive plastic surgery of the eyelid.

Bio-efficacy and wash-fastness of a lambda-cyhalothrin long-lasting insecticide treatment kit (ICON® Maxx) against mosquitoes on various polymer materials

Background Long-lasting efficacy of insecticide-treated nets is a balance between adhesion, retention and migration of insecticide to the surface of netting fibres. ICON® Maxx is a twin-sachet ‘home-treatment kit’ of pyrethroid plus binding agent, recommended by the World Health Organization (WHO) for long-lasting, wash-fast treatment of polyester nets. While knitted polyester netting is widely used, fine woven polyethylene netting is increasingly available and nets made of cotton and nylon are common in Africa and Asia. It is important to investigate whether ICON Maxx is able to fulfill the WHO criteria of long-lasting treatment on a range of domestic fabrics to widen the scope for malaria protection. Methods This study was a controlled comparison of the bio-efficacy and wash-fastness of lambda-cyhalothrin CS, with or without binder, on nets made of cotton, polyethylene, nylon, dyed and undyed polyester. Evaluation compared an array of bioassays: WHO cone and cylinder, median time to knockdown and WHO tunnel tests using Anopheles mosquitoes. Chemical assay revealed further insight. Results ICON Maxx treated polyethylene and polyester netting met the WHO cone and tunnel test bio-efficacy criteria for LLIN after 20 standardized washes. Although nylon and cotton netting failed to meet the WHO cone and cylinder criteria, both materials passed the WHO tunnel test criterion of 80% mortality after 20 washes. All materials treated with standard lambda-cyhalothrin CS without binder failed to meet any of the WHO bio-efficacy criteria within 5 washes. Conclusion The bio-efficacy of ICON Maxx against mosquitoes on netting washed up to 20 times demonstrated wash durability on a range of synthetic polymer and natural fibres: polyester, polyethylene, nylon and cotton. This raises the prospect of making insecticide-binder kits into an effective approach for turning untreated nets, curtains, military clothing, blankets—and tents and tarpaulins as used in disasters and humanitarian emergencies—into effective malaria prevention products. It may provide a solution to the problem of reduced LLIN coverage between campaigns by converting commercially sourced untreated nets into LLINs through community or home treatment. It may also open the door to binding of non-pyrethroid insecticides to nets and textiles for control of pyrethroid resistant vectors.

Mesenchymal Stem Cell Injection in Crohn’s Disease Strictures: A Phase I–II Clinical Study

Background and Aim Mesenchymal stem cells [MSCs] have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for Crohn’s disease [CD] strictures. In this phase I–II pilot trial, we assessed safety and efficacy of local MSC injection to treat CD strictures. Methods CD patients with a short [less than 5 cm in length] non-passable stricture accessible by ileocolonoscopy were included. Allogenic bone-marrow derived MSCs were injected in the four quadrants of the stricture. Adverse events and clinical scores were evaluated at each follow-up visit and endoscopy and magnetic resonance enterography were performed at baseline, Week [W]12 and W48. The main judgement criterion for efficacy was the complete [defined by the ability to pass the ileocolonoscope] or partial [defined by a diameter increase] resolution of the stricture at W12. Second efficacy criteria included assessment of the stricture at W48 and evolution of clinical scores at W12 and W48. Results We performed 11 MSC injections in 10 CD patients [three primary and seven anastomotic strictures; one stricture injected twice]. MSC injections were well tolerated but four hospitalisations for occlusion were reported. At W12, five patients presented a complete or partial resolution of the stricture [two complete and three partial]. Seven patients were re-evaluated at W48 [one dilated, one operated, and one lost to follow-up] and four patients had a complete resolution. The evolution of clinical scores between W0, W12, and W48 was not statistically significant. Conclusions MSCs injection in CD stricture was well tolerated and may offer a benefit.

Effectiveness of a Long-Lasting Insecticide Treatment Kit (ICON® Maxx) for Polyester Nets Over Three Years of Household use: A WHO Phase III Trial in Tanzania

BackgroundICON® Maxx (Syngenta) is an insecticide treatment kit of pyrethroid and binding agent for long-lasting treatment of mosquito nets. Interim recommendation for use on nets was granted by WHO after successful evaluation in experimental huts following multiple washes. A full WHO recommendation is contingent upon demonstration of continued bio-efficacy after 3 years of use. MethodsA household-randomised prospective study design was used to assess ICON Maxx treated nets over 3 years in north-eastern Tanzania. Conventional treated nets (with lambda-cyhalothrin but without binder) served as a positive control. At 6-monthly intervals, cross-sectional household surveys monitored net use and physical integrity, while cone and tunnel tests assessed insecticidal efficacy. Pyrethroid content was determined after 12 and 36 months. A parallel cohort of nets was monitored annually for evidence of net deterioration and attrition. ResultsAfter 12 months’ use, 97% of ICON Maxx treated nets but only 67% of CTN passed the WHO efficacy threshold for insecticidal durability (>80% mortality in cone or tunnel or 90% feeding inhibition in tunnel). After 24- and 36-months use, 67% and 26% of ICON Maxx treated nets met the cone criteria respectively and over 90% met the combined cone and tunnel criteria. Lambda-cyhalothrin content after 36 months was 17% (15.8 ± 4.3 mg/m2) of initial content. ICON Maxx nets were used year-round and washed approximately 4 times per year. In cross-sectional survey after 36 months the average number of holes was 20 and hole index was 740 cm2 per net. Cohort nets had fewer holes and smaller hole index than cross-sectional nets. However, only 15% (40/264) of cohort nets were not lost to follow-up or not worn out after 36 months.ConclusionsBecause more than 80% of nets met the WHO efficacy criteria after 36 months use, ICON Maxx was granted WHO full recommendation. Cross-sectional and cohort surveys were complementary and gave a fuller understanding of net durability. To improve net usage and retention, stronger incentives and health messaging should be introduced in WHO LLIN longitudinal trials. Untreated polyester nets may be made long-lastingly insecticidal in Africa through simple household treatment using ICON Maxx pyrethroid-binder kits.

Bio-efficacy and Wash-fastness of a Lamda-cyhalothrin Long-lasting Insecticide Treatment Kit (ICON® Maxx) Against Mosquitoes on Various Polymer Materials

BackgroundLong-lasting efficacy of insecticide treated nets is a balance between adhesion, retention and migration of insecticide to the surface of netting fibres. ICON® Maxx is a twin-sachet ‘home-treatment kit’ of pyrethroid plus binding agent, recommended by the World Health Organization for long-lasting, wash-fast treatment of polyester nets. While knitted polyester netting is widely used, fine woven polyethylene netting is increasingly available and nets made of cotton and nylon are common in Africa and Asia. It is important to investigate whether ICON Maxx is able to fulfill the WHO criteria of long-lasting treatment on a range of domestic fabrics to widen the scope for malaria protection.Method This study was a controlled comparison of the bio-efficacy and wash-fastness of lambda-cyhalothrin CS, with or without binder, on nets made of cotton, polyethylene, nylon, dyed and undyed polyester. Evaluation compared an array of bioassays, WHO cone and cylinder, median time to knockdown and WHO tunnel tests using Anopheles mosquitoes. Chemical assay revealed further insight. ResultsICON Maxx treated polyethylene and polyester netting met the WHO cone and tunnel test bio-efficacy criteria for LLIN after 20 standardized washes. Although nylon and cotton netting failed to meet the WHO cone and cylinder criteria, both materials passed the WHO tunnel test criterion of 80% mortality after 20 washes. All materials treated with standard lambda-cyhalothrin CS without binder failed to meet any of the WHO bio-efficacy criteria within 5 washes. ConclusionThe bio-efficacy of ICON Maxx against mosquitoes on netting washed up to 20 times demonstrated wash durability on a range of synthetic polymer and natural fibres: polyester, polyethylene, nylon and cotton. This raises the prospect of making the insecticide-binder kit into an effective approach for turning untreated nets, curtains, military clothing, blankets - and tents and tarpaulins as used in disasters and humanitarian emergencies - into effective malaria prevention products. It may provide a solution to the problem of reduced LLIN coverage between campaigns by converting commercially sourced untreated nets into LLINs through community or home treatment. It may also open the door to binding of non-pyrethroid insecticides to nets and textiles for control of pyrethroid resistant vectors.

“Can nature heal and be a possible remedy for the management of Covid- 19?”

Abstract:: The Covid-19 pandemic has become a major challenge for health care professionals and researchers all over the world. The discovery and development of new drugs require time for passing the quality, safety, and efficacy criteria. Hence the only available option is to rely on herbal or natural remedies as well as other existing ones. Nature has its healing power and has the remedy for all the ailments from which life on earth is struggling. For this pandemic situation also, nature should have created a remedy but finding a loophole is in the hands of our researchers. In this hypothesis, a novel combination strategy is introduced with the existing drugs such as hydroxychloroquine and flavonoid in a volatile liquid-based Nanoformulation incorporated into an inhaler as a possible remedy for the management of coronavirus infection. The synergistic activity of this combination shall pave the way for an effective therapeutic strategy for the treatment of COVID- 19 symptoms.

Scientometric analysis of chemotherapy of canine leishmaniasis (2000–2020)

Background Zoonotic visceral leishmaniasis by Leishmania infantum is a first-order pathology in canine veterinary clinics in endemic areas. Moreover, canine infections are considered the main reservoir for human disease; despite their importance in the control of the disease within a One Health approach, no scientometric study has been published. Aims of the study included analyzing the impact of canine leishmaniasis (CanL) on the scientific literature, drugs or combinations used, trends in the period from 2000 to 2020 and efficacy criteria employed. Methods A Web of Science (WOS)-based analysis of publications on CanL and chemotherapy of the disease in the period 2000–2020 was carried out using a stepwise methodology. Data were analyzed by year, geographical origin, chemical groups, drugs and combinations, and efficacy criteria. Results Reports on CanL (n = 3324) represented < 16% of all publications on leishmaniasis (n = 20,968), and of these around 18% (n = 596) were related to chemotherapy. Publication records on CanL followed the distribution of the infection by L. infantum in endemic areas although Mediterranean countries were overrepresented in the reports on chemotherapy of CanL. Publications on the main antileishmanial drugs used in clinical practice showed a sustained tendency in the period analyzed. Pentavalent antimonials (SbV), alone or in combination with allopurinol, represented > 50% of all publications on chemotherapy of CanL despite the availability of more recently marketed drugs. Conclusions Chemotherapy of CanL still relies on SbV and combinations and to a lesser extent on miltefosine (MIL). Reports on chemotherapy are scarce and mostly publicly funded, and the variability of experimental conditions hampers the direct comparison of the efficacy of drugs, combinations and schedules. The vast majority of reports on efficacy do not include any information on supportive therapy; this reduces the actual value of the studies if intended for the practical management of the disease. Complete reports on the chemotherapy (etiological + symptomatic) would add value to the trials performed.

Сonfirmatory study of the efficacy and tolerability of trifluridine/tipiracil (TAS-102) therapy in the Russian population with chemorefractory metastatic colorectal cancer

Introduction. Trifluridine/Tipiracil (FTD/TPI) is a new chemotherapeutic drug approved in more than 60 countries for use in patients with metastatic colorectal cancer who have registered progression or intolerance to treatment with fluoropyrimidines, oxaliplatin and irinotecan, anti-VEGRand anti-EGFR-targeted agents. This study evaluated for the first time the effectiveness and tolerability of FTD/TPI therapy in the Russian patient population.Materials and methods. A confirmatory open-label single-arm non-randomized trial was conducted in 2 clinical centres in Russia. The main criteria for inclusion were: conduction of at least the 2nd line of standard systemic therapy for metastatic colon adenocarcinoma. The primary efficacy criteria were: 2-month progression-free survival; secondary – median progressionfree survival, disease control frequency, safety assessment, overall survival. Research number: NCT03274882.Results. A total of 26 patients were included in the study; the median age was 60.5 years (30 to 78); 19 (73%) women; and 4 patients with ECOG 0 and 22 – with ECOG 1. All patients were previously treated with the inclusion of oxaliplatin, irinotecan, fluoropyrimidines, 21 (81%) – bevacizumab, 6 (23%) – anti-EGFR antibodies, and 2 (7.7%) – regorafenib. The median for treatment courses was 4 (1–21), 11 (42.3%) patients were treated for 6 months or more. The two-month progression-free survival rate was 52% with a median progreesion-free survival rate of 4 months (95% CI 1.8–7.4 months). The median of total survival rate was 11 months (95% CI 5,2–16,8 months). Disease control was achieved in 60%. Neutropenia, nausea, vomiting, anemia, weakness prevailed among undesirable events associated with treatment (≥5 patients). The majority of complications were of the 1st–2nd degree. Among the undesirable events of the 3rd–4th degree, neutropenia was more common, while in 3 patients febrile neutropenia of the 3rd degree was registered.Conclusions. In the Russian population of patients with colorectal chemorefractory cancer, the drug FTD/TPI (TAS-102) shows efficacy and tolerability comparable to the RECOURSE registration study.

Scientometric analysis of chemotherapy of canine leishmaniasis (2000-2020)

Background: Zoonotic visceral leishmaniasis by Leishmania infantum is a first order pathology in veterinary clinics of dogs in endemic areas. Moreover, canine infections are considered the main reservoir for human disease; despite their importance in the control of the disease within a One Health approach no scientometric study has been published. Aims of the study included the impact of canine leishmaniasis (CanL) on scientific literature, drugs or combinations used, trends in the period from 2000-2020 and efficacy criteria employed. Methods: A Web of Science (WOS) based analysis of publications on CanL and chemotherapy of the disease in the period 2000-2020 was carried out using a stepwise methodology. Data were analyzed by year, geographical origin, chemical groups, drugs and combinations, and efficacy criteria. Results: Reports on CanL (n=3,324) represented less than 16% of all publications on leishmaniasis (n=20,968) and from these around 18% (n=596) were related to chemotherapy. Publication records on CanL followed the distribution of the infection by L.infantum in endemic areas although Mediterranean countries were overrepresented in the reports on chemotherapy of CanL. Publications on the main antileishmanial drugs used in clinical practice showed a sustained tendency in the period analyzed. Pentavalent antimonials (Sb V ), alone or in combination with allopurinol, represented over 50% of all publications on chemotherapy of CanL despite the availability of more recently marketed drugs. Conclusions: Chemotherapy of CanL still relies on Sb V and combinations and to a lesser extent on miltefosine (MIL). Reports on chemotherapy are scarce, mostly publicly funded and the variability of experimental conditions hampers the direct comparison of the efficacy of drugs, combinations and schedules. The vast majority of reports on efficacy do not include any information on supportive therapy; this reduces the actual value of the studies if intended for the practical management of the disease. Complete reports of the chemotherapy (etiological + symptomatic) would add value to the trials performed.