Combining organophosphate-treated wall linings and long-lasting insecticidal nets fails to provide additional control over long-lasting insecticidal nets alone against multiple insecticide-resistant <i>Anopheles gambiae</i> in Côte d’Ivoire: an experimental hut trial

&lt;b&gt;Background&lt;/b&gt; Insecticide-treated wall lining (ITWL) is a new concept in malaria vector control. Some &lt;i&gt;Anopheles gambiae&lt;/i&gt; populations in West Africa have developed resistance to all the main classes of insecticides. It needs to be demonstrated whether vector control can be improved or resistance managed when non-pyrethroid ITWL is used alone or together with long-lasting insecticidal nets (LLINs) against multiple insecticide-resistant vector populations.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Two experimental hut trials were carried out as proofs of concept to evaluate pirimiphos methyl (p-methyl)-treated plastic wall lining (WL) and net wall hangings (NWH) used alone and in combination with LLINs against multiple insecticide-resistant &lt;i&gt;An. Gambiae&lt;/i&gt; in Tiassalé, Côte d’Ivoire. Comparison was made to commercial deltamethrin WL and genotypes for &lt;i&gt;kdr&lt;/i&gt; and &lt;i&gt;ace-1R&lt;/i&gt; resistance were monitored.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The &lt;i&gt;kdr&lt;/i&gt; and &lt;i&gt;ace-1R&lt;/i&gt; allele frequencies were 0.83 and 0.44, respectively. &lt;i&gt;Anopheles gambiae&lt;/i&gt; surviving discriminating concentrations of deltamethrin and p-methyl in WHO resistance tests were 57 and 96%, respectively. Mortality of free-flying &lt;i&gt;An. Gambiae&lt;/i&gt; in huts with p-methyl WL and NWH (66 and 50%, respectively) was higher than with pyrethroid WL (32%; P &lt; 0.001). Mortality with LLIN was 63%. Mortality with the combination of LLIN plus p-methyl NWH (61%) or LLIN plus p-methyl WL (73%) did not significantly improve upon the LLIN alone or p-methyl WL or NWH alone. Mosquitoes bearing the &lt;i&gt;ace-1R&lt;/i&gt; were more likely to survive exposure to p-methyl WL and NWH. Selection of heterozygote and homozygote &lt;i&gt;ace-1R&lt;/i&gt; or &lt;i&gt;kdr&lt;/i&gt; genotypes was not less likely after exposure to combined LLIN and p-methyl treatments than to single p-methyl treatment. Blood-feeding rates were lower in huts with the pyrethroid LLIN (19%) than with p-methyl WL (72%) or NWH (76%); only LLIN contributed to personal protection.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Combining p-methyl WL or NWH with LLINs provided no improvement in &lt;i&gt;An. Gambiae&lt;/i&gt; control or personal protection over LLIN alone in southern Côte d’Ivoire; neither did the combination manage resistance. Additional resistance mechanisms to &lt;i&gt;kdr&lt;/i&gt; and &lt;i&gt;ace-1R&lt;/i&gt; probably contributed to the survival of pyrethroid and organophophate-resistant mosquitoes. The study demonstrates the challenge that malaria control programmes will face if resistance to multiple insecticides continues to spread.&lt;p&gt;&lt;/p&gt

Efficacy of ICON® Maxx in the laboratory and against insecticide-resistant Anopheles gambiae in central Côte d'Ivoire

ABSTRACT: BACKGROUND: Long-lasting treatment kits, designed to transform untreated nets into long-lasting insecticidal nets (LLINs), may facilitate high coverage with LLINs where non-treated nets are in place. In this study, the efficacy of ICON(R) Maxx (Syngenta) was evaluated under laboratory conditions and in an experimental hut trial in central Cote d'Ivoire, where Anopheles gambiae s.s. are resistant to pyrethroid insecticides. METHODS: In the laboratory, polyester and polyethylene net samples were treated with ICON(R) Maxx, washed up to 20 times and their efficacy determined in World Health Organization (WHO) cone assays against a susceptible laboratory An. gambiae s.s. colony. Over a 12-month period, the polyester nets were evaluated in a hut trial to determine mosquito deterrence, induced exophily, blood-feeding inhibition and mortality. RESULTS: In the laboratory, ICON(R) Maxx-treated polyethylene nets showed higher efficacy against pyrethroid-susceptible mosquitoes than polyester nets. After 20 washings, insecticidal efficacy in bioassays was 59.4% knockdown (KD) and 22.3% mortality for polyethylene, and 55.3% KD and 17.9% mortality for polyester nets. In experimental huts, treated nets showed strong deterrence, induced exophily and an over three-fold reduction in blood-fed mosquitoes. More than half (61.8%) of the mosquitoes entering the huts with treated nets were found dead the next morning despite high levels of KD resistance. After washing the treated nets, KD and mortality rates were close to or exceeded predefined WHO thresholds in cone bioassays. CONCLUSION: In contrast to previous laboratory investigation, ICON(R) Maxx-treated nets showed only moderate KD and mortality rates. However, under semi-field conditions, in an area where mosquitoes are resistant to pyrethroids, ICON(R) Maxx showed high deterrence, induced exophily and provided a significant reduction in blood-feeding rates; features that are likely to have a positive impact in reducing malaria transmission. The WHO cone test may not always be a good proxy for predicting product performance under field condition

Assessing the impact of the addition of pyriproxyfen on the durability of permethrin-treated bed nets in Burkina Faso: a compound-randomized controlled trial

Background Long-lasting insecticidal nets (LLINs) treated with pyrethroids are the foundation of malaria control in sub-Saharan Africa. Rising pyrethroid resistance in vectors, however, has driven the development of alternative net formulations. Here the durability of polyethylene nets with a novel combination of a pyrethroid, permethrin, and the insect juvenile hormone mimic, pyriproxyfen (PPF), compared to a standard permethrin LLIN, was assessed in rural Burkina Faso. Methods A compound-randomized controlled trial was completed in two villages. In one village 326 of the PPF-permethrin nets (Olyset Duo) and 327 standard LLINs (Olyset) were distributed to assess bioefficacy. In a second village, 170 PPF-permethrin nets and 376 LLINs were distributed to assess survivorship. Nets were followed at 6-monthly intervals for 3 years. Bioefficacy was assessed by exposing permethrin-susceptible and resistant Anopheles gambiae sensu lato mosquito strains to standard World Health Organization (WHO) cone and tunnel tests with impacts on fertility measured in the resistant strain. Insecticide content was measured using high-performance liquid chromatography. LLIN survivorship was recorded with a questionnaire and assessed by comparing the physical integrity using the proportionate hole index (pHI). Results The PPF-permethrin net met WHO bioefficacy criteria (≥ 80% mortality or ≥ 95% knockdown) for the first 18 months, compared to 6 months for the standard LLIN. Mean mosquito mortality for PPF-permethrin nets, across all time points, was 8.6% (CI 2.6–14.6%) higher than the standard LLIN. Fertility rates were reduced after PPF-permethrin net exposure at 1-month post distribution, but not later. Permethrin content of both types of nets remained within the target range of 20 g/kg ± 25% for 242/248 nets tested. The pyriproxyfen content of PPF-permethrin nets declined by 54%, from 10.4 g/kg (CI 10.2–10.6) to 4.7 g/kg (CI 3.5–6.0, p < 0.001) over 36 months. Net survivorship was poor, with only 13% of PPF-permethrin nets and 12% of LLINs still present in the original household after 36 months. There was no difference in the fabric integrity or survivorship between the two net types. Conclusion The PPF-permethrin net, Olyset Duo, met or exceeded the performance of the WHO-recommended standard LLIN (Olyset) in the current study but both net types failed the 3-year WHO bioefficacy criteria

Evaluation de l'efficacité d'insecticides de longue durée sur les vecteurs du paludisme en milieu semi-naturel au centre de la Côte d'Ivoire

Résumé Introduction : L'émergence et la propagation de la résistance des vecteurs du paludisme aux insecticides constituent un obstacle majeur à la lutte anti-vectorielle. Il est par conséquent nécessaire de développer et valider de nouveaux outils de lutte. Objectifs : Cette thèse de doctorat est axée autour de trois objectifs à savoir : (1) évaluer l’efficacité d’un produit de réimprégnation de longue durée des moustiquaires, ICON® Maxx ; (2) évaluer en cases expérimentales trois nouvelles formulations micro-encapsulées du pirimiphos-methyl, insecticide devant etre utilisées comme produits de pulvérisation intra-domiciliaire appartenant à la famille des organophosphorés, dans une zone de résistance aux pyréthrinoïdes ; et (3) étudier quelques aspects bioécologiques des populations d’Anopheles gambiae de la zone d’étude indispensables a la planification du type de méthode de lutte anti-vectorielle utilisée. Méthodes : En vue de déterminer les caractéristiques bioécologiques des populations d’An. gambiae, les moustiques adultes ont été capturés par 72 pièges lumineux, sur sujets humains pour un effort de 72 hommes-nuits de 18 heures à 06 heures, et par pulvérisation intradomiciliaire matinale de 60 chambres au pyrèthre. L’évaluation de ICON® Maxx a été réalisée au laboratoire et en case expérimentale. Au laboratoire, des échantillons de moustiquaires en polyester et en polyéthylène ont été traités, lavés 20 fois et leur efficacité estimée par des tests en cônes sur une colonie d’An. gambiae s.s. sensible élevée au laboratoire. Par la suite, sur une période de 12 mois, des moustiquaires traitées avec ICON® Maxx ont été évaluées en c.ases expérimentales. La formulation originale et les trois nouvelles formulations micro-encapsulées du pirimiphos-méthyl ont été testés et comparés à un témoin positif (ICON 10CS) et un témoin négatif (sans traitement). L’étude a été menée durant 12 mois en case expérimentale. Au total 24 cases expérimentales ont été utilisées, dont 12 construites en parpaing et l’autre moitié en terre battue. Résultats : Au total 10 312 et 7 662 moustiques adultes ont été capturés, respectivement à Abokro et Yaokoffikro. Dans les deux sites d’étude, le genre Anopheles était prépondérant. Les pièges lumineux ont été trois fois plus efficaces à Abokro qu’à Yaokoffikro. Dans les deux villages, les cycles d’agressivité des femelles d’An. gambiae s.s. ont évolué progressivement pour atteindre un pic entre minuit et 01 heure du matin. A Abokro, le comportement d’An. gambiae s.s. était fortement endophage et endophile tandis qu’à Yaokoffikro, le comportement était indépendant de celui des habitants des menages. Au laboratoire, après 20 lavages, le « knock-down » (KD) et le taux de mortalité étaient de 59,4 % et 22,3 % pour les moustiquaires en polyéthylène, et de 55,3 % et 17,9 % pour les moustiquaires en polyester. En case expérimentale, les moustiquaires traitées ont eu un effet significatif sur la dissuasion, l’exophilie induite, le taux de gorgement, et le taux de mortalité (> 60 %). Malgré le lavage des moustiquaires, le KD et le taux de mortalité lors des bioessais, sont restés proches ou excédaient les limites prédéfinies par l’OMS (> 80 %) Comparé aux autres Anopheles, le taux de mortalité dû aux différentes formulations du pirimiphos-méthyl a été plus élevé sur les populations d’An. gambiae résistants aux pyréthrinoïdes. L'efficacité la plus élevée a été obtenue avec la formulation pirimiphos-méthyl CS BM, le taux de mortalité est resté proche ou au-delà de 80 % jusqu’à la 28e semaine dans les cases construites en parpaing et jusqu’à la 19e semaine dans les constructions en terre battue. Ces résultats ont été confirmés par les tests en cône, le taux de mortalité est resté au-delà de 80 % jusqu’à la 30e semaine avec la formulation pirimiphos-méthyl CS BM. Il n’y a pas eu de différences significatives au niveau du taux de gorgement pour les An. gambiae résistants entre les deux types de construction et entre les trois formulations du pirimiphos-méthyl. Conclusion : La lutte anti-vectorielle nécessite d’avoir des connaissances sur la bio-écologie et le niveau de resistance des vecteurs aux insecticides. Ainsi l’étude des caractéristiques bioécologiques des vecteurs du paludisme dans notre zone d’étude permettra d’adopter des mesures de lutte adéquates. Les résultats du laboratoire sur les moustiquaires traitées avec ICON® Maxx ont montré des taux de mortalité et KD modérés. Cependant. Dans des conditions semi-naturelles, en zone de résistance aux pyréthrinoïdes, ICON® Maxx a montré des résultats satisfaisants. ICON® Maxx pourrait avoir un impact positif sur la réduction de la transmission du paludisme. La formulation pirimiphos-méthyl CS BM a montré une grande et stable efficacité sur les populations d’An. gambiae résistantes, particulièrement sur les murs en parpaing, et pourrait par conséquent être recommandé comme insecticide de traitement intra-domiciliaire. Il serait utile de déterminer les aspects entomologiques et parasitologiques dans un contexte de traitement à large échelle de ce nouvel insecticide.---------- Zusammenfassung: Hintergrund: Das zunehmende Auftreten und die Ausbreitung von Insektizid-resistenten Malaria-Vektoren ist eine der wichtigsten Einschränkungen in der Malaria-Vektorkontrolle. Deshalb ist es wichtig neue Insektizide zu entwickeln und zu testen. Ziele: Die vorliegende Dissertation verfolgte drei spezifische Ziele: (1) Beurteilung der Wirksamkeit des langlebigen Insektizids ICON® Maxx für Bettnetze; (2) Beurteilung von drei neuartigen, mikroverkapselten Formulierungen von pirimiphos-methyl zur Indoor Residual Spraying in Versuchshütten in einem durch Pyrethroid-Resistenzen gekennzeichneten Gebiet; und (3) Erforschung von bio-ökologischen Eigenschaften von Anopheles gambiae s.s, welche bei der Wahl der angemessenen Vektorkontrollmethode im Studiengebiet von Bedeutung sind. Methoden: In den Dörfern Abokro und Yaokoffikro wurden adulte Moskitos mit 72 Lichtfallen gefangen, während 72 Mann-Nächten zwischen 6 Uhr abends und 6 Uhr morgens auf Versuchspersonen gesammelt und früh morgens in 60 Versuchshütten durch Pyrethroid Spray flugunfähig gemacht („knock down“) und erfasst. Im Labor wurden Proben von Polyester- und Polyethylen-Netzen mit ICON® Maxx behandelt, bis zu 20 mal gewaschen und die verbleibende Wirksamkeit gegen eine anfällige An. gambiae s.s. Kolonie aus dem Labor mittels sogenannten „World Health Organization (WHO) cone assays“ ermittelt. Während 12 Monaten wurden zudem mit ICON® Maxx behandelte Netze in Versuchshütten bewertet. Die ursprüngliche Formulierung und drei neuartigen, mikroverkapselten Formulierungen des Organophosphat-Insektizids pirimiphos-methyl wurden beurteilt und mit einer positiven (ICON 10CS) und einer negativen Kontrollgruppe (keine Behandlung) verglichen. Insgesamt wurden 24 Versuchshütten verwendet, 12 aus Backsteinen und 12 aus „Banco“. Ergebnisse: Insgesamt wurden 10,312 adulte Moskitos in Abokro und 7,662 adulte Moskitos in Yaokoffikro gesammelt. Anopheles war die dominierende Gattung in beiden Orten. Lichtfallen waren dreimal effizienter in Abokro als in Yaokoffikro. An beiden Orten stieg die Beissrate von An. gambiae s.s. schrittweise an, bis zu einer Spitze zwischen Mitternacht und 1 Uhr morgens. In Abokro war das Verhalten von An. gambiae s.s. endophil und endophagisch, in Yaokoffikro unabhängig vom Haushalt. In den Bioassays im Labor entsprach die Wirksamkeit des Insektizids nach 20-maligem waschen einer Rate von 59.4 % Knock Down (KD) und einer Mortalität von 22.3 % für Polyethylen-Netze und einer Rate von 55.3% KD und einer Mortalität von 17.9 % für Polyester-Netze. In den Versuchshütten zeigten die behandelten Netze signifikante Auswirkungen auf die Abschreckung, die Exophilie, die Rate der Blutmahlzeiten und die Mortalität (>60%). Nach dem Waschen der behandelten Netze waren die Raten für KD und Mortalität nahe an oder über den vorgegebenen WHO Grenzwerten für „cone assays“ (>80%). Die durch die mikroverkapselten Formulierungen von pirimiphos-methyl herbeigeführten Mortalitätsraten waren höher in resistenten An. gambiae s.s. als in anderen Anopheles Spezies. Die Formulierungsvariante pirimiphos-methyl CS BM war am wirksamsten: Die Mortalität blieb über 80% während 28 Wochen in den Backstein-Versuchshütten und während 19 Wochen in den “Banco”-Versuchshütten. Diese Resultate wurden durch die Bioassays bestätigt: Wenn pirimiphos-methyl CS BM verwendet wurde blieb die 24-Stunden-Mortalität während 30 Wochen über dem vorgegebenen Grenzwert von 80%. Keine signifikanten Unterschiede in den mittleren Raten von Blutmahlzeiten von Pyrethroid-resistenten An. gambiae s.s. konnten in Bezug auf die zwei Arten von Versuchshütten und in Bezug auf die drei Varianten von pirimiphos-methyl festgestellt werden. Schlussfolgerung: Zur Vektorkontrolle braucht es Kenntnisse über die bio-ökologischen Eigenschaften und den Grad an Insektizidresistenz des entsprechenden Vektors. Dementsprechend leistet diese Studie einen Beitrag zur Anwendung von angemessenen Kontrollmassnahmen gegen Malaria-Vektoren. Im Labor wiesen durch ICON® Maxx behandelte Netze moderate KD- und Mortalitätsraten auf. Aber unter Quasi-Feldbedingungen in einem Gebiet mit Pyrethroid-resistenten Moskitos lieferte ICON® Maxx zufriedenstellende Ergebnisse, d.h. Eigenschaften, welche wahrscheinlich einen positiven Beitrag zur Reduktion der Malaria-Übertragung leisten können. Die Formulierung pirimiphos-methyl CS BM zeigte eine hohe, anhaltende Wirkung gegen resistente An. gambiae s.s., insbesondere an den Wänden in den Backstein-Versuchshütten. Es wird interessant zu sehen, wie sich dieses neue, nicht auf Pyrethroid basierende Mittel in grossangelegten Feldstudien auf entomologische und parasitologische Indikatoren auswirkt. Summary Introduction : The emergence and spread of resistance of malaria vectors to insecticides is a key limitation of tools for malaria vector control. Hence, there is a need to develop and validate new insecticides. Objectives : Three specific objectives were pursued in this PhD : (1) to assess the efficacy of a long-lasting insecticide for bed-net, ICON® Maxx; (2) to assess in experimental huts three novel micro-encapsulated formulations of pirimiphos-methyl formulations for indoor residual spraying in an pyrethroid resistance site; and (3) to investigate some bio-ecological characteristics of Anopheles gambiae s.s in the study area, important to choose the appropriate method against vectors. Méthods : In the villages of Abokro and Yaokoffikro, adult mosquitoes were captured with 72 light traps, collected on humans subjects at a rate of 72 man-night from 6 p.m. to 6 a.m., and knocked down using pyrethroid spray inside 60 sentinel houses in the early morning. In the laboratory, polyester and polyethylene net samples were treated with ICON® Maxx, washed up to 20 times and their efficacy determined in World Health Organization (WHO) cone assays against a susceptible laboratory An. gambiae s.s. colony. Over a 12-month period, nets treated with ICON® Maxx were evaluated in experimental huts. The original formulation and three novel micro-encapsulated formulations of the organophosphate insecticide, pirimiphos methyl were assessed and compare to positif control (ICON 10CS) and negative control (no treatment). A total of 24 experimental huts were used, 12 huts constructed with bricks and 12 ‘banco’ type huts. Résults : A total of 10,312 adult mosquitoes were collected in Abokro and 7,662 in Yaokoffikro. Anopheles was the dominant genus at both locations. Light traps were three times more efficient in Abokro than in Yaokoffikro. In both places, An. gambiae s.s. biting rates increased gradually up to a peak observed between midnight and 1 a.m. Abokro, An. gambiae s.s. was endophilic and endophagic, while in Yaokoffikro, this species was independant of the household. In the laboratory, after 20 washings, insecticidal efficacy in bioassays was 59.4 % knockdown (KD) and 22.3 % mortality for polyethylene, and 55.3% KD and 17.9 % mortality for polyester nets. In experimental huts, treated nets showed a significant effect on deterrence, induced exophily, blood-feeding rate and mortality (> 60 %). After washing the treated nets, KD and mortality rates were close to or exceeded predefined WHO thresholds in cone bioassays (> 80 %). The mortality rate induced by encapsulated formulations of pirimiphos-methyl was higher in resistant Anopheles gambiae s.s compared to other Anopheles species. Formulation variant pirimiphos-methyl CS BM was the most efficacious; mortality remained above 80% until 28 weeks in huts constructed with bricks and until 19 weeks in ‘banco’ type huts. These results were confirmed with bioassays; the 24-h mortality stayed over the preset threshold of 80% until 30 weeks when using pirimiphos-methyl CS BM. There were no significant differences in mean blood-feeding rates for pyrethroid and metabolic resistant An. gambiae s.s between the two types of huts and between the three variants of pirimiphos-methyl. Conclusion : The vector control need to have knowledge on bio-ecological characteristic and the resistance level to insecticides of vectors. So this study will allow to adopt appropriate control measures against malaria vectors. ICON® Maxx-treated nets showed moderate KD and mortality rates in laboratory. However, under semi-field conditions, in an area where mosquitoes are resistant to pyrethroids, ICON® Maxx showed satisfactory results; features that are likely to have a positive impact in reducing malaria transmission. The formulation pirimiphos-methyl CS BM showed a high and sustained efficacy against resistant An. gambiae, particularly on indoor walls of brick huts. It will be interesting to determine entomological and parasitological outcomes when deploying this novel non-pyrethroid in large-scale field trials

Combining organophosphate treated wall linings and long-lasting insecticidal nets for improved control of pyrethroid resistant Anopheles gambiae.

BACKGROUND: New approaches to delivering insecticides need to be developed to improve malaria vector control. Insecticidal durable wall lining (DL) and net wall hangings (NWH) are novel alternatives to indoor residual spraying which can be produced in a long-lasting format. Non-pyrethroid versions could be used in combination with long-lasting insecticidal nets for improved control and management of insecticide resistant vector populations. METHODS: Experimental hut trials were carried out in Valley du Kou, Burkina Faso to evaluate the efficacy of pirimiphos methyl treated DL and NWH either alone or in combination with LLINs against pyrethroid resistant Anopheles gambiae ss. Comparison was made with pyrethroid DL. Mosquitoes were genotyped for kdr and ace-1R resistant genes to investigate the insecticide resistance management potential of the combination. RESULTS: The overall kdr and ace-1(R) allele frequencies were 0.95 and 0.01 respectively. Mortality with p-methyl DL and NWH alone was higher than with pyrethroid DL alone (>95% vs 40%; P0.1). Combining p-methyl DL or NWH with LLINs reduced biting rates significantly (8-9%) compared to p-methyl DL and NWH alone (>40%) and killed all An gambiae that entered the huts. Mosquitoes bearing the ace-1(R) gene were more likely to survive in huts with p-methyl DL alone (p<0.03) whereas all resistant and susceptible genotypes were killed by the combination. CONCLUSION: P-methyl DL and NWH outperformed pyrethroid DL. Combining p-methyl DL and NWH with LLINs could provide significant epidemiological benefits against a vector population which is resistant to pyrethroids but susceptible to organophosphates. There was evidence that the single intervention would select kdr and ace-1(R) resistance genes and the combination intervention might select less strongly. Technology to bind organophosphates to plastic wall lining would be worth developing

Micro-encapsulated pirimiphos-methyl shows high insecticidal efficacy and long residual activity against pyrethroid-resistant malaria vectors in central Côte d'Ivoire

The wide-scale implementation of insecticide-treated nets and indoor residual spraying (IRS) has contributed to a considerable decrease of malaria morbidity and mortality in sub-Saharan Africa over the last decade. Due to increasing resistance in Anopheles gambiae sensu lato mosquitoes to dichlorodiphenyl trichloroethane (DDT) and pyrethroids, alternative insecticide formulations for IRS with long-lasting residual activity are required to sustain the gains obtained in most malaria-endemic countries.; Three experimental capsule suspension (CS) formulations of the organophosphate pirimiphos-methyl were evaluated together with Actellic 50 EC, an emulsifiable concentrate (EC) of pirimiphos-methyl, and the pyrethroid ICON 10 CS, a lambda-cyhalothrin CS formulation, in an experimental hut trial. The formulations were tested on two types of surfaces: mud and cement. The study with a 12-month follow-up was carried out in Bouaké, central Côte d'Ivoire, where An. gambiae mosquitoes show high levels of resistance against pyrethroids, DDT and carbamates. Residual activity was also tested in cone bioassays with the susceptible An. gambiae KISUMU strain.; One of the CS formulations of pirimiphos-methyl, CS BM, outperformed all other formulations tested. On cement surfaces, the odds ratios of overall insecticidal effect on An. gambiae s.l. of pirimiphos-methyl CS BM compared to Actellic 50 EC were 1.4 (95% confidence interval (CI): 1.2-1.7) for the first three months, 5.6 (95% CI: 4.4-7.2) for the second three months, and 3.6 (95% CI: 3.0-4.4) for the last six months of follow-up. On mud surfaces, the respective odds ratios were 2.5 (95% CI: 1.9-3.3), 3.5 (95% CI: 2.7-4.5), and 1.7 (95% CI: 1.4-2.2). On cement, the residual activity of pirimiphos-methyl CS BM measured using cone tests was similar to that of lambda-cyhalothrin and for both treatments, mortality of susceptible Kisumu laboratory strain was not significantly below the World Health Organization pre-set threshold of 80% for 30 weeks after spraying. Residual activity was shorter on mud surfaces, mortality falling below 80% on both pirimiphos-methyl CS BM and lambda-cyhalothrin treated surfaces at 25 weeks post-treatment.; CS formulations of pirimiphos-methyl are promising alternatives for IRS, as they demonstrate prolonged insecticidal effect and residual activity against malaria mosquitoes

Combining organophosphate-treated wall linings and long-lasting insecticidal nets fails to provide additional control over long-lasting insecticidal nets alone against multiple insecticide-resistant Anopheles gambiae in Côte d'Ivoire: an experimental hut trial.

BACKGROUND: Insecticide-treated wall lining (ITWL) is a new concept in malaria vector control. Some Anopheles gambiae populations in West Africa have developed resistance to all the main classes of insecticides. It needs to be demonstrated whether vector control can be improved or resistance managed when non-pyrethroid ITWL is used alone or together with long-lasting insecticidal nets (LLINs) against multiple insecticide-resistant vector populations. METHODS: Two experimental hut trials were carried out as proofs of concept to evaluate pirimiphos methyl (p-methyl)-treated plastic wall lining (WL) and net wall hangings (NWH) used alone and in combination with LLINs against multiple insecticide-resistant An. gambiae in Tiassalé, Côte d'Ivoire. Comparison was made to commercial deltamethrin WL and genotypes for kdr and ace-1R resistance were monitored. RESULTS: The kdr and ace-1R allele frequencies were 0.83 and 0.44, respectively. Anopheles gambiae surviving discriminating concentrations of deltamethrin and p-methyl in WHO resistance tests were 57 and 96%, respectively. Mortality of free-flying An. gambiae in huts with p-methyl WL and NWH (66 and 50%, respectively) was higher than with pyrethroid WL (32%; P<0.001). Mortality with LLIN was 63%. Mortality with the combination of LLIN plus p-methyl NWH (61%) or LLIN plus p-methyl WL (73%) did not significantly improve upon the LLIN alone or p-methyl WL or NWH alone. Mosquitoes bearing the ace-1R were more likely to survive exposure to p-methyl WL and NWH. Selection of heterozygote and homozygote ace-1R or kdr genotypes was not less likely after exposure to combined LLIN and p-methyl treatments than to single p-methyl treatment. Blood-feeding rates were lower in huts with the pyrethroid LLIN (19%) than with p-methyl WL (72%) or NWH (76%); only LLIN contributed to personal protection. CONCLUSIONS: Combining p-methyl WL or NWH with LLINs provided no improvement in An. gambiae control or personal protection over LLIN alone in southern Côte d'Ivoire; neither did the combination manage resistance. Additional resistance mechanisms to kdr and ace-1R probably contributed to the survival of pyrethroid and organophophate-resistant mosquitoes. The study demonstrates the challenge that malaria control programmes will face if resistance to multiple insecticides continues to spread

Combined use of long-lasting insecticidal nets and Bacillus thuringiensis israelensis larviciding, a promising integrated approach against malaria transmission in northern Côte d'Ivoire

Background: The recent reduction in malaria burden in Côte d’Ivoire is largely attributable to the use of long-lasting insecticidal nets (LLINs). However, this progress is threatened by insecticide resistance and behavioral changes in Anopheles gambiae sensu lato (s.l.) populations and residual malaria transmission, and complementary tools are required. Thus, this study aimed to assess the efficacy of the combined use of LLINs and Bacillus thuringiensis israelensis (Bti), in comparison with LLINs. Methods: This study was conducted in the health district of Korhogo, northern Côte d'Ivoire, within two study arms (LLIN + Bti arm and LLIN-only arm) from March 2019 to February 2020. In the LLIN + Bti arm, Anopheles larval habitats were treated every fortnight with Bti in addition to the use of LLINs. Mosquito larvae and adults were sampled and identified morphologically to genus and species using standard methods. The members of the An. gambiae complex were determined using a polymerase chain reaction technique. Plasmodium infection in An. gambiae s.l. and malaria incidence in local people was also assessed. Results: Overall, Anopheles spp. larval density was lower in the LLIN + Bti arm 0.61 [95% CI 0.41–0.81] larva/dip (l/dip) compared with the LLIN-only arm 3.97 [95% CI 3.56–4.38] l/dip (RR = 6.50; 95% CI 5.81–7.29; P < 0.001). The overall biting rate of An. gambiae s.l. was 0.59 [95% CI 0.43–0.75] biting/person/night in the LLIN + Bti arm against 2.97 [95% CI 2.02–3.93] biting/person/night in LLIN-only arm (P < 0.001). Anopheles gambiae s.l. was predominantly identified as An. gambiae sensu stricto (s.s.) (95.1%, n = 293), followed by Anopheles coluzzii (4.9%; n = 15). The human-blood index was 80.5% (n = 389) in study area. EIR was 1.36 infected bites/person/year (ib/p/y) in the LLIN + Bti arm against 47.71 ib/p/y in the LLIN-only arm. Malaria incidence dramatically declined from 291.8‰ (n = 765) to 111.4‰ (n = 292) in LLIN + Bti arm (P < 0.001). Conclusions: The combined use of LLINs with Bti significantly reduced the incidence of malaria. The LLINs and Bti duo could be a promising integrated approach for effective vector control of An. gambiae for elimination of malaria