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Effects of pyrethroid resistance on the cost effectiveness of a mass distribution of long-lasting insecticidal nets: a modelling study.

ABSTRACT:

Background

The effectiveness of insecticide-treated nets in preventing malaria is threatened by developing resistance against pyrethroids. Little is known about how strongly this affects the effectiveness of vector control programmes.

Methods

Data from experimental hut studies on the effects of long-lasting, insecticidal nets (LLINs) on nine anopheline mosquito populations, with varying levels of mortality in World Health Organization susceptibility tests, were used to parameterize malaria models. Both simple static models predicting population-level insecticidal effectiveness and protection against blood feeding, and complex dynamic epidemiological models, where LLINs decayed over time, were used. The epidemiological models, implemented in OpenMalaria, were employed to study the impact of a single mass distribution of LLINs on malaria, both in terms of episodes prevented during the effective lifetime of the batch of LLINs, and in terms of net health benefits (NHB) expressed in disability-adjusted life years (DALYs) averted during that period, depending on net type (standard pyrethroid-only LLIN or pyrethroid-piperonyl butoxide combination LLIN), resistance status, coverage and pre-intervention transmission level.

Results

There were strong positive correlations between insecticide susceptibility status and predicted population level insecticidal effectiveness of and protection against blood feeding by LLIN intervention programmes. With the most resistant mosquito population, the LLIN mass distribution averted up to about 40% fewer episodes and DALYs during the effective lifetime of the batch than with fully susceptible populations. However, cost effectiveness of LLINs was more sensitive to the pre-intervention transmission level and coverage than to susceptibility status. For four out of the six Anopheles gambiae sensu lato populations where direct comparisons between standard LLINs and combination LLINs were possible, combination nets were more cost effective, despite being more expensive. With one resistant population, both net types were equally effective, and with one of the two susceptible populations, standard LLINs were more cost effective.

Conclusion

Despite being less effective when compared to areas with susceptible mosquito populations, standard and combination LLINs are likely to (still) be cost effective against malaria even in areas with strong pyrethroid resistance. Combination nets are likely to be more cost effective than standard nets in areas with resistant mosquito populations.

SUBMITTER: Briet OJ

PROVIDER: S-EPMC3598792 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Effects of pyrethroid resistance on the cost effectiveness of a mass distribution of long-lasting insecticidal nets: a modelling study.

Briët Olivier J T OJ Penny Melissa A MA Hardy Diggory D Awolola Taiwo S TS Van Bortel Wim W Corbel Vincent V Dabiré Roch K RK Etang Josiane J Koudou Benjamin G BG Tungu Patrick K PK Chitnis Nakul N

Malaria journal 20130225

<h4>Background</h4>The effectiveness of insecticide-treated nets in preventing malaria is threatened by developing resistance against pyrethroids. Little is known about how strongly this affects the effectiveness of vector control programmes.<h4>Methods</h4>Data from experimental hut studies on the effects of long-lasting, insecticidal nets (LLINs) on nine anopheline mosquito populations, with varying levels of mortality in World Health Organization susceptibility tests, were used to parameteriz ...[more]

PMID: 23442575

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Project description:BackgroundThe effectiveness of long-lasting, insecticidal nets (LLINs) in preventing malaria is threatened by the changing biting behaviour of mosquitoes, from nocturnal and endophagic to crepuscular and exophagic, and by their increasing resistance to insecticides.MethodsUsing epidemiological stochastic simulation models, we studied the impact of a mass LLIN distribution on Plasmodium falciparum malaria. Specifically, we looked at impact in terms of episodes prevented during the effective life of the batch and in terms of net health benefits (NHB) expressed in disability adjusted life years (DALYs) averted, depending on biting behaviour, resistance (as measured in experimental hut studies), and on pre-intervention transmission levels.ResultsResults were very sensitive to assumptions about the probabilistic nature of host searching behaviour. With a shift towards crepuscular biting, under the assumption that individual mosquitoes repeat their behaviour each gonotrophic cycle, LLIN effectiveness was far less than when individual mosquitoes were assumed to vary their behaviour between gonotrophic cycles. LLIN effectiveness was equally sensitive to variations in host-searching behaviour (if repeated) and to variations in resistance. LLIN effectiveness was most sensitive to pre-intervention transmission level, with LLINs being least effective at both very low and very high transmission levels, and most effective at around four infectious bites per adult per year. A single LLIN distribution round remained cost effective, except in transmission settings with a pre-intervention inoculation rate of over 128 bites per year and with resistant mosquitoes that displayed a high proportion (over 40%) of determined crepuscular host searching, where some model variants showed negative NHB.ConclusionsShifts towards crepuscular host searching behaviour can be as important in reducing LLIN effectiveness and cost effectiveness as resistance to pyrethroids. As resistance to insecticides is likely to slow down the development of behavioural resistance and vice versa, the two types of resistance are unlikely to occur within the same mosquito population. LLINs are likely cost effective interventions against malaria, even in areas with strong resistance to pyrethroids or where a large proportion of host-mosquito contact occurs during times when LLIN users are not under their nets.

Project description:BackgroundStagnating funds for malaria control have spurred interest in the question of how to sustain the gains of recent successes with long-lasting insecticidal nets (LLINs) and improved case management (CM). This simulation study examined the malaria transmission and disease dynamics in scenarios with sustained LLINs and CM interventions and tried to determine optimal LLIN distribution rates. The effects of abruptly halting LLIN distribution were also examined.MethodsDynamic simulations of malaria in humans and mosquitoes were run on the OpenMalaria platform, using stochastic individual-based simulation models. LLINs were distributed in a range of transmission settings, with varying CM coverage levels.ResultsIn the short-term, LLINs were beneficial over the entire transmission spectrum, reducing both transmission and disease burden. In the long-term, repeated distributions sustainably reduced transmission in all settings. However, because of the resulting reduction in acquired immunity in the population, the malaria disease burden, after initially being reduced, gradually increased and eventually stabilized at a new level. This new level was higher than the pre-intervention level in previously high transmission settings, if there is a maximum disease burden in the relationship between transmission and disease burden at intermediate transmission levels. This result could lead one to conclude that sustained LLIN distribution might not be cost-effective in high transmission settings in the long term. However, improved CM rendered LLINs more cost-effective in higher transmission settings than in those without improved CM and the majority of the African population lives in areas where CM and LLINs are sustainably combined. The effects of changes in LLIN distribution rate on cost-effectiveness were relatively small compared to the effects of changes in transmission setting and CM. Abruptly halting LLIN distribution led to temporary morbidity peaks, which were particularly large in low to intermediate transmission settings.ConclusionsThis study reaffirms the importance of context specific intervention planning. Intervention planning must include combinations of malaria vector control and CM, and must consider both the pre-intervention transmission level and the intervention history to account for the loss of immunity and the potential for rebounds in disease burden.

Project description:BackgroundNigeria carries the greatest malaria burden among countries in the world. As part of the National Malaria Control Strategic Plan, free long-lasting insecticidal nets (LLINs) were distributed in 14 states of Nigeria through mass campaigns led by different organizations (the World Bank, UNICEF, or the Global Fund) between May 2009 and August 2010. The objective of this study was to evaluate the association between LLIN distribution campaigns and child malaria in Nigeria.MethodsData were from the Nigeria Malaria Indicator Survey which was carried out from October to December 2010 on a nationally representative sample of households. Participants were women aged 15-49 years and their children aged less than five years (N?=?4082). The main outcome measure was the presence or absence of malaria parasites in blood samples of children (6-59 months).ResultsCompared with children living in communities with no campaigns, those in the campaign areas were less likely to test positive for malaria after adjusting for geographic locations, community- and individual-level characteristics including child-level use of insecticide-treated nets (ITNs). The protective effects were statistically significant for the World Bank Booster Project areas (OR?=?0.18, 95% CI?=?0.04-0.73) but did not reach statistical significance for other campaign areas. Results also showed that community-level wealth (OR?=?0.51, 95% CI?=?0.34-0.76), community-level maternal knowledge regarding malaria prevention (OR?=?0.70, 95% CI?=?0.50-0.97), and child-level use of ITNs (OR?=?0.79, 95% CI?=?0.63-0.99) were negatively associated with child malaria.ConclusionsThe observed protective effects on child malaria of these campaigns (statistically significant in the World Bank Booster Project areas and non-significant in the other areas) need to be corroborated by future effectiveness studies. Results also show that improving community-level maternal knowledge through appropriate channels might be helpful in preventing child malaria in Nigeria.

Project description:BackgroundWhere resources are available, non-pyrethroid IRS can be deployed to complement standard pyrethroid LLINs with the aim of achieving improved vector control and managing insecticide resistance. The impact of the combination may however depend on the type of IRS insecticide deployed. Studies comparing combinations of pyrethroid LLINs with different types of non-pyrethroid IRS products will be necessary for decision making.MethodsThe efficacy of combining a standard pyrethroid LLIN (DuraNet®) with IRS insecticides from three chemical classes (bendiocarb, chlorfenapyr and pirimiphos-methyl CS) was evaluated in an experimental hut trial against wild pyrethroid-resistant Anopheles gambiae s.l. in Cové, Benin. The combinations were also compared to each intervention alone. WHO cylinder and CDC bottle bioassays were performed to assess susceptibility of the local An. gambiae s.l. vector population at the Cové hut site to insecticides used in the combinations.ResultsSusceptibility bioassays revealed that the vector population at Cové, was resistant to pyrethroids (<20% mortality) but susceptible to carbamates, chlorfenapyr and organophosphates (≥98% mortality). Mortality of wild free-flying pyrethroid resistant An. gambiae s.l. entering the hut with the untreated net control (4%) did not differ significantly from DuraNet® alone (8%, p = 0.169). Pirimiphos-methyl CS IRS induced the highest mortality both on its own (85%) and in combination with DuraNet® (81%). Mortality with the DuraNet® + chlorfenapyr IRS combination was significantly higher than each intervention alone (46% vs. 33% and 8%, p<0.05) demonstrating an additive effect. The DuraNet® + bendiocarb IRS combination induced significantly lower mortality compared to the other combinations (32%, p<0.05). Blood-feeding inhibition was very low with the IRS treatments alone (3-5%) but increased significantly when they were combined with DuraNet® (61% - 71%, p<0.05). Blood-feeding rates in the combinations were similar to the net alone. Adding bendiocarb IRS to DuraNet® induced significantly lower levels of mosquito feeding compared to adding chlorfenapyr IRS (28% vs. 37%, p = 0.015).ConclusionsAdding non-pyrethroid IRS to standard pyrethroid-only LLINs against a pyrethroid-resistant vector population which is susceptible to the IRS insecticide, can provide higher levels of vector mosquito control compared to the pyrethroid net alone or IRS alone. Adding pirimiphos-methyl CS IRS may provide substantial improvements in vector control while adding chlorfenapyr IRS can demonstrate an additive effect relative to both interventions alone. Adding bendiocarb IRS may show limited enhancements in vector control owing to its short residual effect.

Project description:Malaria control today is threatened by widespread insecticide resistance in vector populations. The World Health Organization (WHO) recommends the use of a mixture of unrelated insecticides for indoor residual spraying (IRS) and long-lasting insecticidal nets (LNs) or as a combination of interventions for improved vector control and insecticide resistance management. Studies investigating the efficacy of these different strategies are necessary.The efficacy of Interceptor® G2 LN, a newly developed LN treated with a mixture of chlorfenapyr (a pyrrole) and alpha-cypermethrin (a pyrethroid), was compared to a combined chlorfenapyr IRS and Interceptor® LN (a standard alpha-cypermethrin LN) intervention in experimental huts in Cove Southern Benin, against wild, free-flying, pyrethroid-resistant Anopheles gambiae s.l. A direct comparison was also made with a pyrethroid-only net (Interceptor® LN) alone and chorfenapyr IRS alone.WHO resistance bioassays performed during the trial demonstrated a pyrethroid resistance frequency of >90% in the wild An. gambiae s.l. from the Cove hut site. Mortality in the control (untreated net) hut was 5%. Mortality with Interceptor® LN (24%) was lower than with chlorfenapyr IRS alone (59%, P < 0.001). The combined Interceptor® LN and chlorfenapyr IRS intervention and the mixture net (Interceptor® G2 LN) provided significantly higher mortality rates (73 and 76%, respectively) and these did not differ significantly between both treatments (P = 0.15). Interceptor LN induced 46% blood-feeding inhibition compared to the control untreated net, while chlorfenapyr IRS alone provided none. Both mixture/combination strategies also induced substantial levels of blood-feeding inhibition (38% with combined interventions and 30% with Interceptor® G2 LN). A similar trend of improved mortality of pyrethroid-resistant An. gambiae s.l. from Cove was observed with Interceptor® G2 LN (79%) compared to Interceptor LN (42%, P < 0.001) in WHO tunnel tests.The use of chlorfenapyr and alpha-cypermethrin together as a mixture on nets (Interceptor® G2 LN) or a combined chlorfenapyr IRS and pyrethroid LN intervention provides improved control of pyrethroid-resistant malaria vectors by inducing significantly higher levels of mortality through the chlorfenapyr component and providing personal protection through the pyrethroid component. Both strategies are comparable in their potential to improve the control of malaria transmitted by pyrethroid resistant mosquito vectors.

Project description:BackgroundLong-lasting insecticidal nets (LLINs) are the most widely used malaria prevention and control intervention in Africa. However, their effectiveness may vary depending on their local geographic coverage, ownership and use at household level. This study aimed at assessing LLINs ownership and use following mass distribution campaign in western Kenya.MethodsA cross-sectional study was conducted in November 2017. A total of 160 households were randomly selected from 16 villages. Structured questionnaires were used to collect data on households' knowledge on malaria, LLINs ownership, utilization and their perceived benefits. Data was analyzed using IBM Statistical Package for Social Sciences (SPSS) version 21 for windows. Variables were presented as proportions and associations between variables tested using Pearson's chi-square test.ResultsMalaria was reported to be the most frequently occurring disease (87.5%) in the area. Children under 5 years of age were reported to be at higher risks of malaria infection (28.6%). Around 31% of the respondents reported to have at least one member of the household sick with malaria a week before the interview. Commonly cited signs and symptoms of malaria were; fever (24.1%), headache (17.7%), vomiting (14.5%) feeling cold (12.6%) and loss of appetite (10%). There were 382 reported LLINs among 753 occupants in the 160 households surveyed. The average LLIN ownership was 2.4 nets per household and 1.97 persons per LLIN. Among the surveyed households, 96.9% owned at least one LLIN and 64.1% owned at least one LLIN for every two people. Among those who owned LLINs, 98.1% reported using them the previous night. Ownership per household ranged from 0 to 6 with a mean of 2.39. More than three quarter of the nets were acquired through free mass distribution campaigns and 80% were acquired less than 6 months prior to the survey.ConclusionDespite high net coverage and use, a number of households experienced malaria episodes in the study area. There is need to investigate the likelihood of outdoor malaria transmission and assess the physical integrity of the existing LLINs and their insecticidal effectiveness in protecting household members against malaria.

Project description:BackgroundBetween May 2010 and October 2012, approximately 12.5 million long-lasting insecticidal nets (LLINs) were distributed through a national universal mass distribution campaign in Ghana. The campaign included pre-registration of persons and sleeping places, door-to-door distribution of LLINs with 'hang-up' activities by volunteers and post-distribution 'keep-up' behaviour change communication activities. Hang-up activities were included to encourage high and sustained use.MethodsThe cost and cost-effectiveness of the LLIN Campaign were evaluated using a before-after design in three regions: Brong Ahafo, Central and Western. The incremental cost effectiveness of the 'hang-up' component was estimated using reported variation in the implementation of hang-up activities and LLIN use. Economic costs were estimated from a societal perspective assuming LLINs would be replaced after three years, and included the time of unpaid volunteers and household contributions given to volunteers.ResultsAcross the three regions, 3.6 million campaign LLINs were distributed, and 45.5% of households reported the LLINs received were hung-up by a volunteer. The financial cost of the campaign was USD 6.51 per LLIN delivered. The average annual economic cost was USD 2.90 per LLIN delivered and USD 6,619 per additional child death averted by the campaign. The cost-effectiveness of the campaign was sensitive to the price, lifespan and protective efficacy of LLINs.Hang-up activities constituted 7% of the annual economic cost, though the additional financial cost was modest given the use of volunteers. LLIN use was greater in households in which one or more campaign LLINs were hung by a volunteer (OR=1.57; 95% CI=1.09, 2.27; p=0.02). The additional economic cost of the hang-up activities was USD 0.23 per LLIN delivered, and achieved a net saving per LLIN used and per death averted.ConclusionIn this campaign, hang-up activities were estimated to be net saving if hang-up increased LLIN use by 10% or more. This suggests hang-up activities can make a LLIN campaign more cost-effective.

Project description:BackgroundInsecticide-treated bed nets (ITNs) are widely used for the prevention and control of malaria. In Guatemala, since 2006, ITNs have been distributed free of charge in the highest risk malaria-endemic areas and constitute one of the primary vector control measures in the country. Despite relying on ITNs for almost 15 years, there is a lack of data to inform the timely replacement of ITNs whose effectiveness becomes diminished by routine use.MethodsThe survivorship, physical integrity, insecticide content and bio-efficacy of ITNs were assessed through cross-sectional surveys conducted at 18, 24 and 32 months after a 2012 distribution of PermaNet® 2.0 in a malaria focus in Guatemala. A working definition of 'LLIN providing adequate protection' was developed based on the combination of the previous parameters and usage of the net. A total of 988 ITNs were analysed (290 at 18 months, 349 at 24 months and 349 at 32 months).ResultsThe functional survivorship of bed nets decreased over time, from 92% at 18 months, to 81% at 24 months and 69% at 32 months. Independent of the time of the survey, less than 80% of the bed nets that were still present in the household were reported to have been used the night before. The proportion of bed nets categorized as "in good condition" per World Health Organization (WHO) guidelines of the total hole surface area, diminished from 77% to 18 months to 58% at 32 months. The portion of ITNs with deltamethrin concentration less than 10 mg/m2 increased over time. Among the bed nets for which bioassays were conducted, the percentage that met WHO criteria for efficacy dropped from 90% to 18 months to 52% at 32 months. The proportion of long-lasting insecticidal nets (LLINs) providing adequate protection was 38% at 24 months and 21% at 32 months.ConclusionsAt 32 months, only one in five of the LLINs distributed in the campaign provided adequate protection in terms of survivorship, physical integrity, bio-efficacy and usage. Efforts to encourage the community to retain, use, and properly care for the LLINs may improve their impact. Durability assessments should be included in future campaigns.

Project description:BackgroundThere are major concerns over sustaining the efficacy of current malaria vector control interventions given the rapid spread of resistance, particularly to pyrethroids. This study assessed the bioefficacy of five WHO-recommended long-lasting insecticidal nets (LLINs) against pyrethroid-resistant Anopheles gambiae field populations from Uganda.MethodsAdult An. gambiae from Lira, Tororo, Wakiso and Kanungu districts were exposed to permethrin (0.75%) or deltamethrin (0.05%) in standard WHO susceptibility tests. Cone bioassays were used to measure the bioefficacy of four mono-treated LLINs (Olyset®, Interceptor®, Netprotect® and PermaNet® 2.0) and one combination LLIN (PermaNet® 3.0) against the four mosquito populations. Wireball assays were similarly conducted to determine knockdown rates. Species composition and kdr mutation frequency were determined for a sample of mosquitoes from each population. Chemical assays confirmed that test nets fell within target dose ranges.ResultsAnopheles gambiae s.s. predominated at all four sites (86-99% of Anopheles spp.) with moderate kdr L1014S allelic frequency (0.34-0.37). Confirmed or possible resistance to both permethrin and deltamethrin was identified for all four test populations. Reduced susceptibility to standard LLINs was observed for all four populations, with mortality rates as low as 45.8% even though the nets were unused. The combination LLIN PermaNet®3.0 showed the highest overall bioefficacy against all four An. gambiae s.l. populations (98.5-100% mortality). Wireball assays provided a more sensitive indicator of comparative bioefficacy, and PermaNet 3.0 was again associated with the highest bioefficacy against all four populations (76.5-91.7% mortality after 30 mins).ConclusionsThe bioefficacy of mono-treated LLINs against pyrethroid-resistant field populations of An. gambiae varied by LLIN type and mosquito population, indicating that certain LLINs may be more suitable than others at particular sites. In contrast, the combination LLIN PermaNet 3.0 performed optimally against the four An. gambiae populations tested. The observed reduced susceptibility of malaria vectors to mono-treated LLINs is of particular concern, especially considering all nets were unused. With ongoing scale-up of insecticidal tools in the advent of increasing resistance, it is essential that those interventions with proven enhanced efficacy are given preference particularly in areas with high resistance.

Project description:BACKGROUND:Long-lasting insecticidal nets (LLINs) are the most widely deployed vector control intervention in sub-Saharan Africa to prevent malaria. Recent reports indicate selection of pyrethroid insecticide resistance is widespread in mosquito vectors. This paper explores risk factors associated with malaria infection prevalence and vector density between mass distribution campaigns, changes in net coverage, and loss of protection in an area of high pyrethroid resistance in Northwest Tanzania. METHODS:A cross sectional malaria survey of 3456 children was undertaken in 2014 in Muleba district, Kagera region west of Lake Victoria. Vector density was assessed using indoor light traps and outdoor tent traps. Anophelines were identified to species using PCR and tested for Plasmodium falciparum circumsporozoite protein. Logistic regression was used to identify household and environmental factors associated with malaria infection and regression binomial negative for vector density. RESULTS:LLIN use was 27.7%. Only 16.9% of households had sufficient nets to cover all sleeping places. Malaria infection was independently associated with access to LLINs (OR: 0.57; 95% CI 0.34-0.98). LLINs less than 2 years old were slightly more protective than older LLINs (53 vs 65% prevalence of infection); however, there was no evidence that LLINs in good condition (hole index?<?65) were more protective than LLINs, which were more holed. Other risk factors for malaria infection were age, group, altitude and house construction quality. Independent risk factors for vector density were consistent with malaria outcomes and included altitude, wind, livestock, house quality, open eaves and LLIN usage. Indoor collections comprised 4.6% Anopheles funestus and 95.4% Anopheles gambiae of which 4.5% were Anopheles arabiensis and 93.5% were Anopheles gambiae sensu stricto. CONCLUSION:Three years after the mass distribution campaign and despite top-ups, LLIN usage had declined considerably. While children living in households with access to LLINs were at lower risk of malaria, infection prevalence remained high even among users of LLINs in good condition. While effort should be made to maintain high coverage between campaigns, distribution of standard pyrethroid-only LLINs appears insufficient to prevent malaria transmission in this area of intense pyrethroid resistance.

Dataset Information

Effects of pyrethroid resistance on the cost effectiveness of a mass distribution of long-lasting insecticidal nets: a modelling study.

Background

Methods

Results

Conclusion

Publications

Effects of pyrethroid resistance on the cost effectiveness of a mass distribution of long-lasting insecticidal nets: a modelling study.

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