Optimizing Strategic Insecticide Resistance Management Planning in Malaria Vectors

In the past decade, there has been rapid scale-up of insecticide-based malaria vector control in the context of integrated vector management (IVM). But, the continued efficacy of vector control interventions is threatened by the selection of insecticide resistance. Evidence of insecticide resistance operationally undermining malaria vector control programmes is invariably mounting and is resulting in policy changes. Monitoring and management of resistant disease vectors is essential to limit the selection and spread of insecticide resistance and to maintain the effectiveness of vector control. Thus, countries are encouraged to implement pre-emptive insecticide resistance management (IRM) strategies against malaria vectors according to the Global Plan for IRM. However, substantial challenges for implementation exist at country level. The IVM strategy provides a potential platform that could be exploited for enhanced national strategic IRM planning and operationalisation. Nevertheless, significant coordinated response among stakeholders and political commitment is needed for timely and effective policy implementation within the context of a national health system

Exploiting the Potential of Integrated Vector Management for Combating Malaria in Africa

Integrated Vector Management (IVM) is advocated by the World Health Organization (WHO) as the pivotal platform for vector control. The threat for malaria and emerging and re-emerging vector borne diseases is increasing. However, adoption and deployment of the IVM strategy has been minimal. Though malaria endemic countries are embracing and consolidating the IVM approach, real time entomological data on transmission risk and targeting the right vector with the appropriate intervention is lacking. IVM could be harnessed for circumventing operational constraints for vector control. Herein IVM for combating malaria and other insect-borne diseases is reviewed and ways to maximize its potential and benefits are proposed. IVM promotes operational research for evidence-based, cost-effective and optimally sustainable vector control with judicious integration of available options, improves management of insecticides, and effective mitigation of potential negative health and environmental impacts. IVM enhances institutional arrangements including accountability, collaboration and coordination of stakeholders. IVM will require policies and frameworks to maximize intervention impact; and infrastructure and human resources capacity, community involvement and information sharing, strengthened regulation for registration and quality assurance, procurement, financial management and supply chain management for commodities. However, national health system-based response among stakeholders and political commitment is needed for optimal IVM implementation

The highly polymorphic CYP6M7 cytochrome P450 gene partners with the directionally selected CYP6P9a and CYP6P9b genes to expand the pyrethroid resistance front in the malaria vector Anopheles funestus in Africa

Background: Pyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa. It remains unknown whether this resistance has a unique origin with the same molecular basis or is multifactorial. Knowledge of the origin, mechanisms and evolution of resistance are crucial to designing successful resistance management strategies. Results: Here, we established the resistance profile of a Zambian An. funestus population at the northern range of the resistance front. Similar to other Southern African populations, Zambian An. funestus mosquitoes are resistant to pyrethroids and carbamate, but in contrast to populations in Mozambique and Malawi, these insects are also DDT resistant. Genome-wide microarray-based transcriptional profiling and qRT-PCR revealed that the cytochrome P450 gene CYP6M7 is responsible for extending pyrethroid resistance northwards. Indeed, CYP6M7 is more over-expressed in Zambia [fold-change (FC) 37.7; 13.2 for qRT-PCR] than CYP6P9a (FC15.6; 8.9 for qRT-PCR) and CYP6P9b (FC11.9; 6.5 for qRT-PCR), whereas CYP6P9a and CYP6P9b are more highly over-expressed in Malawi and Mozambique. Transgenic expression of CYP6M7 in Drosophila melanogaster coupled with in vitro assays using recombinant enzymes and assessments of kinetic properties demonstrated that CYP6M7 is as efficient as CYP6P9a and CYP6P9b in conferring pyrethroid resistance. Polymorphism patterns demonstrate that these genes are under contrasting selection forces: the exceptionally diverse CYP6M7 likely evolves neutrally, whereas CYP6P9a and CYP6P9b are directionally selected. The higher variability of CYP6P9a and CYP6P9b observed in Zambia supports their lesser role in resistance in this country. Conclusion: Pyrethroid resistance in Southern Africa probably has multiple origins under different evolutionary forces, which may necessitate the design of different resistance management strategies

Insecticide resistance and the future of malaria control in Zambia.

BACKGROUND: In line with the Global trend to improve malaria control efforts a major campaign of insecticide treated net distribution was initiated in 1999 and indoor residual spraying with DDT or pyrethroids was reintroduced in 2000 in Zambia. In 2006, these efforts were strengthened by the President's Malaria Initiative. This manuscript reports on the monitoring and evaluation of these activities and the potential impact of emerging insecticide resistance on disease transmission. METHODS: Mosquitoes were captured daily through a series of 108 window exit traps located at 18 sentinel sites. Specimens were identified to species and analyzed for sporozoites. Adult Anopheles mosquitoes were collected resting indoors and larva collected in breeding sites were reared to F1 and F0 generations in the lab and tested for insecticide resistance following the standard WHO susceptibility assay protocol. Annual cross sectional household parasite surveys were carried out to monitor the impact of the control programme on prevalence of Plasmodium falciparum in children aged 1 to 14 years. RESULTS: A total of 619 Anopheles gambiae s.l. and 228 Anopheles funestus s.l. were captured from window exit traps throughout the period, of which 203 were An. gambiae malaria vectors and 14 An. funestus s.s.. In 2010 resistance to DDT and the pyrethroids deltamethrin, lambda-cyhalothrin and permethrin was detected in both An. gambiae s.s. and An. funestus s.s.. No sporozoites were detected in either species. Prevalence of P. falciparum in the sentinel sites remained below 10% throughout the study period. CONCLUSION: Both An. gambiae s.s. and An. funestus s.s. were controlled effectively with the ITN and IRS programme in Zambia, maintaining a reduced disease transmission and burden. However, the discovery of DDT and pyrethroid resistance in the country threatens the sustainability of the vector control programme

Numerical modelling of monorail support requirements in decline development

This paper discusses support requirements for the proposed monorail system to be used in decline development. The monorail drilling and loading systems are systems that move on the rail (monorail) installed in the roof of the decline and supported by roof bolts, suspension chains and steel supports. However, due to the weight of the components of the two systems, it is imperative that the force in each roof bolt, suspension chain and steel support capable of suspending the weight of the heaviest component is determined. Numerical models that relate the weight of the monorail drilling and loading components to the required strength in the support system have been developed. Using these developed models, numerical values of the forces in each roof bolt, suspension chain and steel support, required to suspend the weight of the heaviest component of the monorail drilling and loading systems are determined

Underpinning Sustainable Vector Control through Informed Insecticide Resistance Management

Background: There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia’s programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions. Methodology/Principal Findings: A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids,DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s. Conclusions/Significance: Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management pla

Optimizing impact assessment of entomological intervention for malaria control in an operational setting in Zambia

The study aimed at optimally assessing the impact of indoor residual spraying (IRS) and insecticide treated nets (ITNs) on vector species abundance, their infectivity and resistance status, and Plasmodium falciparum prevalence, malaria deaths and case fatality rates in the human population. Malaria prevalence surveys were conducted and routine surveillance data was retrospectively analyzed. The average P. falciparum prevalence in children between the ages of 1 and 14 years was below 10% across the study period. The intervention effect was more pronounced in IRS areas than in ITNs localities but with an incremental protective effect of their combined use. Age-specific comparison showed better intervention effect on children below 5 years than older children 5 to 14 years old. While the average number of deaths and case fatality rates in children under the age of five plunged precipitately, the reductions were more significant in IRS districts than in ITNs districts. Results indicate the need for supplementing parasite prevalence survey data with routine surveillance data in low transmission intensity areas and demonstrate the significance of evidence-based age-specific deployment of interventions. To monitor vector species abundance and infectivity, mosquitoes were collected daily using exit window traps. The three major vectors; An. gambiae s.s, An. arabiensis and An. funestus s.s, and three potential vectors of malaria, An. nili, An. rivulorum and An. funestus-like species were identified. Overall, the biggest impact of IRS and ITNs was on An. gambiae s.s, and An. funestus abundance. No An. gambiae s.s was collected in IRS localities, thus validating the fact that An. gambiae s.s and An. funestus are characteristically more amenable to control by IRS and ITNs than An. arabiensis. The transmission potential for all malaria vectors, as expressed by the calculated transmission index, was zero as none of the trapped mosquitoes tested positive for P. falciparum sporozoites. The identification of An. nili, An. rivulorum and An. funestus-like necessitate further research to determine their role in malaria transmission in the country. The low numbers of mosquitoes collected also indicate a compromise in the efficiency of exit window traps in low transmission settings, suggesting the need for their replacement with a more robust collection tool like the CDC light trap. While the persistence of An. arabiensis suggests the presence of resistance segregating in this population or, that this outdoor species is not in contact with IRS or ITNs, it could as well imply that it’s the one species perpetuating malaria transmission in these meso-to hypo- endemic areas. To determine the impact of interventions on insecticide resistance status of malaria vectors, susceptibility assays using the WHO standard protocol were conducted in 17 localities. High levels of resistance were detected in both An, gambiae s.l and An, funestus s.l to pyrethroids and DDT but with 100% susceptibility to malathion and bendiocarb. The level of resistance was significantly higher in IRS areas than in ITN areas. These findings indicate that resistance has been selected for following extensive vector control. Resistance to both DDT and deltamethrin in IRS localities and ITN areas with intense cotton growing was detected suggesting selection due to either historical use of DDT, gene flow or cross-resistance. All An. gambiae s.s were molecular s-forms and only the west (leu-phe) kdr was detected. Complete susceptibility to the organophosphates and carbamates provides a possibility to switch to these alternative insecticide classes for IRS. The detected increases in the malaria prevalence in localities with high insecticide resistance levels indicate vector control failure. These findings point to the need for information on underlying biochemical and molecular resistance mechanisms to make possible the design of an effective resistance management strategy, and for the assessment of the impact of resistance on interventions. The results indicate that the impact of malaria control can be optimally assessed by using a combination of epidemiological (routine surveillance and prevalence data) and entomological indicators, in the context of a malaria decision support system, to enhance policy formulation for objective implementation of malaria control interventions and rational use of available resources

A cost-effectiveness analysis of provider and community interventions to improve the treatment of uncomplicated malaria in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: There is mounting evidence of poor adherence by health service personnel to clinical guidelines for malaria following a symptomatic diagnosis. In response to this, the World Health Organization (WHO) recommends that in all settings clinical suspicion of malaria should be confirmed by parasitological diagnosis using microscopy or Rapid Diagnostic Test (RDT). The Government of Nigeria plans to introduce RDTs in public health facilities over the coming year. In this context, we will evaluate the effectiveness and cost-effectiveness of two interventions designed to support the roll-out of RDTs and improve the rational use of ACTs. It is feared that without supporting interventions, non-adherence will remain a serious impediment to implementing malaria treatment guidelines. METHODS/DESIGN: A three-arm stratified cluster randomized trial is used to compare the effectiveness and cost-effectiveness of: (1) provider malaria training intervention versus expected standard practice in malaria diagnosis and treatment; (2) provider malaria training intervention plus school-based intervention versus expected standard practice; and (3) the combined provider plus school-based intervention versus provider intervention alone. RDTs will be introduced in all arms of the trial. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit primary health centers, pharmacies, and patent medicine dealers. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider and community knowledge. Costs will be estimated from both a societal and provider perspective using standard economic evaluation methodologies. TRIAL REGISTRATION: Clinicaltrials.gov NCT01350752

Using a Geographical-Information-System-Based Decision Support to Enhance Malaria Vector Control in Zambia

Geographic information systems (GISs) with emerging technologies are being harnessed for studying spatial patterns in vector-borne diseases to reduce transmission. To implement effective vector control, increased knowledge on interactions of epidemiological and entomological malaria transmission determinants in the assessment of impact of interventions is critical. This requires availability of relevant spatial and attribute data to support malaria surveillance, monitoring, and evaluation. Monitoring the impact of vector control through a GIS-based decision support (DSS) has revealed spatial relative change in prevalence of infection and vector susceptibility to insecticides and has enabled measurement of spatial heterogeneity of trend or impact. The revealed trends and interrelationships have allowed the identification of areas with reduced parasitaemia and increased insecticide resistance thus demonstrating the impact of resistance on vector control. The GIS-based DSS provides opportunity for rational policy formulation and cost-effective utilization of limited resources for enhanced malaria vector control