Evaluation of a Novel Long Lasting Insecticidal Net and Indoor Residual Spray Product, Separately and Together, Against Malaria Transmitted by Pyrethroid Resistant Mosquitoes.

JUSTIFICATION OF THE STUDY The district of Muleba has been subjected to IRS with pyrethroid (lambdacyhalothrin) every year for 5 years under the President Malaria Initiative (PMI) programme. The malaria vector Anopheles gambiae s.s. is predominant in Muleba region and shows high level resistance to pyrethroid insecticides [14]. In World Health Organisation (WHO) resistance tests with the pyrethroid used for IRS, An gambiae s.s. showed levels of mortality ranging from 8% to 40%, indicating a high frequency of resistance across the entire district. Mortality to permethrin, the pyrethroid used in the LLIN distributed during the UCC (Olyset Net) was only 22%. Entomological studies by the present authors showed that the pyrethroid resistance mechanism kdr is almost 100% in the Muleba An.gambiae s.s. population and elevated levels of mixed function oxidases and non-specific esterases are involved in the detoxification of pyrethroids. The carbamate bendiocarb was selected by PMI as the new insecticide of choice for IRS in the region. Following two rounds of bendiocarb IRS in January and May 2012, resistance is fast emerging. WHO resistance tests with bendiocarb showed mosquito survival rates rising from 18% in November 2011 to 23% in May 2012 and to 69% in November 2012 [14]. The only insecticide to which An.gambiae shows full susceptibility (100% mortality) is the organophosphate pirimiphos methyl, the proposed new IRS intervention.

No malaria control trial with either Olyset Plus or Actellic CS is currently being proposed elsewhere. Olyset Plus seems ideally suited - judging by the CDC bioassay test with permethrin and the synergist PBO and WHO cone bioassay tests with Olyset Plus - to provide protection against the local pyrethroid resistant An gambiae. IRS with Actellic CS seems ideally suited to provide long term transmission control. A trial of both interventions is essential to restore confidence in vector control. By itself Olyset Plus may be sufficient to provide personal protection if used every night but it may not be sufficient to provide transmission control in the entire community. An effective IRS is probably the more efficient way to reduce transmission quickly but IRS campaigns cannot be sustained year after year because of the expense, nor is this desirable because of the risk of resistance. The combination of LLIN and IRS may be required to drive transmission down to low levels whereafter the Olyset Plus should be sufficient to keep prevalence and transmission low.

2 RESEARCH PLAN 2.1 Main Objective The main objective of this research is to determine the relative effectiveness of 4 vector control interventions for reducing malaria transmission and controlling vector populations in an area where An gambiae s.s is pyrethroid and carbamate resistant: 1/ a standard long lasting insecticidal net (LLIN), 2/ Long lasting insecticidal nets that incorporate the synergist a PBO (Olyset Plus), 3/ Long lasting formulation of the OP insecticide pirimiphos-methyl (Actellic CS) for indoor residual spraying used in conjunction with standard pyrethroid LLIN or 4/ the long lasting indoor residual spray (IRS) formulation used in conjunction with the LLIN which incorporates a PBO synergist.

2.2 Specific Objectives

• To determine whether malaria transmitted by pyrethroid resistant mosquitoes can be controlled using the latest innovative preventive tools, Olyset Plus, Actellic CS IRS and Combination of both products.
• To demonstrate by means of a community randomised trial in NW Tanzania the protective efficacy of each of these interventions on the outcomes measures
• To define a strategy for using and establish in what situations it is possible to deploy just one of the interventions, both interventions, and when to switch from one type of intervention to another.
• To determine the cost-effectiveness of the interventions alone or in combination to facilitate decisions on resource allocation.
• To demonstrate whether combination interventions can serve as a model insecticide resistance management strategy to delay the future selection of resistance.
• To provide international malaria control agencies with evidence to enable them to revise or redefine their malaria control strategy in the face of growing resistance and maintain focus on malaria elimination.