Insecticide resistance adjustment incorporating PBO nets

	A	B	C	D	E	F	G	H	I	J	K	L	N	O
1	Insecticide resistance adjustment, not taking into account PBOs				Overall	DRC	Ghana	Malawi	PNG	Togo	Uganda	Zambia	Source / Notes	Link
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3				Spending		$3,878,023	$7,332,389	$12,204,669	$4,260,000	$5,190,000	$31,658,900	$7,300,000	GiveWell cost-effectiveness analysis (2018 - version 7)	https://docs.google.com/spreadsheets/d/1rszxDuWK3lu7cQBhXB3BOKnvYLrwd--iTVAqKznQ1mQ/edit#gid=1862644804
4				Weight		5%	10%	17%	6%	7%	44%	10%	GiveWell cost-effectiveness analysis (2018 - version 7)	https://docs.google.com/spreadsheets/d/1rszxDuWK3lu7cQBhXB3BOKnvYLrwd--iTVAqKznQ1mQ/edit#gid=1862644804
5
6	Mosquito mortality in pyrethroid 2010-16 (WHO insecticide susceptibility or CDC bottle bioassays using discriminating concentrations)
7				Sites tested		12	46	70	4	5	21	109	WHO Global Report on insecticide resistance 2010-2016 (Annex 1)	http://apps.who.int/iris/bitstream/handle/10665/272533/9789241514057-eng.pdf?sequence=1&isAllowed=y
8				Years		2010-16	2010–2016	2010-15	2015	2011-13	2011-16	2011-16	WHO Global Report on insecticide resistance 2010-2016 (Annex 1)	http://apps.who.int/iris/bitstream/handle/10665/272533/9789241514057-eng.pdf?sequence=1&isAllowed=y
9				Mean		81%	50%	58%	100%	37%	53%	60%	WHO Global Report on insecticide resistance 2010-2016 (Annex 1)	http://apps.who.int/iris/bitstream/handle/10665/272533/9789241514057-eng.pdf?sequence=1&isAllowed=y
10				Min		12%	0%	0%	100%	1%	4%	0%	WHO Global Report on insecticide resistance 2010-2016 (Annex 1)	http://apps.who.int/iris/bitstream/handle/10665/272533/9789241514057-eng.pdf?sequence=1&isAllowed=y
11				Max		100%	100%	100%	100%	93%	100%	100%	WHO Global Report on insecticide resistance 2010-2016 (Annex 1)	http://apps.who.int/iris/bitstream/handle/10665/272533/9789241514057-eng.pdf?sequence=1&isAllowed=y
12				Mosquitoes tested		An. gambiae s.l.	An. coluzzii, An. funestus s.l., An. gambiae s.l.	An. arabiensis, An. funestus s.l., An. funestus s.s., An. gambiae s.l.	Anopheles spp.	An. gambiae s.l.	An. arabiensis, An. funestus s.l., An. gambiae s.l., An. gambiae s.s., An. parensis	An. funestus s.l., An. gambiae s.l., An. gambiae s.s.	WHO Global Report on insecticide resistance 2010-2016 (Annex 1)	http://apps.who.int/iris/bitstream/handle/10665/272533/9789241514057-eng.pdf?sequence=1&isAllowed=y
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14
15	Change over time
16						2010-16	Annual
17				Increase in frequency West Africa		5%	0.83%						We use the estimated increase in median mortality to permethrin. "Trends analyses were conducted to determine whether there were any significant changes between 2010 and 2016 in malaria vector resistance to specific insecticides, and in specific vector groups (Fig. 4.4 and Fig. 4.5). A global increase in resistance frequency was observed for all pyrethroid insecticides tested. Increases were greatest for etofenprox (44% rise, from 7% to 51%), alphacypermethrin (40% rise, from 10% to 50%) and cyfluthrin (28% rise, from 4% to 32%). The increase was less pronounced for the other pyrethroids although these also had a higher initial resistance frequency in 2010: deltamethrin (14% rise, from 20% to 34%), permethrin (5% rise, from 40% to 45%) and lambda-cyhalothrin (3% rise, from 33% to 36%). This indicates that increasing resistance is an issue for all pyrethroids, and that reductions in susceptibility are most marked for those insecticides for which susceptibility was highest in 2010. Further evaluations will be undertaken to identify whether there are differences in resistance frequency and trends over time between insecticides of the pyrethroid class, in order to guide requirements for insecticide resistance monitoring. " Pg. 20 WHO Global Report on insecticide resistance 2010-2016	http://apps.who.int/iris/bitstream/handle/10665/272533/9789241514057-eng.pdf?sequence=1&isAllowed=y
18				Increase in frequency Central Africa		5%	0.83%						We use the estimated increase in median mortality to permethrin. "Trends analyses were conducted to determine whether there were any significant changes between 2010 and 2016 in malaria vector resistance to specific insecticides, and in specific vector groups (Fig. 4.4 and Fig. 4.5). A global increase in resistance frequency was observed for all pyrethroid insecticides tested. Increases were greatest for etofenprox (44% rise, from 7% to 51%), alphacypermethrin (40% rise, from 10% to 50%) and cyfluthrin (28% rise, from 4% to 32%). The increase was less pronounced for the other pyrethroids although these also had a higher initial resistance frequency in 2010: deltamethrin (14% rise, from 20% to 34%), permethrin (5% rise, from 40% to 45%) and lambda-cyhalothrin (3% rise, from 33% to 36%). This indicates that increasing resistance is an issue for all pyrethroids, and that reductions in susceptibility are most marked for those insecticides for which susceptibility was highest in 2010. Further evaluations will be undertaken to identify whether there are differences in resistance frequency and trends over time between insecticides of the pyrethroid class, in order to guide requirements for insecticide resistance monitoring. " Pg. 20 WHO Global Report on insecticide resistance 2010-2016	http://apps.who.int/iris/bitstream/handle/10665/272533/9789241514057-eng.pdf?sequence=1&isAllowed=y
19				Increase in frequency East and Southern Africa		5%	0.83%
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21				Expected annual increase (ppt)		0.83%	0.83%	0.83%	0%	0.83%	0.83%	0.83%	Calculation
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23				Average year bioassays conducted		2013	2013	2012.5	2015	2012	2013.5	2013.5	Calculation
24				Current year		2019	2019	2019	2019	2019	2019	2019	Input
25				Years forecast out		6	6	6.5	4	7	5.5	5.5	Calculation
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27				Reduction in mosquito mortality		5.00%	5.00%	5.42%	0.00%	5.83%	4.58%	4.58%	Calculation
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29				Mosquito mortality in 2019		76%	45%	53%	100%	31%	48%	55%	Calculation
30				Weighted average		53%
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32	IR adjustment before accounting for PBO nets
33				Proportion of protection of LLIN due to physical barrier		27%	27%	27%	27%	27%	27%	27%	See cell formulas to left for reference to calculation on "Insecticide vs Physical Barrier" sheet
34				Proportion of protection of LLIN due to pyrethroid		73%	73%	73%	73%	73%	73%	73%	See cell formulas to left for reference to calculation on "Insecticide vs Physical Barrier" sheet
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36				Effectiveness of LLIN relative to Lengeler		82%	60%	65%	100%	50%	62%	67%	Calculation
37				Reduction in effectiveness		18%	40%	35%	0%	50%	38%	33%	Calculation
38				Weighted average	34.45%
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40				Caveats, Limitations, Assumptions
41				Assumes 80% of effectiveness of LLINs scales linearly with mosquito mortality
42				The sites tested weren't random, or spatially distributed and mosquito mortality has a high variance, suggesting regional variation makes this very uncertain
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44	Evidence from PBO trial; testing the model that 80% of effectiveness of LLINs scales linearly with mosquito mortality
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46		Modelled results of PBO trial we would expect if 80% of effectiveness of LLINs scales linearly with mosquito mortality
47			Standard LLIN modelled effectiveness
48				Muleba mosquito mortality (permethrin alone) in study area	10.50%								"Of the 13 689 Anopheline mosquitoes collected, 13 106 (95·7%) were A gambiae sensu lato and 510 (3·7%) were A funestus. Of the 990 A gambiae sensu lato identified to species, 946 (95·6%) were A gambiae sensu stricto and 44 (4·4%) were A arabiensis."; "The mortality of mosquitoes exposed to permethrin for resistance determination in the WHO cylinder tests was 8·8% (95% CI 5·3–12·3; n/N=54/613) for A gambiae sensu lato and 54·5% (36·8–76·2; n/N=59/108) for A funestus." Propopotoff et al. 2018	https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30427-6/fulltext
49				Expected effectiveness of LLINs relative to Lengeler	35%								Based on model of 80% of effectiveness of LLINs scales linearly with mosquito mortality
50				Standard LLIN Incidence risk reduction (ITT) (i.e. 1 - risk ratio) from Lengeler	0.5								"ITNs reduced the incidence of uncomplicated malarial episodes in areas of stable malaria by 50% compared to no nets, and 39% compared to untreated nets" Lengeler 2004	https://www.ncbi.nlm.nih.gov/pubmed/15106149
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52				Standard LLIN Incidence risk reduction (vs no nets) we would expect	0.17
53				Standard LLIN relative risk (vs no nets) we would expect	0.83
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55			PBO nets modelled effectiveness
56				Muleba mosquito mortality (permethrin + PBO) in study area	93.50%								Matowo et al. 2015	https://www.ncbi.nlm.nih.gov/pubmed/25537754
57				Expected effectiveness of PBOs relative to Lengeler	95.26%
58
59				PBO LLIN Incidence risk reduction vs no nets we would expect	0.4762820815
60				PBO LLIN relative risk vs no nets we would expect	0.5237179185
61
62		Is this model consistent with the results from Propopotoff et al. 2018?
63				Relative risk of PBO vs standard LLINs we'd expect (ITT)	0.63
64				Relative risk of PBO vs standard LLINs we observe (ITT)	0.68
65
66		Conclusions
67				The model is broadly consistent with the results we saw from Propopotoff et al. 2018
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69	Insecticide resistance adjustment, taking into account PBOs
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71				Proportion of pyrethroid-resistant mosquitos which are also resistant to PBO	7%
72				Insecticide resistance adjustment in areas covered by PBOs	2.50%
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74				Insecticide resistance adjustment incorporating PBOs	24.87%
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76				Caveats, Limitations, Assumptions
77				We have used the ITT effect from Propopotoff et al. 2018, with no adjustment for differing levels of coverage (i.e. nets that end up being used) between AMF's programs and Propopotoff et al. 2018
78				We have assumed AMF will distribute PBO nets rather than standard LLINs roughly in proportion to levels of mosquito mortality
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80	What level of mosquito mortality would mean PBO nets are more cost-effective than standard LLINs?
81				Cost of PBO	$2.00								Givewell cost-effectiveness analysis, August 2018
82				Cost of standard LLIN	$2.40								Givewell cost-effectiveness analysis, August 2018
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84				Non-net costs	$2.43								Givewell cost-effectiveness analysis, August 2018
85
86				How much more does delivering a PBO net cost?	9.03%
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88				How much more effective should a PBO net be to justify this additional cost?	9.03%
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90				Proportion of protection of LLIN due to physical barrier	27%
91				Proportion of protection of LLIN due to pyrethroid	73%
92
93				What reduction in mosquito survival do we expect from using PBO, rather than permethrin alone?	92.74%
94
95				What is mosquito mortality with permethrin?	90%								Sensitivity input - arbitrary
96				What is mosquito mortality with PBO?	99%
97
98				How much more effective is PBO than a standard LLIN?	8%
99
100				How much more cost-effective is PBO than a standard LLIN?	1%