Trends in US President’s Malaria Initiative-funded indoor residual spray coverage and insecticide choice in sub-Saharan Africa (2008–2015): urgent need for affordable, long-lasting insecticides

Indoor residual spraying (IRS) of insecticides has produced profound changes in malaria burden in a range of settings, including the elimination of malaria through indoor spraying of DDT (in combination with environmental management, improved housing and treatment) during the Global Malaria Eradication Programme (GMEP, 1955–1969) in the USA, Europe, parts of the Soviet Union, Israel, Lebanon, Syria, Japan, and Taiwan [1]. While IRS in Africa was largely overlooked during the GMEP, sustained IRS programmes have been successfully staged in South Africa, Zambia, Namibia, Swaziland, Zimbabwe and Botswana for several decades since the 1940s and have achieved sizeable reductions in vector populations and malaria incidence [2, 3]. IRS is applicable in many epidemiological settings, including hyperendemic areas of sub-Saharan Africa, provided that policy and programming decisions take into account the operational and resource feasibility [4]. In 2006, the World Health Organization (WHO) reaffirmed the importance of IRS as a primary intervention for reducing or interrupting malaria transmission [5]. The US President’s Malaria Initiative (PMI) was launched in 2005, initially as a 5 year, $1.2 billion programme to rapidly scale up malaria prevention and treatment interventions and reduce malaria-related mortality by 50 % in 15 high-burden countries in sub-Saharan Africa [6]. Priority was given to the scale up of four proven interventions; namely long-lasting insecticidal nets (LLINs), IRS, intermittent preventive treatment in pregnancy (IPTp), and prompt diagnosis with rapid diagnostic tests (RDTs) and treatment with artemisinin-based combination therapy (ACT) [6]. IRS coverage in sub-Saharan Africa increased substantially from <2 % of the at-risk population protected in 2005, to 11 % or 78 million people in 2010 [7]. Increased IRS coverage was successful in a range of diverse epidemiological settings, with substantial reductions for all cause child mortality, malaria parasite prevalence and entomological indicators recorded in several countries including parts of Equatorial Guinea (not a PMI-supported country) [8], Benin [9], Kenya [10], Malawi [11], and Tanzania [12].

The duration of residual efficacy and cost-effectiveness of IRS insecticides are of key importance to the sustainability of IRS programmes. A major challenge facing IRS programmes is to sustain such gains in the face of technical problems, such as vector resistance to insecticides, lack of affordable alternative insecticides and limited resources for annual renewal of each intervention. In this article the changing pattern of PMI-supported IRS in sub-Saharan Africa between 2008 and 2015 is documented and the technical challenges being faced are examined. A limitation is that data was not included for IRS conducted through other funding sources such as UK Department for International Development (DFID), The Global Fund to Fight AIDS, Tuberculosis and Malaria, private companies and national Governments.

Despite the Stockholm Convention on Persistent Organic Pollutants stipulating that, ‘countries using DDT should eliminate the use of DDT over time and switch to alternative insecticides’, the use of DDT for malaria control has been allowed to continue under exemption [19, 20]. DDT has a long residual action of more than 6 months and is relatively inexpensive, with a cost similar to pyrethroids [14, 15]. However, there is high frequency of mutations in the knockdown resistance gene (kdr) across sub-Saharan Africa, conferring cross-resistance to DDT and pyrethroid insecticides [17]; in addition there is political resistance, with several countries reluctant to register or utilize DDT due to perceived environmental or export concerns [21, 22].

The carbamate bendiocarb is highly effective, but has a short residual duration, meaning that multiple spray cycles may be required for optimal protection in areas of prolonged transmission [23, 24]. Propoxur is a carbamate insecticide that is currently used for IRS in Ethiopia, but is not utilized through the PMI as the product specifications are not listed under the Joint FAO/WHO Meeting on Pesticide Specifications (JMPS) [25].

Pirimiphos-methyl (p-methyl) emulsifiable concentrate (EC), an organophosphate insecticide that was developed in the 1970s, shows high toxicity to Anopheles mosquitoes but has infrequently been utilized despite having WHO recommendation for IRS [15, 26]. Between 2009 and 2012, p-methyl EC was sprayed in Malawi, Benin and Zambia but was subsequently replaced due to the prohibitive expense and short residual activity [27, 28]. In 2013, a new formulation of p-methyl capsule suspension (CS) was recommended by WHO for IRS, with experimental hut trials demonstrating vastly improved residual duration of up to 12 months [29–31].

The spread and intensification of pyrethroid resistance in malaria vectors has led to policy changes regarding insecticide choice for IRS programmes. There is limited epidemiological evidence of pyrethroid IRS or LLIN failure, possibly due to a shortage of suitable data collection or alternatively pyrethroid insecticides may successfully kill older, less resistant infective mosquitoes and also provide some protection through repellency and the physical barrier effect of LLINs [32]. WHO cylinder bioassays have demonstrated an increased frequency of resistant malaria vectors and this has led many control programmes to stop spraying pyrethroids in favour of alternative insecticides [28, 33].

In 2009, 87 % (13/15) of PMI-funded countries with IRS programmes sprayed pyrethroid IRS (Fig. 1). This proportion decreased annually, with only 44 % (7/16) of countries having sprayed pyrethroids in 2013, while carbamate use increased during the same period from 7 % (1/15) in 2009 to 56 % (9/16) in 2013 (Fig. 1). Bendiocarb was sprayed despite being relatively expensive and having a limited residual duration, as there were few viable alternatives (namely DDT and organophosphates). P-methyl EC was rarely utilized and was sprayed in <10 % of countries between 2009 and 2012. Following the development of a long-lasting formulation of p-methyl CS came a dramatic shift in usage, with 85 % (11/13) of PMI-supported countries spraying p-methyl CS in 2015 (Fig. 1), compared with 31 % (5/16) in the first year of production in 2013. The gradual replacement of relatively inexpensive pyrethroids firstly with bendiocarb (carbamate) and subsequently with p-methyl CS (organophosphate) has also led to substantial changes in IRS spray coverage. The cost of a pyrethroid (Icon™ lambdacyhalothrin capsule suspension (CS) 10 % ai, Syngenta) sachet is estimated to be $5, compared with $12 for bendiocarb (Ficam™ WP 80 % ai, Bayer CropScience), $20 for a container of p-methyl EC (Actellic™ EC, 50 % ai, Syngenta) and $23.50 for p-methyl CS (Actellic™ CS, 30 % ai, Syngenta), all with equivalent quantity of active ingredient to spray 250 m² at WHO recommended target dosages [34]. It should be noted that there are additional insecticide cost drivers such as shipping, disposal of insecticide packaging, and environmental precautions, which vary according to formulation. For example, DDT WP may be the cheapest formulation at $2 but the additional environmental precautions and testing needed can increase overall costs considerably [35]. The type of insecticide formulation purchased is one of the most important cost drivers for spray programmes. In 2014, insecticides were the second largest cost category across PMI IRS programmes (per 100 m²) and accounted for 28 % of the total unit cost (across all countries regardless of insecticide formulation sprayed) [36]. For the few countries where pyrethroids were sprayed, insecticide accounted for only 6 % of all costs compared with 37 % where organophosphates were used [36]. However, it should be noted that there was considerable variation between countries in spray operations costs.

The proportion of PMI-supported countries spraying bendiocarb increased greatly between 2011 and 2013 (Fig. 1), yet the number of structures sprayed remained high in most countries despite the increased cost compared to pyrethroids (12 countries reached peak numbers of structures sprayed between 2011 and 2013 (Table 2). This increase in cost was exacerbated by subsequent replacement with more expensive p-methyl CS, which, by 2015, had become the insecticide of choice for the majority of PMI-funded spray programmes (Fig. 1). Despite the increased cost, p-methyl CS was preferred to bendiocarb WP due to the extended duration of action (offsetting some of the added cost) and also in response to increasing reports of bendiocarb resistance in countries including Malawi, Benin, Ghana, Ethiopia and Senegal (Fig. 2) [4, 37, 38].

Country	Year of peak coverage	Structures sprayed in year of peak coverage	Structures sprayed in 2015	% Reduction in structures sprayed
Angola	2011	145,264	0	100
Benin	2014	254,072	252,706	1
Ethiopia	2011	858,657	670,303	22
Ghana	2012	371,362	231,345	38
Kenya	2008	764,050	0	100
Liberia	2012	96,901	0	100
Madagascar	2010	576,320	254,986	56
Malawi	2010	97,329	0	100
Mali	2013	228,985	131,894	42
Mozambique	2011	660,064	440,579	33
Nigeria	2013	62,592	0	100
Rwanda	2011	358,804	213,271	41
Senegal	2012	306,916	111,201	64
Tanzania	2012	1,224,095	389,714	68
Uganda	2011	908,627	850,000	6
Zambia	2010	1,300,000	482,077	63
Zanzibar	2008	200,731	66,497	67
Zimbabwe	2013	622,300	163,922	74
Total	NA	9,037,069	4,258,495	53

The substantial increase in insecticide cost, firstly caused by increased use of carbamates (2011–2014), followed by replacement with organophosphates (2014–2015), has led to the scaling-down of most PMI-funded IRS programmes. Overall, there was a decrease of 53 % in the total number of structures sprayed between years of peak coverage to 2015 estimates (Table 2). In Malawi, PMI supported the spraying of 97,329 structures in 2010, but the spread of pyrethroid and carbamate resistance resulted in the withdrawal of IRS support in 2012, due to the ‘high cost and short residual action of p-methyl EC’ [27] (Table 2). While the majority of IRS programmes have continued, there is a clear downward trend in coverage from the heights achieved when pyrethroids were the insecticide of choice (Table 2). In Tanzania (mainland), a total of 1,224,095 structures were sprayed in 2012, compared with 389,714 in 2015, with the reduction attributed to ‘the high cost of p-methyl CS’ [39]. Similar sizeable reductions in the number of structures sprayed were reported in Ghana (38 %), Madagascar (56 %), Mali (42 %), and Zambia (63 %). The most commonly cited reasons for the reduced spray coverage were the limited availability of alternative insecticides and increased cost of insecticides, as vector resistance necessitated switching from pyrethroids to organophosphates [40, 41]. PMI-funded IRS was also withdrawn from Angola, Liberia and temporarily in Kenya, although in Kenya political and insecticide registration issues were the main drivers, rather than increased cost of insecticides [21, 42, 43]. In Nigeria, the PMI-funded IRS programme was only intended as a pilot to demonstrate IRS feasibility [44]. It is also important to note that in some countries IRS has been partially funded through other sources, for example in Ethiopia where the Government has taken over spray operations in graduated districts where PMI has developed sufficient capacity [45].

A change in policy from blanket spraying towards focal targeted coverage is a valid, cost-effective strategy in areas of low transmission or at the pre-elimination phase [46, 47]. In the archipelago of Zanzibar, a combination of vector control and improved access to diagnosis and treatment has resulted in a new target of malaria elimination by 2020 [47]. In such a setting the decrease in structures sprayed from a peak of 200,731 in 2008 down to 66,497 in 2015, while maintaining universal LLIN coverage, is perfectly justifiable (Table 2). However, failure to maintain adequate vector control coverage (LLIN and IRS) is likely to result in malaria resurgence to pre-intervention levels. A notorious example of resurgence following withdrawal of IRS is the eradication programme of Zanzibar (1957–1968) which consisted of annual spraying with dieldrin or DDT and had reduced malaria prevalence from 50–60 % to 0–3 % by 1968. In 1979, 11 years after cessation of spraying, malaria had rebounded to close to pre-intervention levels [48].

PMI has ensured that universal coverage with LLINs has been achieved in areas where IRS has been scaled back or withdrawn. Despite this, reducing the number of structures sprayed with IRS is likely to result in an increase in malaria transmission unless complementary control measures in addition to LLINs are implemented. In addition, behavior change communication (BCC) is likely to be important in areas where IRS was previously used and mosquito net use is not yet ingrained [49]. There are already worrying preliminary reports of rapid resurgence following IRS withdrawal.