Background
Long-lasting, insecticide-treated nets (LLINs) are one of the most efficacious preventive interventions against malaria morbidity and mortality available[
1] and form a cornerstone of the Roll Back Malaria (RBM) Partnership’s scaling-up for impact strategy to reduce malaria-related mortality by 75% from 2000 levels by 2015[
2]. To achieve this level of impact, RBM has set the target of reaching and sustaining 80% universal coverage with LLINs, meaning that 80% of all members of populations at risk of malaria should be sleeping under an ITN. Although this represents a move away from the previous emphasis on targeting pregnant women and children under five years, these vulnerable groups are still a priority for control programmes[
2].
The RBM strategic plan recommends that the 80% universal coverage target is achieved using a combination of campaigns and continuous channels such as routine antenatal clinics (ANC) and the expanded programme of immunization (EPI) for LLIN delivery[
2], the so-called “catch-up” and “keep-up” approach[
3]. According to the 2011 World Malaria Report, 38 African countries have adopted a policy of LLIN distribution through ANC clinics, 29 through EPI clinics, and 36 through mass campaigns (not mutually exclusive figures)[
4]. In practice, largely due to infrastructural challenges and equity concerns, significant emphasis has so far been placed on mass campaigns through which hundreds of millions of LLINs have been distributed in sub-Saharan Africa since 2002.
Despite these tremendous efforts, emerging data indicate that use of LLINs is not sustained at high levels over time. For example, in Togo and Sierra Leone, the percentage of children under five sleeping under a net dropped to around 50% a year after mass distribution campaigns, and was only 25-30% 18 months later[
5,
6]. In other countries such as Rwanda and Kenya, use has remained constant for a longer period after an initial dropout, albeit only half or less of children were using LLINs, which still falls considerably short of the 80% coverage target[
5]. Routine delivery can achieve high coverage among vulnerable groups, for example, a study of LLINs distributed free through ANC in one district in Uganda showed 99% retention and use seven months after distribution[
7]. Household ownership and use of LLINs by children under five both approximately doubled to around 80% and 60%, respectively, following free distribution to infants at completion of their EPI schedule in Malawi; no significant improvement in either indicator was seen in a comparison district[
8].
Nationally representative data on LLIN ownership and utilization used to measure progress towards the RBM targets is collected via standard RBM malaria modules included in Demographic and Health Surveys (DHS), UNICEF Multiple Indicator Cluster Surveys (MICS) and Malaria Indicator Surveys (MIS). However, questions on the source of LLINs being used by household members is a relatively recent addition and very few countries, therefore, have data on the relative contribution of campaigns and specific routine or continuous delivery channels (e g, ANC, EPI, school- or community-based delivery) to LLIN ownership[
9]. Thus, although the RBM strategic plan calls for a combination of routine and campaign delivery, there are currently few publicly documented studies or datasets from which strategy and implementation questions can be answered.
Coverage achieved by different delivery systems will influence the potential impact on mortality that LLIN programmes can have, likewise the well-documented discrepancy between ownership and use[
10]. Universal campaigns can at least initially achieve high coverage across the population, reducing transmission and potentially achieving high vector mortality, thereby protecting even those in the community not sleeping under nets. However, in addition to coverage, the timing at which LLINs reach children may also have important implications for optimizing mortality impact since risk of mortality and LLIN effectiveness are not constant parameters over time: risk of death from malaria tends to decrease with a child’s age in areas of high transmission, while the mortality burden may peak in older age groups as malaria transmission intensity decreases[
11]; and an LLIN gradually loses insecticide and gains holes, making it less effective over time[
12]. This study therefore hypothesized that the greatest potential impact on mortality will be achieved by covering children with a new LLIN at the age that they are most vulnerable. This may have implications for the optimal choice of delivery system or the delivery system mix.
It is clear from available evidence that campaigns alone are not currently achieving or sustaining the 80% targets for LLIN use[
5,
13,
14]. Conversely, it is unclear how routine delivery can be optimized to complement campaigns, as recommended by RBM. In the context of the Millennium Development Goals (MDG), there is a need to investigate potential achievements beyond improving universal ownership and use of LLINs towards impact on under-five mortality. To answer these questions in the absence of complete empirical data, a simple mathematical model has been designed that uses the best available data to make predictions about the expected impact of different LLIN distribution strategies. In addition to assessing which distribution strategies could maximize mortality impact, the model also explores the potential mortality impact per LLIN delivered, which is an intermediate step towards cost-effectiveness and value for money. Efficiency is increasingly important as malaria-endemic countries and their major health donors face increasing financing constraints for health programmes. For example after years of increase, global funding for malaria levelled off in 2010 compared to 2009[
15].
Discussion
This model supports the hypothesis that the maximum impact of LLINs in terms of reduction in under-five mortality will be achieved if a child receives and uses a new LLIN nearest to the age at which they are at greatest risk of dying from malaria. If delivering LLINs through two different channels, then a combination of one routine delivery channel that gives LLINs to infants together with a targeted or universal campaign is predicted to achieve optimal impact, since new nets reach both younger and older children. This analysis found that delivering nets through additional channels in any combination of ANC, EPI and a targeted or universal campaign always prevented a higher number of deaths (i e, saturation of LLINs in the community was not predicted). If considering ‘efficiency’ where the impact on mortality is presented in relation to the number of LLINs delivered, delivery of a very large number of nets will improve mortality outcomes but reduce efficiency since there will be some overlap in coverage. The balance between effectiveness and efficiency presents a dilemma for control programmes and ministries of health. This model predicts the greatest efficiency for delivery of LLINs through ANC or EPI if only one delivery channel is used; however these routine delivery systems alone do not achieve high enough coverage. Maximum effectiveness is achieved by delivering through as many channels as possible. Perhaps the compromise is LLIN delivery through one routine channel, the choice of which will depend upon context in terms of transmission intensity, together with regular campaigns, which would achieve good levels of effectiveness for a medium level of efficiency.
Nevertheless, the cost per LLIN delivered for each delivery system combination has to be considered. Provider-side financial cost per treated net delivered through routine ANC at district scale ranged from US$7.64 in Kenya[
32] to US$8.83 in Uganda[
7] and US$8.20 in Burkina Faso[
33]. National-level distribution through ANC in Eritrea had an estimated financial cost of US$10.67 per treated net[
34]. Provider-side financial cost per treated net delivered through a district-scale targeted campaign ranged from US$3.71 in Tanzania[
35] to US$11.53 in Ghana[
36] and $10.88 in Zambia[
37], where treated net delivery was integrated with immunization campaigns and US$8.30 in Uganda[
7] where LLINs were delivered through a stand-alone targeted campaign. Note, all figures are adjusted for inflation and are presented in 2010 US$[
38]. Although difficult to ascertain with confidence due to methodological differences in the studies, the data suggest that LLIN delivery costs are comparable across delivery channels; national-level routine net distributions in Eritrea and Malawi suggest that there may be economies of scale[
34,
39]. So far there are no published studies of the costs of universal campaigns, which represent a relatively recent shift in policy. Similarly, the authors are not aware of data on costs and effects of combinations of delivery channels
Equity should also be considered, and evidence suggests that the same children may be missed by all interventions[
40] due to low socio-economic status or living in remote areas that may be underserved even by mass campaigns. Although socio-economic equity tends to increase with LLIN coverage and will become less of an issue as coverage reaches over 80%[
41], sustained coverage of this magnitude is still elusive in most countries. It was considered that ANC and EPI attendance are not independent, with mothers more likely to attend both ANC and EPI or neither[
25], however it was assumed that LLIN delivery through routine and campaign channels is independent, which may not be correct, particularly if routine health facilities are utilized for mass campaign distribution. This assumption was made in large part due to a lack of empirical evidence on the level of overlap between children or households reached by routine and campaign LLINs; to overcome this limitation requires data on source of each LLIN in a household, not currently collected in a standard manner by nationally representative surveys. Furthermore correlations between individuals in a household in terms of net receipt or use were not considered.
The results presented here support the RBM-recommended strategy of a combination of routine and campaign LLIN delivery. However, the focus over the last few years has been on campaigns and the process of ‘catch up’ to progress towards the universal coverage goal. Reasonable results have been shown for a number of routine delivery strategies[
7,
8,
28,
34], although progress towards ownership and use targets is inevitably slower than that achieved by mass campaign distributions[
41], reflecting the complexity of delivering interventions through the infrastructure of a health system[
9]. Although many countries have policies for delivery of LLINs through ANC and/or EPI[
4], it is not clear that the policies are effectively implemented in all countries. The model predicts that without the contribution of routine LLINs then the mortality impact achievable in the under-five group by campaigns alone is less impressive, particularly in the years between campaigns, and achievement of the mortality MDG becomes less likely. More information is needed on the facilitating factors and barriers to successful LLIN distribution through routine channels. In addition, the question remains of how to reach the children likely to be missed by both routine and campaign channels; any LLIN delivery strategy is likely to need some mechanism of extended outreach for covering hard-to-reach individuals and communities[
40,
42].
This analysis used a simple model, which has the advantage of greater transparency and fewer assumptions about uncertain factors, but also has limitations. For example, the data used to model household structure and its influence on net use is specific to Tanzania and this may show different patterns in other countries with alternative household structures; it would be of interest to explore the effect of altering these parameters on model predictions in future analyses. The model also does not allow for changing immunity profiles as a result of LLIN introduction, which may shift mortality burden to older age groups. This factor was not included because the timescale over which immunity is lost is highly uncertain, and therefore any model dependent on this would be extremely reliant on which assumptions were made. So far there is no evidence that LLINs do shift mortality to older ages[
43‐
45]. However if such a change did occur, having good coverage of mass campaigns in combination with routine services would be especially important to ensure older as well as younger children access new and efficacious nets. Benefits to members of the population over five years old are not quantified, which may be important with declining malaria transmission levels in many countries. However the results are valid for under five-year-olds, and the decision to focus on this group reflects the importance of health impact for children under five in the early randomized controlled trials that demonstrated the potential of insecticide-treated nets as a highly effective malaria control tool, and the continued MDG focus on reducing child mortality as well as focus of health indicators on the under fives. The focus on under-fives has particular implications for the interpretation of the predicted impact of targeted campaigns, where further benefit was not tracked once the child is older than five years, nor use of the LLIN by others in the household after this time. Furthermore, the focus on under-five mortality only may underestimate the benefit of universal campaigns in comparison to campaigns targeted to the under fives[
10]. Ideally the model would be fitted to mortality reductions observed over time in one or more large-scale LLIN delivery programmes. However, a suitable dataset would require detailed data on LLIN distributions, household ownership, usage and mortality over time, which to our knowledge is not available in any existing dataset.
A constant relative risk of malaria mortality among LLIN users
vs non-users was assumed throughout the under-five cohort, as supported by evidence from an intervention trial[
20]. However in a different trial, insecticide-treated nets appeared to have a larger effect among younger children (<3 years)[
46]. If this is the case, the results presented in this analysis would underestimate the difference between the impact of ANC and EPI, compared to campaign delivery. This analysis also does not quantify benefits to the mother (or newborn) due to prevention of malaria in pregnancy by the use of an LLIN and, therefore, the benefit of ANC delivery is likely to be underestimated. The use of LLINs during pregnancy has been shown to increase mean birth weight and reduce the risk of miscarriages or stillbirth[
47]. Although maternal malaria appears to influence the risk of infant mortality[
48], this relationship is complex and the true magnitude of an effect or the potential reduction in infant mortality that may be achievable by LLIN use during pregnancy is unclear[
19,
49]. Therefore, these factors were not included in the current model in order to avoid the introduction of additional uncertainty and complexity.
One of the arguments for the expansion of LLIN delivery to all age groups rather than only the biologically vulnerable is the potential reduction in transmission and related health burden at the community level (the mass effect), which has been demonstrated by field data[
30,
50] and supported by mathematical models[
29,
51]. The inclusion of mass effect in this model goes some way to investigating the influence of universal coverage strategies on predicted health impact. Nevertheless, uncertainties remain around the threshold of LLIN use that is needed to achieve benefits for non-users[
29] and the present model predictions were sensitive to the inclusion and pattern of mass effect. The magnitude of impact was larger and the difference in impact between routine and campaign delivery was smaller when mass effect was included. More empirical field data is needed to understand the magnitude of benefits for non-users at different levels of LLIN use.
There is some evidence that the proportional reduction in all-cause under-five mortality achieved by insecticide-treated nets is higher at low transmission intensities[
1] but this variation is not well quantified and therefore was not included. While the exact mortality rate ratio affects the estimate of the number of deaths averted, it does not affect comparison of the relative impact of different delivery strategies. Malaria mortality is notoriously difficult to measure, since malaria symptoms resemble other illnesses and malaria may exacerbate other health conditions, causing indirect deaths; therefore, while the parameters in this model are based on detailed reviews[
11,
17‐
19], the absolute number of deaths prevented should be interpreted cautiously. Nonetheless, this analysis should provide a robust comparison of different strategies and broadly contrast areas where malaria deaths peak in younger
vs older children. We assumed homogeneous conditions across the modelled population, for example regarding transmission intensity and use of nets. To capture a more realistic heterogeneous population, for example to model potential impact of campaigns targeted at particular geographical areas, it would be necessary to vary these factors in order to represent sub-populations of interest.
Previous mathematical models have examined the effects of LLINs on malaria transmission at a population level, using a full transmission model framework and focusing on reductions in prevalence of infection and effects on the vector population[
51‐
53]; different modes of delivery and lifespan and efficacy of nets have also been considered[
53]. In this analysis a simpler framework is used and focus is specifically on mortality outcomes and the influence of overlap in net efficacy and age-specific mortality patterns within a vulnerable group, the under fives. Future work will incorporate these factors and outcomes within a full transmission model framework, enabling exploration of a range of outcomes in different age groups and the influence of dynamic changes in immunity and mortality impact of LLINs over time as transmission is reduced.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
JL, LSP, JW and KH devised the study design and objectives. LO developed the model. LO, LSP, JL, JW and KH contributed to parameterization, analysis and interpretation. LSP and LO wrote the first draft of the manuscript. All authors read, commented on and approved the final manuscript.