Advertisement
  • Loading metrics

Preventing Childhood Malaria in Africa by Protecting Adults from Mosquitoes with Insecticide-Treated Nets

  • Gerry F Killeen ,

    To whom correspondence should be addressed. E-mail: gkilleen@ihrdc.or.tz

    Affiliations Ifakara Health Research and Development Centre, Ifakara, Morogoro, United Republic of Tanzania , Department of Biological and Biomedical Sciences, University of Durham, Durham, United Kingdom

  • Tom A Smith,

    Affiliation Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, Switzerland

  • Heather M Ferguson,

    Affiliations Ifakara Health Research and Development Centre, Ifakara, Morogoro, United Republic of Tanzania , Division of Infection and Immunity, Glasgow University, Glasgow, United Kingdom , Division of Environmental and Evolutionary Biology, Glasgow University, Glasgow, United Kingdom

  • Hassan Mshinda,

    Affiliation Ifakara Health Research and Development Centre, Ifakara, Morogoro, United Republic of Tanzania

  • Salim Abdulla,

    Affiliation Ifakara Health Research and Development Centre, Ifakara, Morogoro, United Republic of Tanzania

  • Christian Lengeler,

    Affiliation Department of Public Health and Epidemiology, Swiss Tropical Institute, Basel, Switzerland

  • Steven P Kachur

    Affiliations Ifakara Health Research and Development Centre, Ifakara, Morogoro, United Republic of Tanzania , United States Public Health Service Commissioned Corps and Malaria Branch, Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

Preventing Childhood Malaria in Africa by Protecting Adults from Mosquitoes with Insecticide-Treated Nets

  • Gerry F Killeen, 
  • Tom A Smith, 
  • Heather M Ferguson, 
  • Hassan Mshinda, 
  • Salim Abdulla, 
  • Christian Lengeler, 
  • Steven P Kachur
PLOS
x

Abstract

Background

Malaria prevention in Africa merits particular attention as the world strives toward a better life for the poorest. Insecticide-treated nets (ITNs) represent a practical means to prevent malaria in Africa, so scaling up coverage to at least 80% of young children and pregnant women by 2010 is integral to the Millennium Development Goals (MDG). Targeting individual protection to vulnerable groups is an accepted priority, but community-level impacts of broader population coverage are largely ignored even though they may be just as important. We therefore estimated coverage thresholds for entire populations at which individual- and community-level protection are equivalent, representing rational targets for ITN coverage beyond vulnerable groups.

Methods and Findings

Using field-parameterized malaria transmission models, we show that high (80% use) but exclusively targeted coverage of young children and pregnant women (representing <20% of the population) will deliver limited protection and equity for these vulnerable groups. In contrast, relatively modest coverage (35%–65% use, with this threshold depending on ecological scenario and net quality) of all adults and children, rather than just vulnerable groups, can achieve equitable community-wide benefits equivalent to or greater than personal protection.

Conclusions

Coverage of entire populations will be required to accomplish large reductions of the malaria burden in Africa. While coverage of vulnerable groups should still be prioritized, the equitable and communal benefits of wide-scale ITN use by older children and adults should be explicitly promoted and evaluated by national malaria control programmes. ITN use by the majority of entire populations could protect all children in such communities, even those not actually covered by achieving existing personal protection targets of the MDG, Roll Back Malaria Partnership, or the US President's Malaria Initiative.

Editors' Summary

Background.

Malaria—a parasitic disease common in tropical and subtropical countries—causes about a million deaths every year, mainly among young children and pregnant women living in sub-Saharan Africa. The parasite responsible for most of these deaths is Plasmodium falciparum. Like all malaria parasites, it has a complex life cycle, part of which takes place inside mosquitoes. When a malaria-carrying mosquito bites a person (usually at night), parasites enter the human blood stream and travel to the liver where they reproduce before invading red blood cells. Here, they multiply again before bursting out and infecting more red blood cells as well as causing a high fever and sometimes damaging the nervous system, liver, and kidneys. When a mosquito bites someone who is infected, it often picks up parasites in its blood meal (mosquitoes need mammalian blood for successful reproduction), thus completing the malarial transmission cycle.

Why Was This Study Done?

One way to break this cycle and reduce malarial transmission is to decrease the number of contacts between people and mosquitoes by encouraging people to sleep under insecticide-treated nets (ITNs). Field studies have shown that ITN use reduces deaths from malaria, so the Roll Back Malaria Partnership, the United Nations Millennium Development Goals, and the US President's Malaria Initiative have set a target of at least 80% use of ITNs by young children and pregnant women (the people most vulnerable to malaria) by 2010. But would broader population coverage with ITNs interrupt the malarial transmission cycle more effectively? Might the wider use of ITNs (which both directly kill mosquitoes and repel them so that mosquitoes have to travel farther to get the blood they need to reproduce) be a more effective way to reduce local mosquito numbers and, consequently, human–mosquito contacts and malarial transmission? In this study, the researchers used mathematical modeling to ask how much community-wide coverage with ITNs is needed to protect vulnerable individuals against malaria without them personally using an ITN.

What Did the Researchers Do and Find?

The researchers developed a model for the transmission of the malaria parasite using data collected in Tanzanian villages where malaria is common, and used it to investigate how different patterns of ITN use might affect the individual protection of ITN users and the communal protection of nonusers. High (80%) coverage targeted at young children and pregnant women (less than 20% of the population) provided limited but valuable protection to these vulnerable individuals. However, the model predicted that a similar degree of community-wide protection would result if 35% of the whole population slept under ITNs provided there was no nonhuman blood supply for the mosquitoes. In other words, the vulnerable individuals in the population received the same degree of protection from this intervention as they would have got from personally using an ITN. If an alternative blood supply for the mosquitoes (for example, cattle) was included in the model, just over half of the population needed to sleep under ITNs to provide the same degree of community-wide protection as targeted ITN use.

What Do These Findings Mean?

Although the use of ITNs by vulnerable groups should remain a priority, these findings suggest that the wide-scale ITN use by the entire population should also be promoted. The use of ITNs by about half the population, predict the researchers, could protect all the young children in that population, even those who did not sleep under a net. As with all mathematical models, the accuracy of this prediction depends on the assumptions and data incorporated into the model. So before recommending community-wide use of ITNs, the actual level of communal protection provided by increased ITN coverage must be measured by rigorously evaluating ongoing national programmes. If such surveillance data confirm this model's predictions, wide coverage with ITNs might do more for public health in Africa than previously thought, suggest the researchers, provided the financial and logistical challenges associated with achieving high ITN coverage in this poor region of the world can be solved.

Additional Information.

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040229.

Introduction

The massive malaria burden in Africa merits particular attention as the world struggles to realize a better life for the poorest [1,2]. The Anopheles mosquitoes that act as vectors for human Plasmodium parasites must access sugar, blood, and aquatic oviposition sites to complete their life cycle and maintain parasite transmission. The availability of such ecological resources to mosquitoes has long been recognized as a crucial determinant of malaria transmission [3], but quantitative understanding of this process, as well as viable means to prevent it, remain poorly developed compared with other disease [4] and pest systems [5]. Recent theoretical work highlights the enormous influence of blood source and aquatic habitat availability in determining malaria transmission intensity, disease burden, and their responsiveness to various forms of control [612]. Here we apply field-parameterized kinetic models of mosquito host availability [11,13] to identify important shortcomings of current global targets for delivering insecticide treated nets (ITNs) [2,14,15], the most important vector control tool in Africa today. Not only does the model outline the limitations of existing strategies that emphasize targeting of vulnerable groups such as young children and pregnant women [1618], it also indicates how complementary strategies to promote coverage of whole populations, including nonvulnerable adults and older children [19], will achieve greater and more equitable reduction of disease burden than otherwise would be possible.

Insecticide-treated nets (ITNs) represent a practical and effective means to prevent malaria in Africa [20], so scaling up coverage to at least 80% use by young children and pregnant women by 2010 is a consensus target of the Millennium Development Goals (MDGs), the Roll Back Malaria Partnership, and the US President's Malaria Initiative [2,14,15]. Targeting individual protection to these vulnerable groups [1618] is a well-founded and explicitly accepted priority of all three initiatives, because these groups bear the highest risk of morbidity and mortality from malaria. However, this strategy largely ignores the potentially greater community-wide benefits of broader population coverage [19], and no explicit resources, targets, or strategies have been proposed to achieve these benefits.

ITNs can protect not only the individuals and households that use them, but also members of the surrounding community [19,2126]. This is because they kill adult mosquitoes directly or force them to undertake longer, more hazardous foraging expeditions in search of vertebrate blood and aquatic habits [11]. Plasmodium falciparum, the malaria parasite responsible for the bulk of deaths in Africa, requires at least 8 d to develop from imbibed gametocytes into mature sporozoites within the salivary glands of the vector mosquito. This means that most malaria transmission is carried out by mosquitoes that are at least 10 d old and have taken several previous blood meals at intervals of 2–5 d [27,28]. By even modestly increasing mosquito mortality while they attempt to feed on humans, ITNs can greatly reduce the number of mosquitoes that survive repeated hazardous encounters with protected humans [11]. Also, the excito-repellent properties of ITNs can reduce the frequency with which mosquitoes successfully acquire blood, often diverting them to feed on other mammals that do not host the malaria parasite, resulting in greatly reduced prevalence of sporozoite infection [11]. This theoretical rationale is strongly supported by detailed observations from experimental hut studies [2934] and from larger village-scale trials: ITNs have been clearly shown to reduce malaria risk among unprotected individuals by suppressing the density [3537], survival [3537], human blood indices [38,39], and feeding frequency [39] of malaria vector populations.

Large reductions of transmission are required to appreciably reduce malaria burden in most of Africa [17,40], particularly in the longer term as exposure and immunity re-equilibrate [41]. ITNs can address this challenging need through direct personal protection and area-wide suppression of the malaria transmission intensity that benefits even nonusers. It has been suggested that such communal benefits can make large impacts on disease burden only if appreciable levels of coverage are achieved in the human population as a whole [11,12,19], but precise coverage targets for achieving this remain to be determined. So how much coverage is enough to protect individuals who do not use an ITN?

Methods

Overview

Here we used recently developed kinetic models of mosquito behaviour and mortality [11,13] to answer this question by considering the impact of ITNs on human host availability and feeding hazards to mosquitoes, as well as the consequences of such changes for malaria transmission intensity. Protection was estimated in terms of protection against exposure to infectious mosquito bites, expressed as the relative change in the entomological inoculation rate (EIR). EIR is a proven epidemiological indicator of malaria transmission intensity and a key determinant of disease burden [17,40].

Two common but ecologically distinct African malaria transmission systems are considered. First, we modelled an Anopheles gambiae Giles or An. arabienis Patton (sibling species from the same species complex known as An. gambiae sensu lato) population with access to human blood only. Second, we considered An. arabiensis populations in the presence of abundant cattle, which can act as alternative blood sources. An. gambiae greatly prefers humans, but An. arabiensis will readily feed upon cattle [42,43], so populations of these species respond quite differently to increasing ITN coverage, with malaria transmission by the latter typically being lower to begin with but less sensitive to control with ITNs [11].

In both transmission systems we considered ITNs with properties typical of those evaluated in rigorous clinical trials [20] or those of emerging technologies with improved operational durability [4447]. Note that coverage is expressed as the proportion of the total human population using an ITN each night, rather than in terms of ownership, because this value is the most direct indicator of both personal and communal protection.

Figure 1 provides an overview of how mosquito behaviour and survival were modelled as a function of host availability, ITN properties, compliance, and coverage. The approach described is essentially a behaviourally explicit extension of existing vector biodemography [48] models, which predict epidemiologically relevant outcomes such as exposure to transmission (the biodemography–epidemiology model). The principles and utility of the biodemography–epidemiology models we have used [27,49,50], as well as several others that are based on similar assumptions [6,18,28,51], are well established. Notably, this family of models realistically assumes that mosquito behaviour cycles between host seeking, feeding, resting, oviposition-site seeking, oviposition, and back to host seeking again [51]. Similarly to recent analyses of the importance of oviposition [7,8,10] and host acquisition [11,12] processes, here we explicitly modelled the underlying behavioural events that determine the input parameters of these biodemographic processes (the behaviour–biodemography model). Detailed consideration of mosquito behaviour and mortality upon encounter with individual hosts (the individual-level submodel) allows simulation of the impact of ITNs upon the foraging requirements and risks for mosquito populations at the community level (the community-level submodel). This hierarchical approach links individual- and community-level submodels into an integrated behaviour–biodemography model, which drives the outcome of the biodemography–epidemiology model and allows the influence of ITNs upon malaria transmission intensity to be estimated in terms of EIR experienced by both users and nonusers [11,27,50].

thumbnail
Figure 1. A Schematic Outline of the Two-Tier Model Used for This Analysis, Adapted from Previous Detailed Descriptions

A detailed model of mosquito behaviour and survival as a function of host availability, ITN properties, compliance, and coverage [11,13] was used to estimate the key biodemographic parameters that determine malaria transmission intensity (behaviour–biodemography model). This model allowed the influence of ITN usage upon malaria transmission intensity to be estimated (biodemography–epidemiology model) in terms of EIR experienced by both users and nonusers [11,27,50]. All terms and symbols are defined in detail elsewhere [11,27,50,52] and are summarized in Methods.

https://doi.org/10.1371/journal.pmed.0040229.g001

The specific modelling approach described here is almost identical to our recent exploration of the optimal properties of ITNs as a function of local ecology [11], apart from subtle improvements in terms calculating mosquito diversion, mortality, and feeding probabilities per host encounter. It is also similar to and consistent with the approaches of others [6,12] but accounts for the fact that ITNs can act only during times of the night when they are actually in use, so that their overall protection is also influenced by subtle variations in the behavioural interactions between humans and mosquitoes [13]. This model has already been evaluated through improved iterations in terms of sensitivity to variations in the assumed parameter values for the insecticidal and excito-repellent properties of ITNs [11], the survival rate of mosquitoes while foraging for resources [11], the innate resource preferences of vector populations [11,50,52], and the availability of those resources, including oviposition sites [50] and alternative blood meal hosts [11,50].

While the analysis outlined here could be implemented with either of the recently developed (and perhaps more elegant) alternative models [6,12], this particular form captures all of the same processes without necessitating the mathematical subtleties of integration, differentiation, equilibrium analysis, or limits. While these are inherently valuable tools for mathematical modelling, they often constitute “black boxes” to nonmathematicians, including several authors of this article. We therefore chose a model that does not require mathematical complexities that might limit accessibility to some of the field biologists and epidemiologists for whom this analysis is most relevant. The model is presented as a downloadable spreadsheet (see Protocol S1) and has proven valuable for teaching the ecological basis of malaria epidemiology and control to students in both the developed and developing world.

Modelling Mosquito Behaviour and Mortality at the Individual Level

Here we describe a submodel of behavioural and mortality processes that occur at the level of individual mosquitoes seeking, encountering, attacking, and feeding upon individual blood hosts. Another important simplification to consider is that, like most deterministic malaria transmission models, our approach assumed a “malaria in a bottle” scenario in which populations of identical parasites, vectors, and hosts are mixed homogenously within an enclosed system [53]. One important corollary of this assumption is that well-established variations of vulnerability to malaria infection within human populations [16,17] or associated variations in attractiveness and availability to mosquitoes [9,5456] are not explicitly modelled.

As defined previously [52], the availability (a) of any host (j) of any species (s) is the product of the rate at which individual vectors encounter it s,j) and the probability that, once encountered, they will feed upon it s,j):

Note that this kinetic definition of availability as a rate per unit time is consistent with applications of the same term to acquisition of oviposition sites [10], the term attraction rate for blood sources [6,57], and the terms feeding rate and oviposition rate for both resources [8,12].

We considered successful feeding as just one of three possible outcomes of a host encounter by a female vector, the other two being death while attempting to feed and diversion to seek another host (Figure 1). We considered this a two-stage process in which the vector first either attacks the encountered host or is diverted away and searches for another, the probabilities of which we denote as γ and Δ, respectively. This definition of diversion includes the combined effects of noncontact repellency and contact-mediated irritancy, often referred to as excito-repellency [58,59]. Considering mean values for hosts of any given species (s), the sum of these two probabilities is:

We then considered the second stage of the blood acquisition process, namely feeding. Knowing the probabilities that the vector will either feed successfully s) or die in the attempt s) per attack (rather than per encounter) allowed us to calculate the probability of a successful feed per encounter:

Specifically, the cases of cattle (c) and unprotected humans (h,u) were dealt with in a straightforward manner as follows, where Δu and μu represent a common parameter value for both types of host (Table 1):

thumbnail
Table 1.

Behavioural and Host Availability Input Parameters for Both Vector Species

https://doi.org/10.1371/journal.pmed.0040229.t001

Personal protection measures such as bed nets, repellents, or domestic insecticide use were envisaged as three possible outcomes, the probabilities of which sum to 1: For a vector that would normally choose to feed upon an encountered unprotected human with a probability of ϕh,u, the presence of a net or other intervention is expected to influence this probability for protected humans h,p) as a function of the excess probability of diverting p) and killing p) that vector (Figure 1). The combined baseline and net-induced probabilities of diversion u + p) or mortality u + p) were calculated as follows: and

These parameters allowed us to calculate the feeding probability for a human who always uses and is protected by a net h,p):

These equations are parameterized using data from experimental hut trials in which the human participants slept within the net throughout the period of data collection (Table 1). However, very few human beings spend their entire day asleep or using a net [13] so the true probability of feeding upon a typical net user ( ) is calculated by weighting ϕh,u and ϕh,p according to the proportion of normal exposure during which the host is actually covered i):

Equations 5-7 differ slightly from those previously proposed [11], which treated diversion and killing as independent events, conditional on the host having and using a net. At low values of πi these changes relative to [11] make little difference, but the model described here is more realistic at high values of πi.

Extrapolating Impacts of Insecticide-Treated Nets to the Community Level

Given the above submodel for the interactions of mosquitoes with individual mammalian hosts, it was possible to extrapolate the likely large-area effects of these small-scale influences on entire vector populations and the human communities they feed upon.

For any given number of cattle (Nc), unprotected humans (Nh,u), and protected humans (Nh,p), the mean seeking interval for vertebrate hosts v) can be calculated as the reciprocal of total host availability (A) [52], using estimates of these feeding probabilities and their corresponding encounter rates, adapting Equation 1 from our original formulation [50]: where As refers to the total availability of all hosts of species s. In this case, the species or species categories considered were unprotected humans (h,u), protected humans (h,p), and cattle (c). Values for ac and ah,u (previously ah [50]) were estimated exactly as described previously [50] and ah,p was calculated as follows: where λp is the relative availability of protected versus unprotected hosts, estimated in terms of the ratio of their feeding probabilities:

Foraging for resources is an intrinsically dangerous undertaking for mosquitoes, and it is commonly assumed that survival during these phases is lower than while resting in houses [6,60]. We adapted Equation 3 from our previous formulation [50] to estimate the survival rate per feeding cycle (Pf) as the product of the probability of surviving the eventual attack on a host that may be protected (Pγ) and the probabilities of surviving the gestation (g), oviposition site-seeking o), and vertebrate host-seeking v) intervals, with distinct daily survival probabilities for the resting (P), foraging for either oviposition sites or vertebrate hosts (Pov), and attacking (Pγ) phases:

The mean probability of mosquitoes surviving their eventual chosen host attack (Pγ) was calculated assuming that the proportion of all attacks that end in death is the sum of the mortality probabilities for attacking protected and unprotected hosts, weighted according to the proportion of all encounters that will occur on such hosts. Assuming that protection does not affect encounter rates, and that these rates are proportional to availability when unprotected, we applied this weighting approach to estimate total attack-related mortality rate and consequent survival as follows:

Similarly, the human blood index is calculated as the proportion of total host availability accounted for by humans [52], similarly to Equation 9:

The EIR for protected and unprotected individuals was then calculated from the total number of infectious bites upon humans that occur in the population as a whole (β E) [27,49], the share of the total human availability represented by that group, and the population size of that group: where β is the mean number of infectious human bites each emerging mosquito takes in its lifetime and E is the emergence rate of mosquitoes [27]. Dividing Equation 16 by Equation 15, substituting with Equation 10, and rearranging also leads to an intuitively satisfactory solution, consistent with independently formulated models of personal protection [13]:

Otherwise, we modelled malaria transmission exactly as previously described [50]. Note that this model has been adapted [11,50] from its original formulation [27] to account for superinfection of mosquitoes [28] and daily time increments to smooth the effects of changing host availability patterns on feeding cycle length [50]. For ease of comparison and interpretation, the impact of ITNs is presented in terms of the relative transmission intensity EIRC/EIR0 at a given coverage level (C; note distinction from c, which denotes cattle hosts) as a result of personal and communal protection amongst users and nonusers:

Baseline Mosquito Behaviour, Host Availability, and Survival Parameters

The parameter definitions and values used to implement this analysis are summarized in Table 1. Namwawala, in the Kilombero Valley, southern Tanzania is the primary centre for parameterising our model because of the exceptionally detailed quantitative characterisation of malaria transmission and vector biodemography in this village and the surrounding area. This is a holoendemic village with intense seasonal transmission, stable high parasite prevalence in humans, and a heavy burden of clinical malaria [6168]. At this site the bulk of transmission is mediated by An. gambiae sensu lato (of which the main species involved in transmission is An. arabiensis) and transmission intensity has been modelled with available field data [27,49].

As previously described [27,49], we based our estimate of human population size [62] approximately upon those reported for this particular village during the early 1990s. Nevertheless, we used a human population size of 1,000 and, where relevant, a bovine population of the same size so that the EIR experienced by users and nonusers could be easily calculated at net coverage levels approaching 0% and 100%. By setting coverage to 0.001 or 0.999, this model simulates a single user or nonuser in the population, respectively.

Infectiousness of humans (κ) is set to 0.030, reflecting a more precise recent estimate [69] than was available previously [61,63]. In a typical holoendemic scenario, the infectiousness of the human population is thought to be largely insensitive to reductions in transmission intensity [69]. In the interests of making conservative and generalizable predictions, we assumed that increasing coverage with ITNs will not affect κ [69], even though reduction of κ is likely at EIR values below 10 infectious bites per person per year [56].

We set mean daily survival of the resting phase (P) at 0.90, reflecting a median value of daily survival at four well-characterised holoendemic sites [27] and estimated daily indoor survival for An. gambiae s.l. in Tanzania [70]. As previously described, the daily survival rate of mosquitoes while foraging for blood or oviposition sites (Pov) was set at 0.80, representing a median value of plausible field values [11]. The results of experimental hut studies [34] were combined with host-choice evaluations [71] and appropriate analytical models [50,52] to define the attack and mortality probabilities of An. arabiensis encountering cattle or humans: we set the probability that An. arabiensis will attack unprotected cattle or humans u), conditional upon encountering them, to be 0.90 and the chance that they will die in the attempt u) at 0.10.

Using these parameters and Equation 3, we calculated that, for An. arabiensis, the overall feeding probability upon either cattle c) or unprotected humans h,u) would be 0.81, a value similar to previous estimates of approximately 0.80–0.85 for the feeding success of An. gambiae sensu lato on sleeping humans in Tanzania [34,62]. We also applied these same probabilities of attacking u), feeding h,u), and dying u) to An. gambiae sensu stricto encountering unprotected humans. The availabilities of unprotected humans and cattle were calculated for An. arabiensis using field measurements of the duration of the feeding cycle and were extended to An. gambiae s.s., accounting for the lower estimated relative availability of cattle c) to this mosquito species as previously described [52]. Note that λc is assumed to modify ac by affecting the encounter rate only, indicating that these mosquitoes can differentiate between preferred and nonpreferred hosts at long ranges [7274]. In the case of An. arabiensis this assumption is consistent with the longer spatial range of attraction of cows relative to humans for zoophilic members of the An. gambiae complex [7274].

Parameters Reflecting the Effects of Insecticide-Treated Bed Nets

The parameter definitions and values describing the impacts of ITNs on vector behaviour and mortality at the level of individual interactions are listed in Table 1. The impacts of ITNs very much depend on their excito-repellent and insecticidal properties, which are most representatively evaluated using well-established experimental hut methodologies [59,75,76] that have been extensively applied to this particular intervention [2934]. Furthermore, the interaction of these two properties, to yield varying levels of personal and communal protection, is complex and has crucial implications for ITN programmes across Africa [11]. Sensitivity analysis of models similar to those used in this paper [11] have previously been used to explore the influence that these properties might have upon the magnitude and equity of protection afforded by ITNs (Figure 2). In order to validate this slightly revised model (see Equations 4-8) and similarly investigate such interactions at ITN coverage levels that can be plausibly sustained, we examined usage data collected during routine socioeconomic status surveys of a long-standing demographic surveillance system in the Kilombero Valley, southern Tanzania, where social marketing programmes have been well established since 1997 [77,78]. Data from the annual ITN usage survey in 2004 were used because they overlap with detailed entomological surveys of malaria transmission (which will be reported elsewhere). These surveys of randomly sampled residents from across two rural districts indicate that 75% (11,982/16,086) net use was achieved although most of these nets were not effectively treated [79]. In this sensitivity analysis, we assumed that new long-lasting ITN technologies [4447] will enable sustained coverage with nets that are effectively treated even under the most rigorous programmatic field conditions.

thumbnail
Figure 2. The Simulated Protection ITNs Afford against Exposure to Malaria Transmission as a Function of Their Ability to Divert and Kill Host-Seeking Mosquitoes

Protection is expressed as relative exposure to malaria transmission (EIRC/EIRo) for individuals with (Equation 19) and without (Equation 18) nets is plotted as a function of their ability to divert p) and kill p) mosquitoes attacking protected humans. To simulate the likely field properties of existing long-lasting insecticidal nets with a full range of insecticidal and excito-repellent properties, the parameters of this model reflecting increased mosquito mortality p) and diversion p) were varied across a plausible range of 0–0.8. As described in the main text and previous publications, these results represent simulations in two distinctive scenarios: An. gambiae sensu lato in the absence of cattle (results for both sibling species are identical) and An. arabiensis in the presence of one head of cattle per person. The biodemographic parameters of the interacting vector and parasite are also exactly as described previously [11,13] with survival of foraging mosquitoes (Pov) set at 0.8 per day. Coverage levels of 75% net usage was assumed, consistent with the results of surveys in the Kilombero Valley, southern Tanzania (see Methods: Parameters Reflecting the Effects of Insecticide-Treated Bed Nets).

https://doi.org/10.1371/journal.pmed.0040229.g002

Figure 2 shows that, for the comparatively zoophilic vector An. arabiensis, in the presence of alternative hosts, excito-repellency consistently enhances the benefits for both users and nonusers, regardless of the insecticidal properties of the net. Consistent with previous analyses using this model [11], this simulation suggests that nets that are purely excito-repellent and lack insecticidal properties could slightly increase exposure of nonusers to An. gambiae sensu lato by diverting mosquitoes to them where no alternative sources of blood are available. Thus, purely diversionary vector control strategies may indeed be ethically questionable, as was previously suggested [31,34,80,81]. Nevertheless, even modest insecticidal properties are expected to counterbalance this inequity and confer a useful communal reduction of EIR. While repellent properties do slightly reduce the benefits to nonusers exposed to anthropophagic vectors lacking an alternative host, this slight disadvantage is likely to be outweighed in practice by the advantage of improved personal protection for users: Excito-repellent properties and physical barriers add to the effectiveness of insecticides for personal protection because these two incentives constitute the major motivating force behind ITN uptake and use at the individual and subsequently the community level. It is also reassuring to note that the predictions and epidemiological implications of this slightly revised model are very similar to those reported for its previous iteration [11].

We therefore concluded that the simulations described in the main text should consider ITNs with both insecticidal and excito-repellent properties, consistent with those of products currently on the market that have been evaluated in a variety of settings and experimental designs.

To simulate the likely properties of established ITNs under programmatic conditions, we conservatively assumed they will both divert and kill 40% more mosquitoes than an unprotected human (μp = 0.4 and Δp = 0.4). A net with such proper-ties would protect against 64% of indoor exposure (1 − [(1 − 0.4) × (1 − 0.4)] = 0.64), as measured in a typical experimental hut trial [46,76]. To explore the best possible future scenario for the development of highly durable ITNs [4447] or regular retreatment services [82], we also simulated increasing co-verage with nets that divert and kill 80% more mosquitoes than with an unprotected human (μp = 0.8 and Δp = 0.8), providing 96% protection (1 − [(1 − 0.8) × (1 − 0.8)] = 0.96). The proportion of normal biting exposure that occurs while nets are actually in use i) has been estimated as 90% for A. gambiae in southern Tanzania [13], so we set πi to a value of 0.90.

Results

Figure 3 illustrates how increasing community-level protection of ITN nonusers and users alike combines with constant individual protection to reduce exposure to malaria. Regardless of vector species or the availability of alternative hosts, modestly effective conventional ITNs achieve much greater impact upon human exposure, even that of users, if approximately half or more of the whole human population is covered. While this principle has already been suggested by field trials [19] and two independently formulated models [11,12], here we have identified specific coverage thresholds at which communal protection becomes greater than or equal to individual personal protection. Where alternative hosts for vector mosquitoes are absent, 35% of the human population must sleep under regular ITNs to achieve equivalence of personal and communal protection mechanisms, resulting in major community-wide suppression of exposure. The same target is achieved at 55% coverage where alternative hosts such as cattle are present.

thumbnail
Figure 3. Relative Exposure to Malaria Transmission (EIRC/EIRo) as a Function of Increasing Coverage with Insecticide-Treated Nets

We express coverage as the proportion of the total human population using an ITN each night, and protection as the proportional reduction of infectious bites to which a resident is exposed (see Methods). Individual protection afforded to users (thin solid line; Equation 20) and communal protection afforded to nonusers (thick dashed line; Equation 18), as well as their combined effect on users (thick solid line; Equation 19) are separately calculated [11,13]. Two distinct but common and broadly distributed ecological scenarios in Africa are considered: (1) An. gambiae or An. arabienis (sibling species of the same species complex known as An. gambiae sensu lato) populations in the absence of alternative blood sources and (2) vector populations dominated by An. arabiensis in the presence of abundant cattle as alternative hosts. Both scenarios are simulated with ITNs that have either standard or improved properties (See Methods). Grey shading represents an approximate absolute maximum for community-level coverage achievable by covering vulnerable under five years of age and pregnant population groups only with perfect targeting efficiency. Arrows extrapolate the thresholds at which communal and personal protection are equivalent.

https://doi.org/10.1371/journal.pmed.0040229.g003

The insecticidal and excito-repellent properties of ITNs that define levels of personal protection also determine the extent of community-wide alleviation of exposure amongst users and nonusers alike [11], so improved ITN properties consistently result in improved overall impact. In our model, slightly higher usage rates were required to achieve equivalence of individual and communal effects, with thresholds of 40% and 64% coverage for vector populations with and without alternative hosts, respectively (Figure 3). While emerging ITN technologies with long-lasting insecticidal properties under programmatic conditions [44] would confer useful personal protection even at low coverage levels, personal protection was greatly enhanced by communal protection. At the 75% total population coverage recently achieved with largely untreated nets in southern Tanzania (Killeen et al., unpublished data), net users and nonusers are predicted to receive >98% and >90% protection, respectively, regardless of ecological scenario, if those nets were to be replaced with improved long-lasting insecticidal nets. Even for users of improved ITNs, this level of protection against African vector species is impossible without the contribution of community-level transmission suppression, because at least 10% of exposure occurs outdoors during times of the night when nets are not in use [13,83]. We conclude that modest coverage (thresholds of approximately 35%–65% use, depending on ecological scenario) of entire malaria-endemic populations, rather than just the most vulnerable minority, is needed to realize the full potential of ITNs, even with longer-lasting products or regular retreatment services [14,44]. This range of modelled thresholds is remarkably consistent with the figure of 50% suggested by large-scale field trials using approximately equivalent technology [19].

Discussion

In addition to the direct impacts on vector populations explicitly modelled above, coverage of adults and older children is likely to have further benefits arising from subtleties of mosquito resource utilization that are often under-appreciated. Over 80% of human-to-mosquito transmission originates from adults and children over five years of age, because these groups constitute the bulk of the population and are more attractive to mosquitoes [56]. Where the entomological inoculation rate is fewer than ten infectious bites per person per year, the distributions of infectiousness [56,69], morbidity, and mortality will all shift into these older age groups, necessitating protection of all members of the population. Under such conditions, ITNs could suppress transmission not only through direct impacts on mosquito mortality, host choice, and feeding frequency [11], but also by limiting the prevalence, density, and infectiousness of malaria parasites in the human population [56].

An under-emphasized feature of communal protection is the enhancement of ITN programme equity, regardless of ecological scenario or ITN effectiveness: If the majority of people living in malaria-endemic Africa regularly used existing ITN technologies, nonusers would receive communal protection at least equivalent to using the only ITN in an otherwise unprotected population (Figure 3). This means that all children would equitably receive communal protection at least equivalent to the personal protection of an ITN, with users receiving multiplicative combined effects on exposure of both personal and communal benefits. While the wisdom of targeting interventions to protect at-risk individuals is based on solid scientific grounds [9,18,84] and is widely accepted [16], this approach should not preclude efforts to maximize communal protection through less selective delivery mechanisms. Targeting limited subsidies to maximize personal protection of the most vulnerable should remain a priority, but more equitable and effective suppression of risk for entire populations, including vulnerable groups, can be attained with quite modest coverage across all ages. Most field evaluations of ITNs have been conducted at reasonably high coverage levels [19], and all five mortality trials [21,8588] that estimated that ITNs save 5.5 lives for every 1,000 children protected [20] covered large portions of entire communities rather than only the children themselves.

The choice of ITN delivery strategy has proven contentious in recent years [89,90], but proponents of both market-based and public-sector approaches equally emphasize targeting strategies [9,16,84] to enhance equity and minimize leakage of subsidized ITNs beyond intended target groups [9194]. While optimal targeting of finite subsidies is highly desirable, there are fundamental limitations to the impact that can be achieved: Even if resources were perfectly targeted, 80% coverage of pregnant women and children under five years of age could be accomplished with less than 20% coverage of the whole population, and even less of the total human host availability [11,56], as well as the infectious parasite reservoir [56,69]. Even if the ITN coverage targets of the MDGs were attained with flawless targeting efficiency, the substantial and equitable benefits of communal protection would not be achieved. Specifically, the target of 70% less exposure to transmission [13] would not be attained by the remaining minority of vulnerable individuals who are not covered and do not use an ITN, regardless of ecological scenario or ITN properties (Figure 3). We therefore highlight an important caveat to the following conclusion of the current Global Strategic Framework for ITN scaleup in Africa [95]: “In order to achieve maximum public health impact, ITN coverage needs to be maximized amongst those population groups that are most vulnerable to malaria infection and its consequences, primarily pregnant women and children under five years of age.”

Specifically, we conclude that protecting the vulnerable can achieve maximum public health impact only if complemented by strategies that also achieve broad coverage of the population as a whole.

In reality, the targets for coverage of vulnerable groups will not be reached without some leakage and inequity. Our analysis suggests that such concerns may be less of a problem than the targets themselves and may be minimized by extending coverage priorities to include all age groups. Fortunately, consensus is finally emerging that a range of approaches to ITN deployment merit investigation, development, and comparative evaluation at scales for which no precedent yet exists [95]. Note that this analysis supports the implementation of any of the diverse and rapidly emerging delivery strategies as long as high coverage with long-lasting ITNs is sustained across entire malaria-endemic populations on national scales. Perhaps the most important remaining question is: How can such population-wide coverage levels be affordably and cost-effectively sustained?

Growing financial support for malaria control globally [14,15,95] may enable fully subsidized provision to entire populations [82] of the world's most impoverished, malaria-afflicted nations. Existing evidence, based largely on individual protection alone, indicates that ITNs are as cost-effective as childhood immunization [96], and future analyses should explicitly consider the additional benefits of communal protection. Implementing this goal may be relatively straightforward for programmes that are primarily subsidized and implemented through the public sector, such as recent successful initiatives associated with vaccination campaigns [91]. By comparison, social marketing approaches, including hybrid systems that deliver public subsidies through the private sector, may require more detailed consideration, particularly where cost sharing with the target population is substantial and biased toward the nonpregnant adults and older children who are key to communal protection.

Although social marketing approaches to ITN distribution face substantial challenges [93,97,98], notable success in terms of coverage and impact have been reported in a variety of settings [94,99,100], including the KINET programme in Kilombero Valley, southern Tanzania where ITNs have been promoted and subsidized since 1996 [77,78]. Much of the essential experience generated by KINET was later integrated into the ITN promotion strategy of the National Malaria Control Programme of Tanzania, which supports private sector distribution through a voucher system that subsidizes purchase by vulnerable priority groups [101]. In the meantime, the preceding KINET pilot in Kilombero has achieved 75 % net use amongst randomly sampled residents of all ages (Killeen et al., unpublished data). It is particularly noteworthy that substantial levels of communal protection were achieved [102] (unpublished data) even though most of these nets were untreated or poorly treated at the time of evaluation [79] (unpublished data). Reassuringly, the model applied here approximately reproduces these patterns of communal protection using plausible parameter estimates for the net properties, vector behaviours, and host demographics of the area (unpublished data). We therefore recommend that the cost-effectiveness of such hybrid approaches be explicitly evaluated in terms of the complementary respective contributions of public-sector subsidies and cost-sharing by target populations to personal and communal protection.

While appropriate engagement and sensitization of malaria-afflicted populations is essential to the success of any ITN promotion programme, this is likely to be especially true where cost-sharing by the target population will be needed to complement limited public subsidies. Such cost-sharing schemes may be the only affordable means to support full population coverage where available subsidies are inadequate. In such resource-limited circumstances, high levels of awareness, acceptance, and willingness to pay will be essential to enable concerted use of ITNs by adults and shared protection of all children within their communities.

Overly confident extrapolation from mathematical models to set operational targets for malaria control has proved to be a grave mistake in the past [103]. A number of complications not captured by this model could emerge as ITN coverage increases, not least of which might be increased selection for insecticide resistance [104,105]. While we urge caution in interpreting the numerical results of our analysis, the phenomenon outlined is well established and has clear implications for malaria control in Africa and beyond [19]. In fact, the analysis presented here provides a generalizable rationale that strongly supports the conclusions of the most recent and meticulous evaluations of the community-level benefits of ITNs: “High coverage with ITNs will do more for public health in Africa than previously imagined” [19].

We therefore suggest that further field data, analyzed with appropriate theoretical models and cost-effectiveness frameworks, are required to verify and quantify the levels of communal protection afforded by increasing ITN use across Africa. International targets [2,14,15] should be amended to include thresholds for coverage of entire populations and monitored accordingly. By making life increasingly difficult for mosquitoes through programmes that promote ITN use by the majority of their human victims, it may be possible to protect the 15%–20% of children and pregnant women in African communities who would not otherwise be covered even if existing personal protection targets of the MDGs [2], the Roll Back Malaria Partnership [14], or the U.S. President's Malaria Initiative [15] were to be achieved.

Supporting Information

Protocol S1. Model Spreadsheet

A Microsoft Excel spreadsheet version of all model simulations presented here is available to download.

https://doi.org/10.1371/journal.pmed.0040229.sd001

(1.1 MB XLS)

Acknowledgments

We thank Dr. R. Nathan and the Ifakara Health Research and Development Centre demographic surveillance team for providing ITN coverage data, and the people of the Kilombero Valley in southern Tanzania for cheerfully participating in the series of surveys leading to this work. We thank Dr. R. Nathan, Dr J. R. M. Armstrong-Schellenberg, Dr. L. Slutzker, and Prof. S. W. Lindsay for their critical comments on the manuscript. The findings and conclusions presented in this paper are those of the authors and do not necessarily represent those of the United States Public Health Service nor the Centers for Disease Control and Prevention. This paper is published with kind permission of Dr A. Kitua, Director of the National Institute for Medical Research, United Republic of Tanzania.

Author Contributions

GFK formulated the model in consultation with TAS; conceived the study hypothesis in consultation with HMF, SA, and SPK; applied the model to test this hypothesis; and drafted the manuscript in consultation with all the other authors. TAS, HM, SA, and CL participated in design of the ITN surveys and contributed to drafting of the manuscript. HMF, SA, and SPK contributed to formulation of the hypothesis and drafting of the manuscript. All authors approved the final submitted version of the manuscript.

References

  1. 1. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI (2005) The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434: 214–217.RW SnowCA GuerraAM NoorHY MyintSI Hay2005The global distribution of clinical episodes of Plasmodium falciparum malaria.Nature434214217
  2. 2. Millennium Project (2005) Final report to United Nations Secretary General. London/Sterling VA: United Nations. 356 p.Millennium Project2005Final report to United Nations Secretary GeneralLondon/Sterling VAUnited Nations356
  3. 3. Ross R (1911) The prevention of malaria. London: Murray. 669 p.R. Ross1911The prevention of malariaLondonMurray669
  4. 4. Cohen JE, Gurtler RE (2001) Modeling household transmission of American trypanosomiasis. Science 293: 694–698.JE CohenRE Gurtler2001Modeling household transmission of American trypanosomiasis.Science293694698
  5. 5. Khan ZR, Ampong-Nyarko K, Chiliswa P, Hassanali A, Kimani S, et al. (1997) Intercropping increases parasitism of pests. Nature 388: 631–632.ZR KhanK. Ampong-NyarkoP. ChiliswaA. HassanaliS. Kimani1997Intercropping increases parasitism of pests.Nature388631632
  6. 6. Saul A (2003) Zooprophylaxis or zoopotentiation: The outcome of introducing animals on vector transmission is highly dependent on the mosquito mortality while searching. Malar J 2: 32.A. Saul2003Zooprophylaxis or zoopotentiation: The outcome of introducing animals on vector transmission is highly dependent on the mosquito mortality while searching.Malar J232
  7. 7. Smith DL, Dushoff J, McKenzie FE (2004) The risk of a mosquito-borne infection in a heterogeneous environment. PLoS Biol 2: e368.. DL SmithJ. DushoffFE McKenzie2004The risk of a mosquito-borne infection in a heterogeneous environment.PLoS Biol2e368.
  8. 8. Le Manach A, McKenzie FE, Flahault A, Smith DL (2005) The unexpected importance of mosquito oviposition behaviour for malaria: Non-productive larval habitats can be sources for malaria transmission. Malar J 4: 23.A. Le ManachFE McKenzieA. FlahaultDL Smith2005The unexpected importance of mosquito oviposition behaviour for malaria: Non-productive larval habitats can be sources for malaria transmission.Malar J423
  9. 9. Smith TA, Maire N, Dietz K, Killeen GF, Vounatsou P, et al. (2006) Relationship between entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria. Am J Trop Med Hyg 75(Suppl 2): 11–18.TA SmithN. MaireK. DietzGF KilleenP. Vounatsou2006Relationship between entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria.Am J Trop Med Hyg75(Suppl 2)1118
  10. 10. Gu W, Regens JL, Beier JC, Novak RJ (2006) Source reduction of mosquito larval habitats has unexpected consequences on malaria transmission. Proc Natl Acad Sci U S A 103: 17560–17563.W. GuJL RegensJC BeierRJ Novak2006Source reduction of mosquito larval habitats has unexpected consequences on malaria transmission.Proc Natl Acad Sci U S A1031756017563
  11. 11. Killeen GF, Smith TA (2007) Exploring the contributions of bednets, cattle, insecticides and excito-repellency to malaria control: A deterministic model of mosquito host-seeking behaviour and mortality. Trans R Soc Trop Med Hyg. GF KilleenTA Smith2007Exploring the contributions of bednets, cattle, insecticides and excito-repellency to malaria control: A deterministic model of mosquito host-seeking behaviour and mortality.Trans R Soc Trop Med HygIn press. In press.
  12. 12. Le Menach A, Takala S, McKenzie FE, Perisse A, Harris A, et al. (2007) An elaborated feeding cycle model for reductions in vectorial capacity of night-biting mosquitoes by insecticide-treated nets. Malar J 6: 10.A. Le MenachS. TakalaFE McKenzieA. PerisseA. Harris2007An elaborated feeding cycle model for reductions in vectorial capacity of night-biting mosquitoes by insecticide-treated nets.Malar J610
  13. 13. Killeen GF, Kihonda J, Lyimo E, Okech FR, Kotas ME, et al. (2006) Quantifying behavioural interactions between humans and mosquitoes: Evaluating the protective efficacy of insecticidal nets against malaria transmission in rural Tanzania. BMC Infect Dis 6: 161.GF KilleenJ. KihondaE. LyimoFR OkechME Kotas2006Quantifying behavioural interactions between humans and mosquitoes: Evaluating the protective efficacy of insecticidal nets against malaria transmission in rural Tanzania.BMC Infect Dis6161
  14. 14. Roll Back Malaria Partnership (2005) Roll Back Malaria Global Strategic Plan 2005–2015. Geneva: WHO. 52 p. Roll Back Malaria Partnership2005Roll Back Malaria Global Strategic Plan 2005–2015Geneva: WHO52Available at: http://www.rollbackmalaria.org/forumV/docs/gsp_en.pdf. Accessed 28 May 2007. Available at: http://www.rollbackmalaria.org/forumV/docs/gsp_en.pdf. Accessed 28 May 2007.
  15. 15. (2006) The US President's Malaria Initiative. Lancet 368: 1.2006The US President's Malaria Initiative.Lancet3681
  16. 16. Nafo-Traore F, Judd EJ, Okwo-Bele J-M (2005) Protecting vulnerable groups in malaria-endemic areas in Africa through accelerated deployment of insecticide-treated nets: A joint WHO-UNICEF statement. Geneva: WHO/UNICEF. 2 p. F. Nafo-TraoreEJ JuddJ-M Okwo-Bele2005Protecting vulnerable groups in malaria-endemic areas in Africa through accelerated deployment of insecticide-treated nets: A joint WHO-UNICEF statementGenevaWHO/UNICEF2Publication number WHO/HTM/RBM/2005.57. Available at: http://www.who.int/malaria/rbm/Attachment/20050318/RBM-UNICEF-english3.pdf. Accessed 28 May 2007. Publication number WHO/HTM/RBM/2005.57. Available at: http://www.who.int/malaria/rbm/Attachment/20050318/RBM-UNICEF-english3.pdf. Accessed 28 May 2007.
  17. 17. Smith DL, Dushoff J, Snow RW, Hay SI (2005) The entomological inoculation rate and Plasmodium falciparum infection in African children. Nature 438: 492–495.DL SmithJ. DushoffRW SnowSI Hay2005The entomological inoculation rate and Plasmodium falciparum infection in African children.Nature438492495
  18. 18. Smith DL, McKenzie FE, Snow RW, Hay SI (2007) Revisiting the basic reproductive number for malaria and its implications for malaria control. PLoS Biol 5: e42.. DL SmithFE McKenzieRW SnowSI Hay2007Revisiting the basic reproductive number for malaria and its implications for malaria control.PLoS Biol5e42.
  19. 19. Hawley WA, Phillips-Howard PA, ter Kuile FO, Terlouw DJ, Vulule JM, et al. (2003) Community-wide effects of permethrin-treated bednets on child mortality and malaria morbidity in western Kenya. Am J Trop Med Hyg 68(Suppl 4): 121–127.WA HawleyPA Phillips-HowardFO ter KuileDJ TerlouwJM Vulule2003Community-wide effects of permethrin-treated bednets on child mortality and malaria morbidity in western Kenya.Am J Trop Med Hyg68(Suppl 4)121127
  20. 20. Lengeler C (2004) Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database Syst Rev: CD000363. C. Lengeler2004Insecticide-treated bed nets and curtains for preventing malaria.Cochrane Database Syst Rev: CD000363
  21. 21. Binka FN, Indome F, Smith T (1998) Impact of spatial distribution of permethrin-impregnated bed nets on child mortality in rural Northern Ghana. Am J Trop Med Hyg 59: 8085.FN BinkaF. IndomeT. Smith1998Impact of spatial distribution of permethrin-impregnated bed nets on child mortality in rural Northern Ghana.Am J Trop Med Hyg598085
  22. 22. Gimnig JE, Kolczak MS, Hightower AW, Vulule JM, Schoute E, et al. (2003) Effect of permethrin-treated bed nets on the spatial distribution of malaria vectors in western Kenya. Am J Trop Med Hyg 68: 115–120.JE GimnigMS KolczakAW HightowerJM VululeE. Schoute2003Effect of permethrin-treated bed nets on the spatial distribution of malaria vectors in western Kenya.Am J Trop Med Hyg68115120
  23. 23. Gimnig JE, Vulule JM, Lo TQ, Kamau L, Kolczak MS, et al. (2003) Impact of permethrin-treated bed nets on entomologic indices in an area of intense year-round malaria transmission. Am J Trop Med Hyg 68: 16–22.JE GimnigJM VululeTQ LoL. KamauMS Kolczak2003Impact of permethrin-treated bed nets on entomologic indices in an area of intense year-round malaria transmission.Am J Trop Med Hyg681622
  24. 24. Hii JLK, Smith T, Vounatsou P, Alexander N, Mai A, et al. (2001) Area effects of bednet use in a malaria-endemic area in Papua New Guinea. Trans R Soc Trop Med Hyg 95: 7–13.JLK HiiT. SmithP. VounatsouN. AlexanderA. Mai2001Area effects of bednet use in a malaria-endemic area in Papua New Guinea.Trans R Soc Trop Med Hyg95713
  25. 25. Howard SC, Omumbo J, Nevill CG, Some ES, Donnelly CA, et al. (2000) Evidence for a mass community effect of insecticide treated bednets on the incidence of malaria on the Kenyan coast. Trans R Soc Trop Med Hyg 94: 357–360.SC HowardJ. OmumboCG NevillES SomeCA Donnelly2000Evidence for a mass community effect of insecticide treated bednets on the incidence of malaria on the Kenyan coast.Trans R Soc Trop Med Hyg94357360
  26. 26. Maxwell CA, Msuya E, Sudi M, Njunwa KJ, Carneiro IA, et al. (2002) Effect of community-wide use of insecticide-treated nets for 3–4 years on malarial morbidity in Tanzania. Trop Med Int Health 7: 1003–1008.CA MaxwellE. MsuyaM. SudiKJ NjunwaIA Carneiro2002Effect of community-wide use of insecticide-treated nets for 3–4 years on malarial morbidity in Tanzania.Trop Med Int Health710031008
  27. 27. Killeen GF, McKenzie FE, Foy BD, Schieffelin C, Billingsley PF, et al. (2000) A simplified model for predicting malaria entomologic inoculation rates based on entomologic and parasitologic parameters relevant to control. Am J Trop Med Hyg 62: 535–544.GF KilleenFE McKenzieBD FoyC. SchieffelinPF Billingsley2000A simplified model for predicting malaria entomologic inoculation rates based on entomologic and parasitologic parameters relevant to control.Am J Trop Med Hyg62535544
  28. 28. Smith DL, McKenzie FE (2004) Statics and dynamics of malaria infection in Anopheles mosquitoes. Malar J 3: 13.DL SmithFE McKenzie2004Statics and dynamics of malaria infection in Anopheles mosquitoes.Malar J313
  29. 29. Lindsay SW, Snow RW, Broomfield GL, Semega Janneh M, Wirtz RA, et al. (1989) Impact of permethrin-treated bednets on malaria transmission by the Anopheles gambaie complex in The Gambia. Med Vet Entomol 3: 263–271.SW LindsayRW SnowGL BroomfieldM. Semega JannehRA Wirtz1989Impact of permethrin-treated bednets on malaria transmission by the Anopheles gambaie complex in The Gambia.Med Vet Entomol3263271
  30. 30. Lindsay SW, Adiamah JH, Miller JE, Armstrong JRM (1991) Pyrethroid-treated bednet effects on mosquitoes of the Anopheles gambiae complex. Med Vet Entomol 5: 477–483.SW LindsayJH AdiamahJE MillerJRM Armstrong1991Pyrethroid-treated bednet effects on mosquitoes of the Anopheles gambiae complex.Med Vet Entomol5477483
  31. 31. Lindsay SW, Adiamah JH, Armstrong JRM (1992) The effect of permethrin-impregnated bed nets on house entry by mosquitoes in The Gambia. Bull Entomol Res 82: 49–55.SW LindsayJH AdiamahJRM Armstrong1992The effect of permethrin-impregnated bed nets on house entry by mosquitoes in The Gambia.Bull Entomol Res824955
  32. 32. Miller JE, Lindsay SW, Armstrong JRM (1991) Experimental hut trials of bednet impregnated with synthetic pyrethroid and organophosphate insecticides for mosquito control in The Gambia. Med Vet Entomol 5: 465–476.JE MillerSW LindsayJRM Armstrong1991Experimental hut trials of bednet impregnated with synthetic pyrethroid and organophosphate insecticides for mosquito control in The Gambia.Med Vet Entomol5465476
  33. 33. Pleass RJ, Armstrong JRM, Curtis CF, Jawara M, Lindsay SW (1993) Comparison of permethrin treatments for bednets in The Gambia. Bull Entomol Research 83: 133–140.RJ PleassJRM ArmstrongCF CurtisM. JawaraSW Lindsay1993Comparison of permethrin treatments for bednets in The Gambia.Bull Entomol Research83133140
  34. 34. Lines JD, Myamba J, Curtis CF (1987) Experimental hut trials of permethrin-impregnated mosquito nets and eave curtains against malaria vectors in Tanzania. Med Vet Entomol 1: 37–51.JD LinesJ. MyambaCF Curtis1987Experimental hut trials of permethrin-impregnated mosquito nets and eave curtains against malaria vectors in Tanzania.Med Vet Entomol13751
  35. 35. Carnevale P, Robert V, Boudin C, Halna JM, Pazart L, et al. (1988) La lutte contre le plaudisme par des moustiquaires impregnees de pyrethroides au Burkina Faso. Bull Soc Path Ex 81: 832–846.P. CarnevaleV. RobertC. BoudinJM HalnaL. Pazart1988La lutte contre le plaudisme par des moustiquaires impregnees de pyrethroides au Burkina Faso.Bull Soc Path Ex81832846
  36. 36. Magesa SM, Wilkes TJ, Mnzava AEP, Njunwa KJ, Myamba J, et al. (1991) Trial of pyrethroid impregnated bednets in an area of Tanzania holoendemic for malaria. Part 2: Effects on the malaria vector population. Acta Tropica 49: 97–108.SM MagesaTJ WilkesAEP MnzavaKJ NjunwaJ. Myamba1991Trial of pyrethroid impregnated bednets in an area of Tanzania holoendemic for malaria. Part 2: Effects on the malaria vector population.Acta Tropica4997108
  37. 37. Robert V, Carnevale P (1991) Influence of deltamethrin treatment of bed nets on malaria transmission in the Kou valley, Burkina Faso. Bull World Health Organ 69: 735–740.V. RobertP. Carnevale1991Influence of deltamethrin treatment of bed nets on malaria transmission in the Kou valley, Burkina Faso.Bull World Health Organ69735740
  38. 38. Bøgh C, Pedersen EM, Mukoko DA, Ouma JH (1998) Permethrin-impregnated bed net effects on resting and feeding behaviour of lymphatic filariasis vector mosquitoes in Kenya. Med Vet Entomol 12: 52–59.C. BøghEM PedersenDA MukokoJH Ouma1998Permethrin-impregnated bed net effects on resting and feeding behaviour of lymphatic filariasis vector mosquitoes in Kenya.Med Vet Entomol125259
  39. 39. Charlwood JD, Qassim M, Elnsur EI, Donnelly M, Petrarca V, et al. (2001) The impact of indoor residual spraying with malathion on malaria in refugee camps eastern Sudan. Acta Tropica 80: 1–8.JD CharlwoodM. QassimEI ElnsurM. DonnellyV. Petrarca2001The impact of indoor residual spraying with malathion on malaria in refugee camps eastern Sudan.Acta Tropica8018
  40. 40. Smith TA, Leuenberger R, Lengeler C (2001) Child mortality and malaria transmission intensity in Africa. Trends Parasitol 17: 145–149.TA SmithR. LeuenbergerC. Lengeler2001Child mortality and malaria transmission intensity in Africa.Trends Parasitol17145149
  41. 41. Maire N, Tediosi F, Ross A, Smith TA (2006) Predictions of the epidemiological impact of introducing a pre-erythrocytic vaccine into the expanded program on immunization in sub-Saharan Africa. Am J Trop Med Hyg 75(Suppl 2): 111–118.N. MaireF. TediosiA. RossTA Smith2006Predictions of the epidemiological impact of introducing a pre-erythrocytic vaccine into the expanded program on immunization in sub-Saharan Africa.Am J Trop Med Hyg75(Suppl 2)111118
  42. 42. Gillies MT, Coetzee M (1987) A supplement to the Anophelinae of Africa South of the Sahara (Afrotropical region). Johannesburg: South African Medical Research Institute. 156 p.MT GilliesM. Coetzee1987A supplement to the Anophelinae of Africa South of the Sahara (Afrotropical region)JohannesburgSouth African Medical Research Institute156
  43. 43. White GB (1974) Anopheles gambiae complex and disease transmission in Africa. Trans R Soc Trop Med Hyg 68: 279–301.GB White1974Anopheles gambiae complex and disease transmission in Africa.Trans R Soc Trop Med Hyg68279301
  44. 44. Guillet P, Alnwick D, Cham MK, Neira M, Zim M, et al. (2001) Long-lasting treated mosquito nets: A breakthrough in malaria prevention. Bull World Health Organ 79: 998.P. GuilletD. AlnwickMK ChamM. NeiraM. Zim2001Long-lasting treated mosquito nets: A breakthrough in malaria prevention.Bull World Health Organ79998
  45. 45. Graham K, Kayedi MH, Maxwell C, Kaur H, Rehman H, et al. (2005) Multi-country field trials comparing wash-resistance of PermaNet and conventional insecticide-treated nets against anopheline and culicine mosquitoes. Med Vet Entomol 19: 72–83.K. GrahamMH KayediC. MaxwellH. KaurH. Rehman2005Multi-country field trials comparing wash-resistance of PermaNet and conventional insecticide-treated nets against anopheline and culicine mosquitoes.Med Vet Entomol197283
  46. 46. Maxwell CA, Myamba J, Magoma J, Rwegoshora RT, Magesa SM, et al. (2006) Tests of Olyset nets by bioassay and in experimental huts. J Vector Borne Dis 43: 1–6.CA MaxwellJ. MyambaJ. MagomaRT RwegoshoraSM Magesa2006Tests of Olyset nets by bioassay and in experimental huts.J Vector Borne Dis4316
  47. 47. Asidi AN, N'Guessan R, Hutchinson RA, Traore-Lamizana M, Carnevale P, et al. (2004) Experimental hut comparisons of nets treated with carbamate or pyrethroid insecticides, washed or unwashed, against pyrethroid-resistant mosquitoes. Med Vet Entomol 18: 134–140.AN AsidiR. N'GuessanRA HutchinsonM. Traore-LamizanaP. Carnevale2004Experimental hut comparisons of nets treated with carbamate or pyrethroid insecticides, washed or unwashed, against pyrethroid-resistant mosquitoes.Med Vet Entomol18134140
  48. 48. Carey JR (2001) Insect biodemography. Ann Rev Entomol 46: 79–110.JR Carey2001Insect biodemography.Ann Rev Entomol4679110
  49. 49. Killeen GF, McKenzie FE, Foy BD, Schieffelin C, Billingsley PF, et al. (2000) The potential impacts of integrated malaria transmission control on entomologic inoculation rate in highly endemic areas. Am J Trop Med Hyg 62: 545–551.GF KilleenFE McKenzieBD FoyC. SchieffelinPF Billingsley2000The potential impacts of integrated malaria transmission control on entomologic inoculation rate in highly endemic areas.Am J Trop Med Hyg62545551
  50. 50. Killeen GF, Seyoum A, Knols BGJ (2004) Rationalizing historical successes of malaria control in Africa in terms of mosquito resource availability management. Am J Trop Med Hyg 71(Suppl 2): 87–93.GF KilleenA. SeyoumBGJ Knols2004Rationalizing historical successes of malaria control in Africa in terms of mosquito resource availability management.Am J Trop Med Hyg71(Suppl 2)8793
  51. 51. Saul AJ, Graves PM, Kay BH (1990) A cyclical feeding model for pathogen transmission and its application to determine vectorial capacity from vector infection rates. J Appl Ecol 27: 123–133.AJ SaulPM GravesBH Kay1990A cyclical feeding model for pathogen transmission and its application to determine vectorial capacity from vector infection rates.J Appl Ecol27123133
  52. 52. Killeen GF, McKenzie FE, Foy BD, Bøgh C, Beier JC (2001) The availability of potential hosts as a determinant of feeding behaviours and malaria transmission by mosquito populations. Trans R Soc Trop Med Hyg 95: 469–476.GF KilleenFE McKenzieBD FoyC. BøghJC Beier2001The availability of potential hosts as a determinant of feeding behaviours and malaria transmission by mosquito populations.Trans R Soc Trop Med Hyg95469476
  53. 53. Killeen GF, Knols BG, Gu W (2003) Taking malaria transmission out of the bottle: Implications of mosquito dispersal for vector-control interventions. Lancet Infect Dis 3: 297–303.GF KilleenBG KnolsW. Gu2003Taking malaria transmission out of the bottle: Implications of mosquito dispersal for vector-control interventions.Lancet Infect Dis3297303
  54. 54. Lindsay S, Ansell J, Selman C, Cox V, Hamilton K, et al. (2000) Effect of pregnancy on exposure to malaria mosquitoes. Lancet 355: 1972.S. LindsayJ. AnsellC. SelmanV. CoxK. Hamilton2000Effect of pregnancy on exposure to malaria mosquitoes.Lancet3551972
  55. 55. Lacroix R, Mukabana WR, Gouagna LC, Koella JC (2005) Malaria infection increases attractiveness of humans to mosquitoes. PLoS Biol 3: e298.. R. LacroixWR MukabanaLC GouagnaJC Koella2005Malaria infection increases attractiveness of humans to mosquitoes.PLoS Biol3e298.
  56. 56. Ross A, Killeen GF, Smith TA (2006) Relationships of host infectivity to mosquitoes and asexual parasite density in Plasmodium falciparum. Am J Trop Med Hyg 75(Suppl 2): 32–37.A. RossGF KilleenTA Smith2006Relationships of host infectivity to mosquitoes and asexual parasite density in Plasmodium falciparum.Am J Trop Med Hyg75(Suppl 2)3237
  57. 57. Sota T, Mogi M (1989) Effectiveness of zooprophylaxis in malaria control: A theoretical inquiry with a model for mosquito populations with two bloodmeal hosts. Med Vet Entomol 3: 337–345.T. SotaM. Mogi1989Effectiveness of zooprophylaxis in malaria control: A theoretical inquiry with a model for mosquito populations with two bloodmeal hosts.Med Vet Entomol3337345
  58. 58. Muirhead-Thomson RC (1960) The significance of irritability, behaviouristic avoidance and allied phenomena in malaria eradication. Bull World Health Organ 22: 721–734.RC Muirhead-Thomson1960The significance of irritability, behaviouristic avoidance and allied phenomena in malaria eradication.Bull World Health Organ22721734
  59. 59. Roberts DR, Alecrim WD, Hshieh P, Grieco JP, Bangs M, et al. (2000) A probability model of vector behavior: Effects of DDT repellency, irritancy, and toxicity in malaria control. J Vector Ecol 25: 48–61.DR RobertsWD AlecrimP. HshiehJP GriecoM. Bangs2000A probability model of vector behavior: Effects of DDT repellency, irritancy, and toxicity in malaria control.J Vector Ecol254861
  60. 60. Kelly DW, Thompson CE (2000) Epidemiology and optimal foraging: Modeling the ideal free distribution of insect vectors. Parasitology 120: 319–327.DW KellyCE Thompson2000Epidemiology and optimal foraging: Modeling the ideal free distribution of insect vectors.Parasitology120319327
  61. 61. Charlwood JD, Kihonda J, Sama S, Billingsley PF, Hadji H, et al. (1995) The rise and fall of Anopheles arabiensis (Diptera: Culicidae) in a Tanzanian village. Bull Entomol Res 85: 37–44.JD CharlwoodJ. KihondaS. SamaPF BillingsleyH. Hadji1995The rise and fall of Anopheles arabiensis (Diptera: Culicidae) in a Tanzanian village.Bull Entomol Res853744
  62. 62. Charlwood JD, Smith T, Kihonda J, Heiz B, Billingsley PF, et al. (1995) Density independent feeding success of malaria vectors (Diptera: Culicidae) in Tanzania. Bull Entomol Res 85: 29–35.JD CharlwoodT. SmithJ. KihondaB. HeizPF Billingsley1995Density independent feeding success of malaria vectors (Diptera: Culicidae) in Tanzania.Bull Entomol Res852935
  63. 63. Charlwood JD, Smith T, Billingsley PF, Takken W, Lyimo EOL, et al. (1997) Survival and infection probabilities of anthropophagic anophelines from an area of high prevalence of Plasmodium falciparum in humans. Bull Entomol Res 87: 445–453.JD CharlwoodT. SmithPF BillingsleyW. TakkenEOL Lyimo1997Survival and infection probabilities of anthropophagic anophelines from an area of high prevalence of Plasmodium falciparum in humans.Bull Entomol Res87445453
  64. 64. Charlwood JD, Smith T, Lyimo E, Kitua AY, Masanja H, et al. (1998) Incidence of Plasmodium falciparum infection in infants in relation to exposure to sporozoite-infected anophelines. Am J Trop Med Hyg 59: 243–251.JD CharlwoodT. SmithE. LyimoAY KituaH. Masanja1998Incidence of Plasmodium falciparum infection in infants in relation to exposure to sporozoite-infected anophelines.Am J Trop Med Hyg59243251
  65. 65. Kitua AY, Smith T, Alonso PL, Masanja H, Urassa H, et al. (1996) Plasmodium falciparum malaria in the first year of life in an area of intense and perenial transmssion. Trop Med Intl Health 1: 475–484.AY KituaT. SmithPL AlonsoH. MasanjaH. Urassa1996Plasmodium falciparum malaria in the first year of life in an area of intense and perenial transmssion.Trop Med Intl Health1475484
  66. 66. Smith T, Charlwood JD, Kihonda J, Mwankusye S, Billingsley P, et al. (1993) Absence of seasonal variation in malaria parasitemia in an area of intense seasonal transmission. Acta Tropica 54: 55–72.T. SmithJD CharlwoodJ. KihondaS. MwankusyeP. Billingsley1993Absence of seasonal variation in malaria parasitemia in an area of intense seasonal transmission.Acta Tropica545572
  67. 67. Smith T, Charlwood JD, Takken W, Tanner M, Spiegelhalter DJ (1995) Mapping densities of malaria vectors within a single village. Acta Tropica 59: 1–18.T. SmithJD CharlwoodW. TakkenM. TannerDJ Spiegelhalter1995Mapping densities of malaria vectors within a single village.Acta Tropica59118
  68. 68. Smith T, Charlwood JD, Kitua AY, Masanja H, Mwankusye S, et al. (1998) Relationship of malaria morbidity with exposure to Plasmodium falciparum in young children in a highly endemic area. Am J Trop Med Hyg 59: 252–257.T. SmithJD CharlwoodAY KituaH. MasanjaS. Mwankusye1998Relationship of malaria morbidity with exposure to Plasmodium falciparum in young children in a highly endemic area.Am J Trop Med Hyg59252257
  69. 69. Killeen GF, Ross A, Smith TA (2006) Infectiousness of malaria-endemic human populations to vector mosquitoes. Am J Trop Med Hyg 76(Suppl 2): 38–45.GF KilleenA. RossTA Smith2006Infectiousness of malaria-endemic human populations to vector mosquitoes.Am J Trop Med Hyg76(Suppl 2)3845
  70. 70. Gillies MT (1954) Studies in house-leaving and outside resting of Anopheles gambiae Giles and Anopheles funestus Giles in East Africa. Bull Entomol Res 45: 375–387.MT Gillies1954Studies in house-leaving and outside resting of Anopheles gambiae Giles and Anopheles funestus Giles in East Africa.Bull Entomol Res45375387
  71. 71. White GB, Magayuka SA, Boreham PFL (1972) Comparative studies on sibling species of the Anopheles gambiae Giles complex (Dipt., Culicidae): Bionomics and vectorial activity of species A and species B at Segera, Tanzania. Bull Entomol Res 62: 295–317.GB WhiteSA MagayukaPFL Boreham1972Comparative studies on sibling species of the Anopheles gambiae Giles complex (Dipt., Culicidae): Bionomics and vectorial activity of species A and species B at Segera, Tanzania.Bull Entomol Res62295317
  72. 72. Gillies MT, Wilkes TJ (1969) A comparison of the range of attraction of animal baits for some West African mosquitoes. Bull Entomol Res 59: 441–456.MT GilliesTJ Wilkes1969A comparison of the range of attraction of animal baits for some West African mosquitoes.Bull Entomol Res59441456
  73. 73. Gillies MT, Wilkes TJ (1970) The range of attraction of single baits for some West African mosquitoes. Bull Entomol Res 60: 225–235.MT GilliesTJ Wilkes1970The range of attraction of single baits for some West African mosquitoes.Bull Entomol Res60225235
  74. 74. Gillies MT, Wilkes TJ (1972) The range of attraction of animal baits and carbon dioxide for mosquitoes. Studies in a freshwater area of West Africa. Bull Entomol Res 61: 389–404.MT GilliesTJ Wilkes1972The range of attraction of animal baits and carbon dioxide for mosquitoes. Studies in a freshwater area of West Africa.Bull Entomol Res61389404
  75. 75. Smith A, Webley DJ (1969) A verandah trap for studying the house-frequenting habits of mosquitoes and for assessing insecticides. Part 3. The effect of DDT on behaviour and mortality. Bull Entomol Res 59: 33–46.A. SmithDJ Webley1969A verandah trap for studying the house-frequenting habits of mosquitoes and for assessing insecticides. Part 3. The effect of DDT on behaviour and mortality.Bull Entomol Res593346
  76. 76. Lindsay SW, Jawara M, Paine K, Pinder M, Walraven GE, et al. (2003) Changes in house design reduce exposure to malaria mosquitoes. Trop Med Int Health 8: 512–517.SW LindsayM. JawaraK. PaineM. PinderGE Walraven2003Changes in house design reduce exposure to malaria mosquitoes.Trop Med Int Health8512517
  77. 77. Schellenberg JR, Abdulla S, Nathan R, Mukasa O, Marchant TJ, et al. (2001) Effect of large-scale social marketing of insecticide-treated nets on child survival in rural Tanzania. Lancet 357: 1241–1247.JR SchellenbergS. AbdullaR. NathanO. MukasaTJ Marchant2001Effect of large-scale social marketing of insecticide-treated nets on child survival in rural Tanzania.Lancet35712411247
  78. 78. Nathan R, Masanja H, Mshinda H, Schellenberg JA, de Savigny D, et al. (2004) Mosquito nets and the poor: Can social marketing redress inequities in access? Trop Med Int Health 9: 1121–1126.R. NathanH. MasanjaH. MshindaJA SchellenbergD. de Savigny2004Mosquito nets and the poor: Can social marketing redress inequities in access?Trop Med Int Health911211126
  79. 79. Erlanger TE, Enayati AA, Hemingway J, Mshinda H, Tami A, et al. (2004) Field issues related to effectiveness of insecticide-treated nets in Tanzania. Med Vet Entomol 18: 153–160.TE ErlangerAA EnayatiJ. HemingwayH. MshindaA. Tami2004Field issues related to effectiveness of insecticide-treated nets in Tanzania.Med Vet Entomol18153160
  80. 80. Genton B, Hii J, al-Yaman F, Paru R, Beck HP, et al. (1994) The use of untreated bednets and malaria infection, morbidity and immunity. Ann Trop Med Parasitol 88: 263–270.B. GentonJ. HiiF. al-YamanR. ParuHP Beck1994The use of untreated bednets and malaria infection, morbidity and immunity.Ann Trop Med Parasitol88263270
  81. 81. Moore SJ, Davies C, Cameron MM (2007) Are mosquitoes diverted from repellent-using individuals to non-users? Results of a field study in Bolivia. Trop Med Int Health 12: 532–529.SJ MooreC. DaviesMM Cameron2007Are mosquitoes diverted from repellent-using individuals to non-users? Results of a field study in Bolivia.Trop Med Int Health12532529
  82. 82. Maxwell CA, Rwegoshora RT, Magesa SM, Curtis CF (2006) Comparison of coverage with insecticide-treated nets in a Tanzanian town and villages where nets and insecticide are either marketed or provided free of charge. Malar J 5: 44.CA MaxwellRT RwegoshoraSM MagesaCF Curtis2006Comparison of coverage with insecticide-treated nets in a Tanzanian town and villages where nets and insecticide are either marketed or provided free of charge.Malar J544
  83. 83. Lindsay SW, Armstrong Schellenberg JRM, Zeiler HA, Daly RJ, Salum FM, et al. (1995) Exposure of Gambian children to Anopheles gambiae vectors in an irrigated rice production area. Med Vet Entomol 9: 50–58.SW LindsayJRM Armstrong SchellenbergHA ZeilerRJ DalyFM Salum1995Exposure of Gambian children to Anopheles gambiae vectors in an irrigated rice production area.Med Vet Entomol95058
  84. 84. Woolhouse MEJ, Dye C, Etard JF, Smith T, Charlwood JD, et al. (1997) Heterogeneities in the transmission of infectious agents: implications for the design of control programs. Proc Natl Acad Sci U S A 94: 338–342.MEJ WoolhouseC. DyeJF EtardT. SmithJD Charlwood1997Heterogeneities in the transmission of infectious agents: implications for the design of control programs.Proc Natl Acad Sci U S A94338342
  85. 85. D'Alessandro U, Olaleye BO, McGuire W, Langerock P, Bennett S, et al. (1995) Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme. Lancet 345: 479–483.U. D'AlessandroBO OlaleyeW. McGuireP. LangerockS. Bennett1995Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme.Lancet345479483
  86. 86. Nevill CG, Some ES, Mung'ala VO, Mutemi W, New L, et al. (1996) Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast. Trop Med Int Health 1: 139–146.CG NevillES SomeVO Mung'alaW. MutemiL. New1996Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast.Trop Med Int Health1139146
  87. 87. Habluetzel A, Diallo DA, Esposito F, Lamizana L, Pagnoni F, et al. (1997) Do insecticide-treated curtains reduce all-cause mortality in Burkina Faso? Trop Med Int Health 2: 855–862.A. HabluetzelDA DialloF. EspositoL. LamizanaF. Pagnoni1997Do insecticide-treated curtains reduce all-cause mortality in Burkina Faso?Trop Med Int Health2855862
  88. 88. Phillips-Howard PA, Nahlen BL, Kolczak MS, Hightower AW, ter Kuile FO, et al. (2003) Efficacy of permethrin-treated bed nets in the prevention of mortality in young children in an area of high perennial malaria transmission in western Kenya. Am J Trop Med Hyg 68: 23–29.PA Phillips-HowardBL NahlenMS KolczakAW HightowerFO ter Kuile2003Efficacy of permethrin-treated bed nets in the prevention of mortality in young children in an area of high perennial malaria transmission in western Kenya.Am J Trop Med Hyg682329
  89. 89. Curtis C, Maxwell C, Lemnge M, Kilama WL, Steketee RW, et al. (2003) Scaling-up coverage with insecticide-treated nets against malaria in Africa: Who should pay? Lancet Infect Dis 3: 304–307.C. CurtisC. MaxwellM. LemngeWL KilamaRW Steketee2003Scaling-up coverage with insecticide-treated nets against malaria in Africa: Who should pay?Lancet Infect Dis3304307
  90. 90. Lines J, Lengeler C, Cham K, de Savigny D, Chimumbwa J, et al. (2003) Scaling-up and sustaining insecticide-treated net coverage. Lancet Infect Dis 3: 465–466.J. LinesC. LengelerK. ChamD. de SavignyJ. Chimumbwa2003Scaling-up and sustaining insecticide-treated net coverage.Lancet Infect Dis3465466discussion. discussion.
  91. 91. Grabowsky M, Nobiya T, Ahun M, Donna R, Lengor M, et al. (2005) Distributing insecticide-treated bednets during measles vaccination: A low-cost means of achieving high and equitable coverage. Bull World Health Organ 83: 195–201.M. GrabowskyT. NobiyaM. AhunR. DonnaM. Lengor2005Distributing insecticide-treated bednets during measles vaccination: A low-cost means of achieving high and equitable coverage.Bull World Health Organ83195201
  92. 92. (2006) Distribution of insecticide-treated nets during a polio immunization campaign in Niger. MMWR Morb Mortal Wkly Rep 55: 913–916.2006Distribution of insecticide-treated nets during a polio immunization campaign in Niger.MMWR Morb Mortal Wkly Rep55913916
  93. 93. Tami A, Mbati J, Nathan R, Mponda H, Lengeler C, et al. (2006) Use and misuse of a discount voucher scheme as a subsidy for insecticide-treated nets for malaria control in southern Tanzania. Health Policy Plann 21: 1–9.A. TamiJ. MbatiR. NathanH. MpondaC. Lengeler2006Use and misuse of a discount voucher scheme as a subsidy for insecticide-treated nets for malaria control in southern Tanzania.Health Policy Plann2119
  94. 94. Webster J, Lines J, Armstrong-Schellenberg JRM, Hanson K (2005) Which delivery systems reach the poor: A review of equity of coverage of ever-treated nets, never-treated nets and immunization to reduce childhood mortality in Africa. Lancet Infect Dis 5: 709–717.J. WebsterJ. LinesJRM Armstrong-SchellenbergK. Hanson2005Which delivery systems reach the poor: A review of equity of coverage of ever-treated nets, never-treated nets and immunization to reduce childhood mortality in Africa.Lancet Infect Dis5709717
  95. 95. Roll Back Malaria Partnership (2005) Scaling up insecticide treated netting programmes in Africa: A strategic framework for coordinated national action. Geneva: World Health Organization. 26 p. Roll Back Malaria Partnership2005Scaling up insecticide treated netting programmes in Africa: A strategic framework for coordinated national actionGenevaWorld Health Organization26Available at: http://www.rollbackmalaria.org/partnership/wg/wg_itn/docs/WINITN_StrategicFramework.pdf. Accessed 28 May 2007. Available at: http://www.rollbackmalaria.org/partnership/wg/wg_itn/docs/WINITN_StrategicFramework.pdf. Accessed 28 May 2007.
  96. 96. Hanson K, Kikumbih N, Armstrong Schellenberg J, Mponda H, Nathan R, et al. (2003) Cost-effectiveness of social marketing of insecticide-treated nets for malaria control in the United Republic of Tanzania. Bull World Health Organ 81: 269–276.K. HansonN. KikumbihJ. Armstrong SchellenbergH. MpondaR. Nathan2003Cost-effectiveness of social marketing of insecticide-treated nets for malaria control in the United Republic of Tanzania.Bull World Health Organ81269276
  97. 97. Agha S, Van Rossem R, Stallworthy G, Kusanthan T (2007) The impact of a hybrid social marketing intervention on inequities in access, ownership and use of insecticide-treated nets. Malar J 6: 13.S. AghaR. Van RossemG. StallworthyT. Kusanthan2007The impact of a hybrid social marketing intervention on inequities in access, ownership and use of insecticide-treated nets.Malar J613
  98. 98. Kweku M, Webster J, Taylor I, Burns S, Dedzo M (2007) Public-private delivery of insecticide-treated nets: A voucher scheme in Volta Region, Ghana. Malar J 6: 14.M. KwekuJ. WebsterI. TaylorS. BurnsM. Dedzo2007Public-private delivery of insecticide-treated nets: A voucher scheme in Volta Region, Ghana.Malar J614
  99. 99. Mathanga DP, Campbell CH, Taylor TE, Barlow R, Wilson ML (2005) Reduction of childhood malaria by social marketing of insecticide treated nets: A case-control study of effectiveness. Am J Trop Med Hyg 73: 622–625.DP MathangaCH CampbellTE TaylorR. BarlowML Wilson2005Reduction of childhood malaria by social marketing of insecticide treated nets: A case-control study of effectiveness.Am J Trop Med Hyg73622625
  100. 100. Rowland M, Webster J, Saleh P, Chandramohan D, Freeman T, et al. (2002) Prevention of malaria in Afghanistan through social marketing of insecticide-treated nets: Evaluation of coverage and effectiveness by cross-sectional surveys and passive surveillance. Trop Med Int Health 7: 813–822.M. RowlandJ. WebsterP. SalehD. ChandramohanT. Freeman2002Prevention of malaria in Afghanistan through social marketing of insecticide-treated nets: Evaluation of coverage and effectiveness by cross-sectional surveys and passive surveillance.Trop Med Int Health7813822
  101. 101. Magesa SM, Lengeler C, deSavigny D, Miller JE, Njau RJ, et al. (2005) Creating an “enabling environment” for taking insecticide treated nets to national scale: The Tanzanian experience. Malar J 4: 34.SM MagesaC. LengelerD. deSavignyJE MillerRJ Njau2005Creating an “enabling environment” for taking insecticide treated nets to national scale: The Tanzanian experience.Malar J434
  102. 102. Abdulla S, Gemperli A, Mukasa O, Armstrong Schellenberg JR, Lengeler C, et al. (2005) Spatial effects of the social marketing of insecticide-treated nets on malaria morbidity. Trop Med Int Health 10: 11–18.S. AbdullaA. GemperliO. MukasaJR Armstrong SchellenbergC. Lengeler2005Spatial effects of the social marketing of insecticide-treated nets on malaria morbidity.Trop Med Int Health101118
  103. 103. Garrett-Jones C (1964) Prognosis for interruption of malaria transmission through assessment of the mosquito's vectorial capacity. Nature 204: 1173–1175.C. Garrett-Jones1964Prognosis for interruption of malaria transmission through assessment of the mosquito's vectorial capacity.Nature20411731175
  104. 104. Hemingway J, Field L, Vontas J (2002) An overview of insecticide resistance. Science 298: 96–97.J. HemingwayL. FieldJ. Vontas2002An overview of insecticide resistance.Science2989697
  105. 105. N'Guessan R, Corbel V, Akogbeto M, Rowland M (2007) Reduced efficacy of insectcide-treated nets and indoor residual spraying for malaria control in a pyrethroid resistance area, Benin. Emerg Infect Dis 13: 199–206.R. N'GuessanV. CorbelM. AkogbetoM. Rowland2007Reduced efficacy of insectcide-treated nets and indoor residual spraying for malaria control in a pyrethroid resistance area, Benin.Emerg Infect Dis13199206