- Record: found
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Predictors of knowledge and use of long-lasting insecticidal nets for the prevention of malaria among the pregnant women in Pakistan
research-article
Author(s):
Ramesh Kumar
1
,
3
,
,
Midhat Farzeen
1 ,
Jamil Ahmed
2 ,
Manohar Lal
1 ,
Ratana Somrongthong
3
Publication date (Electronic):
23 August 2021
Journal:
Malaria Journal
Publisher:
BioMed Central
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Abstract
Background
Malaria is endemic to Pakistan with high prevalence among pregnant women and linked with maternal anaemia, intrauterine growth retardation, preterm birth, and low birth weight. The use of long-lasting insecticidal nets (LLINs) is a proven and cost-effective intervention preventing malaria among pregnant women. The present study aimed to explore predictors of knowledge and use of LLINs among pregnant women in Pakistan.
Methods
This was part of a quasi-experimental study of 200 pregnant women conducted in a rural district of Sindh province in Pakistan. Data were collected using Malaria Indicator Survey questionnaires developed by Roll Back Malaria Partnership to end Malaria Monitoring and Evaluation Reference Group. Pregnant women and mothers with newborns of six months of age were interviewed in their homes.
Results
The age of the women was from 18 to 45, two thirds of the respondents (72.5%) were uneducated and married (77%). Majority (92%) of the women had received antenatal care during pregnancy, and 29.5% women had received counseling on malaria during their antenatal care visits. Multiple linear regression showed that the type of latrine was the most significant (β = 0.285, p < 0.001) determinant of knowledge about malaria among pregnant women followed by the death of a newborn (β = 0.271, p < 0.001). The use of mobile phone was the most significant (β = 0.247, p < 0.001) predictor of usage of LLINs among pregnant women followed by the death of a newborn (β = 0.232, p < 0.05).
Conclusions
Maternal education, type of latrine, use of mobile phone, malaria during previous pregnancy and newborn death were strong predictors of knowledge and use of LLINs in pregnant women in Pakistan. There is a need to scale-up programmes that aim to create awareness regarding malaria among pregnant women. Mobile phone technology can be used to implement awareness programmes focusing on malaria prevention among women.
Related collections
Most cited references38
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Preventing Childhood Malaria in Africa by Protecting Adults from Mosquitoes with Insecticide-Treated Nets
Gerry F. Killeen, Tom Smith, Heather M Ferguson … (2007)
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 [6–12]. 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 [16–18], 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 [16–18] 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 [19,21–26]. 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 [29–34] and from larger village-scale trials: ITNs have been clearly shown to reduce malaria risk among unprotected individuals by suppressing the density [35–37], survival [35–37], 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 [44–47]. 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]. 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. 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 [9,54–56] 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 (ɛs,j) and the probability that, once encountered, they will feed upon it (φs,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 (φs) or die in the attempt (μs) 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): Table 1 Behavioural and Host Availability Input Parameters for Both Vector Species 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 (φh,p) as a function of the excess probability of diverting (Δp) and killing (μp) that vector (Figure 1). The combined baseline and net-induced probabilities of diversion (Δu + p ) or mortality (μu + 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 (φh,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 (πi): 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 (ηv) 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 (ηo), and vertebrate host-seeking (ηv) 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 EIR C /EIR 0 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 [61–68]. 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 (γu), conditional upon encountering them, to be 0.90 and the chance that they will die in the attempt (μu) at 0.10. Using these parameters and Equation 3, we calculated that, for An. arabiensis, the overall feeding probability upon either cattle (φc) or unprotected humans (φh,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 (γu), feeding (φh,u), and dying (μu) 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 (λc) to this mosquito species as previously described [52]. Note that λc is assumed to modify a c by affecting the encounter rate only, indicating that these mosquitoes can differentiate between preferred and nonpreferred hosts at long ranges [72–74]. 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 [72–74]. 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 [29–34]. 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 [44–47] will enable sustained coverage with nets that are effectively treated even under the most rigorous programmatic field conditions. 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 (EIR C /EIR o ) for individuals with (Equation 19) and without (Equation 18) nets is plotted as a function of their ability to divert (Δp) and kill (μp) 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 (μp) and diversion (Δp) 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). 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 [44–47] 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 (πi) 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. Figure 3 Relative Exposure to Malaria Transmission (EIR C /EIR o ) 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. 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 [21,85–88] 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 [91–94]. 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. (1.1 MB XLS) Click here for additional data file.
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- Abstract: found
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Insecticide-Treated Nets for the Prevention of Malaria in Pregnancy: A Systematic Review of Randomised Controlled Trials
Carol Gamble, Paul J Ekwaru, Paul Garner … (2007)
Introduction Approximately 50 million pregnant women are exposed to malaria each year. Pregnant women are more susceptible to malaria, placing both mother and fetus at risk of the adverse consequences [1–3]. In areas of low and unstable transmission, such as in many regions in Asia and the Americas, women do not acquire substantial antimalarial immunity, and are susceptible to episodes of acute and sometimes severe malaria, and fetal and maternal death [4]. In areas with stable malaria transmission, such as in most of sub-Saharan Africa, infection with Plasmodium falciparum in pregnancy is characterised by predominantly low-grade, sometimes sub-patent, persistent or recurrent parasitaemia. These infections frequently do not result in acute symptoms yet are a substantial cause of severe maternal anaemia [5] and of low birth weight (LBW) [3], and as such are a potential indirect cause of early infant mortality [6–8]. Because most of these infections remain asymptomatic, and therefore undetected and untreated, prevention of malaria in pregnancy is especially important in these settings. The World Health Organization (WHO) advocates a three-pronged approach to malaria control in pregnancy that includes the use of insecticide-treated bednets (ITNs), intermittent preventive treatment (IPT), and case management (treatment) [9]. In areas of stable malaria transmission in sub-Saharan Africa, ITNs are highly effective in reducing childhood mortality and morbidity from malaria [10]. Although ITNs are promoted as a major tool in the fight against malaria in pregnancy, the available evidence about their efficacy in pregnancy has been inconsistent. In this review, we summarise the available data from randomised controlled trials that compared the effects of ITNs to no nets, or to untreated nets, on the health of pregnant women and birth outcome. Methods A protocol was developed for this review [11], and the standard search strategy of the Cochrane Infectious Diseases Group was used to identify potentially relevant trials [12]. The inclusion criteria were all trials that randomised individuals (pregnant women) or clusters (community or antenatal clinics) in areas where malaria transmission occurs. Where cluster-randomised trials were identified, the methods of analysis were checked to ensure that the precision of the data extracted from the reports was correctly estimated. The authors needed to have adjusted for clustering, as ignoring the clustering provides the correct point estimate of the magnitude of the trial effect but may overestimate the precision, resulting in potentially incorrect conclusions [13]. Primary outcomes selected were mean haemoglobin and anaemia, and mean birthweight and LBW; secondary outcomes included peripheral malaria in the mother assessed by finger prick during pregnancy or at birth, placental malaria assessed by microscopy, clinical malaria, pre-term birth, fetal loss (defined as miscarriage or stillbirth), and maternal death. Trial quality was assessed as adequate, inadequate, or unclear based on the methods used to generate the allocation sequence and allocation concealment [14]. Minimisation of loss to follow-up was considered adequate (≥90% of the participants randomised included in the analysis), inadequate ( 50% representing moderate heterogeneity) [17]. To minimise the anticipated heterogeneity, no attempt was made to combine trials that compared ITNs to no nets and those that compared ITNs to untreated nets [10]. Because all the included studies from Africa compared ITNs to no nets, and the one study comparing ITNs to untreated net was conducted in Thailand, this also resulted in stratification by the major malaria transmission regions (Africa versus non-Africa), which differ in transmission intensity, parasite species, predominant vector, and vector behaviour. The effect of ITNs was expected to be greatest in the first few pregnancies because women develop pregnancy-specific immunity against placental parasites over successive pregnancies as a consequence of repeated exposure [18]. Because gravidity was considered the greatest potential modifier of the effect of ITNs, analyses were stratified a priori by gravidity groups whenever this was possible based on the details provided. Other potential sources of effect modifications that were explored included concomitant use of IPT in pregnancy (IPTp), and differences between trials that used individual randomisation, in which women benefit primarily from personal protection by treated nets, and trials that used cluster randomisation. In the latter trials, ITNs were distributed to whole communities, which may result in a mass or community effect due to area-wide killing of the malaria-transmitting mosquitoes [19–21]. Women in the cluster-randomised trials were mostly provided with ITNs prior to becoming pregnant and were thus protected throughout pregnancy. In the individually randomised trials, nets were provided as part of antenatal care, i.e., typically from 20 to 24 wk onwards. We could not explore other potential sources of heterogeneity because the number of trials identified was too few. Results Description of Trials Six trials were identified; we excluded one trial as the analysis had not adjusted for clustering, and loss to follow-up was high (Text S1) [22]. Of the five included trials (Table 1), two were individually randomised [23,24], and three were cluster-randomised with analysis that took design effects into account [25–27]. Four trials were conducted in stable malaria-endemic areas in Africa (three in Kenya [24,26,27] and one in northern Ghana [25]), all with entomological inoculation rate (EIR) > 1/y, and one in Karen refugee camps along the Thailand–Myanmar border in an area with low and markedly seasonal malaria where P. falciparum and P. vivax coexist (EIR 0.5/y) [23]. The African trials compared ITNs to no nets; 6,418 women were enrolled [24–27]. The remaining trial from Thailand randomised individual women to receive either ITNs, untreated nets, or no nets [23]. In the “no nets” arm, a large proportion of women received nets from another donor independent of the study, and the researchers split the results in this control arm into women using donor nets and women not using donor nets. Because this compromised the validity of the control arm, we included only the comparison of ITNs with untreated nets (n = 223). All African trials gave double- or family-sized nets to each household. The nets used in Thailand were smaller single-sized nets (70 × 180 × 150 cm). All trials used the widely available insecticide permethrin (500 g/m2), except one trial that used cyfluthrin [24]. One trial included IPTp-SP in a factorial design [24]. Women were allocated to receive (1) ITNs plus IPTp-SP, (2) IPTp-SP alone, (3) ITNs plus IPTp-SP placebo, or (4) IPTp-SP placebo alone (“control”). None of the other trials included IPT. In the four trials from Africa, only women having their first baby were included in one trial [26], women having their first or second baby in another [24], and women of all gravidity in the remaining two trials (Table 1) [25,27]. In the trials including pregnant women of all gravidity, the authors analysed them differently: ter Kuile et al. grouped by gravidity 1 to 4 (G1–G4) and gravidity 5 and above (G5+) [27]. Browne et al. grouped by first pregnancy (G1), second pregnancy (G2), and third pregnancy and above (G3+) for continuous endpoints [25]. To allow for sub-group analysis by gravidity group, we grouped the G3+ group from Browne et al. and the G5+ group from ter Kuile et al. into one sub-group, referred to as “high gravidity”, and the G1 from Shulman et al., the G1 and G2 groups from Browne et al. and the G1–G4 group from ter Kuile et al. into another sub-group, referred to as “low gravidity” [25–27]. The study by Browne et al. also provided sub-group analyses for dichotomous endpoints, but unlike in the analysis for continuous endpoints they were not adjusted for cluster randomisation [25].The study by Dolan et al. in Asia did not provide estimates by gravidity group, with the exception of the effect on birth weight [23]. Treated Nets versus No Nets (Four Trials in Africa) Primary outcomes. All four trials reported the effect of ITNs on haemoglobin (Hb) levels and anaemia. Because of the variations in trial design and reporting, it was not possible to combine the results from all four trials for anaemia (Hb < 100 or 110 g/l) and severe anaemia (Hb < 70 or 80 g/l) [28]. The results for mean haemoglobin are provided by the time of assessment (third trimester or delivery) and by gravidity group (Figure 1). There was no evidence for improved haemoglobin levels in women having their first or second babies in the two trials that assessed haemoglobin levels in the third trimester [25,26]. The overall (i.e., all gravidae) summary odds ratio (OR) for any anaemia in the third trimester was 0.88 (95% confidence interval [CI] 0.71–1.10, p = 0.26, one trial) and for severe anaemia was 0.77 (0.56–1.08, p = 0.13, two trials). Insufficient details were reported to provide sub-group analysis by gravidity group. There was significant heterogeneity of treatment effect between the two other trials and sub-groups that assessed haemoglobin levels at delivery, with no evidence for a consistent effect overall (Figure 1) [24,27]. Mean haemoglobin levels were significantly higher in G1–G4 in the trial by ter Kuile et al., who also reported a significant delay in the time to the first episode of any anaemia (Hb < 110 g/l) in G1–G4 (hazard ratio [HR] 0.79, 95% CI 0.65–0.96, p = 0.02), but not in G5+ (HR 1.00, 0.86–1.18, p = 0.97) [27]. Njagi et al. did not find a significant increase in the mean haemoglobin levels of primi- and secundigravidae (Figure 1) or a significant overall reduction in any anaemia, although sub-group analysis by gravidity showed that a significant reduction in any anaemia was found in primigravidae and not secundigravidae (not shown) [29]. All four trials comparing nets to no nets reported on mean birth weight (Table 2; Figure 2). The average birth weight was 55 g higher in the ITN group in women of low gravidity, but no difference was detected in women of higher gravidity groups. For LBW, two trials contributed (Table 2), indicating women of low gravidity had a 23% reduction in LBW, but there was no apparent effect in women of high gravidity in the one trial measuring this [27]. There was also no evidence for an effect in women receiving IPTp with sulfadoxine-pyrimethamine (IPTp-SP) (one trial) (Figure 2). Browne reported the overall OR adjusted for clustering for all gravidity as 0.87 (95% CI 0.63–1.19); as no information was provided by gravidity group, and because LBW was a common event in this trial, the OR could not be pooled with the relative risk (RR) estimates from the other trials. Secondary outcomes. All four RCTs reported on malaria parasitaemia. One trial tested women every month and showed time to first infection in the ITN group was reduced (HR 0.67, 95% CI 0.52–0.86, p = 0.002) [27]. The prevalence of parasitaemia was less common in the ITN groups when assessed in the third trimester (OR 0.88, 073–1.06, p = 0.19, two trials) [25,26] or at the time of delivery (RR 0.76, 0.67–0.86, p < 0.001, two trials) [24,27]. Placental malaria parasitaemia was lower with ITNs by 23% (95% CI 10–34, three trials; Table 2). There was no evidence for an effect on the prevalence of peripheral or placental malaria in women who were provided IPTp-SP (one trial, Figure 3) [24]. Geometric mean parasite densities in peripheral blood tended to be lower in the ITN groups in women having their first or second baby, although the result was not statistically significant (geometric mean ratio 0.82, 95% CI 0.66–1.02, p = 0.07, two trials) [24,25]. There was no evidence for a beneficial effect in G3+ in the trial by Browne et al. (geometric mean ratio 1.28, 0.90–1.82, p = 0.17). Ter Kuile reported that maternal and placental parasite densities were identical in parasitaemic women from ITN and control villages, but insufficient details were provided for inclusion in this analysis [27]. Clinical malaria was reported in two trials, and episodes were less frequent in the ITN than in the control groups in both trials, but this was not significant. Shulman et al. reported on self-reported illness with parasitaemia (OR 0.85, 95% CI 0.47–1.54) [26], and ter Kuile et al. reported on any documented parasitaemia with documented fever based on monthly assessments in G1–G4 (HR 0.72, 95% CI 0.19–2.78) [27]. No effect was demonstrated in the one trial measuring pre-term delivery (<37 wk of gestation) [27] (Table 2). The three trials reporting on fetal loss (miscarriage or stillbirth) showed a consistent reduction in fetal loss associated with ITNs in low gravidity women (33%, 95% CI 3–53, p = 0.03; Figure 4; Table 2). Browne et al. [25] did not provide a breakdown by intervention group. Maternal death was reported by Njagi [24] (five deaths), with no trends evident by group; Shulman et al. [26] reported four deaths but did not specify the groups. ITNs versus Untreated Nets (One Trial from Thailand) This trial was conducted on the Thailand–Myanmar border, with individual randomisation [23]. Fewer women experienced peripheral malaria parasitaemia in the ITN group, but this was not significant (RR 0.73, 95% CI 0.47–1.04); however, in women infected with malaria, the geometric mean parasite density was lower in the ITN group (507 versus 1,096, p = 0.049), and anaemia (hematocrit < 30%) was less frequent with ITNs (RR 0.63, 95% CI 0.42–0.93). Mean birth weight was similar between the two groups (ITN group, 2,858 g, standard deviation 486, n = 94, versus untreated net group, 2,891 g, standard deviation 481, n = 85), as was LBW (RR 1.04, 95% CI 0.52–2.07) and pre-term delivery (RR 0.92, 95% CI 0.45–1.88). Fetal loss was significantly lower in the ITN group (2/102, 2%) than the untreated net group (10/97, 10%) (RR 0.21, 95% CI 0.05–0.92). The number of maternal deaths was similar (ITN group, 0/103, versus untreated net group, 2/100). Discussion This systematic review shows that ITNs were associated with some important health benefits for pregnant women and their babies. Women of low gravidity randomised to ITNs delivered fewer LBW babies and were less likely to experience fetal loss (miscarriage or stillbirth). Although the latter was not a primary endpoint in the trials, it is an important outcome. No significant decrease was observed in pre-term deliveries in the single trial that assessed this outcome. The consistent reduction observed in the miscarriage and stillbirth rates suggests that the attributable effect of malaria on fetal loss may be underestimated in malaria-endemic Africa, where most women remain asymptomatic when infected with P. falciparum. Despite the reduction in malaria infections, no overall effect on mean haemoglobin was demonstrated, and data on maternal anaemia were inconsistent. WHO currently recommends that women in malaria-endemic areas of Africa use both IPTp-SP and ITNs in pregnancy to prevent malaria. One of the two trials from western Kenya assessed the effect of ITNs and IPTp-SP simultaneously, using a factorial design. This trial showed that ITNs provided benefits in primigravidae when used alone, but it did not demonstrate additional benefits of the combined interventions over either of the single interventions [24,29]. The main benefit of ITNs in women protected by IPTp-SP may thus occur after birth through protection of infants from malaria, since infants typically share sleeping space with the mother for the first several months to years [30]. Similar considerations apply to the benefit of ITNs in grand-multigravidae (G5+), as no direct beneficial effect on the developing fetus in terms of birth weight or fetal loss was apparent in this group. The only trial included in this analysis that compared ITNs to untreated nets was also the only trial conducted outside of Africa, in an area with highly seasonal P. falciparum and P. vivax malaria on the Thailand–Myanmar border. It showed a statistically significant reduction in anaemia and fetal loss in all gravidae, but no evidence for a beneficial effect on birth weight or gestational age [23]. Extrapolation of results from the three cluster-randomised trials to predict the potential impact of programmes that distribute ITNs to individual pregnant women as part of antenatal care should be done with caution. Firstly, nets distributed as part of antenatal care will leave most women exposed to malaria in the first third or half of pregnancy, when the risk of peripheral malaria parasitaemia is greatest [3]. By contrast, most women in the cluster-randomised trials became pregnant after ITNs were distributed and were as such protected throughout pregnancy. Secondly, the effect of ITNs in the cluster-randomised trials reflects the combined effects of personal protection (individual barrier protection) and area-wide reductions in malaria transmission (community or mass effect) [19–21]. It is possible that the mass killing effect on mosquito populations in areas with a high ITN coverage will result in stronger treatment effects of ITNs than can be achieved with individual nets. It is also likely that the community effect in the cluster-randomised trials resulted in a slight underestimation of the magnitude of the effect of ITNs because women living in control households from adjacent villages not using ITNs will have benefited from the area-wide reductions in vector populations, as has been shown for effect estimates in young children [19]. Similar considerations apply to the trial comparing ITNs with untreated nets from the Thailand–Myanmar border [23]. Although, this trial randomised individual women, all trial participants lived in the same densely populated refugee camps and some mass effect by the treated nets cannot be excluded. The most recent trial from western Kenya by Njagi et al. is informative in this respect, as it is the only trial that compared the effects of ITNs versus no nets using simple randomisation by individual in an area with low ITN coverage (little or no mass effect) [24,29]. This trial and the community-randomised trial by ter Kuile et al. [27] were conducted simultaneously in contiguous areas with similar malaria transmission at baseline, and similar socioeconomic and educational status and ethnicity of the trial population. The effect estimates were similar between the two trials (in women not randomised to IPTp-SP), suggesting that ITNs may work equally well when provided to individuals as part of antenatal care in the second trimester or when provided to entire communities. The systematic review was informative, but there were some limitations stemming from the variety in trial designs and the number of trials. Outcome data were often expressed in different ways, and inclusion or analysis of gravidity groups was different. How anaemia and peripheral parasitaemia were detected and treated varied, with different periods of follow-up and different cut-offs, limiting our ability to provide summary estimates for some of the endpoints, or to provide sub-group analysis by gravidity group where desired. Shulman et al. and Njagi et al. tested and treated women only if they were suspected of being anaemic or of having malaria, but Dolan et al. performed weekly blood tests, and ter Kuile et al. tested monthly. The number of studies included in the analysis was limited. All four African studies were conducted in areas with stable malaria transmission with EIRs ranging from 10/y to 300/y. Three of the four were conducted in Kenya, and two of these in adjacent areas with similarly intense perennial transmission. These two studies had the greatest influence (expressed as the weight in the figures) on the overall results of the systematic review, particularly for the effect on placental malaria because in the trial by Shulman et al. [26] data were available for only 25.8% of women (those that delivered in the hospital). It is plausible that the 25.8% were different to those delivering at home and may not be representative of all those randomised. This may also explain some of the observed heterogeneity of the effect of ITNs on placental malaria. Although relatively few trials have been conducted and some questions on the efficacy of ITNs in pregnant women in Africa remain, the four trials comparing ITNs with no nets suggest significant beneficial effects of ITNs on birth weight and fetal loss in the first few pregnancies in areas with moderate to intense malaria transmission in sub-Saharan Africa. These findings are consistent with a non-randomised trial of the effect of socially marketed ITNs conducted in an area with intense perennial malaria transmission in southern Tanzania [31], and with an excluded randomised controlled trial from The Gambia, which has lower and highly seasonal transmission [22]. These observed beneficial effects of ITNs during the first few pregnancies, together with the absence of apparent harm to the developing fetus, the potential beneficial effect on the infant when the net continues to be used after birth [10], and the potential for ITNs to reduce malaria transmission through a mass killing effect on mosquito populations, support the current recommendations from WHO to provide ITNs for pregnant women in all regions with stable malaria transmission throughout sub-Saharan Africa, regardless of the degree of malaria transmission intensity. Further evaluation of the potential effect of ITNs on pregnant women and their infants is warranted in malaria regions including the Americas, Asia, and the southwest Pacific, which represent approximately half of all pregnant women exposed annually to malaria. The more complex vector populations with exophagic, exophilic, and early biting behaviour in some of these areas may result in lower efficacy of ITNs than in Africa, where Anopheles gambiae s.s. is the most important vector. These studies should include women of all gravidae, and ideally address the interaction between ITNs and drug-based prevention such as IPTp, which is also largely untested outside of Africa. In Africa, it took over a decade for the evidence of ITN or IPTp efficacy in pregnant women to accumulate. It would be more efficient if trials had a common design, and if systematic reviews used individual patient data to allow appropriate collection of design effects, more accurate and standardised handling of the data, and more robust sub-group analysis. In order to enhance the rate at which evidence becomes available and is translated into policy, future trials would clearly benefit from better co-ordination between research groups. Supporting Information Text S1 QUOROM Flowchart Screened, excluded, and included number of randomised controlled trials. (24 KB PPT) Click here for additional data file.
- Record: found
- Abstract: found
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Reduction of malaria during pregnancy by permethrin-treated bed nets in an area of intense perennial malaria transmission in western Kenya.
Dana Howard, J. Vulule, B Nahlen … (2003)
The impact of insecticide (permethrin)-treated bed nets (ITNs) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control villages two years later. Complete data on birth outcome were available on 2,754 (89.6%) of 3,072 deliveries. Women (n = 780) were followed monthly throughout pregnancy in 19 of 79 villages. Among gravidae 1-4, ITNs were associated with reductions of 38% (95% confidence interval [CI] = 17-54%) in the incidence of malaria parasitemia and 47% (95% CI = 6-71%) in the incidence of severe malarial anemia (hemoglobin level < 8 g/dL with parasitemia) during pregnancy. At the time of delivery, mean hemoglobin levels were 0.6 g/dL (95% CI = 0.01-1.2 g/dL) higher, the prevalence of placental or maternal malaria was reduced by 35% (95% CI = 20-47%), and the prevalence of low birth weight was reduced by 28% (95% CI = 2-47%) in gravidae 1-4 from ITN villages. No beneficial impact was observed in gravidae five or higher. In areas of intense perennial malaria transmission, permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies.
Author and article information
Contributors
Ramesh Kumar:
ORCID: http://orcid.org/0000-0002-9701-3179
drramesh1978@gmail.com
Journal
Journal ID (nlm-ta): Malar J
Journal ID (iso-abbrev): Malar J
Title:
Malaria Journal
Publisher:
BioMed Central
(London
)
ISSN
(Electronic):
1475-2875
Publication date
(Electronic):
23
August
2021
Publication date PMC-release: 23
August
2021
Publication date Collection: 2021
Volume: 20
Electronic Location Identifier: 347
Affiliations
[1
]GRID grid.484191.1, ISNI 0000 0004 0433 7882, Health Services Academy, Ministry of National Health Services Regulation and Coordination,
, Government of Pakistan, ; Islamabad, Pakistan
Author information
Ramesh Kumar
http://orcid.org/0000-0002-9701-3179
Jamil Ahmed
http://orcid.org/0000-0002-3635-7912
Ratana Somrongthong
http://orcid.org/0000-0003-4425-1760
Article
Publisher ID: 3878DOI: 10.1186/s12936-021-03878-w
PMC ID: 8381575
SO-VID: 33b61a2a-9bb6-4233-915a-1d8208e7fc22
Copyright © © The Author(s) 2021
License:
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
History
Date
received
: 19
May
2021
Date
accepted
: 15
August
2021
Categories
Subject:
Research
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issue-copyright-statement © The Author(s) 2021
ScienceOpen disciplines: Infectious disease & Microbiology
Data availability:
ScienceOpen disciplines: Infectious disease & Microbiology