Malaria Prevention with insecticide treated nets

How long does a long-lasting insecticidal net last in the field?

Albert Kilian, Malaria Consortium

Insecticide treated mosquito nets (ITN) have been around for over 20 years and their efficacy and effectiveness under various epidemiological settings proven for at least 10 years. But only in the last three to four years has implementation in malaria exposed countries reached or surpassed target levels of coverage (60-80% of households with at least one ITN) in a good number of countries and we are beginning to see significant impact on malaria epidemiology, e.g. in Zanzibar, Bioko Island, Ethiopia or Rwanda. There are two major reasons for this change. First, the shift to massive public free net distributions either to young children and pregnant women or to the general population. Second, the firm establishment of long-lasting insecticidal nets (LN) as the standard ITN at least for public distributions but increasingly also in the commercial sector.

What is a long-lasting insecticidal net?The term “long-lasting” refers to the effect of the insecticide on the net and not the net itself. That is why the term “long-lasting insecticidal net” is preferable over “long-lasting insecticide treated net”. And “long” means that this insecticidal effect is considerably longer than what can be achieved by a simple dipping of the net in an insecticide solution (conventional treatment) in which case the protective effect is lost after three to 12 months of use. The criteria currently used by the WHO Pesticide Evaluation Scheme (WHOPES) to evaluate that the “long” quality has been reached is that at least 80% of nets used in the field for three years must pass the strict criteria for mosquito knockdown and killing1.

The principle of any LN is that a high dose of insecticide is applied in such a way that a small portion of insecticide is present on the surface of the net while the remainder is kept in a “reservoir” either within or on the netting yarn. As surface insecticide is used, washed or rubbed off or otherwise lost, it will be re-established from the reservoir ensuring that the repellent or killing capacity against the Anopheles mosquitoes stays intact until all insecticide is gone. Currently two techniques are applied depending on the netting material. For polyethylene the pyrethroid insecticide can be directly incorporated into the netting material due to its low melting point and favorable diffusion characteristics. In contrast, for polyester a coating of some kind has to be used to serve as the insecticide “reservoir”. This coating or binding agent sticks firmly to the netting material and allows the shift of insecticide to the surface as needed. To date six LN products have been recommended by WHOPES for public health and these are shown in Table 1. Why is the “life” of an LN important?From the very start of mosquito net use for malaria prevention the question of how long a net lasts has been discussed among experts. But until recently that question had not been in the focus of considerations as the vast majority of nets were obtained from the commercial market

1 Either ≥95% knock down within 60 minutes or mortality ≥80% within 24 hours following a three minute exposure of Anopheles mosquitoes on the netting.

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and could be replaced whenever the users felt they needed to or had the funds and access to do so. However, with the scale-up of public sector distributions, most of which are done through mass campaigns, the question of when and how to replace these nets has become crucial for the efforts to sustain high coverage achieved initially. This has intensified the debate and lead to the recently established notion that there are two kinds of LN, those with an average life span in the field of three and five years respectively. And many times it has been assumed that the former applies to the most commonly used polyester net of 75 Denier2 and the latter to a polyethylene net of 150 to 180 Denier. Although there is no official WHO statement to this effect, the terms “three year” and “five year” LN have appeared in many working papers or documents going so far that some ministries of health have issued statements that only “five year” LN should be used for public distribution.

In this situation it appears crucial to review the existing evidence regarding the life span of different nets under different conditions in order to shed some light on what we actually know and better define what additional research is needed. Even more importantly, we need to critically look at the concept of the “life” of the net, its components and determinants so that a common understanding is reached of what we are discussing.

Components of the life of an LNA number of terms have been used to describe how long a net will last: net age, longevity, durability, net “life” and “useful life”. The last term already indicates that some aspect of net usage or at least usability needs to be considered beyond the pure existence of the net. In the case of LN an additional major component has to be taken into account with respect to the “usefulness”, i.e. the duration of insecticidal protection which is hoped to be at least as long as the physical net to make it a functional LN.

Physical “survival” of the net

The conceptWe define the life of a net as the time from obtaining it until it is lost and needs replacement. We then consider the reasons why the net may be gone and the frequency of this event over time which is equivalent to its “survival” rate (see Figure 1). On a population scale we describe net disappearance either from the side of the still existing nets, i.e. the proportion of nets given out that have been retained after time x (retention), or from the side of the nets no longer present (loss) and the rate at which this happens at different time intervals following the net distribution is the loss function.

It is obvious, however, that evaluating the mere presence or absence of a net does not sufficiently capture the “useful” aspect of the net life which implies hat the net can be used for its purpose of covering the sleeper sufficiently to protect from insects. The net may still be present but in such a poor physical condition (torn, full of holes) that it can neither be hanged nor cover the sleeping place. Or it has become unattractive to the user due to holes and/or dirt that he or she is hesitant to use it and eventually puts it either to other uses or away for good. Furthermore, the physical condition can prevent an effective protection even in the presence of insecticide if the holes are too many or too large. Therefore, the physical condition or integrity

2 Denier is a measure of the linear mass density of filaments or yarn commonly used in the textile industry. It is defined as the mass in grams of 9000 meters of filament and describes the thickness of the material.

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of the net has to be considered as a potential functional loss or “death” when evaluating its “useful life”.

Both components, net retention/loss and the physical condition of the net include some behavioral aspects and it will be useful to look at these more closely (Figure 2). They can be divided into two categories or scenarios. First, the net “loss” may be intended by the user, i.e. the net is not wanted for a variety of reasons, given away to others (including being sold) or used for other purposes such as fishing or material for a wedding gown. This is what usually is referred to as non-retention in the strict sense of the word. The second scenario is characterized by the loss of the net although the user has best intentions to used it. Being destroyed by fire (often with the whole hut or house) is a clear example, being stolen another although in this case the net may still benefit another person. One has to assume that the physical deterioration of the net is usually unintentional. Nonetheless, the care someone takes to protect the net from getting holes and repairing existing ones will significantly influence the duration of its “useful life”. Similarly, the decision not to use it anymore may be influenced as much by the number of holes present as by the availability of a replacement.

Although intentional as well as unintentional losses may occur at any time it is likely that the former dominates the early losses, particularly following public distributions which may not always meet the exact preferences or may oversupply some families, and the latter, namely physical destruction, is more prominent at the far end of the time axis. It is also intuitively clear that even with a given average “useful life” net loss will occur at all times and is very likely to be slow in the beginning, when nets are new, as well as at the end, when only few nets which are kept exceptionally well survive, while the middle section of the loss function is more or less steep. Based on these hypothetical consideration and observations from phase III WHOPES studies on LN Malaria Consortium with support from the Swiss Tropical Institute has developed loss functions for two types of nets representing the three and five year average “useful life” (Figure 3). These have been used in a model to project LN need and expected ITN coverage resulting from known LN distributions but still need to be validated by actual data.

How can it be measured and evaluated?

Net survivalNet retention can best be evaluated following public distribution of free LN through routine health services (ante-natal care or immunization services) or mass campaigns and this has been increasingly done in the recent years. In the case of routine health services net recipients are typically sampled from the distribution registers and then tracked to their homes and interviewed. For mass campaign a general household survey is more common which establishes whether a family received any LN and how many and then determines the presence or absence of each net. As in these cases the time of distribution is known, retention or loss rates can be related to time since distribution. The methodological challenge is to establish data on the middle and end part of the “survival” curve of nets. The approach most commonly taken is to capture “time since net was obtained” for each net found in cross sectional surveys. The major limitation of this approach is that the net age distribution found in a cross sectional sample is strongly dependent on recent net input and would only reflect the “useful life” of the nets if the system has been in a steady state (stable coverage) over a number of years. It therefore would underestimate the mean survival of the nets if net influx has been higher than net loss such as following mass campaigns, and would

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overestimate if no further net input has occurred for three or more years as nets with a short survival are not captured.

Since prospective studies of nets for more than a few years are difficult to do without biasing the net survival (as people know the net is being followed up and are likely to keep it longer than they would otherwise) the best approach appears to be a mix of “age of net” of currently present nets and detailed a detailed “net history” including net age at time of loss for recently owned nets.

Physical condition Textile industry has developed a number of standardized measures of the physical strength and durability of yarn such as tenacity, bursting or tear strength which is measured in the laboratory under controlled conditions (see previous article by Severine Huchet). Measuring the physical condition of nets in the field is not yet standardized at all and faces a number of challenges.The first is the accuracy and reliability of the assessment. Ideally the net is collected and examined in the lab using a frame or at least allowing a detailed inspection of all sections under optimal light conditions. Checking a net for holes in the field potentially underestimates the number of holes as light conditions are often poor and interviewers stressed for time tending to overlook small holes or misjudging the total number. This is particularly a concern if the holes are very few or the net so torn that large parts are missing making any assessment difficult. Secondly, holes come in many shapes and forms from burn holes and small circular tears to irregular and multiple holes from repeated rubbing or rodents “eating” the net, large horizontal or vertical tears or open seams or even complete sections missing (Figure 4-5). It can be difficult to determine a diameter or size measure and a more robust categorization is desirable.

Finally, there is not yet an agreement or standardization of how the physical condition of nets is evaluated. Different studies have used very different criteria of what is a good or poor condition and when a net is “too damaged”. Unfortunately there not yet clear information on how many holes are too many, particularly for LN. We know that a few small holes will cause no reduction in its protective effectiveness and it is evident that a net in a condition shown in Figure 5 (left) will have a significantly reduced protective effect even when insecticide levels are high. But were exactly the point of “too many holes” is between these extremes is currently only speculation. In this situation the best approach is to just measure the physical condition in some semi-quantitative way and correlate this with the net usage and possibly biological protection. One possible way is being explored by Malaria Consortium by calculating a hole index in analogy to the classical spleen index in malariology: holes are grouped into three categories of size and the number of each category recorded. Multiplying the number of holes with the size category then gives the hole index of the net and calculating a mean hole index per sample including the nets with no holes provides a measure that combines the proportion of nets with any holes with an assessment of the magnitude of destruction of those with holes.

Currently available data on life of net

In general, data on net retention or loss and the physical condition of surviving nets is scarce compared to the overall literature on nets, ITN and LN. The best source are the increasingly undertaken net retention and use surveys following large distribution campaigns. Data from nine published reports (Togo, Uganda, Sudan, Nigeria, Ethiopia, Mozambique and Kenya) and

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five unpublished surveys undertaken by Malaria Consortium in Uganda and Mozambique seem to support the slow initial loss rate in the first 1-2 years (Figure 3). Although data points for the type II polyethylene 150-180 Denier net are very few, they are in keeping with a slower loss rate of these nets. Figure 3 also shows data from studies in Uganda, Kenya, and Tanzania which were either prospective LN studies with close follow-up of all nets or observations in well defined project areas. All of the data points, for type I as well as type II nets, are beyond what would be expected if the median survival was three and five years respectively. This observation supports the previously stated hypothesis that data from these sources are likely to be biased upwards and do not represent the average net survival.

These retention studies have also attempted to explore the reasons for the loss of the net. Surprisingly and against what some might have expected there is no evidence that selling the net is a significant factor at the household level. Most “lost” nets are either destroyed or given away to other family members outside the immediate household.

Estimates of the average age of existing nets have been published for many years and almost exclusively refer to nets from the commercial sector and mostly of unknown material and quality although the majority of nets would be polyester of 50-75 Denier. Mean age has ranged from one to three years. Only one study from Tanzania also included the duration of ownership of past nets giving an overall mean of 21 months but type and the quality of the nets was not stated. Recent analysis of data on net age of over 6000 nets that was obtained by Malaria Consortium in Uganda in various surveys 2005-2009 confirms the significant impact of recent distributions on the mean age of the net. Following a mass campaign with 1-3 nets per household the mean age of all nets irrespective of source six months after the campaign was 0.75 years, following distribution through ante-natal care services 1.0 years and in general household surveys without free net distribution 1.4 years. Nonetheless, in all settings a long tale of “old” nets of ages above three and up to 11 years was found suggesting that the hypothesized upper end of the loss function (Figure 3) indeed is realistic.

Given that methods of quantifying the severity of net damage differ so widely between studies only the proportion of nets with any holes can be compared. For 75 Denier polyester nets (type I) this proportion has been reported as 40-60% after one year and 60-90% after 2-3 years. For 150-180 Denier polyethylene nets (type II) 30% has been reported after 18 months and 40% after 2-3 years. However, irrespective of methodological problems discussed earlier, the stress on nets varies significantly from place to place and can also change over time in the same setting as people learn to take better care of them. A sound comparison between nets of different material and/or yarn thickness can therefore only be made in a direct comparison. This has been done by Centers of Disease Control and Prevention (CDC) in Togo after nets had been in use for three years. Although the type I net PermaNet® tended to have more seam failures and more large holes the overall difference in proportion with “acceptable” condition did not differ significantly compared to the type II Olyset® net. A similar result is obtained from an analysis of 978 PermaNet® and 930 Olyset® nets that were assessed by Malaria Consortium after 5-7 months filed use in the context of net retention surveys in four districts in Uganda. After controlling for district, net age and use no difference was found between the two types neither in proportion with any net, mean hole index or proportion with severe damage (hole index>20). These data do not exclude that a difference exists in the “useful life” of these nets but suggests that this difference may not be as big as initially thought and also may be due to the yarn thickness rather than the material per se. Further evidence in this direction comes from first

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results from a direct comparison of 100 and 150 Denier polyester nets Malaria Consortium is carrying out in Uganda. After six months the proportion of nets with any holes was 33% for 100 Denier nets, similar what had previously been observed for 75 Denier nets, but only 18% for 150 Denier nets. Mean hole index also differed 2.2 vs. 1.5 respectively.

Preliminary experience with the hole index suggest that this is a rather robust measure of overall physical condition. In three LN phase three studies plus data from over 2000 nets from other surveys the increase of hole index with age of net was very similar in all of them reaching a mean index of about 4-6 after one year, 10-15 after 2-3 years and 20-30 after 4-5 years. Data also suggest that nets with a hole index of 30 or more are used less and more often stored away, an observation that has also been made by a qualitative net study in Ethiopia.

Duration of insecticidal protection

If data on the life of the net is scarce, results on longevity of the insecticidal protection beyond one to two years of field use for the LN products shown in table 1 is even scarcer. This is in part due to the fact that only two products have been around for over five years: Olyset® and PermaNet® and these also have received full recommendation by WHOPES. The others are still undergoing three year field trials and have an interim recommendation.

For Olyset® results are available from three, five and seven years of field use. Some of these studies have very small sample size and have been done before a standard field protocol had been developed by WHOPES. They show generally sufficient insecticide protection although in the CDC study in Togo the result after three years was borderline with 72% fulfilling the criteria for an LN. The best studied product clearly is PermaNet® for which results from three studies and six countries are available with a follow-up of three years. In Uganda, Angola and Zambia 80% or more passed the WHOPES criteria, Togo was split with one study showing 83% passing and the other (the above mentioned CDC study) 68%. In Ghana the result was also borderline (75%) and in Madagascar only 50% of nets passed the criteria.

While there is significant variation from site to site performance of polyester LN with coating technology seems to be consistent under the same conditions. In the ongoing phase III trials Malaria Consortium is undertaking in Uganda the average rate of insecticide loss of three different products was almost identical with 20-25% of the loading dose lost per year leaving 30-40% after three years.

The factors that clearly influence the loss of insecticidal protection are washing frequency and regular use and handling. Interestingly, the two countries with the lowest results for PermaNet® in the WHO study (Madagascar and Ghana) were also the ones with the highest washing rates. Whether or not and if so to which extent temperature or humidity and dirt on the net contribute to insecticide loss is still under debate and no clear results are available yet.

What does this mean for malaria prevention with ITN?

The first conclusion clearly is that more work needs to be done on many aspects of the “useful life” of an LN under field conditions. These include

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Agreement on a standardized way to measure the physical condition of nets and its application to study the correlation of physical condition and usage and/or effective protection to better identify the point at which a net ceases to be useful

Use of a combination of examination of currently present nets and a history of previously owned nets to more clearly define the average life of various net types

Direct comparison of nets of different materials and yarn qualities in the same setting and over longer periods of time to identify the factors that influence net durability the most

Identification and quantification of other factors than washing and handling that may influence loss of insecticidal activity

Secondly, from the available data to date it can be concluded that the loss of nets for various reasons – and therefore the need to replace them – is a continuous process with a non-linear decline. This implies that repeated mass campaigns every three or five years are most likely not an optimal solution. Wherever possible net replacement should be done through continuous delivery strategies. Where this is not possible mechanisms have to be developed that will allow a demand driven distribution algorithm, i.e. replace those nets that need replacement.

Finally, from the limited data on the insecticidal activity under field condition it is evident that some few nets will always fail before the physical net reaches the end of its “useful life”. While it is questionable whether this will lead to a failure of control programs at community level given the mass effect at high coverage levels, it nonetheless implies that some net users will have reduced protection and this question needs to be addressed.

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Table 1: LN products currently recommended by WHOPES and some of their attributes

Net/Brand Material Denier g/9000m

Meshholes/inch²

Insecticide loading mg/m²

Olyset® Polyethylene 150-180 75 Permethrin1000

Duranet® Polyethylene 145 132 Alphacypermethrin260

Netprotect® IconLife® Polyethylene 100-115 136, 200 Deltamethrin

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Permanet 2.0® Polyester 75, 100 156-177 Deltamthrin55

Interceptor® Polyester 75, 100 156-177 Alphacypermethrin200

Dawa Plus 2.0® Polyester 75, 100, 150 156-177 Deltamethrin80

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Figure 1: Schematic representation of the “useful life” of a net, how it may change over time and how it can be measured

Figure 2: Categories of net loss and their expected contribution to overall loss over time

Net is gone or

unusable

Net is there

and used

Time

lossfunction

Loss RateProportion Lost

Retention RateProportion Retained Net is

gone or unusable

Net is there

and used

TimeTime

lossfunction

Loss RateProportion Lost

Retention RateProportion Retained

Intentionally given up

“doesn’t want net”

Lost unintentionally

“wants net”

Sold or given awayUsed for other purposes

(e.g. fishing)

Destroyed (burnt)Stolen

Useless due to holes(tear, burn, rodent)

Non-Retention

Physical net loss“Death of net”

Time

Among nets lost

Intentional

Unintentional

Intentionally given up

“doesn’t want net”

Lost unintentionally

“wants net”

Intentionally given up

“doesn’t want net”

Lost unintentionally

“wants net”

Sold or given awayUsed for other purposes

(e.g. fishing)

Destroyed (burnt)Stolen

Useless due to holes(tear, burn, rodent)

Sold or given awayUsed for other purposes

(e.g. fishing)

Destroyed (burnt)Stolen

Useless due to holes(tear, burn, rodent)

Non-Retention

Physical net loss“Death of net”

Non-Retention

Physical net loss“Death of net”

Time

Among nets lost

Intentional

Unintentional

TimeTime

Among nets lost

Intentional

Unintentional

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Figure 3: Modeled loss function for two net types, one with a 3 year (type I in red) and one with a five year (type II in blue) average survival. Data points represent data from net retention studies (red squares type I, blue squares type II). Green data points are indirect loss estimates by comparing coverage rates in two consecutive cross-sectional surveys in areas with minimal or no net input between data points, open circles represent prospective LN studies or data from smaller projects.

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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

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Figure 4: Typical holes observed in polyester nets (75 Denier)

Figure 5: Two polyester nets (75 denier) after three years of regular use in a WHOPES phase III LN study demonstrating the variability of physical deterioration. It also shows that in such a study nets are kept which otherwise would have been discarded.

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