Practical Info

The current WHO policy recommendation for ITNs applies only to those mosquito nets that have been prequalified by WHO and that contain only an insecticide of the pyrethroid class (categorized as ‘pyrethroid-only LLINs’) (24). For ITNs that currently do not have a policy recommendation, including nets treated with another class of insecticide either alone or in addition to a pyrethroid insecticide, WHO will determine the data requirements for assessing their public health value based on technical advice from the Vector Control Advisory Group (VCAG).

Evidence To Decision

Justification

The systematic review (44) followed the original 2003 analysis, which included insecticide-treated curtains and ITNs together and included two studies solely evaluating insecticide-treated curtains and one study evaluating both ITNs and insecticide-treated curtains. There was no obvious heterogeneity that would lead to a subgroup analysis to examine whether the effects were different, and the results from studies evaluating insecticide-treated curtains were consistent with the results of those evaluating ITNs. The GDG drew on the analysis to make recommendations related to ITNs only.

The systematic review (44) produced high-certainty evidence that, compared to no nets, ITNs are effective at reducing the rate of all-cause child mortality, the rate of uncomplicated episodes of P. falciparum, the incidence rate of severe malaria episodes, and the prevalence of P. falciparum. ITNs may also reduce the prevalence of P. vivax, but here the evidence of an effect is less certain.

Compared to untreated nets, there is high certainty evidence that ITNs reduce the rate of uncomplicated episodes of P. falciparum and reduce the prevalence of P. falciparum. There is moderate certainty evidence that ITNs also reduce all-cause child mortality compared to untreated nets. The effects on the incidence of uncomplicated P. vivax episodes and P. vivax prevalence are less clear.

The systematic review did not identify any undesirable effects of pyrethroid ITNs.

Research needs:

• Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection), as well as potential harms and/or unintended consequences of new types of nets and insecticides in areas where resistance to pyrethroids is high.
• Determine the comparative effectiveness and durability of different net types.
• Determine the effectiveness of nets in situations of residual/outdoor transmission.
• Determine the impact of ITNs in transmission ‘hotspots’ and elimination settings.

Practical Info

Mosquito nets that include both a pyrethroid insecticide and the synergist PBO have become available. PBO acts by inhibiting certain metabolic enzymes (e.g., mixed-function oxidases) within the mosquito that detoxify or sequester insecticides before they can have a toxic effect on the mosquito. Therefore, compared to a pyrethroid-only net, a pyrethroid-PBO net should, in theory, have an increased killing effect on malaria vectors that express such resistance mechanisms. However, the entomological and epidemiological impact of pyrethroid-PBO nets may vary depending on the bioavailability and retention of PBO in the net, and on the design of the net (i.e. whether only some or all of the panels are treated with PBO). At present, it is unknown how these differences in the design/composition of pyrethroid-PBO nets affect their relative efficacy. A non-inferiority design for experimental hut studies with entomological endpoints is being explored by WHO as a means to provide clarity in this respect.

Evidence To Decision

Justification

Pyrethroid-PBO nets combine pyrethroids and a synergist. The synergist inhibits certain metabolic enzymes within the mosquito that would otherwise provide a protective effect against the insecticide. Therefore, compared to a pyrethroid-only net, a pyrethroid-PBO net should have an increased killing effect on malaria vectors that express such resistance mechanisms.

The systematic review (45) identified one cluster RCT in the United Republic of Tanzania with epidemiological data (46). The study indicated that a pyrethroid-PBO net product had additional public health value compared to a pyrethroid-only LLIN product in an area where the principal malaria vector(s) had confirmed pyrethroid resistance (results from CDC bottle bioassays indicated that <30% of mosquitoes were killed following exposure to pyrethroids). Resistance was conferred (at least in part) by monooxygenase-based resistance mechanisms, as determined by standard procedures. Mathematical modelling work, drawing on mosquito mortality data obtained from WHO test kit assays, CDC bottle bioassays and experimental hut trials, indicated that the added benefit of pyrethroid-PBO nets compared to pyrethroid-only LLINs is expected to be greatest where pyrethroid resistance is at “intermediate levels”, which was defined as a range of 10% to 80% mosquito mortality after exposure to a pyrethroid insecticide in WHO test kits or CDC bottle bioassays (47).

Based on the above evidence, WHO concluded and recommended the following in 2017:

• Based on the epidemiological findings and the need to deploy products that are effective against pyrethroid-resistant mosquitoes, pyrethroid-PBO nets were given a conditional endorsement as a new WHO class of vector control products.
• National malaria control programmes and their partners should consider the deployment of pyrethroid-PBO nets in areas where the principal malaria vector(s) have pyrethroid resistance that is: a) confirmed, b) of an intermediate level (as defined above by the mathematical modelling studies), and c) conferred (at least in part) by a monooxygenase-based resistance mechanism, as determined by standard procedures. Deployment of pyrethroid-PBO nets must only be considered in situations where coverage with effective vector control (primarily ITNs or IRS) will not be reduced. The primary goal must be to ensure continued access and use of ITNs at levels that ensure optimal coverage for all people at risk of malaria as part of an intervention package.
• Pyrethroid-PBO nets should not be considered a tool that can alone effectively manage insecticide resistance in malaria vectors. It is an urgent task to develop and evaluate ITNs treated with non-pyrethroid insecticides and other innovative vector control interventions for deployment across all settings, in order to provide alternatives for use in a comprehensive IRM strategy.

The conditional recommendation will be reviewed and potentially revised once the 2018 systematic review (45) has been updated to include data from a second trial on pyrethroid-PBO nets which was completed in Uganda in 2020.

Research needs:

• Further evidence is needed on the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection), as well as potential harms and/or unintended consequences of pyrethroid-PBO nets.

Practical Info

To achieve and maintain optimal ITN coverage, countries should apply a combination of mass free net distribution through campaigns and continuous distribution through multiple channels, in particular through ANC clinics and the EPI. Mass campaigns are the only proven cost-effective way to rapidly achieve high and equitable coverage. Complementary continuous distribution channels are also required because coverage gaps can start to appear almost immediately post-campaign due to net deterioration, loss of nets, and population growth.

Mass campaigns should distribute one ITN for every two persons at risk of malaria. However, for procurement purposes, the calculation to determine the number of ITNs required needs to be adjusted at the population level, since many households have an odd number of members. Therefore, a ratio of one ITN for every 1.8 persons in the target population should be used to estimate ITN requirements, unless data to inform a different quantification ratio are available. In places where the most recent population census is more than five years old, countries can consider including a buffer (e.g. adding 10% after the 1.8 ratio has been applied) or using data from previous ITN campaigns to justify an alternative buffer amount. Campaigns should also normally be repeated every three years, unless available empirical evidence justifies the use of a longer or shorter interval between campaigns. In addition to these data-driven decisions, a shorter distribution interval may be justified during humanitarian emergencies, as the resulting increase in population movement may leave populations uncovered by vector control and potentially increasing their risk of infection as well as the risk of epidemics.

Continuous distribution through ANC and EPI channels should remain functional before, during and after mass distribution campaigns. In determining the optimal mix of ITN delivery mechanisms to ensure optimal coverage and maximized efficiency, consideration should be given to the required number of nets, the cost per net distributed and coverage over time. For example, during mass distribution campaign years, other delivery schemes may need to be altered to avoid-over supply of ITNs.

‘Top-up’ campaigns (i.e., ITN distributions that take into account existing nets in households and provide each household only with the additional number of nets needed to bring it up to the target number) are not recommended. Substantial field experience has shown that accurate quantification for such campaigns is generally not feasible and the cost of accounting for existing nets outweighs the benefits.

There should be a single national ITN plan and policy that includes both continuous and campaign distribution strategies. This should be developed and implemented under the leadership of the national malaria control programme, based on an analysis of local opportunities and constraints, and identification of a combination of distribution channels with which to achieve optimal coverage and minimize gaps. This unified plan should include a comprehensive net quantification and gap analysis for all public sector ITN distribution channels. As much as possible, the plan should include major ITN contributions by the private sector.

Therefore, in addition to mass campaigns, the distribution strategy could include:

• ANC, EPI and other child health clinics: These should be considered high-priority continuous ITN distribution channels in countries where these services are used by a large proportion of the population at risk of malaria, as occurs in much of sub-Saharan Africa.
• Schools, faith- and community-based networks, and agricultural and food-security support schemes: These can also be explored as channels for ITN distribution in countries where such approaches are feasible and equitable. Investigating the potential use of these distribution channels in complex emergencies is particularly important.
• Occupation-related distribution channels: In some settings, particularly in Asia, the risk of malaria may be strongly associated with specific occupations (e.g., plantation and farm workers and their families, miners, soldiers and forest workers). In these settings, opportunities for distribution through channels such as private sector employers, workplace programmes and farmers’ organizations may be explored.
• Private or commercial sector channels: These can be important channels for supplementing free ITN distribution through public sector channels. Access to ITNs can also be expanded by facilitating the exchange of vouchers or coupons provided through public sector channels for a free or subsidized ITN at participating retail outlets. ITN products distributed through the private sector should be regulated by the national registrar of pesticides in order to ensure that product quality is in line with WHO recommendations.

The procurement of ITNs with attributes that are more costly (e.g., nets of conical shape) is not recommended for countries in sub-Saharan Africa, unless nationally representative data clearly show that the use of ITNs with particular attributes increases significantly among populations at risk of malaria.

To build an evidence base to support the purchase of more costly nets, investigation into the preferences and into whether meeting preferences translates into increased use of ITNs may also be warranted, particularly in situations where standard nets are unlikely to suit the lifestyle of specific population groups at risk of malaria, such as may be the case for nomadic populations.

The lifespans of ITNs can vary widely among individual nets used within a single household or community, as well as among nets used in different settings. This makes it difficult to plan the rate or frequency at which replacement nets need to be procured and delivered. All malaria programmes that have undertaken medium- to large-scale ITN distributions should conduct ITN durability monitoring in line with available guidance to inform appropriate replacement intervals. Where there is evidence that ITNs are not being adequately cared for or used, programmes should design and implement BCC activities aimed at improving these behaviours.

In countries where untreated nets are widely available, national malaria control programmes should promote access to ITNs. Strategies for treating untreated nets can also be considered, for example, by supporting access to insecticide treatment kits.

As national malaria control programmes implement different mixes of distribution methods in different geographic areas, there will be a need to accurately track ITN coverage at subnational levels. Subnational responses should be triggered if coverage falls below programmatic targets. Tracking should differentiate among the contributions of various delivery channels to overall ITN coverage.

Countries should generate data on defined standard indicators of coverage and access rates in order to ascertain whether optimal coverage has been achieved and maintained. The data should also inform changes in implementation in order to improve performance and progress towards the achievement of programmatic targets. Currently, the three basic survey indicators are: i) the proportion of households with at least one ITN; ii) the proportion of the population with access to an ITN within their household; and iii) the proportion of the population reporting having slept under an ITN the previous night (by age [<5 years; 5–14 years; 15+ years], gender and access to ITN).

Justification

In December 2017, WHO published updated recommendations on Achieving and maintaining universal coverage with LLINs for malaria control (48). These recommendations were developed and revised based on expert opinion through broad consultation, including multiple rounds of reviews by the Malaria Policy Advisory Group (MPAG). Under the section on ‘practical information’, these recommendations have been summarized and slightly revised to clarify that these recommendations are not specific to LLINs, but apply to ITNs in general.

Practical Info

It is important to determine whether the environmental benefits outweigh the costs when identifying the best disposal option for old ITNs and their packaging. For malaria programmes in most endemic countries, there are limited options for dealing with ITN collection. Recycling is not currently a practical option in most malaria-endemic countries (with some exceptions for countries with a well-developed plastics industry). High-temperature incineration is likely to be logistically difficult and expensive in most settings. In practice, when malaria programmes have retained or collected packaging material in the process of distributing ITNs, it has mostly been burned in the open air. This method of disposal may lead to the release of dioxins, which are harmful to human health.

If such plastic material (with packaging an issue at the point of distribution and old ITNs an intermittent issue at household level when the net is no longer in use) is left in the community, it is likely to be re-used in a variety of ways. While the insecticide exposure entailed by this kind of re-use has yet to be fully studied, the expected negative health and environmental impacts of leaving the waste in the community are considered to be less than amassing it in one location and/or burning it in the open air.

Since the material from nets represents only a small proportion of total plastic consumption, it will often be more efficient for old ITNs to be dealt with as part of larger and more general solid-waste programmes. National environment management authorities have an obligation to consider and plan for what happens to old ITNs and packing materials in the environment in collaboration with other relevant partners.

Justification

Currently, ITNs and the vast majority of their packaging (bags and baling materials) are made of non-biodegradable plastics (49).The large-scale deployment of ITNs has given rise to questions as to the most appropriate and cost-effective way to deal with the resulting plastic waste, particularly given that most endemic countries do not currently have the resources to manage ITN collection and waste disposal programmes.

A pilot study was conducted to examine patterns of ITN usage and disposal in three African countries (Kenya, Madagascar and United Republic of Tanzania). Findings of this pilot study, along with other background information were used to generate recommendations through the WHO Vector Control Technical Working Group (VCTEG) and MPAG on best practices with respect to managing waste.

The following are the main findings from the pilot study and other background material:

• ITNs entering domestic use in Africa each year contribute approximately 100 000 tonnes of plastic and represent a per capita rate of plastic consumption of 200 grams per year. This is substantial in absolute terms; however, it constitutes only approximately 1% to 5% of the total plastic consumption in Africa and thus is small compared to other sources of plastic and other forms of plastic consumption.
• The plastic from ITNs is treated with a small amount of pyrethroid insecticide (less than 1% per unit mass for most products), and plastic packaging is therefore considered a pesticide product/container.
• Old ITNs and other nets may be used for a variety of alternative purposes, usually due to the perceived ineffectiveness of the net, loss of net physical integrity or presence of another net.
• ITNs that no longer serve a purpose are generally disposed of at the community level along with other household waste by discarding them in the environment, burning them in the open, or placing them into pits.
• ITN collection was not implemented on a large scale or sustained in any of the pilot study countries. It may be feasible to recycle ITNs, but it is not practical or cost-effective at this point, as there would need to be specialized adaptation and upgrading of recycling facilities before insecticide-contaminated materials could be included in this process.
• Two important and potentially hazardous practices are: i) routinely removing ITNs from bags at the point of distribution and burning discarded bags and old ITNs, which can produce highly toxic fumes including dioxins, and ii) discarding old ITNs and their packaging in water, as they may contain high concentrations of residual insecticides that are toxic to aquatic organisms, particularly fish.
• Insecticide-treated plastics can be incinerated safely in high-temperature furnaces, but suitable facilities are lacking in most countries. Burial away from water sources and preferably in non-permeable soil is an appropriate method to dispose of net bags and old ITNs in the absence of a suitable high-temperature incinerator.
• In most countries, ministries of environment (national environment management authorities) are responsible for setting up and enforcing laws/regulations to manage plastic waste broadly. Although some countries have established procedures for dealing with pesticide-contaminated plastics, it is unrealistic to expect national malaria control and elimination programmes to single-handedly address the problem of managing waste from ITNs. Environmental regulations; leadership and guidance from national environmental authorities; and oversight from international agencies, such as the United Nations Environment Programme, are all necessary.

Practical Info

Insecticide formulations currently used for IRS (24) fall into five major insecticide classes with three modes of action, based on their primary target site in the vector. These are listed below, where applicable with examples of the active ingredients contained in IRS products that have been prequalified by WHO:

Sodium channel modulators

• Pyrethroids: alphacypermethrin, deltamethrin, lambda-cyhalothrin, etofenprox, bifenthrin
• Organochlorines: No prequalified product available

Acetylcholinesterase inhibitors

• Organophosphates: malathion, fenitrothion, pirimiphos-methyl
• Carbamates: bendiocarb, propoxur

Nicotinic acetylcholine receptor competitive modulators

• Neonicotinoids: clothianidin

IRS products using four of these insecticide classes have been prequalified by WHO; as of August 2020, there were no organochlorine IRS formulations prequalified (24), but DDT continues to be used in a few countries. The prequalified products have been assessed for their safety, quality and entomological efficacy, which includes evaluation of their mortality effect on mosquitoes when applied to a range of interior surfaces of dwellings found in malaria-endemic areas. Residual efficacy needs to continue for at least three months after the application of the insecticide to the substrate, usually cement, mud or wood (51). Insecticides are available in various formulations to increase their longevity on different surfaces.

IRS is considered an appropriate intervention where:

• the majority of the vector population feeds and rests indoors;
• the vectors are susceptible to the insecticide that is being deployed;
• people mainly sleep indoors at night;
• the malaria transmission pattern is such that the population can be protected by one or two rounds of IRS per year;
• the majority of structures are suitable for spraying; and
• structures are not scattered over a wide area, resulting in high transportation and other logistical costs.

Evidence To Decision

Justification

When carried out correctly, IRS has historically been shown to be a powerful intervention to reduce adult mosquito vector density and longevity and, therefore, to reduce malaria transmission. However, despite its long tradition and the large body of associated operational experience, few RCTs have been conducted on IRS and so the availability of data suitable for use in a meta-analysis is limited (50). The GDG determined that the data from these randomized trials, as well as the large body of evidence generated from other studies, warranted the continued recommendation of IRS for malaria prevention and control. An updated systematic review of data on IRS interventions from recent studies, RCTs and other designs is needed to further underpin this recommendation or modify it as appropriate.

Research needs:

• Further evidence is needed of the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of IRS.
• Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as harms and/or unintended consequences of IRS in urbanized areas with changing housing designs.
• Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of IRS using new insecticides in areas where mosquitoes are resistant to currently deployed insecticides.
• Determine the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) of IRS in areas with different mosquito behaviours (such as in areas with outdoor transmission).
• Given the relatively high cost of implementing IRS, especially in the context of growing insecticide resistance, and when delivering IRS in more remote areas, there is a need to investigate new approaches to delivering IRS to increase the cost-effectiveness of this intervention.

Evidence To Decision

Justification

In terms of the relative effectiveness of IRS compared to ITNs, the systematic review published in 2010 (50) reported was only low certainty evidence available for areas of intense transmission and for areas with unstable transmission. It was therefore not possible to arrive at a definitive conclusion on their comparative effectiveness. WHO therefore currently views these two interventions as being of equal effectiveness, and there is no general recommendation to guide the selection of one over the other. Preferences of national malaria programmes, beneficiaries or donors are usually based on operational factors, such as perceived or actual implementation challenges (see Section 4.1.6.2) and the requirement for insecticide resistance prevention, mitigation and management (see Section 4.1). Financial considerations such as cost and cost-effectiveness are also major drivers of decision-making, and selection of malaria vector control interventions should thus be embedded in a prioritization process that considers the cost and effectiveness of all available malaria interventions and aims at achieving maximum impact with the available resources. Evaluations of the relative cost and cost-effectiveness of ITNs and IRS are ongoing to inform revision of the Guidelines.

Practical Info

Given the resource constraints across malaria-endemic countries, the deployment of a second vector control intervention on top of optimal coverage with an existing one should only be considered as part of a broader prioritization analysis aimed at achieving maximum impact with the available resources. In many settings, a switch from ITNs to IRS or vice versa, rather than their combination, is likely to be the only financially feasible option.

Evidence To Decision

Justification

The systematic review published in 2019 (53) on the deployment of IRS in combination with ITNs (specifically pyrethroid-only LLINs) provided evidence that, in settings where there is optimal coverage with ITNs and where these remain effective, IRS may have limited utility in reducing malaria morbidity and mortality. WHO guidance was developed accordingly to emphasize the need for good-quality implementation of either ITNs or IRS, rather than deploying both in the same area (54). However, the combination of these interventions may be considered for resistance prevention, mitigation or management should sufficient resources be available

Insecticide resistance threatens the effectiveness of insecticidal interventions and hence is a key consideration in determining which vector control interventions to select to ensure impact of is maximized. One approach to the prevention, mitigation and management of vector insecticide resistance is the co-deployment (or combination) of interventions with different insecticides (see Section 4.1 on ‘Prevention, mitigation and management of insecticide resistance’). Therefore, WHO guidance developed based on systematic review (53) differentiated between the effect of combined interventions on malaria morbidity and mortality versus the utility of this approach in a resistance management strategy (54).

A summary of the conclusions (with slight updates for clarity) used to develop the above recommendations is as follows:

• In settings with high ITN coverage where ITNs remain effective, IRS may have limited utility in reducing malaria morbidity and mortality. However, IRS may be implemented as part of an IRM strategy in areas where there are ITNs (19).
• Malaria control and elimination programmes should prioritize the delivery of ITNs or IRS at optimal coverage and to a high standard, rather than introducing the second intervention as a means to compensate for deficiencies in the implementation of the first intervention.
• If ITNs and IRS are to be deployed together in the same geographical location, IRS should be conducted with a non-pyrethroid insecticide.
• Evidence is needed to determine the effectiveness of combining IRS and ITNs in malaria transmission foci, including in low transmission settings. Evidence is also needed from different eco-epidemiological settings outside of Africa.
• All programmes in any transmission setting that decide to prioritize the combined deployment of ITNs and IRS over other potential use of their financial resources should include a rigorous programme of M&E (e.g., a stepped wedge introduction of the combination) in order to confirm whether the additional inputs are having the desired impact. Countries that are already using both interventions should similarly undertake an evaluation of the effectiveness of the combination versus either ITNs or IRS alone.
• The approach of combining interventions for resistance management was developed largely based on experience with agricultural pest management, and the evidence base from public health remains weak.

These findings and conclusions were substantiated by a systematic review of the evidence published in 2019 (53). The review is currently being updated with evidence from further trials that have been conducted since. Once published, the evidence will be reviewed by WHO.

Research needs:

• Further evidence is needed on the impact (incidence of malaria [infection or clinical] and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of combining non-pyrethroid IRS with ITNs vs ITNs only in areas with insecticide resistant mosquito populations.
• Determine whether there are comparative benefits (incidence of malaria [infection or clinical] and/or prevalence of malaria infection), as well as potential harms and/or unintended consequences of combining non-pyrethroid IRS with ITNs vs IRS only in areas with insecticide-resistant mosquito populations.
• Determine the acceptability of combining IRS and ITNs among householders and communities.
• Evaluate new tools for monitoring the quality of IRS and ITN interventions.

Practical Info

Access to effective vector control interventions will need to be maintained in the majority of countries and locations where malaria control has been effective. This includes settings with ongoing malaria transmission, as well as those in which transmission has been interrupted but in which some level of receptivity and importation risk remains. Malaria elimination is defined as the interruption of local transmission (reduction to zero incidence of indigenous cases) of a specified malaria parasite species in a defined geographical area as a result of deliberate intervention activities. Following elimination, continued measures to prevent re-establishment of transmission are usually required (29). Interventions are no longer required once eradication has been achieved. Malaria eradication is defined as the permanent reduction to zero of the worldwide incidence of infection caused by all human malaria parasite species as a result of deliberate activities.

There is a critical need for all countries with ongoing malaria transmission, and in particular those approaching elimination, to build and maintain strong capacity in disease and entomological surveillance and health systems. The capacity to detect and respond to possible resurgences with appropriate vector control relies on having the necessary entomological information (i.e., susceptibility status of vectors to insecticides, as well as their biting and resting preferences). Such capacity is also required for the detailed assessment of malariogenic potential, which is a pre-condition for determining whether vector control can be scaled back (or focalized).

If areas where transmission has been interrupted are identified, the decision to scale-back vector control should be based on a detailed analysis that includes assessment of the receptivity and importation risk of the area, as well as an assessment of the active disease surveillance system, and capacity for case management and vector control response.

Justification

A comprehensive review of historical evidence and mathematical simulation modelling undertaken for WHO in 2015 indicated that the scale-back of malaria vector control was associated with a high probability of malaria resurgence, including for most scenarios in areas where malaria transmission was very low or had been interrupted (30). Both the historical review and the simulation modelling clearly indicated that the risk of resurgence was significantly greater at higher EIRs and case importation rates, and lower coverage of active case detection and case management.

Once transmission has been reduced to very low levels approaching elimination, ensuring optimal access to vector control for at-risk populations remains a priority, even though the size and demographics of the at-risk populations may change as malaria transmission is reduced.

As malaria incidence falls and elimination is approached, increasing heterogeneity in transmission will result in foci with ongoing transmission in which vector control may need to be optimized and enhanced. Such foci may be the result of particularly high vectorial capacity, lapsed prevention and treatment services, changes in parasites that make the current strategies less effective, or reintroduction of malaria parasites by the movement of infected people or infected mosquitoes. Monitoring the coverage, quality and impact of vector control interventions is essential to maintain the effectiveness of control. Guidance on entomological surveillance across the continuum from control to elimination is provided elsewhere (29).

Once elimination has been achieved, vector control may need to be continued by targeting defined at-risk populations to prevent reintroduction or re-establishment of local transmission.

It is acknowledged that malaria transmission can persist following the implementation of a widely effective malaria programme. The sources and risks of residual transmission may vary by location, time and the existing components of the current malaria programme. This variation is potentially due to a combination of both mosquito and human behaviours, such as when people live in or visit forest areas or do not sleep in protected houses, or when local mosquito vector species bite and/or rest outdoors and thereby avoid contact with IRS or ITNs/LLINs.

Once elimination has been achieved, optimal vector control coverage should be maintained in receptive areas where there is a substantial risk for reintroduction.

Practical Info

Larviciding is most likely to be cost-effective in urban areas where the appropriate conditions are more likely to be present. Larviciding is not generally recommended in rural settings, unless there are particular circumstances limiting the larval habitats and specific evidence confirming that such measures can reduce malaria incidence in the local setting.

WHO’s 2013 Operational manual on larval source management (60) concluded that ITNs and IRS remain the backbone of malaria vector control, but LSM represents an additional (supplementary) strategy for malaria control in Africa. Larviciding will generally be most effective in areas where larval habitats are few, fixed and findable, and likely less feasible in areas where the aquatic habitats are abundant, scattered and variable. Determination of whether or not specific habitats are suitable for larviciding should be based on assessment by an entomologist. The WHO operational manual focuses on sub-Saharan Africa, but the principles espoused are likely to hold for other geographic regions that fit the same criteria. The following settings are potentially the most suitable for larviciding as a supplementary measure implemented alongside ITNs or IRS:

• urban areas: where breeding sites are relatively few, fixed and findable in relation to houses (which are targeted for ITNs or IRS);
• arid regions: where larval habitats may be few and fixed throughout much of the year.

Evidence To Decision

Justification

Larviciding is deployed for malaria control in several countries, including Somalia and Sudan. However, the systematic review on larviciding conducted in 2019 (59) assessed that the certainty of evidence of impact on malaria incidence or parasite prevalence was moderate or low in non-extensive habitats. Since larviciding only reduces vector density, it does not have the same potential for health impact as ITNs and IRS – both of which reduce vector longevity (a key determinant of transmission intensity) and provide protection from biting vectors. As a result, larviciding should never be seen as a substitute for ITNs or IRS in areas with significant malaria risk.

Practical Info

Although the available evidence which met the inclusion criteria for the systematic review was considered insufficient to develop specific recommendations, national programmes may decide to use environmental management (habitat modification and/or manipulation) to avoid the creation, and reduce the availability of, larval habitats, where deemed appropriate, based on expert guidance and local knowledge. If such strategies are employed, the selection of the specific intervention(s) should be highly contextual, i.e., it should take into account the specific environment the type of intervention(s) that are relevant to that environment, the resources needed and their availability, the feasibility of the intervention(s), their acceptability by local stakeholders and how they might impact equity. The selection should also take into account previous experience either gained locally or from other areas of similar ecological and epidemiological characteristics where such intervention(s) have been implemented. Additionally, the selection of the comparator should consider other interventions that are known to be cost-effective, for example, larviciding. Where the decision is taken to invest resources into larval habitat modification and/or larval habitat manipulation, the intervention(s) should be designed and conducted with the explicit aim of generating data to demonstrate effective malaria control and preferably, supported with environmental and entomological data as secondary end-points.

When assessing the impact of environmental management against malaria, it is important that the testing of the intervention(s) being investigated is/are specifically conducted for the purpose of preventing or controlling malaria by reducing the availability and productivity of larval habitats. For example, dams are generally constructed for water management, irrigation or power production purposes, not for malaria control. In fact, in some cases, their construction may result in increased larval production due to the creation of standing water bodies. The controlled release of water from the impoundment of a dam, however, is considered an example of habitat manipulation, a recurrent activity which potentially controls mosquito larvae by increasing the flow rate of downstream water with the aim of preventing mosquito development and so controlling malaria transmission. This is one example of the multitude of interventions that fall under the broad category of habitat modification and/or manipulation. To be able to generate evidence on the efficacy of larval habitat modification and/or manipulation in preventing malaria, and to facilitate the interpretation of the evidence once generated, it is important to well define the interventions that are being evaluated and, importantly, compare how the water conditions of larval habitats at the intervention and control sites are affected. For example, if the intervention aimed to increase the water flow of downstream areas, the evaluation should include an assessment of whether this was achieved, as well as to what extent this impacted the development of the immature and adult stages of the mosquito and, ultimately, whether there was an epidemiological impact on against malaria in the intervention arms compared to control areas. This information will then support the evolution of WHO guidance in this area and, ultimately, guide the choice and implementation of efficacious interventions.

Evidence To Decision

Justification

The systematic review to inform WHO recommendations in this area identified only two controlled before-and-after studies meeting the inclusion criteria with epidemiological outcomes that investigated the impact of larval habitat manipulation/modification alone. Two other identified studies combined habitat manipulation with larviciding and so the effect of the two could not be separated. The two eligible studies investigated the impact of larval habitat manipulation against malaria (Martello, E., Yogeswaran, G. & Leonardi-Bee, J. unpublished findings). One study was conducted in an urban area of the Philippines in 1960 and the other in a forested area of India in 2008 where annual IRS was also conducted. The studies provided low or very low certainty evidence that the controlled release of water from flood gates of dams to discharge excess water or using spillways (overflow channels) across streams to automatically flush downstream areas with water (continually or intermittently) reduced clinical malaria incidence or parasite prevalence. The evidence was downgraded due to the lack of appropriate randomization or poor statistical reporting. The studies examined very specific interventions, each studied in a single site, which limited their generalizability. The systematic review reported a number of other studies with only entomological outcomes investigating a wide range of highly heterogeneous interventions falling under the broad term of larval habitat manipulation and/or modification, some of which may only be appropriate in specific ecologies. Given the broad range of interventions and settings in which larval habitat manipulation and/or modification may be applied, the potential impact, feasibility, acceptability and resource needs for each intervention is likely to be highly variable.

Although it is acknowledged that there is a wealth of historical research on environmental management of malaria, unfortunately this literature was insufficiently robust to be included in this systematic review. Therefore, there remains a continued need to robustly demonstrate the epidemiological impact environmental management (habitat modification and/or manipulation) through measurement of malaria incidence or prevalence through further well-designed intervention studies.

Research needs:

The GDG encourages funding of high-quality research on the impact of habitat manipulation and/or modification on malaria transmission to inform the development of specific WHO recommendations in this area. A number of evidence gaps and associated requirements were identified:

• Determine the impact (incidence of clinical malaria and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of the different interventions.
• Epidemiological evidence is required on the efficacy against malaria of the same intervention implemented in different settings (where vector species may differ).
• Detailed descriptions of the interventions deployed, as well as larval habitat types and vector species targeted. The impact of the intervention on the water conditions of the larval habitats should be assessed, i.e. properties of the habitat that the intervention aims to modify such as water flow, volume, sunlight penetration, salinity or other physical conditions.
• Evidence on contextual factors, (i.e., acceptability, feasibility, resource use, cost-effectiveness, equity, values and preferences) related to larval habitat modification and/or manipulation is needed.

Evidence To Decision

Justification

The systematic review conducted in 2017 on use of larvivorous fish (61) did not identify any studies demonstrating impact on malaria and so there is insufficient evidence to support a recommendation. The GDG recognizes that there are specific settings in which the intervention is currently implemented, and in these specific settings programme staff consider it to be effective. In some of the settings where larvivorous fish are being deployed, programmatic evidence exists; however, this was not determined appropriate for inclusion in the systematic review due to unsuitable study design or other concerns. The GDG acknowledges that there may be data at country/programme level that it is not aware of.

Research needs:

• Determine the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of the use of larvivorous fish.

Evidence To Decision

Justification

The evidence from the RCTs included in the systematic review conducted in 2018 (62) provided low certainty evidence of a possible effect of topical repellents on malaria parasitaemia (P. falciparum and P. vivax). The evidence is insufficiently robust to determine whether topical repellents have an effect on clinical malaria.

Research needs:

• Determine the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of topical repellents for individuals in specific settings and target populations.

Evidence To Decision

Justification

The systematic review carried out in 2018 (62) provided low certainty evidence that insecticide-treated clothing may have protective efficacy against P. falciparum and P. vivax cases, at least in certain specific populations (refugees, military personnel and others engaged in occupations that place them at high risk) and where ITNs were not in use. There was no evidence available on epidemiological effects in the general at-risk population.

Research needs:

• Determine the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of insecticide-treated clothing in the general population.
• Identification of approaches to enhance acceptability/desirability and increase uptake and adherence is needed.
• Development of formulations that improve the durability of insecticidal efficacy is needed.

Evidence To Decision

Justification

The systematic review published in 2018 (62) concluded that there is very low certainty evidence that spatial or airborne repellents may have a protective efficacy against malaria parasitaemia. Therefore, no recommendation on the use of spatial/airborne repellents in the prevention and control of malaria can be made until more studies assessing malaria epidemiological outcomes have been conducted.

Research needs:

• Determine the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of spatial/airborne repellents.
• Development of spatial repellent insecticide formulations that provide a long-lasting effect is required.

Evidence To Decision

Justification

Only observational studies were identified by the systematic review and the certainty of the evidence was graded as very low (63). The lack of data from RCTs, other trial designs or quasi-experimental studies has therefore hampered a comprehensive assessment of this intervention and the review concluded that it is unknown whether space spraying causes a reduction in incidence of malaria. Anticipated desirable effects of space spraying are likely to be small, as insecticide formulations used are short-lived. Anopheles mosquitoes are generally considered to be less susceptible to space spraying than Culex or Aedes. Space spraying is frequently applied when cases are at their peak, which is followed by a decline in cases, whether or not control measures are applied. Nevertheless, space spraying is often deployed in response to outbreaks of mosquito-borne disease. Due to the high visibility of this intervention, the decision to use this approach is usually made to demonstrate that the authorities are taking action in response to the outbreak. This practice should be strongly discouraged given the limited evidence of the intervention’s effectiveness, the high cost and the potential for wastage of resources. The GDG therefore felt it necessary to develop a clear recommendation against space spraying for malaria control.

Research needs:

• Determine the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) as well as potential harms and/or unintended consequences of space spraying, particularly in emergency situations.

Practical Info

If house screening is being considered as a means to prevent malaria, it is important to identify who the end-user will be and how the intervention will be implemented, i.e. whether this would be a tool that the program promotes for individuals or communities to implement at their own cost, or if screening of houses is undertaken as a programmatic initiative. Depending on the approach, the resources needed, feasibility, up-take and impact on equity may vary and would need to be considered.

Screening of houses may be done post-construction or could be a standard feature for new homes. Intersectoral collaboration, for example between health, housing and environmental sectors, is crucial in the implementation of house screening. It is also important to consider what standards and criteria, if any, need to be set for screening materials and designs as they are for buildings.

Screening of residential houses should be part of an integrated vector management (IVM) approach as promoted under the Global Vector Control Response (13) and deployment of interventions recommended for large-scale deployment (such as ITN or IRS) should be maintained.

In settings where national or local government authorities are not able to provide screening of residential houses as a public health strategy (e.g., due to feasibility/ resource challenges), they should promote its use amongst affected communities.

If house screening is deployed or adopted by communities to prevent malaria, post-distribution monitoring of the intervention is needed to assess material durability, usage, and coverage. This information should guide how regularly screens require replacement or repair and provide information on the sustainability of the intervention.

Evidence To Decision

Justification

The systematic review to inform WHO guidance in this area identified only two eligible published studies assessing epidemiological outcomes (64). Both studies investigated the impact of house screening (screening of windows, ceilings, doors and/or eaves) with untreated materials against malaria. The evidence for the assessed outcomes was rated as low to moderate certainty due to risk of bias and imprecision. In the trials included in the systematic review, research teams deployed screening at the community level and as a result, currently there is no evidence as to the benefits and harms of individuals or communities deploying screens themselves. The review identified several studies that were yet to be published on the efficacy of insecticide-treated screening, eave tubes or other forms of housing interventions but the data were not yet available for inclusion in the review. The panel concluded that untreated screening of residential houses may prevent malaria and reduce malaria transmission. The panel judged that policy makers considering house screening should assess the feasibility, acceptability, impact on equity and resources needed for screening houses in their contexts.

Research needs:

WHO encourages funding of high-quality research on the impact of interventions under the broad category of ‘housing modifications’ to further inform the development of specific WHO recommendations. Four trial results awaiting publication are likely to enrich the current evidence-base on housing modifications for preventing malaria and controlling malaria transmission, and publication of these studies is strongly encouraged.

A number of specific evidence gaps and associated requirements were identified:

• Further evidence is required on the impact (incidence of malaria (infection or clinical) and/or prevalence of malaria infection) and potential harms/unintended consequences of house screening, as well as other house modification interventions deployed singly or in combination.
• Epidemiological evidence is required on the efficacy against malaria of the same intervention implemented in different settings (where vector species may differ).
• Evidence on contextual factors (i.e., acceptability, feasibility, resource use, cost-effectiveness, equity, values and preferences) related to house screening, as well as other house modification interventions is needed.
• Resources needed, costs and cost-effectiveness, for various deployment options (at the programme-, community-, individual-level) of house screening need to be identified.
• Deployment mechanisms and community buy-in for house screening as well as other house modification interventions.

Residual transmission

WHO acknowledges that even full implementation of ITNs or IRS will not be sufficient to completely halt malaria parasite transmission across all settings (65). Some residual malaria parasite transmission will occur, even with optimal access to and usage of ITNs or in areas with high IRS coverage. Residual transmission occurs as a result of a combination of human and vector behaviours, for example, when people reside in or visit forest areas or do not sleep in protected houses, or when local mosquito vector species exhibit one or more behaviours that allow them to avoid ITNs or IRS, such as biting outside early in the evening before people have retired indoors and/or resting outdoors.

There is an urgent need for greatly improved knowledge of the bionomics of the different sibling species within malaria vector species complexes, and new interventions and strategies in order to effectively address residual transmission. While this knowledge is being gained and interventions are being developed, national malaria control programmes must prioritize the effective implementation of current interventions to reduce transmission to the lowest level possible. At the same time, they should collaborate with academic or research institutions to generate local evidence on the magnitude of the problem of residual transmission of malaria, including information on human and vector behaviours, and the effectiveness of existing and novel interventions.

Residual transmission is difficult to measure, as is the specific impact of supplementary tools on this component of ongoing transmission. Standardized methods for quantifying and characterizing this component of transmission are required in order to evaluate the effectiveness of single or combined interventions in addressing this biological challenge to malaria prevention and control and elimination.

Epidemics and humanitarian emergencies

In the acute phase of a humanitarian emergency, the first priorities for malaria control are prompt and effective diagnosis and treatment. Vector control also has the potential to play an important role in reducing transmission. However, the evidence base on the effectiveness of vector control interventions deployed in these settings is weak (66).

During the acute phase, decisions on vector control and prevention will depend on:

• Malaria infection risk;
• Behaviour of the human population (e.g. mobility, where they are sleeping or being exposed to vector mosquitoes);
• Behaviour of the local vector population (e.g. indoor resting, indoor biting, early evening or night biting);
• The type of shelter available (e.g. ad-hoc refuse materials, plastic sheeting, tents, more permanent housing).

Effective case management can be supplemented with distribution of ITNs, first targeting population groups most susceptible to developing severe malaria, but with the ultimate goal of achieving and maintaining optimal coverage. IRS can also be applied in well-organized settings, such as transit camps, but is generally unsuitable where dwellings are scattered widely, of a temporary nature (less than three months) or constructed with surfaces that are unsuitable for spraying. IRS is best suited for protecting larger populations in more compact settings, where shelters are more permanent and solid.

Some vector control interventions and personal protection measures have been specifically designed for deployment in acute emergency situations. Plastic sheeting is sometimes provided in the early stages of humanitarian emergencies to enable affected communities to construct temporary shelters. In these new settlements, where shelter is very basic, use of insecticide-treated plastic sheeting (ITPS) to construct shelters may be a practical, acceptable and feasible approach. Laminated polyethylene tarpaulins that are impregnated with a pyrethroid during manufacture are suitable for constructing such shelters. As with IRS, ITPS is only effective against indoor resting mosquitoes, but the degree to which it impacts transmission has yet to be confirmed. Moreover, pyrethroid-treated plastic sheeting should not be deployed in areas where the local malaria vectors are resistant to pyrethroids.

Another intervention with potential for deployment in emergency situations is the long-lasting insecticide impregnated blanket or topsheet. Blankets or lightweight topsheets are often included in emergency relief kits. One advantage of blankets and topsheets is that they can be used anywhere people sleep (e.g. indoors, outdoors, any type of shelter). However, as with ITPS, the evidence base regarding the effectiveness of this approach is currently limited. Data from community RCTs of long-lasting pyrethroid-treated wash-resistant blankets and topsheets would be required to determine public health value and develop specific policy recommendations for such interventions.

In the post-acute phase, optimal coverage with ITNs or IRS may be feasible. Deployment of insecticide-treated plastic sheeting for shelter construction may be more practical in situations where ITN use or the application of IRS is not possible, although currently there is no WHO policy recommendation for this intervention.

Migrant populations and populations engaged in high-risk activities

As noted above, topical repellents and insecticide-treated clothing may be practical interventions for providing personal protection to specific populations at risk of malaria due to occupational exposure, e.g. military personnel, night-shift workers, forestry workers. However, the available evidence does not support the large-scale deployment of such interventions for reducing or preventing infection and/or disease in humans when assessed at the population level and few studies have reported disease outcomes at the individual level. Data demonstrating epidemiological impact would be required to determine their public health value for these populations.

Acceptability, participation and ethical considerations

Acceptability and end-user suitability of the vector control interventions included in the Guidelines were considered when developing the Evidence-to-Decision Frameworks, as part of the GRADE process.

ITNs are generally acceptable to most communities. In many malaria-endemic countries, untreated nets were in use for many years prior to the introduction of ITNs and, even where there is not a long history of their use, they have become familiar tools for preventing mosquito bites. Individuals often appreciate the extra privacy afforded by a net, as well as its effectiveness in controlling other nuisance insects. In very hot climates, ITNs may be less acceptable, as they are perceived to reduce air flow, making it too hot to allow for a comfortable sleep. In areas where mosquito densities are low or where malaria transmission is low, individuals and communities may perceive less benefit in using nets.

Community acceptance of IRS is critical to the programme’s success, particularly as it involves disruption to the household, requiring householders to remove certain articles and allow spray teams to enter all rooms of the house. Repeated, frequent spraying of houses over extended periods can lead to refusal by householders. Reduced acceptance has been an impediment to effective IRS implementation in various parts of the world (68).

Larviciding for malaria vector control is currently not deployed at the scale of ITNs or IRS, and many communities are therefore unfamiliar with it. Larviciding is likely to be more acceptable in communities that have a good understanding of the lifecycle of mosquitoes and the link with the transmission of malaria or other diseases. Community members may have concerns about larvicides being applied to drinking water or other domestic water sources. A well-designed community sensitization programme is required to ensure that communities fully understand the intervention and that any concerns about health and safety aspects are addressed.

Community participation in the implementation of vector control interventions is often in the form of “instruction” and “information”, with decisions about the need for interventions being made at international and national levels. Taking into account communities’ views on the recommended interventions may promote acceptance and adherence to the intervention. Increased levels of participation (e.g. consultation, inclusion and shared decision-making) should ideally be included in the future development of improved and new vector control interventions, from inception through to the planning and implementation stages.

WHO acknowledges that appropriate policy-making often requires explicit consideration of ethical matters in addition to scientific evidence. However, the ethical issues relevant to vector-borne disease control and research have not previously received the analysis necessary to further improve public health programmes. Moreover, WHO Member States lack specific guidance in this area. The Seventieth World Health Assembly (69) requested the Director-General “to continue to develop and disseminate normative guidance, policy advice and implementation guidance that provides support to Member States to reduce the burden and threat of vector-borne diseases, including to strengthen human-resource capacity and capability for effective, locally adapted, sustainable and ethically sensitive vector control; to review and provide technical guidance on the ethical aspects and issues associated with the implementation of new vector control approaches in order to develop mitigating strategies and solutions; and to undertake a review of the ethical aspects and related issues associated with vector control implementation that include social determinants of health, in order to develop mitigating strategies and solutions to tackle health inequities.” As a first step towards developing appropriate guidelines within the next two years, a scoping meeting was convened by WHO to identify the ethical issues associated with vector-borne diseases (70). Further work has been undertaken to develop guidance. Once available, it will be reflected in the Guidelines.

Unique ethical issues associated with vector control that were identified at the February 2017 scoping meeting include the ethics of coercive or mandated vector control, the deployment of insecticides (and growing vector resistance to insecticides), and research on and/or deployment of new vector control technologies. Genetically modified mosquitoes are one such innovation that presents potential challenges, including how to prevent their spread beyond the intended geographical target areas and limit potential effects on the local fauna. WHO has established a robust evaluation process for new vector control interventions (31) in order to ensure that these are fully and properly assessed prior to any WHO recommendation for their deployment.

Equity, gender and human rights

The aim of all of the work of WHO is to improve population health and decrease health inequities. Sustained improvements to physical, mental and social well-being require actions in which careful attention is paid to equity, human rights principles, gender and other social determinants of health. A heightened focus on equity, human rights, gender and social determinants is expressed in the WHO Thirteenth General Programme of Work.

In pursuit of this outcome, WHO is committed to providing guidance on the integration of sustainable approaches that advance health equity, promote and protect human rights, are gender-responsive and address social determinants into WHO programmes and institutional mechanisms; promoting disaggregated data analysis and health inequality monitoring; and providing guidance on the integration of sustainable approaches that advance health equity, promote and protect human rights, are gender-responsive and address social determinants into WHO’s support at country level (71).

WHO advocates for optimal coverage with recommended vector control interventions. As such, malaria vector control is expected to be implemented without discrimination on the basis of age, sex, ethnicity, religion or other characteristics. In some cases, special effort is required to reach populations that are geographically isolated or adopt a nomadic lifestyle.

In contrast to the situation observed with HIV and TB, malaria has not been associated with systematic discrimination against individuals or groups assumed to be at a high risk of infection. However, malaria disproportionately affects the most vulnerable populations, including the rural poor, pregnant women, children, migrants, refugees, prisoners and indigenous populations. For these populations, social inequality and political marginalization may impede access to health services, and there may be additional barriers created by language, culture, poor sanitation, lack of access to health information, lack of informed consent in testing and treatment, and inability to pay user fees for medical services. National malaria control programmes are increasingly encouraged to identify vulnerable groups and situations of inequitable access to services and to design approaches, strategies and specific activities to remove human rights and gender-related inequities.

Resource implications and prioritization

In this edition of the Guidelines, resource implications and the cost-effectiveness of vector control interventions were largely addressed by drawing on expert opinion within the GDG due to limited data to inform discussions. Although it is recognized that resource considerations should ideally be based on evidence, there was insufficient clarity on how to collate and present such data to the GDG and how to reflect this within the Guidelines at the time of writing. For future revisions of the Guidelines, it is envisaged that this area will be expanded upon for both new and existing recommendations.

The most recent systematic review of the cost and cost-effectiveness of vector control interventions was published in 2011, drawing on studies published between 1990 and 2010 (72). The body of evidence collated was based on the use of ITNs/LLINs and IRS in a few sites in sub-Saharan Africa. The authors found large variations in the costs of intervention delivery, which reflected not only the different contexts but also the various types of costing methodologies employed; these studies were rarely undertaken alongside clinical and epidemiological evaluations. The review reported that, while ITNs/LLINs and IRS were consistently found to be cost-effective across studies, evidence to determine their comparative cost-effectiveness was insufficient. WHO GMP is working with partners to update the evidence review on the cost and cost-effectiveness evidence of the vector control interventions as part of an ongoing broader systematic review on the cost and cost-effectiveness of malaria control interventions and this review will be drawn upon in future GDG discussions. WHO GMP is also working with partners to ensure that the internal database on the cost and cost-effectiveness evidence of malaria control interventions is maintained, to support future GDG deliberations. It is also planned that systematic reviews commissioned in future will include a search of the literature on both the cost and cost-effectiveness of interventions under consideration. This information will be collated in advance of the GDG meetings to be considered as part of the evidence to decision framework alongside other evidence for an intervention, such as its epidemiological impact, acceptability, feasibility, and impact on equity. Furthermore, it is envisaged that the gaps in the economic evidence for the previously approved recommendations will be gradually closed by means of systematic searches of the literature for studies adding to the evidence in this area.

Given that resource considerations are highly context-specific and that the guideline content will not be sufficient to inform resource prioritization at (sub-)national levels, GMP is conducting further work to support country-level decision-making as part of the High burden to high impact initiative, and will expand on this work with a particular focus on informing deployment of an increasing number of interventions across different settings.

Human resources and entomological capacity

The Global vector control response 2017–2030 (13) notes that effective and sustainable vector control is achievable only with sufficient human resources, an enabling infrastructure and a functional health system. A vector control needs assessment (15) will help to appraise current capacity, define what is needed to conduct proposed activities, identify opportunities for improved efficiencies in vector control, and guide resource mobilization.

Formulating an inventory of existing human, infrastructural (functioning insectary and entomological laboratory for species identification and resistance testing, vehicles, spray equipment, etc.), institutional and financial resources available, and making an appraisal of existing organizational structures for vector control are essential first steps. The inventory should cover all resources available at national and subnational levels, including districts. A broader appraisal of relevant resources available outside of the vector-borne disease programme, including in municipal governments, non-health ministries, research institutions and implementing partners, should be conducted. An evaluation of career structures within national and subnational programmes is also important. A comprehensive plan for developing the necessary human, infrastructural and institutional capacity within programmes should be formulated. The plan should identify any additional resources and associated costs involved in achieving the desired objectives and set out clear terms of reference for the different staffing positions required.

Capacity-building priorities for established staff should be defined through a comprehensive training needs assessment led by the ministry of health and aligned with available WHO guidance (73).

Quality assurance of vector control interventions

Quality assurance is the implementation of systematic and well-planned activities to prevent substandard services or products.

Lower than expected effectiveness may be due to a variety of factors related to implementation. These can include incorrect application of the intervention, inadequate procurement planning, poor quality of deployed products and failure to achieve optimal coverage. Quality assurance efforts should be continuous, systematic and independent. Continuous monitoring and supervision are required to ensure that staff are adequately trained and follow technical guidelines for pesticide application and personal safety. Vector control programmes must include a quality assurance programme designed to monitor the effectiveness of the control activities. A quality assurance programme should monitor applicator performance and control outcomes.

The WHO Model Quality Assurance System for Procurement Agencies (74) details the quality assurance steps and processes involved in procuring pharmaceutical products and diagnostics, but the principles are equally applicable to vector control products.

For vector control products, the key elements of quality assurance are:

• Sourcing only products prequalified by WHO for deployment against malaria vectors;
• Requesting the supplier/manufacturer to provide a Certificate of Analysis for each batch of the product actually being supplied;
• Pre-shipment inspection and sampling according to WHO guidance and/or International Organization for Standardization (ISO) standards, performed by an independent sampling agent;
• Pre-shipment testing conducted by an independent quality control laboratory (WHO prequalified, or ISO 17025 or Good Laboratory Practice accredited) to determine that the product conforms to approved specifications according to the WHO/CIPAC test methods;
• Testing on receipt in country (post-shipment quality control testing) should only be conducted if specific risks related to transport have been identified or specific concerns over potential product performance justify this additional expense;
• Tender conditions should include provisions for free-of-cost replacement of shipments that fail quality control checks and disposal of failed lots;
• Post-marketing surveillance may be required, depending on the product and context, to monitor performance over time in order to ensure that products continue to conform to their specifications and/or recommended performance as set by WHO. For ITNs, this may require testing both physical durability and insecticidal efficacy. For IRS products, bioefficacy on sprayed surfaces of a different nature (e.g. mud, brick), as applicable, should be periodically tested according to WHO procedures when an insecticide is first introduced into a country. Subsequent measurement of insecticide decay on sprayed surfaces should be done only if necessary, as it will incur additional expense. Countries can make post-marketing surveillance a priority in cases where there are no country-specific data on certain ITNs or IRS products, or where anecdotal data on poor performance of certain products may exist. Agreement on the need and scope of the proposed activities should be reached by all in-country stakeholders, including the national regulatory authority. All evaluations should follow WHO guidance.

Quality assurance of the field application of vector control interventions should form an integral part of the national programme’s strategy and should include:

• High-quality training for all staff engaged in field implementation of vector control interventions;
• Regular supervision, monitoring and follow-up of field operations;
• Periodic testing of the quality of IRS operations through WHO cone bioassay of sprayed surfaces;
• Periodic testing of the insecticide concentration on ITNs using WHO cone bioassay and/or chemical analysis.

The WHO cone bioassay (preferably using fully susceptible anophelines obtained from insectaries) is currently the only tool available for assessing the bioefficacy of ITNs and the quality of the application of IRS insecticides to walls and other internal surfaces. Colorimetric assays are under development that aim to rapidly quantify the amount of insecticide on a sprayed surface in the field without the need for a bioassay on live mosquitoes. These colorimetric assays, when available, should enable programmes to increase the speed and ease of quality assurance testing of IRS applications.

GRADE

In a systematic review of IPTp, seven trials involving direct comparison of two doses of SP with three or more doses monthly were evaluated (81). The trials were conducted in Burkina Faso, Kenya, Malawi, Mali and Zambia between 1996 and 2008.

In comparison with two doses of SP, three or more doses:

• increased the mean birth weight by about 56 g (95% CI, 29–83; seven trials, 2190 participants, high-quality evidence);
• reduced the number of low-birth-weight infants by about 20% (RR, 0.80; 95% CI, 0.69–0.94; seven trials, 2190 participants, high-quality evidence);
• reduced placental parasitaemia by about 50% (RR, 0.51; 95% CI, 0.38– 0.68; six trials, 1436 participants, high-quality evidence); and
• reduced maternal parasitaemia by about 33% (RR, 0.68; 95% CI, 0.52– 0.89; seven trials, 2096 participants, high-quality evidence).

The trials conducted to date have not been large enough to detect or exclude effects on spontaneous miscarriage, stillbirth or neonatal mortality (very low- quality evidence).

Other considerations

The guideline development group noted that the beneficial effects were obvious in women in their first and second pregnancies. There was less information on women in their third or later pregnancy, but the available information was consistent with benefit.

Rationale for the recommendation

The Guideline Development Group noted that effects were seen in women in their first and second pregnancy. Less information was available on women in their third or later pregnancy, but this information was consistent with benefit.

Evidence supporting the recommendation

The recommendation is based on a pooled analysis of 6 randomized placebo-controlled studies on SP-IPTi conducted in areas of moderate to high transmission of malaria (83):

SP-IPTi delivered through EPI provides an overall protection in the first year of life against clinical malaria [30.3% (95% CI: 19.8%–39.4%)], anaemia [21.3% (95% CI: 8.3%–32.5%)], hospital admissions associated with malaria parasitaemia [38.1% (95% CI 12.5%–56.2%)], and all-cause hospital admissions [22.9% (95% CI: 10.0%–34.0%)]. SP-IPTi offers a personal protection against clinical malaria for a period of approximately 35 days following the administration of each dose.

Other considerations

The recommendation was formulated at the fourth consultative meeting of the Technical Expert Group of Preventive Chemotherapy, GMP, WHO, April 2009 which reviewed all evidence available at the time. The quality of evidence has not been formally assessed.

Remarks

The recommendation is based on a pooled analysis of 6 randomized placebo-controlled studies on SP-IPTi conducted in areas of moderate to high transmission of malaria: SP-IPTi delivered through EPI provides an overall protection in the first year of life against clinical malaria [30.3% (95% CI: 19.8%–39.4%)], anaemia [21.3% (95% CI: 8.3%–32.5%)], hospital admissions associated with malaria parasitaemia [38.1% (95% CI 12.5%–56.2%)], and all-cause hospital admissions [22.9% (95% CI: 10.0%–34.0%)]. SP-IPTi offers a personal protection against clinical malaria for a period of approximately 35 days following the administration of each dose.

Rationale for the recommendation

The recommendation was formulated at the fourth consultative meeting of the Technical Expert Group (TEG) of Preventive Chemotherapy, GMP, WHO, April 2009 which reviewed all evidence available at the time. The evidence was not re-evaluated during this guideline process and therefore the quality of evidence has not been formally assessed.

GRADE

In a systematic review (85), SMC was directly compared with no prophylaxis in seven trials with a total of 12 589 children. All the trials were conducted in West Africa, and six of seven trials were restricted to children < 5 years.

In comparison with no chemoprophylaxis, SMC:

• prevented up to 75% of malaria episodes (rate ratio, 0.26; 95% CI, 0.17–0.38; six trials, 9321 participants, high-quality evidence);
• prevented up to 75% of severe malaria episodes (rate ratio, 0.27; 95% CI, 0.10–0.76; two trials, 5964 participants, high-quality evidence); and
• may be associated with a reduction in mortality (risk ratio, 0.66; 95% CI, 0.31–1.39; six trials, 9533 participants, moderate-quality evidence).

These effects remained even when use of insecticide-treated nets was high (two trials, 5964 participants, high-quality evidence).

The current regimen (amodiaquine + SP) caused vomiting after the first dose in some children (high-quality evidence).

Remarks

The target areas for implementation are those where:

• malaria transmission and most clinical malaria cases occur during a short period of about 4 months;
• the clinical attack rate of malaria is > 0.1 episode per child during the transmission season; and
• amodiaquine + sulfadoxine–pyrimethamine remains efficacious (> 90% efficacy).

SMC should not be given to children with severe current illness, who are already taking co-trimoxazole or with a known allergy to amodiaquine or sulfadoxine–pyrimethamine.

Rationale for the recommendation

The Guideline Development Group endorsed the previous recommendation for SMC made by the WHO Technical Expert Group on Preventive Chemotherapy in May 2011, subsequently reviewed and endorsed by the WHO Malaria Policy Advisory Committee in January 2012.