‘Will anti-malarial bednets for children in developing countries significantly decrease resilience against malaria? Is preventing infection really a better social solution than adaptable immune systems?‘
Short answer: Truly prodigious in its parasitic capabilities, with >100 malaria parasite species capable of infecting a stupendous range of animals from primates to rodents to birds, even lizards and snakes, malaria is estimated to have co-evolved with humans for ~half a million years, cutting a swath through human populations all through history ().
Given this history, framing one approach (human-made interventions) versus another (natural anti-malaria immunity) fails to get to grips with how to manage such an ancient and wily parasite. It’s also important to keep in mind that natural resistance to malaria builds up over time after multiple infections.
Maternal malaria during any stage of pregnancy can and often does adversely impact the fetus and newborn while babies are disproportionately prone to malaria death. This is why a major focus of public health interventions is preventing malaria during pregnancy and in babies.
Insecticide-treated bed nets (ITNs) are deployed to break the malaria transmission cycle by not just preventing infection but also killing mosquitoes. ITN isn’t the only large scale public health intervention in malaria-endemic African countries, which are presently the principal site of malaria morbidity and mortality. Rather, it is part of a four-pronged approach with the other three being Artemisinin-based combination therapy (ACT), intermittent preventive treatment in pregnancy (IPTp) and indoor residual spraying (IRS).
Problem is a single class of insecticide (pyrethroids) is approved for ITN use while prohibitive cost of the other three classes of insecticide also restricts IRS to mainly pyrethroids. Such mono insecticide use has led to development of insecticide resistance in Anopheles mosquitoes, resistance that is being reported from more and more countries. It also appears to drive mosquito behavior modification, changing indoor feeding to outdoors.
Longer answer expands on the known pros & cons of ITNs.
Important to note that currently, Africa, specifically sub-Saharan Africa, remains the main redoubt for malaria morbidity and mortality (see below from). For this reason, sub-Saharan Africa is the epicenter of malaria control.
Insecticide-treated Bed Nets (ITNs): Pros
Cheap and durable, commercially manufactured ITNs are considered a cost-effective public health intervention capable of serving as both a physical barrier as well as a mosquito killer. The WHO recommends using long-lasting commercial ITNs where the insecticide is either coated around or even incorporated into the net fibers, allowing for the insecticide’s biological activity to withstand multiple washes (3). Obviously ITN are most effective in areas where the mosquitoes feed indoors and where maximal biting occurs at night.
ITN breaks the malaria transmission cycle by preventing both a malaria-laden mosquito from biting a malaria-free human host as well as a malaria-free mosquito from biting a malaria-infected human host. Studies in the 1980s showing pyrethroids being able to repel and kill mosquitoes even as they were safe for humans () opened the door for their widespread use.
For these reasons the WHO has recommended widespread ITN use across malaria-endemic regions since at least 2000 (). Antenatal clinics made large numbers of ITNs available to pregnant women at greatly subsidized prices as part of mass distribution campaigns launched by the ministries of health in various malaria-endemic countries ( ).
Starting in 2003, a stream of studies have reported ITNs being able to kill substantial numbers of anopheline mosquitoes and reduce malaria transmission (, , , , ). Given such results and the large scale push by both the WHO and various health ministries, the proportion of households owning at least one such bed net in sub-Saharan Africa increased dramatically in just a handful years (see below left from ). However, such a bird’s eye analysis glosses over the extremely wide variation in ITN coverage between different countries and even regions within the same country (see below right from ).
Insecticide-treated Bed Nets (ITNs): Cons
On its face, a commendable aim is being achieved through economical means within the reach of millions across malaria-endemic African countries. Problem is only one class of insecticide, the, has been approved for use in ITNs. TB and HIV have already shown time and again that monotherapy antimicrobial use is a gateway to drug resistance. Likewise, intense monotherapy with insecticide imposes strong selection pressure leading to mosquito insecticide resistance, which has skyrocketed in recent years ( , , , , , 17, see below from ), the biggest danger stemming from reports of mosquito populations being found resistant to all four classes of insecticide currently available for mosquito control ( , 19).
The other three insecticide classes being prohibitively expensive (, ) renders them beyond reach of most individuals in malaria-endemic countries and indeed even beyond reach of local public health authorities.
In its 2015 report, the WHO notes that only 52 of 97 countries with ITN and IRS vector control programs reported insecticide resistance in 2014 (). Many malaria-endemic countries failing to conduct routine malaria vector surveillance means insecticide resistance can be easily missed.
Insecticide resistance develops not abruptly but gradually over a number of years, and so can be and indeed is easily missed. This happened in Mexico where sentinel sites reported very low levels of resistance between 2000 and 2003 and yet recorded >80% resistance frequency by 2007, which is why some authors consider insecticide resistance entails a tipping point (see below from).
Research also shows mosquito behavior modification in response to ITNs, mosquitoes previously known to be indoor feeders showing up instead in outdoor feeding ().
Given the high likelihood that monotherapy would lead to resistance, clearly, widespread deployment of pyrethroid-based ILNs was ill-conceived. Scrambling to push out new classes of insecticide is underway. Will it undo the damage already done remains an open question.
2. World Health Organization. “Global plan for insecticide resistance management in malaria vectors.” (2012).
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4. Lengeler, Christian. “Insecticide‐treated bed nets and curtains for preventing malaria.” The Cochrane Library (2004).
5. World Health Organization. “Achieving and maintaining universal coverage with long-lasting insecticidal nets for malaria control.” (2017).
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16. Alout, Haoues, et al. “Consequences of insecticide resistance on malaria transmission.” PLoS pathogens 13.9 (2017): e1006499.
17. Fouet, Caroline, Peter Atkinson, and Colince Kamdem. “Human Interventions: Driving Forces of Mosquito Evolution.” Trends in parasitology (2018).
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19. Ranson, Hilary, and Natalie Lissenden. “Insecticide resistance in African Anopheles mosquitoes: a worsening situation that needs urgent action to maintain malaria control.” Trends in parasitology 32.3 (2016): 187-196.
20. McCoy, Amanda, et al. “Towards an economics policy framework to combat malaria, in an era of insecticide resistance.” (2017).
21. Russell, Tanya L., et al. “Increased proportions of outdoor feeding among residual malaria vector populations following increased use of insecticide-treated nets in rural Tanzania.” Malaria journal 10.1 (2011): 80.