No flight, no bite: 'Mosquito grounding' bed net nearly halves malaria infection in Tanzanian children
First new insecticide for 40 years that's shown to be safe and effective
for use on nets could save many young lives

Date:
March 25, 2022
Source:
London School of Hygiene & Tropical Medicine
Summary:
A novel class of bed net that kills mosquitoes resistant to
traditional insecticides by making them unable to move or fly,
significantly reduces malaria infection in children, according to
new research published in The Lancet. Unlike other insecticides
which kill the mosquito via the nervous system, the effects of
the new bed net mean the mosquito dies from starvation or being
unable to fend for itself.



FULL STORY ==========================================================================
A novel class of bed net that kills mosquitoes resistant to traditional insecticides by making them unable to move or fly, significantly reduces malaria infection in children, according to new research published in
The Lancet.


========================================================================== Unlike other insecticides which kill the mosquito via the nervous system,
the effects of the new bed net mean the mosquito dies from starvation
or being unable to fend for itself.

The two-year community randomised trial involved more than 39,000
households and followed over 4,500 children aged 6 months to 14 years in Tanzania. It found that a long-lasting insecticidal net treated with two insecticides, chlorfenapyr and pyrethroid (chlorfenapyr LLIN), reduced
the prevalence of malaria by 43% and 37% in the first and second year respectively, compared to the standard pyrethroid only long-lasting insecticidal net (LLIN).

Chlorfenapyr LLIN also reduced clinical episodes of malaria by 44% over
the two years and the number of malaria-infected mosquitoes captured
by 85%.

The study was conducted by the London School of Hygiene & Tropical
Medicine (LSHTM), National Institute for Medical Research, Kilimanjaro Christian Medical University College in Tanzania, and the University of
Ottawa, Canada.

Long-lasting insecticidal nets are the cornerstones of malaria control
in sub- Saharan Africa. However, in the past few years the decline in
malaria has stalled and even reversed in some countries. In 2020, there
were 627,000deaths from malaria, mainly in Africa and occurring mostly
in children.



========================================================================== Malaria's resurgence is partly due to the bed nets' effectiveness
being compromised by widespread resistance to pyrethroid insecticides
in Anopheles mosquitoes. Chlorfenapyr works very differently to
pyrethroid, causing wing muscle cramps that stop the flight muscles from functioning. This prevents mosquitoes from making further host contacts
or biting, ultimately leading to their death.

The research team says the novel net could lead to significant malaria
control gains in sub-Saharan Africa, but more research is needed to
examine feasibility of scale-up, and on resistance management strategies
needed to preserve their effectiveness long term.

Dr Jacklin F. Mosha from the National Institute for Medical Research,
Tanzania, the study's first author, said: "Malaria remains a huge problem across sub- Saharan Africa and is one of the leading causes of death
in Tanzania. We urgently need new interventions to get control efforts
back on track and protect young people from this deadly disease. These
exciting results highlight that we have another effective tool to help
control malaria." Children from 72 villages in Misungwi, where high
levels of resistance to pyrethroids have been reported, were randomised
into groups and received one of three of the most promising new generation
of bed nets. Children were then tested for malaria at the end of each
rainy season.

After 24 months, malaria infection was reduced by 37% in children that
received the chlorfenapyr LLIN (326/1272) compared to those receiving
standard pyrethroid LLIN (549/1199).



==========================================================================
A bednet treated with a piperonyl butoxide (PBO) to enhance the potency
of pyrethroid reduced malaria infection by 27% over the first 12 months
of the trial, but after two years malaria infection in this group was
similar to the standard net. This is likely due to it being used less
regularly as holes appeared in this net more quickly.

A third type of bednet, treated with pyrethroid and pyriproxyfen which sterilises female mosquitoes, had little additional effect compared
to the standard pyrethroid net. The reason is not fully understood but
likely due to insufficient pyriproxyfen remaining on the net over time.

Dr Manisha Kulkarni, a scientist at the University of Ottawa's Faculty
of Medicine, said: "By essentially `grounding' the mosquito, our work on
adding chlorfenapyr to standard pyrethroid bed nets has great potential
to maintain control of malaria transmitted by resistant mosquitoes
in Africa." The higher costs of the chlorfenapyr LLIN were offset
by the savings from reducing the number of malaria cases requiring
treatment. Distributing chlorfenapyr nets is therefore expected to cost households and society less overall than standard, PBO, or pyriproxyfen
nets.

Dr Natacha Protopopoff, from LSHTM and study Principal Investigator, said: "We've shown chlorfenapyr LLINs are safe, decrease malaria infection
in children and are cost-effective. This is important evidence for the
World Health Organization and malaria control programmes when they
are assessing whether these new nets should be deployed in areas of
insecticide resistance when standard bed nets have failed.

"However, caution is needed. The massive scale-up of standard
pyrethroid LLINs 10-20 years ago led to the rapid spread of pyrethroid resistance. The challenge now is to preserve chlorfenapyr's effectiveness
by developing rational resistance management strategies.

"National malaria control programs and stakeholders should urgently
advocate for better textile and insecticide durability for all novel
classes of bed nets to maximise their longevity and potential."
LSHTM scientists first identified the potential of the chlorfenapyr
insecticide on malaria mosquitoes almost 20 years ago. The chlorfenapyr
LLIN was subsequently developed by the manufacturer BASF in Germany,
together with LSHTM.

Professor Mark Rowland, from LSHTM, explained: "When it comes to
resistance to standard nets we were running out of options, but
chlorfenapyr has come to the rescue. Although it may appear this has
happened overnight, in reality there were twists and turns over many
years to show how the new class of insecticide truly works ,to develop
improved formulations to confirm effectiveness and safety on nets,
and finally to demonstrate control of malaria in large scale trials.

"What really threw us for a long time was that in daytime tests the chlorfenapyr was not very toxic to the mosquito, but at night when
the malaria mosquitoes naturally fly up against the treated bednet it
gets a severe case of muscle cramps so it buckles and falls to where
it is likely to be carried off by scavenging ants. No other mosquito insecticide works like this, and because of the unique mode of action
it kills all kind of mosquito that have evolved resistance to other insecticides. It should have a long future." Professor Franklin W. Mosha, Principal Investigator from the Kilimanjaro Christian Medical College, Tanzania, said: "This achievement has only been made possible through partnership between research institutes, manufacturing industry and
funding agencies like the Bill & Melinda Gates Foundation and then
the Innovative Vector Control Consortium We can all take pride in our respective roles in getting us to this exciting point." The authors acknowledge limitations of the study, including the rapid decrease in
use of trial LLINs, within a context of high overall net usage, which
may in part explain the relative lack of effectiveness of PBO LLINs and pyriproxyfen LLINs over the two years compared to standard LLINs.

This is the first of two trials of chlorfenapyr nets. The second in Benin
in West Africa with the Centre de Recherche Entomologique de Cotonou and
LSHTM is due to report later this year. This will confirm if chlorfenapyr
LLINs are also more effective in a different malaria setting and if pyriproxyfen LLINs could perform better when net usage is higher.

The research was funded by the Joint Global Health Trials: Foreign, Commonwealth and Development Office, Medical Research Council, Wellcome
and Department of Health and Social Care.


========================================================================== Story Source: Materials provided by London_School_of_Hygiene_&_Tropical_Medicine. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Jacklin F Mosha, Manisha A Kulkarni, Eliud Lukole, Nancy S Matowo,
Catherine Pitt, Louisa A Messenger, Elizabeth Mallya, Mohamed
Jumanne, Tatu Aziz, Robert Kaaya, Boniface A Shirima, Gladness
Isaya, Monica Taljaard, Jacklin Martin, Ramadhan Hashim, Charles
Thickstun, Alphaxard Manjurano, Immo Kleinschmidt, Franklin
W Mosha, Mark Rowland, Natacha Protopopoff. Effectiveness
and cost-effectiveness against malaria of three types of
dual-active-ingredient long-lasting insecticidal nets (LLINs)
compared with pyrethroid-only LLINs in Tanzania: a four-arm,
cluster-randomised trial. The Lancet, 2022; 399 (10331): 1227 DOI:
10.1016/S0140-6736(21)02499-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220325093920.htm

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