Methods
of reducing mosquito-borne diseases
METHODS OF preventing infection, transmission and
exposure to mosquito-borne diseases and the
controversies, ethics and objections in the field
(aka Harry POTTER AND THE METHODS OF REDUCING MOSQUITO
BORNE DISEASE BURDENS)
(AKA Lord of the flies, ticks and other
anthropods)
(AKA THE CREATURE IN THE RYE)
Information hazards:
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information.
Some research (despite public and open source) that has
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attack vectors or weaknesses of some techniques have been either removed or
redacted.
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A big picture
literature review regarding methods of management of mosquito borne disease
transmission. An overview of the main
diseases that mosquitos can transmit and avenues to reduce mosquito
populations, mosquito infection and animal and human exposures.
2.1) Mosquitos
Mosquitos comprise
3,600 species and come from the Spanish and Portuguese words for 'little fly'. In
terms of evolutionary biology, mosquitoes are considered micro predators. They
typically parasitice larger animals and are efficient vectors for disease both due
to their immunoprotection to many common agents, as well the fact mosquitos
usually don't kill the animals they bite so the host can then incubate and
spread an infectious agent further.
Common mosquito-borne
diseases that make up the majority of morbidity and mortality outcomes are
covered in detail of their spread, symptoms, prevention, treatment (or lack
thereof) and vaccine status.
Big picture overviews
of types of prevention and mosquito reduction measures are then discussed.
2.1.1) Disease Overview
The US CDC
placed vector borne mosquito disease burden at over a million deaths worldwide
per year and over 700 million annual exposures, and mosquitos boast the moniker
of 'world's deadliest animal' despite being a common pest and only 2.5g on
average.
The
pathogens typically transmitted include protozoa such as the causative agent
for malaria (Plasmodium spread by 5 species of female Anopheles genus
mosquitos). Protoazoic infections from mosquitos account for the leading cause
of premature mortality worldwide and the leading killer of children under 5
with over half a million deaths per year due to malaria according to the WHO
Mosquito Control Association in 2013 and the World Malaria Report in 2012, with
numbers expected to have substantially risen in the last decade.
Bacterial
pathogens are also rife, and genetic similarity of mosquito Mycobacterium
ulcerans (causative agent of Buruli ulcer disease) was near identical to that
isolated in possums and humans, one 2024 Australian team found, suggesting
mosquitos are once again responsible for the transmission of the disease agent.
Mammal-exclusive
parasites (myiasis) are also spread with mosquitos acting as an intermediate
vector (the agent in the host mammal being carried by a mosquito who bites an
infected host to a new susceptible host and transfers the pathogen), whilst
others such as Botflies use mosquitos to deposit eggs on a new host by
attaching to the underside of a mosquito and then when mosquitos bite a new
human the heat of a new host induces the larvae to hatch onto the new
individual and parasitise them.
Worms are
also carried by many mosquitos including most elephantiasis transmission
occurring through mosquito-borne carriage, with over 40 million cases of severe
disability worldwide.
Finally,
viral diseases such as Yellow Fever, Dengue, Zika, chikungunya, Rift Valley
fever and most of the equine encephalitis (West, East, St Louis, West Nile) are
also caused due to mosquito bites either directly on humans or through spread
to birds, sheep, and horses.
Mosquito
borne disease burden is disparate geographically in strains of disease and
frequency.
Due to the
high mortality (and relative lack of other common mosquito diseases), EEE and
WEE are regarded as the 2 most serious mosquito borne diseases in the US
infectious disease candidate rank, especially due to high rates of coma and
death. In most Nothern regions, current domestic cases of diseases such as
malaria are not expected (usually coming from international travel to endemic
regions), however some mosquito-borne diseases have managed to become endemic
in recent years even in areas with non-tropical weather and with high access to
healthcare.
The
viruses that insect arthropods can carry (such as mosquitos and ticks) are
called arboviruses and some countries have had introductions of non-native
diseases purely from imported mosquitos, such as West Nile virus in US 1999
which then in just 4 years spread to 50 states with 3000 yearly cases.
Whilst
malaria, Zika and other mosquito borne diseases are not considered a domestic
burden yet in countries such as North Europe, UK or US, experts warn due to an
increase in zones of mosquito reproductive suitability and warming areas, the
susceptible country spread which had previously remained near the equator has
grown, and may eventually introduce domestic transmission of more deadly
diseases further up the globe.
Most
mosquito-borne diseases are undetected until symptoms arise, and labarotory
tests for causative pathogens are costly and usually yield results too late for
clinical aid. The bite which injects the pathogen during blood-feasting being
ignored, hidden, mistaken or unnoticed tends to delay treatment or surveillance
of infected individuals. Especially at risk groups such as those who work with
animals (vets, farmers), gardeners, those who spend evenings outdoors, those in
open air, those near stagnant water, those in tropic climates, and those who
have unvaccinated outdoor pets- are all likely to either not notice or not act
on insect bites as they can be mild and common.
Some
pathogens (such as parasitic botflies which latch onto the surface of the
mosquito) are external intermediates, whilst others can pass into or even
utilise the mosquito's immune system to grow or mutate. Mosquito bites may
become inflamed and itchy for 24-48 hours but the body does tend to gain
antibodies to the mosquito fluids so subsequent bites, especially in children,
can cause severe immunemediated allergies or responses, such as bursting
capillaries, bruising, bleeding and Skeeter syndrome.
These
reactions are not to the disease-causing pathogens but simply to the foreign
fluids exchanged from the mosquito, rather than a protective mechanism to any
disease agents exchanged.
One study
did find, however, certain mosquito-borne disease infections can attract
mosquito bites through changing the odour of a host, such as Dengue and Zika,
thus attracting more mosquitos which become infected vectors capable of
spreading the agents.
Pathogens
such as malaria also integrate into different forms whether they are in a
mosquito or infected human, and with no detriment to the mosquito, can incubate
and develop in their body until coming into the salivary glands ready to be
released to a new host during a bite.
2.1.2) Mechanism of vectors
Mosquitos
can typically display no ill health from arboviruses due to their immune
systems being capable of detecting virions. The genetic code of most viruses
have distinct features not found in mosquito DNA, therefore protective
mechanisms of 'chopping up' genetic snippets that match these foreign patterns
enables them to remove functional viral particles which may have caused
infection.
For
example, a female mosquito infected with an arbovirus pathogen, which is
partially 'chopped' to smaller virions, whilst low level of intact genetic code
still remain, accumulates in the salivary glands of the mosquito until it
penetrates a human host where the virions and intact viral particles can then
colonise and infect the individual.
Non-viral
pathogens such as eukaryotic agents also appear to be carried with no harm to
the mosquito, but the protective mechanism for this hasn't been determined.
Take WEE
and Yellow Fever viruses which are single stranded, positive sense RNA viruses.
Inside the mosquito, the foreign antigen (much like in humans) is recognised
and immune cells perform receptor-mediated endocytosis (like macrophages or
neutrophils might in humans), but, aside from blunt ingestion and hydrolysis of
the virus, the viral RNA material undergoes changes inside the cell and can
still release more viral RNA to neighbouring cells inside the host. This means
viruses aren't fully destroyed in first stage immune response to the point that
viral load is low enough (through endocytosis or 'chopping' virions) to not
harm the mosquito whilst still remaining capable of infecting other hosts upon
release.
Mosquito
flaviviruses also encode viral antagonists into the innate cells to reduce
endocytosis through first line immune responses, and this increases viral load
passed on during bites.
Through
warming regions spreading to the poles, disruption of typical land, increased
stagnation of water through dams and shallow troughs, stagnant outdoor water
and puddles associated with Urban environments, increased local heating in
areas with concrete and buildings, and higher trade globalisation leading to
spread of eggs or mosquito infected cargo, the rates of mosquito borne diseases
have increased in both singular locations and worldwide.
Mosquito
borne diseases tend to be indirectly contagious through geographical hotspots
rather than human to human, therefore preventing human and animal bites,
reducing populations of infective mosquitos, and removing sources of mosquito
breeding can also reduce the disease load.
1. 2.1.3)
Main mosquito borne diseases
To better
understand why mosquito borne diseases place such a high risk to humans and
animals, highlighting the most common or threatening diseases, and the typical
lack of preventative medication or immunisation which protects from exposure,
can demonstrate why mosquitos are a considerably substantial target to reduce
early deaths worldwide.
Malaria
- Protist Plasmodium spread by female Anopheles mosquitos
- Spread directly during bites, minority spread through contaminated
needles with infected blood and congenital in utero
- Agnostic to most innate risk factors but sickle cell uni-recessive
carriers appear to be immune, and external factors are mainly climatic region
(living in endemic countries, near equator, international travel),
malnutrition, working outdoors especially during evenings, working with animals
- children or elderly are more susceptible
- 90% of malarial deaths occur in Africa south of the Sahara and
most are in children under 5
- Testing is recommended after suspected bites or during local
outbreaks, through microscopic blood smears or RDTs (expensive but can detect
small pieces of malarial parasites), or lab PCR testing (most accurate
especially to determine species but highly rare, specialised and very expensive)
- Prevention involves removing stagnant water, pouring oil in wells,
reducing malarial breeding, spraying insecticides, barrier nets, remaining
indoors and during peak mosquito periods, staying away from hotspots, and more
- Currently no protective individual measures are highly effective,
some very expensive chemicals (especially DEET insect repellants) are good
external measures but can cause injury to living beings, and anti malarial
drugs have questionable protection or cost effectiveness
- Treatment depends on the type of malaria and severity of illness,
and is usually artemisinin-based combination therapy (ACT) and are typically
used for chloroquine-resistant malaria
- Treatments can not be given preventatively in a cheap or safe way,
and have severe side effects, or contribute to resistance if incorrect
treatments are given (eg chloroquine phosphates for resistant strains)
Chikungunya
- Found usually in Africa, Americas, Asia, Europe and Indian islands
but infected travellers can spread further
- Most common symptoms are fevers and joint pain so can be confused
or mistreated as other conditions such as flu
- No medication to treat chikungunya so only prevention to either
limit likelihood of being bitten or having vaccinations before travels
- A type of alphavirus (such as Mayaro and Ross River virus), and
spreads during bites, and people with high enough levels of virus in their
blood (viremia) in the first few days can transmit the virus to new mosquitos
that bite them, or spread during blood exchanges such as transfusions, in
utero, during organ transplants, through contaminated needles and more
- The virus is not spread through touching, coughing or person to
person however many fear campaigns and misinformation around it can cause
isolation which further complicates access to care and can be detrimental to
the social and emotional wellbeing of infected individuals
- One vaccine (IXCHIQ) is available (mainly in the US for foreign
travellers) but is very expensive and not approved for under 18s
Dengue
fever
- Of most of these diseases, dengue is the most likely to get better
on its own and is usually mild, but in some people can cause severe illness
including post dengue haemorraghic fever
- Found mainly in tropical areas, but also in Croatia, France,
Italy, Spain and Portugal
- Symptoms are once again vague, such as temperature, headache, pain
behind the eyes, muscle and joint pain and rash
- Severe dengue can lead to seizures, dehydration, bleeding gums,
and death
- Treatment is usually resting and fluids and over the counter
painkillers, but anti inflammatories such as NSAIDs (aspirin, ibuprofen) can
intensify bleeding
- Dengue is also multiinfective and having dengue previously
increases the risk of severe illness at reinfection
- The only prevention is preventing mosquito bites, a vaccine is
available but is usually limited to US and UK travellers and is only privately
funded
Yellow
fever
- Found mainly in Africa, the South and Central America
- Vaccines are much more common but still only readibly available in
countries that have robust healthcare access
- Aside from vaccines, the only prevention is avoiding mosquito
bites, and symptoms are once again common such as temperature and headache, but
can also lead to bleeding from the eyes and mouth, dark pee and jaundice
- Treatment also includes over the counter painkillers and fluids,
but yellow fever tends to be quite deadly in young children, those with
preexisting liver conditions, and elderly
- Unlike the previous disorders, the vaccine is more available (for
a price) and is highly effective and safe for anyone over 9 months old, and
recommendations include vaccines at least 10 days before travelling to at risk
areas, and revaccination is also safe if past exposure is unknown
- The prophylaxis effect is lifelong, the cost tends to be around £85
which is highly affordable for most travellers, but out of reach for most
endemic countries
Eastern
Equine Encephalitis
- Found mainly in North America and the Caribbean and is one of the
2 most deadly mosquito-borne diseases in the US, and is closely related to
Madariaga virus
- Can circulate between mosquitos and birds that are near freshwater
hardwood swamps, some animals (emus) can also become bridge vectors by feeding
birds and humans, whilst people (and horses) are ‘dead end’ hosts as they do
not spread the virus, even if they get infected. (but one case did have 3
recipients of organ transplants from an infected donor who were infected)
- Prevention also relies on preventing mosquito bites, and no
specific treatment exists, only pain
control and hydration to try to reduce meningeal symptoms as supportive
measures
West Equine
Encephalitis
- Very similar to EEE but most people who get infected don’t get
sick, no vaccines or prevention aside from avoiding bites, and tends to cause
sporadic outbreaks of disease in horses and people, but risk increases from
summer to fall
St Louis
Encephalitis
- Very similar to previous diseases, but most people don’t display
symptoms, however encephalitis complications and meningitis is common in at
risk groups, and no vaccine or prevention aside from avoiding bites exists
West Nile
- 80% of people don’t display symptoms but about 1% develop severe
CNS encephalitis and 50% of infections occur in over 60s, about 10% of those
who get nervous inflammation pass away
- No specific treatment or vaccine but lifelong immunity is common
in healthy individuals after a past infection
haemorrhagic
fever complications
- Case fatality around 50%, vary from 24% with complete support and
88% fatality in areas with lack of healthcare
- Supportive treatment of rehydration and symptom management, no
cure
- Currently no approved vaccines, antivirals in the works but lack
efficacy
Zika
- no specific treatment aside from symptom management or
vaccination
- vague symptoms such as headache and fever
Complications including to a developing fetus including
microcephaly, and asymptomatic carriers can both shed the virus and also for up
to 3 months after infection can pass to a baby, some Zika cases also cause GBS
paralysis
The
importance of reducing mosquito borne diseases through preventing mosquito
infection, reducing mosquito vectors and mosquito populations, and reducing
human and animal exposure to mosquito bites cannot be understate, not only for
their innate health benefit, but also since the most common and deadly
illnesses have mostly no vaccines, prevention or treatment and rely on avoiding
bites.
2.2)
How mosquitos remain ‘IMMUNE’
Aside from the mentioned mechanism to reduce
viral load, defence mechanisms include small RNAs (siRNA) that can target and
degrade viral RNA, and the protein Argonaute 2 (Agot 2) is used as a regulatory
marker for viral RNA snipping.
Aside from observational mechanisms we have
deduced, experimentation in manipulating mechanisms of immunity provide
experimental evidence in support, and potential avenues to either make
mosquitos susceptible to ill health from pathogen (reducing silent vector
transmission and increasing dead end hosts) or making the viral degradation
amplified so all potential viral particles transmitted in a bite cannot then
functionally reproduce or affect the host.
Manipulation of the Agot2 protein can make
mosquitos vulnerable to viral pathogens, but mechanisms of manipulation or
particular case studies have been redacted in advisement, but can be shared to
individuals working on reducing risks who can prove safety policies in place
for handling the information.
Redacted areas can be released (after
advisement) to select individuals by emailing sofiia.furman@reachout.gmail.com
Private or hazardous sources are not linked but
can be signposted to select individuals.
There are also many ethical, religious, animal
welfare, cultural and biodiversity risks and concerns with specific methods of
reducing mosquito reproduction and populations, increasing mosquito
susceptibility to disease, and socioeconomic barriers to reducing animal and
human exposure to mosquitos.
3) Methods
OF MANAGEMENT
3.1) Genetic engineering
The Environmental Protection Agency in US regulated
genetically modified (GM) mosquitoes whilst the WHO provides a framework for
worldwide best practices. Producing GM mosquitoes is usually initially genetic
substitution in lab specimens, for either a self limiting gene (e.g. one that
disfavours females or only allows male zygotes) or a fluorescent gene marker to
identify GM mosquitoes to track integration. With this method, numbers of the
Ae. Aegypti mosquito in an area will steadily decrease, and only female
mosquitoes bite so an eventual male-dominated ratio will both prevent
reproduction and prevent infection and transmission.
GM mosquitoes have been used successfully in some parts
of Brazil, Cayman Islands, Panama and India for Ae. Aegypti mosquitoes, and
since 2019 over 1 billion have been released. However, the decline and plateau
in numbers reverts to initial populational size (and sex ratios) if GM
mosquitoes stop being released, so it is not a one off solution. The species
specific reproductive cap also doesn’t affect other species, so for better
(such as allowing other mosquitoes to increase competition and pollination) or
worse (allowing other species to also spread disease), mosquitoes still remain
as a whole.
GM mosquitoes are classified as negligible (the lowest)
risk to people, animals and the environment, and areas with releases have seen
reduction in certain mosquito borne diseases, however areas must first be
screened and acquire a permit to release GM mosquitoes, and it is a continual
resource-intensive solution.
3.1.1) GERMLINE ENGINEERING
Germline engineering refers to sex cell and gametocyte
inhibition, either coding in genes to favour only male offspring, or to prevent
the attachment of a female zygote. These genes will reduce mosquito numbers
through generations and shift sex ratios (or simply reduce fertility in both
sexes) and will decrease populations.
This engineering usually involved a proportion of
engineered parental mosquitoes who then reproduce and the affect is on
offspring generations.
3.1.2) SOMATIC ENGINEERING
Somatic
engineering refers to producing an effect or change in the asexually
reproductive cells of an already living mosquito in the current generation,
such as inhibiting the Ago2 protein to make mosquitoes susceptible to disease,
or by amplifying virion detection to reduce transferred viral load. These are
typically more time intensive as they require consistent reengineering due to
continual mass-scale divisions which result in errors and dilution of any
programmed changes. However, somatic cell changes can also be a subtype of
non-reproductive offspring changes, wherein some mosquitoes carry genes to pass
on to hamper immunoprotection or increase viral chopping, but the reproductive
rate are not affected, so offspring continue to grow in steady numbers and the
population remains relatively stable, but will overtime reduce the amount of
mosquitoes with the ability to act as silent vectors or the amount of viral
load mosquitoes are capable of transmitting.
Some examples
of non gene edited but multi-generational non-reproductive engineering are
detailed in further sections.
3.2)
Reproduction
An initial mechanism for the technique used to
induce sex cell favouring in female mosquitoes or to reduce or prevent
ovulation as a whole were mentioned here. These have been removed from
precautionary information integrity. Sources for this section have also been
removed from the bibliography.
3.2.1) MALE LINEAGE
REMOVED
3.2.2) OVULATION INHIBITION
REMOVED
REMOVED
3.3)
Physical inhibition
3.3.1) BARRIERS
Typical barriers such as mosquito nets, wearing
long sleeved clothing, tucking in loose clothes, wearing hats or veils, and
closing windows or doors have been proven to be effective, but have amplified
exposure reduction if coating in chemicals and sprays (external) which repel,
kill or inhibit mosquitoes
Some more innovative solutions have also been
touted as potentially more cost effective and a better long term solution for
buildings, outdoor environments or for at risk individuals.
A 2024 study in Gambian communities focused on
the main risk of bites during indoor nights, through simply raising the home
base. The elevation of huts was achieved through local materials and was
feasibly quick and simple with the skills that locals possessed. The study
collected mosquitoes with light traps and measured CO2 levels indoors and
outdoors in control huts, raised huts and before and after intervention.
The huts were also split to 3 groups aside from
the control: air-permeable walls, solid walls and open. Of the 4 groups (3 hut
types that were raised and a control group), randomised interventions were
measured for effect. In 32 nights, indoor temperature, mosquito numbers and CO2
differential found a statistically significant difference in raised huts
compared to ground level. All types of huts displayed reduced mosquito numbers,
but solid wall huts had the most reduction of 873 compared to an initial 1259,
whilst air-permeable and open huts also showed a reduction of mosquitoes and
indications of mosquitoes when raised, but less of a difference than solid-wall
huts.
However, further analysis of mosquito species
found female Anopheles mosquitoes (such as malarial species) were reduced in
number by between 24%-53% for the lower and upper bound depending on hut type,
but Culex mosquitoes had no change in number by elevation. Follow ups with
Mansonia mosquitoes which spread diseases in the region were also reduced as
found in Anopheles, suggesting certain species may be better suited to this
intervention than others as a way of reducing mosquito borne disease.
Another potential solution in development is
graphene barrier layers, through dry state multilayer sheets that prevent
mosquitoes sensing sweat or skin odours that allow them to locate blood. The
graphene barriers is mechanical so avoids internal side effects or adverse
chemical reactions, as the carbon structure is flexible (due to layered
hexagonal rings) and inert. Wearable technology with graphene or allotropes of
carbon have been used for polymer protection as a lightweight option, but are
typically expensive. However, utilising natural properties of graphene sheets
in a thin layer application can be a lot more cost effective. Graphene oxide
nanosheets also show effective results on live human skin however they do not
have the same mechanical puncture resistance as pure graphene which suggests
other functions of protection to be explored. However, graphene oxide can react
with externally placed water and sweat to form hydrogel pores which attract
mosquitoes and are not resistant to mechanical stress.
In a slightly tangential experiment, teams then
measured the puncture force of mosquito bites and are replicating it to make
microneedle or needleless drug administration routes to reduce fear, cost,
waste and contaminated fluid transmission.
DEET repellent has been shown to be the best
external application, and botanicals can be less potent but have reduced side
effects to be used for children or those with sensitive skin. Around 20-30%
DEET concentration is a good substance for skin application, as well as
picaridin in combination. Many anecdotal repellants have been disproven
including citronella candles, wristbands or citrus. Another issue is the
controversies, despite DEET being non-carciongenic and not a pesticide
(incapable of killing insects), it has had issues with sounding like DDT (a
very potent banned chemical), not being safe for multiple daily exposures, and
potential irritation to eyes or clothed skin.
DEET concentration should be no more than 30%
for young children but is safe for those over 2 months if used as directed.
However the surface coverage is only direct, and mosquitoes can bite from just
4 cms away from a treated area.
Other products have shown some promise but do
not have the same regulations or long standing evidence to back their
widespread use.
Other compounds utilising behavioural change
such as aversive memory construction and positive punishment associated to
scents, have been developed, and hydrophobic solutions (to prevent sweat based
erosion) are being used to repel Aedes albopictus on human skin samples.
3.4)
Transmission prevention for animals
3.4.1) COLLARS AND BARRIER EQUIPMENT
Animals, whether pets, domesticated, wild or
farmed, are at risk of mosquito-animal transmission, or sometimes animal-animal
transmission of mosquito borne diseases. The most common issue of mosquito
disease in animals is not zoonotic (human infective) in HICs, so heartworm
prevention is a common oral preventative. However, other mosquito borne
diseases preventatives or managements are typically less popularised in animal
circles. Some companies boast collars, sprays, drops, tablets or external
powders. However regulation on integrity is lacking and so most show either
minimal effect, or effects only on ticks and non mosquito anthropods. Another
issue is some external applications and powders have been linked to cancers or
breathing issues in nearby animals and humans, and can leak into water sources.
However, oral treatments against mosquito borne diseases can come with many
side effects and can be expensive, so also are not typically prescribed on
preventative grounds.
3.5)
Transmission prevention for humans
3.5.1) LIFESTYLE MODIFICATION OF RISKS
Groups at risk include:
Those that work with animals (farmers, vets),
and these occupational hazards are mitigated through workplace policies such as
screening, vaccination (if available), reporting procedures for suspected
bites, surveillance of animal health, wearing protective clothing or residing
in areas with nets and light traps.
For domesticated animals, transmission to humans
and other animals can be reduced through vaccination, wearing collars, or area
spraying in hotspots such as during outbreaks in Queens, NY.
Other risk factors include being outdoors,
especially during times mosquitoes are active, whether time of day (evening),
seasonal or during weather events. Shifting patterns of time outdoors or
spending time in the shade, with repellent, under nets, with hats or long
sleeved clothing can reduce exposed skin for bites.
Risk groups for getting ill include those who
are immunocompromised, elderly or under 5, who should be kept away from
geographic hotspots, outdoor activities (Such as gardening) and animals
Other measures such as checking for bites,
pouring oil on stagnant water, removing outdoor water troughs and bowls, and
disrupting stagnant puddles can be useful to reduce breeding, mosquito
populations and risk of being exposed to infected mosquitoes.
3.5.2) VACCINES OR MEDICATION
Vaccines are highly disparate in their
availability or existence in mosquito borne diseases. Some have no approved
vaccines, whilst others have highly available drugs, and others have clinical
trials and partial positives without definitive guidelines or reasonable
access. Countries with robust healthcare usually provide privately funded
vaccines before travelling to an at risk destination for at risk groups,
including vaccines for yellow fever, Japanese encephalitis, and more. However
access to these vaccines or treatments is limited in areas most at risk of
infection.
3.5.3) ANECDOTAL AND NATURAL
There are many anecdotal preventions or
treatments to mosquito borne diseases. Breaking down each one requires nuance
and multiple perspectives, but the spread of targeted disinformation and
targeted preying on vulnerable individuals (including patients or worried
parents) has resulted in the outlook of natural remedies being mutually
exclusive to evidence-based medicine, and the issue is exacerbated by
polarisation of the treatment avenues, and individuals may avoid seeking proven
treatment or medical attention (or be unable to for financial, time, cultural,
spiritual, access and many more reasons), which means they may never get
preventative or early treatment options that would otherwise cure, reduce or avoid
poor health outcomes.
3.6) Broad scope mosquito reduction
3.6.1) MOSQUITO HABITAT OVERLOADING
One suggestion is reducing the carrying capacity
of a habitat, either for certain species (such as previously measured sexually
GM mosquitoes carrying self-limiting genes to change the proportion of a
targeted species), or by removing breeding grounds or suitability for
reproduction (such as stagnant water or reducing the warming of regions around
the globe), and introducing other living organisms to compete for the limited
resources who reduce populational size.
One innovative solution is being undertaken by
the World Mosquito Program which introduces a non harmful and naturally found
bacteria into mosquito populations which can be passed to offspring but doesn’t
limit reproduction. The species size remains stable (so continuous
reintroduction isn’t needed unlike self limiting GM mosquitoes), and bacteria
can live harmlessly in mosquitoes and has negligible effect on environment,
humans and animals. The Wolbachia bacteria is non GMO and competes for internal
resources that viruses and pathogens need. Disease causing microbes would
otherwise use reserves such as cholesterol in the mosquito during replication
and incubation before being transmitted, and Wolbachia dominance reduces the
available supply to reduce proliferation of disease causing microbes.
3.6.2) GENE DRIVES
Gene drives are ‘selfish genetic elements that
are transmitted to progeny at super-Mendelian >50% frequencies’- which in
simpler terms means a gene or trait is passed down to offspring in a biased way
(more than random chance), and alters the probability for an allele
(characteristic or type of trait) to emerge in a population. Gene drives are
potential vector reducing mechanisms, with CRISPR-Cas9 mediated gene drives
used in some case studies. The anti parasitic effector molecules can be
adjusted to limit infection of mosquitoes. For example, during blood-feasting
on a human host, mosquitoes release Plasmodium sporozoites (in malarial infection)
which come into peripheral circulation (such as vein in the arm) that is then
taken through hepatic pathways to central circulation (or deposited in liver
cells as merozoites) and replicate in an exo-erythocytic cycle (outside of the
mosquito and not from their own replication machinery, instead using the
erythrocytic mature blood cells to host their replication). The start of the
intraerythrocytic cycle (inside the red blood cell) begins asexually for
pathogenesis (producing new particles) and then a fraction undergo sexual
development cycles to gametocytes that can be transmitted to an uninfected
mosquito. The red blood cell can then burst with the gametes that can attract
mosquitoes (odour attraction mentioned in introduction) and the fully mature
malarial pathogens to cause damage to the host, and this mass lysis leads to
the initial symptoms, and cyclic temperatures and patterns are due to this variation
in development through time.
Gene drives come into this through sterile
insect techniques SIT, since the 1950s with mass rearing males (y-rays and
chemosterilent gene drives) that decline the population but require continuous
deployment of modified self-limiting mosquitoes, and some somatic gene drives
through radiation damage to reduce fertility and sterilise males. However, SIT
and surveillance needs continuous vector management and newer gene drives have
been proposed to be safer and less invasive, whilst also requiring less continuous
involvement in terms of cost and scientific technologies.
RIDL (dominant lethal traits that cause death,
sterility or offspring inhibition) are growing out of favour to progeny biased
gene drives for vector-capability suppression over populational reduction.
Anopheles genome screening has identified traits that allow mosquito
immunoprotection and blood-seeking behaviours, along with viral load reduction
mechanisms, that gene drives have addressed (such as the mentioned Ago2 protein
regulator or the virion regulators). However, Wolbachia bacterial symbionts are
now more utilised than RIDL or non-RIDL gene drives as sex-distortion
phenotypes are reduced (compared to feminisation, male culling or
parthenogenesis) and reduces wild-modified incompatibility diversions.
Deleterious culling for mosquitoes is targeted to species so reducing one
usually increases other species or reduces pollination and biodiversity, so
simply killing off populations of mosquitoes through gene drives is being fazed
out.
Novel gene drives including cleaved endonuclease
genes targeted to immunomediation genes using CRISPR and HEG gene drives have
been used in somatic diploid cells, and germline single guide RNA (sgRNA) has
been used to create non-limiting but vector-reducing gene changes.
Gene drives are also usually very slow through
populations and single chromosome alleles are only inherited by at most half
the population. Homing to produce a proportion of homozygotic germline cells
can increase the number inherited for modified genes, and doublesex fertility
gene drives usually take about 10 generations to achieve a ~100% inheritance
bias. High conservation of An. Gambiae (part of human-infective anopheles
genus) breeding and blood-locating genes mean recessive heterozygotes are
viable but all homozygous recessive (which by homing we increase proportions
of) become modified offspring.
Work has also been done on reducing suitable
regions by mitigating enhanced global warming, and work on vaccine and anti
viral candidates.
3.7) Ethics and Controversy
3.7.1) WORLD MOSQUITO PROGRAM
Despite great efforts to sustain communication
with communities in the program, and a majority positive response and evidence,
targeted campaigns with false information including Wolbachia harms such as
‘making people homosexual’ have been widespread and led to multiple delays in
rolling out modified interventions in some communities
3.7.2) PUBLIC AND GLOBAL HEALTH FUNDING
Many services and agencies are underfunded or
understaffed, many science agencies more so, many public life sciences services
even more, and global and public health sits at the intersection of complex,
nuanced, controversial, politisised, diverse, over generalised, underfunded,
underdeveloped, disbelieved, targeted, attacked and more. From many biological
study niches, public and global health usually finds itself on the backfoot in
support and funding. Surveillance in countries outside of HICs to better understand
early transmission and hotspots is usually a hit or miss opportunity, and is
dependant on aid and funding, since health is a global problem, and no disease
or pattern of health is ever limited to one group, country or location.
Preventing, detecting and researching all health problems leads to better
savings, understanding and outcomes for all. But funding and opportunity means
prioritising different interventions, locations, groups, modifications, risks
and more, which is complicated to justify, explore or action.
3.7.3) GENETIC TRANSFER TO WILD SPECIES
Spreading altered traits amongst wild
populations and integrating alleles non naturally found or found in minority
proportions can affect the behaviours, reproduction and survival of organisms.
Viability of self-limiting reproduction gene drives, homing and double sex
drives, and somatic adjustment drives all have potential to cause speciation,
division in mating compatibility, and loss of species. Favoured gene drives
also surpass Mendelian inheritance patterns so have a further bias to increase
above typical evolutionary constraints through our technical external
interference. Gene drives in abandoned populations can also spread or become
deleterious if not continuously upheld, monitored or controlled.
Homing gene drives in Anopheles gambiae strains
also show rapid transfer with minimal flanking sequence carryover, with
targeted dsDNA wild type alleles (recipient) being converted to super-Mendelian
inheritance biased alleles of homologous donor drive patterns. Chromosomal
breakage at cleavage locations showed 80% homing, and even surpassed upper
bound inheritance rates above the fitness point tradeoff. This would be
unlikely to be found in nature and we are unsure what affects this may have
(Especially due to limited trials and computer simulations). Populational
modification and suppression drives have shown reduced cargo transfer using
CRISPR techniques and 97% to 100% inheritance at multiple target sites,
suggesting a highly refined and conserver donor (non wild type) gene maintained
in populations whether it increases competitive advantage or not. HEGs selfish
gene drives tend to bypass repair chromosome sequences and still favour the
foreign donor allele, and germline HEG progeny favours homozygous non-wild type
alleles.
3.7.4) CULTURAL AND RELIGIOUS OBJECTIONS
Some spiritual or religious arguments debate the
ethics or permit of interfering in nature, causing harm or suffering to animals
(welfare of mass cullings or causing disease) or of GM organisms. Furthermore,
community outreach and engagement can make or break the responsiveness of a
local community to an intervention, and ensuring language and norm barriers are
identified and resolved ensures better health transparency, communication and
system maintenance. Global health can be hard to coordinate but local based
responses tend to respond well to consulting with affected populations and
communities.
Other safeguarding issues include health and
social effects to communities, or bias of risk wherein communities are
unilaterally exposed to gene drives or interventions and reap local risks
without having a say or consent. Exploiting potential misuse or unilateral
decisions can be intentional (such as releasing gene drives that lead to crop
failure) or negligent/ignored (such as releasing gene drives that are not
studied for their local effects).
GM self-limiting sexual gene drives have a 96%
pre maturity death rate in Aedes aegypti and Grand Cayman Islands had a 80%
reduction in mosquito numbers and dengue cases. However, the work was secret
and research on environmental effects was not done pre release. The backlash of
GM mosquitoes has also led to conspiracies or religious and cultural backlash
which dampers future collaborations. A GM mosquito drive in Florida has been
postponed for over a decade due to protests, and 100,000 participants in the area
petitioned against insect releases. Dengue has reemerged in that area in
Florida after a 65 year absence and other preventative measures haven’t worked
effectively, but conspiracies including the released mosquitoes being ‘spy
drones’ or ‘turning people gay’ (which were very false) to more valid concerns
such as ‘crop effects’ were not communicated with the public and so resentment
spread and the project was closed. Brazillian communities with GM mosquitoes
showed high positive reactions when they had pre-release consultations with
community leaders, whilst other communities had projects shut down due to
perception and backlash. Effects such as biodiversity loss or crop failures
also tend not to be studied.
Biodiversity issues could include food chain
pressure, such as mosquito larvae being a vital source for fish and frogs, and
bats populations which feast on mosquitoes. And reducing mosquito competition
for resources in a habitat could give rise to a new species or organism that
could be deadlier or more capable of spreading disease, or favour resistant or
highly advantageous mosquitoes who survive the intervention and then have very
little competition to be able to reproduce rapidly and create a more adapted
strain.
3.7.5) CHEMICAL EXPOSURE
N,N-diethyl-3-methylbenzamide (carbonyl nitrogen
N substituted alkyl molecule) that comprises the colloquial substance DEET can
cause irritation to eyes or clothed skin (due to higher rates of absorption)
and sometimes inhalation in concentrated amounts can cause vomiting, seizure,
coma and ataxia. However, putting it on exposed skin before going outdoors for
over 2 month olds at a concentration no more than 30% is deemed safe, non
carcinogenic and with negligible risk to humans, animals and environment.
However, past DDT chemical insecticides have
been banned and linked to certain diseases, and other substances used can cause
allergic reactions, irritation, or contact burns.
Other exposures such as to mosquito coil traps
that emit smoke can cause acute or chronic asphyxiation or breathing issues and
high exposure can increase the risk of lung and throat cancers.
However, vaporised mosquito repellents (even
with safe concentrations and chemicals) can have deleterious effects on
conservation areas by being toxic to aquatic life, pollinating insects and
flowering plants. D-allethrin which is used in most repellants is highly toxic
if swallowed or inhaled by humans or animals, and biota doses can be much lower
for harm.
3.7.6) MALICIOUS ACTORS UTILISATION AND
INFORMATION HAZARDS
MOSTLY REMOVED
3.7.7) RESISTANCE AND MASS MUTATION
Mosquitoes have been resistant to make
pesticides, or able to avoid ill effects of pathogens, chemicals or even
repellants. They have also managed to sustain or share behavioural methods to
avoid traps and poisons. Mosquitoes have a relatively short life cycle and
breed rapidly so have many random chance mutations, overlaps, homologous
chromosome crossing over, and sexual reproduction random fertilisation
patterns, meaning that resistance mutations can be frequent, fast and spread widely.
This can invalidate decades of money, time and effort to develop the
interventions and create future more complex prevention or protection needs.
A mutation in just one target site for DDT (a
now banned insecticide chemical) and to pyrethroids, organophosphates and
carbamates has been shown to have occurred in both wild type mosquitoes and in
single-allele modification trials. Mosquitoes with the kdr allele that promotes
resistance to Ace-1R (target site for DDT/pyrethroid) show broad spectrum
resistance and An. Gambiae have high levels of phenotypical resistance for
nearly all widely used malaria control measures.
Irrigation of larvae can create short term
reductions in infected mosquitoes or in populational numbers, but can cause
higher rates of resistance overall, and early gradient exposure to chemical
treatments increase mutations in favour of resistance more than adult cell
exposure, due to compounding rates of mutation in quickly dividing
early-organism development.
3 gene mutations (G11PS, L1014F, L1014S) have
been identified via the PCR-SINE method with restriction fragment length
polymorphism (to allow quicker monitoring) that account for the An. Gambiae
mosquito population in Tiassale to be resistant to all insecticide classes, and
more than 2/3 of mosquitoes samples from that location had survived the
diagnostic dose for 4 of the 5 most common insecticides. An. Gambiae exposed to
pyrethroid derivatives or carbamate bendiocarbs in differential timings showed
strong resistance phenotypes to both insecticides, with 4 hours of exposure
required to kill 50% (median lethal time) whilst non resistant Kisumu
mosquitoes had a median lethal time of less than 2 minutes (Resistance ratio
138), and Bendiocarb median lethal time was 5 hours for Tiassale strain and
only 12 minutes for Kisumu (resistance ratio 24).
If not controlled this population, or for
factors that led to the high resistance, this mutation can spread over Africa
and threaten even highly effective mosquito chemicals.
These methods are
diverse and each have their own limitations, benefits and risks, so going ahead
with a combination after careful consideration of effects, especially with
affected communities, seems to be the future that global health interventions
to reduce mosquito borne diseases is headed. The strides we have taken have
been amazing, but to defeat the ‘world’s deadliest animal’, it is imperative
open collaboration, research, innovation and intervention is funded, explored
and cautiously actioned, for a better future for all.
INTRODUCTION SOURCES
cross-referenced from, date last accessed 29/1/25:
Mayo Clinic, Symptoms
and Causes for illness
www.mayoclinic.org
WHO, mosquito diseases
https://www.who.int/news-room/questions-and-answers/item/emergencies-mosquitoes
CDC, mosquito borne
diseases
https://www.cdc.gov/mosquitoes/index.html
Against Malaria
Foundation, mosquito disease burden
https://www.againstmalaria.com/
Givewell, mosquito
disease reduction
https://www.givewell.org/charities/top-charities
Malaria Consortium, mosquito
disease burden
https://www.malariaconsortium.org/
NHS, approved
prevention, treatment and vaccination
w.nhs.uk
FDA, approved
prevention, treatment and vaccination
https://www.fda.gov/animal-veterinary/intentional-genomic-alterations-igas-animals/mosquito-related-products
Gov.uk, travel
information for mosquito borne disease
https://www.gov.uk/government/collections/mosquitoes
Our world in data, geographic
data
https://ourworldindata.org/malaria
World Mosquito
Program, mosquito prevention broad scope
https://www.worldmosquitoprogram.org/
NIH, papers on
mechanisms of manipulation, redacted titles under advisement
REMOVED 6 SOURCES
Imperial College
London, information on mechanisms of mosquito immunity, redacted titles
presumptively
REMOVED 2 SOURCES
BBC, media responses
to mosquito borne disease outbreaks
https://www.bbc.co.uk/news/topics/c3499gyr535t
WebMD, symptoms of
mosquito diseases
https://www.webmd.com/skin-problems-and-treatments/illnesses-mosquito-bites
Nature, risks in
mosquito eradication, redacted title at request
ONE SOURCE REDACTED
Unnamed source,
mosquito reduction exploitation vectors
REDACTED
Unnamed source, past
experiments in mosquito borne disease human trials
REDACTED
University of Oxford,
content and information removed
REMOVED
Pfizer, mosquito borne
disease clinical trials and development
European centre for
disease control, Europe mosquito borne disease facts
https://www.ecdc.europa.eu/assets/mosquito-borne-diseases-2024/index.html#/
SPECIFIC SOURCES for
INTRODUCTION on mosquito biology, disease, and health information:
https://www.pfizer.com/news/articles/mosquito_as_deadly_menace#.Yweo2_DM88I.link
http://www.health.state.mn.us/divs/idepc/dtopics/mosquitoborne/diseases.html
http://www.mosquito.org/page/diseases
https://www.cdc.gov/ncidod/diseases/list_mosquitoborne.htm
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501887
METHODS SOURCES:
3.1 Genetic
engineering
https://www.cdc.gov/mosquitoes/mosquito-control/genetically-modified-mosquitoes.html
https://www.who.int/publications/i/item/9789240025233
3.2 REMOVED
3.3 Physical
inhibition and chemicals
https://malariajournal.biomedcentral.com/articles/10.1186/s12936-024-04889-z
https://www.pnas.org/doi/10.1073/pnas.1906612116
https://www.labce.com/spg2105838_physical_barriers_to_mosquito_bites.aspx?srsltid=AfmBOoozTG6GFwHyg6f74kVCMtQ-S6JHymqNrKAOrsTJXaxjG1DBE9f5
https://www.nature.com/articles/s41598-024-55975-w
https://www.webmd.com/allergies/features/avoid-mosquito-bites
https://www.nbcnews.com/id/wbna6847440
https://www.science.org/content/article/want-repel-mosquitoes-don-t-use-citronella-candles
3.4 animal
transmission
Royal veterinary
society
Royal College of
Veterinary Surgeons
World Veterinary
Association
3.5 human transmission
NHS, CDC, WHO
modification for lifestyle adjustments
CDC, NHS, FDA,
MayoClinic vaccinations and treatment
3.6 broad scope
https://www.nature.com/articles/s41434-024-00468-8
https://pmc.ncbi.nlm.nih.gov/articles/PMC6305154/
https://www.worldmosquitoprogram.org/en/work/wolbachia-method/how-it-works
https://www.scielo.br/j/mioc/a/Ls4LwJrfBJwRqXf3SPQLP4s/
https://www.cgdev.org/blog/are-global-health-funds-falling-behind-financial-innovation
https://pmc.ncbi.nlm.nih.gov/articles/PMC4117217/
https://www.nature.com/articles/s41467-024-51225-9
https://pmc.ncbi.nlm.nih.gov/articles/PMC3620724/
https://pmc.ncbi.nlm.nih.gov/articles/PMC6882470/
https://www.sciencedirect.com/science/article/pii/S0048733319302355
https://www.ncbi.nlm.nih.gov/books/NBK585176/
https://www.nature.com/articles/466432a
https://www.nature.com/articles/466432a
https://www.ivcc.com/vector-control/irm/
https://forum.effectivealtruism.org/posts/86bJ6JmbQq9YKHbrz/do-eas-feel-bad-for-killing-a-mosquito-should-they-feel-bad
(all 3.7.6 sources
removed from bibliography and content)
I wrote this paper as a way to share information from
public open source information that I cross references from what I hope are
reputable enough locations. I am not aware of conflicting interests or
conscious biases or affiliations.
I am not qualified and wrote this for fun, please let
me know if I made a mistake and I will be happy to issue a correction.
Redactions are a combination of advisement from people who kindly looked
through, and edits done precautiously about potential information hazards in
this area of study.
I am aware limitations may be present in the data and
this is a big picture overview, but I hope it was helpful or at least
informatively entertaining.
Advice, critiques and feedback appreciated.
Sofiiafurman.reachout@gmail.com
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