aka The Creature in the Rye
BITING BACK:
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:
After advisement from biosecurity and global health researchers, meta honesty has been deemed the safest method of sharing this information.
Some research (despite public and open source) that has been related to methods of potential misuse or malicious exploitation for attack vectors or weaknesses of some techniques have been either removed or redacted.
The sources that are potentially sensitive have been removed, and any information shared has been approved for full public sharing.
Information may be inaccurate, biased, limited or wrong so please contact me if I have made a mistake in need of correction, or if you are requesting access to sources or information for select uses.
Email sofiiafurman.reachout@gmail.com
External contacts include the EA Community Health team or Biosecurity Information Sharing teams- contacts can be found online or here:
You can contact Chris, anonymously or non-anonymously, through this short form. You can also reach out to Andrew Snyder-Beattie here or Tessa Alexanian (who is not a grantmaker in this space) here. If you’re raising concrete infohazard concerns, please don’t detail them – we can follow up more securely.
1) Abstract
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) Introduction
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.
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
3.2.3) GENETIC MUTATIONS
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.
3.3.2) SPRAYS AND CHEMICALS
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.
4) Conclusion
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.
5) Bibliography
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)
6) Disclaimer
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