Wolbachia and the Prevention of Mosquito-Borne Diseases
A Potentially Useful Parasite
Wolbachia is a common insect parasite that appears to be harmless to humans. The bacterium may not kill its host, but it does affect the insect's biology. Researchers have discovered that Wolbachia inhibits the replication of viruses in mosquitoes. This ability could be very useful, since mosquitoes transmit some unpleasant and sometimes dangerous viral diseases. Deliberately infecting the mosquito population with the bacterium may prevent several illnesses in humans, including dengue and Zika virus disease.
Some people may wonder why scientists are infecting mosquitoes with bacteria instead of killing the insects outright. One reason is that once enough female mosquitoes are infected, the infection process is self-sustaining because the females pass bacteria to their offspring. Another reason is that mosquitoes are becoming resistant to the present insecticides. In addition, some insecticides are harmful for the environment. This is why research into mosquito control methods and vaccines for humans is so important.
Wolbachia was discovered in 1924 by S. Burt Wolbach and Marshall Hertig. They found the bacterium in Culex pipiens, a widespread insect generally known as the common house mosquito.
The Wolbachia Bacterium
Insects belong to the phylum Arthropoda. Wolbachia is found in many insects, other arthropods, and some members of the phylum Nematoda (roundworms). It occurs naturally in some mosquitoes and has been added successfully to others.
Wolbachia is said to be a heritable microorganism because it passes from one generation to the next. It lives inside its host's cells, including those of the ovaries and testes. Some bacteria enter the egg cells. During fertilization, a sperm inserts its nucleus into an egg. As the fertlized egg multipliies to make an insect, the bacteria in the egg reproduce and become part of the new individual.
Wolbachia affects its host's reproductive biology in intriguing ways that are not well understood. The bacterium favours the production of female offspring and hinders the production of males. Since Wolbachia is passed from one generation to the next in eggs, increasing the percentage of females in the population is beneficial for the bacterium.
Exploring Wolbachia Bacteria in Mosquitoes
How Does Wolbachia Favour the Production of Females?
Researchers have found that the bacterium can control the gender of host offspring in the following ways, although it may not produce each effect in every type of host.
- Male killing: males die during the larval stage of their development
- Feminization: larval males develop into females or infertile males
- Parthenogenesis: reproduction occurs without the presence of males, making all the offspring females
Cytoplasmic Incompatibility in Infected Mosquitoes
Wolbachia has another interesting effect on its host's reproduction. The effect is known as cytoplasmic incompatibility (CI in the table below) and has been observed in at least some of the mosquitoes that cause disease. As a result of the bacterium's presence, under certain conditions the eggs and sperm are no longer compatible and can no longer produce viable offspring.
Cytoplasmic incompatibility operates when the following conditions exist, as shown in the table.
- An infected male mates with an uninfected female.
- An infected male mates with a female infected by a different strain of Wolbachia.
An infected female is able to reproduce when she mates with an uninfected male or with a male infected by the same strain of Wolbachia. The net effect of cytoplasmic incompatibility is the spreading of the female's strain of Wolbachia to the next generation. The table illustrates this with colour coding
Cytoplasmic Incompatibility Induced by Wolbachia
The species of Wolbachia used in mosquito experiments is Wolbachia pipientis. The species exists in slightly different forms known as strains. Different strains have different effects on mosquitoes.
Mosquitoes That Transmit Dengue and Zika Virus Disease
The insect with the scientific name Aedes aegypti has the common name yellow fever mosquito. As this name suggests, the insect can transmit the disease known as yellow fever to humans. It can also transmit chikungunya, dengue (pronounced dengee), and Zika virus disease. It's the main vector or transmitter for these diseases. It's native to Africa but has spread to tropical and semitropical areas of the United States.
Aedes albopictus also transmits viruses to humans, including the dengue and Zika viruses, but to a lesser extent than its relative. It's native to Southeast Asia but has spread to the United States. Its range has extended further north than that of its relative because it can tolerate a cooler environment.
Mosquito Bites and Disease
Only female mosquitoes bite humans and suck up blood. They need some of the nutrients in blood in order to produce their eggs. The females inject saliva containing an anticoagulant into the wounds that they create. The anticoagulant stops coagulation or blood clotting, enabling a mosquito to get a good drink. The injected saliva may contain viruses that can cause disease. These viruses enter the saliva from the insect's salivary glands and travel into the victim's bloodstream with the anticoagulant.
When a mosquito withdraws blood from an infected person, it may withdraw viruses as well. If these viruses get into the salivary glands, they may pass into the bloodstream of an uninfected person during a mosquito bite.
The Three Phases of Dengue Fever
Hypotension is low blood pressure. Pleural effusion is the collection of fluid around the lungs. Ascites is the collection of fluid between the lining of the abdominal cavity and the organs in the cavity.
Dengue or dengue fever is a tropical, flu-like illness that is often mild but is sometimes serious. It's caused by the dengue virus. Possible symptoms are shown in the illustration above. A patient may not experience all of the symptoms when they have the disease. The disorder is also known as breakbone fever because of the pain that it sometimes causes.
Dengue fever is classified as uncomplicated or severe. A "complication" of a disease is a secondary effect or disease that develops after the main illness. Patients generally recover from uncomplicated dengue. Severe dengue often requires hospital treatment and may even be deadly, however.
In some parts of the world, dengue is a major and widespread public health issue. Both dengue and Zika virus disease (sometimes called Zika fever) generally occur in warm climates outside of North America. Recently outbreaks of each disease have occurred in the United States, however—dengue in Hawaii and Zika virus disease in Florida. The Zika virus has also been found in Texas.
Information About the Zika Virus
Zika Virus Disease
The Zika virus is named after the Zika Forest in Uganda, where it was discovered in 1947. (This is why its name always begins with a capital letter.) It's transmitted mainly by a bite from a mosquito in the genus Aedes, especially Aedes aegypti. More rarely, it's transmitted by sexual contact. The infection often causes mild symptoms or even none at all. The complications may be far from mild, however.
Symptoms that may develop from a Zika virus infection include a fever, a rash, joint pain, and conjunctivitis (inflammation of the conjunctiva, or the membrane covering the surface of the eye and the inside of the eyelid). The affected person may also experience a headache and muscle pain.
Zika infection during pregnancy can cause a serious birth defect called microcephaly and other severe fetal brain defects. Guillain-Barre syndrome (GBS), an uncommon sickness of the nervous system, is also very likely triggered by Zika in a small number of cases.— CDC (Centers for Disease Control and Prevention)
Complications of Zika-Virus Disease
As can be seen from the quotes shown above and below, scientists say that Zika virus disease can cause microcephaly. This is a condition in which a baby is born with an unusually small head. The condition is often (but not always) accompanied by incomplete brain development and lifelong problems for the child. Zika virus infection of the mother during pregnancy is one cause of microcephaly. The virus is thought to cross the placenta and reach the developing baby, although how it does this is still unknown.
The Zika virus very likely causes Guillain-Barré syndrome as well as microcephaly. As can be seen in the different wording of the WHO and CDC quotes, however, some scientists consider this association to be less obvious than the link between the virus and microcephaly.
After a comprehensive review of evidence, there is scientific consensus that Zika virus is a cause of microcephaly and Guillain-Barré syndrome.— WHO (World Health Organization)
Guillain-Barré syndrome is an uncommon disorder in which a person's immune system attacks part of their nervous system. Symptoms of the disorder include weakness, tingling, and in severe cases, paralysis. The latter situation is a medical emergency because the paralysis may involve the breathing muscles and the muscle in the heart. The syndrome can be treated, however, and most people recover. Some are left with residual symptoms such as weakness. In many cases, the syndrome appears after the person has experienced a viral infection.
How a Virus Replicates
The Zika virus and the dengue virus are related to one another. They belong to a group known as flaviviruses.
Wolbachia enables at least some mosquitoes to avoid infection by specific viruses. It works by stopping the viruses from replicating inside a mosquito's cells. During an infection of an insect cell (or of our cells), a virus particle enters the cell and "forces" it to make new virus particles. These leave the cell and invade new ones, repeating the replication process. A large viral population is often produced.
The discovery that Wolbachia can somehow stop the replication of certain disease-causing viruses is an exciting one. Without virus particles in its salivary gland, a mosquito will be unable to spread viral diseases when it bites humans.
Controlling Dengue With Wolbachia
Effects of Wolbachia on Mosquitoes and Dengue
Wolbachia doesn't occur naturally in Aedes aegypti. Wolbachia insertion is already being used experimentally in an attempt to fight dengue, however. Researchers have learned how to insert the bacteria into mosquito eggs without killing the eggs.
The World Mosquito Program is an international effort led by Monash University in Australia. The program was until quite recently known as the Eliminate Dengue program. Its main goal is not to reduce the number of mosquitoes but to prevent them from carrying the dengue virus. The scientists in the program rear mosquitoes with added bacteria and then release the adults into the environment, where they mate with wild mosquitoes. The inserted bacteria stay alive in their hosts and gradually spread through the population via the eggs of infected females. They also appear to reduce the incidence of dengue in the area. Quantitative data is needed to demonstrate the correlation between altered mosquitoes and dengue reduction, however.
Increasing the percentage of bacteria in a mosquito population takes time, but it should be a safe and self-sustaining process. The researchers are monitoring the results of their experiments carefully. So far, there is no evidence that the mosquitoes with added bacteria are harmful for humans or the environment.
Some researchers are using a different tactic to control mosquitoes. They are creating bacterially-altered mosquitoes in order to decrease the insect population by cytoplasmic incompatibility.
Wolbachia and Zika Virus Disease
Given the preliminary success of Wolbachia in the fight against dengue, some researchers suspect that the same results will be obtained with the Zika virus. Encouraging results have been obtained with mosquitoes in the lab. Researchers have shown that infection by a specific strain of Wolbachia decreases the amount of Zika virus in mosquitoes and eliminates the virus from their salivary glands. It has not yet been demonstrated that these altered mosquitoes lack the ability to transmit Zika virus disease to humans, but the possibility is tantalizing.
In April, 2017, male mosquitoes infected by Wolbachia were released in Florida. Males were chosen because unlike the females they don't bite humans. The hope is that the overall population of mosquitoes will decrease due to cytoplasmic incompatibility, greatly reducing the risk of Zika virus infection.
The use of Wolbachia is being investigated in relation to other mosquito-borne diseases, including malaria. It would be wonderful to have an effective and environmentally safe method to control diseases transmitted by mosquitoes. They are annoying and troubling insects.
References and Resources
An estimate of Aedes aegypti and Aedes albopictus range in the United States from the CDC (Centers for Disease Control and Prevention)
Dengue outbreak in Hawaii 2015-2016 from the State of Hawaii, Department of Health
Zika Virus in Florida from Florida Health
Facts and news about the Zika virus from the CDC
The World Mosquito Program (formerly known as the Eliminate Dengue Program)
Wolbachia and the Zika virus from the Nature journal
FlorIda releases experimental mosquitoes to fight Zika virus from CNN
© 2016 Linda Crampton