Chytridiomycosis ( / k aɪ ˌ t r ɪ d i ə m aɪ ˈ k oʊ s ɪ s / ky- TRID -ee-ə-my- KOH -sis ) is a disease that affects amphibians, caused by two types of fungi: Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans. This disease has been linked to large drops in amphibian numbers or complete disappearances in areas such as western North America, Central America, South America, eastern Australia, east Africa (Tanzania), and the Caribbean islands of Dominica and Montserrat. Much of the New World may also face the risk of this disease in the near future. The fungus can cause some amphibians to die in certain populations, while all amphibians may die in others. There is no known way to control the disease in wild populations. Amphibians with the disease may show different symptoms. Several methods have been suggested to control the fungus, but none have worked well on a large scale. The disease has been suggested as a reason for the decline in amphibian populations worldwide, which may affect about 30% of all amphibian species. Some studies found not enough proof to connect the fungi and the disease to global amphibian declines, but more recent studies show a link and suggest the disease spreads through trade between countries.
History
It is not clear whether chytridiomycosis is a new disease or an existing pathogen that has recently become more harmful. The disease was first noticed in 1993 in dead and dying frogs in Queensland, Australia. However, the fungus causing the disease had been present in Australia since at least 1978 and is now found in many regions, including Africa, the Americas, Europe, New Zealand, and Oceania. In Australia, Panama, and New Zealand, the fungus appeared suddenly and spread widely around the same time frog populations declined. In the Americas, the fungus was first found in Venezuela in 1987 and then spread across the continent. It was also discovered in the lower part of Central America in 1987, where it moved toward the north to meet the spread from South America. It is possible that the fungus has always been present in nature but was only recently identified because it has become more harmful, more common in the environment, or because frog populations have become less able to resist it. The fungus has been found in four areas of Australia—the east coast, Adelaide, southwest Western Australia, and the Kimberley—and is likely present in other regions as well. A recent study compared the genetic makeup of 234 samples of the fungus, Batrachochytrium dendrobatidis, and found that a group from the Korean peninsula may have caused the global spread of the disease.
The oldest recorded case of the fungus in frogs comes from a Titicaca water frog collected in 1863, and the oldest case in salamanders is from a Japanese giant salamander collected in 1902. However, the strains of the fungus found in these animals were not linked to large-scale deaths of amphibians. A later case involved an African clawed frog (Xenopus laevis) collected in 1938, and this species does not seem to be affected by the disease, making it a possible carrier of the fungus. This frog was used in a medical test for human pregnancy, which led to widespread international trade of the species more than 60 years ago. If the fungus originated in Africa, the African clawed frog may have helped spread it beyond the continent. The first well-documented case of chytridiomycosis was found in an American bullfrog (Rana catesbeiana) collected in 1978.
Range
The geographic range of chytridiomycosis is hard to determine. The disease only occurs in areas where the fungus B. dendrobatidis is present. However, the disease is not always found in places where the fungus lives. Scientists often describe reasons for amphibian population declines as "mysterious" because the causes are not fully known. It is unclear why some areas are affected by the fungus while others are not. Factors such as climate, habitat quality, and population size may influence whether the fungus infects amphibians in a specific area. Therefore, when studying the geographic range of chytridiomycosis, the range of B. dendrobatidis must be considered. Recent maps show that B. dendrobatidis is found in many parts of the world. It has been detected in 56 out of 82 countries and in 516 out of 1,240 (42%) species, based on data from more than 36,000 individuals. The fungus is widely found in the Americas and appears occasionally in Africa, Asia, and Europe. For example, Asia has a prevalence rate of 2.35%.
In the New World, areas with the highest suitability for B. dendrobatidis include habitats with the greatest diversity of amphibians. At-risk regions include the Sierra Madre Pine Oak Occidental Forest, the Sonoran and Sinaloan dry forests, the Veracruz moist forest, Central America east of the Isthmus of Tehuantepec, the Caribbean Islands, temperate forests in Chile and western Argentina south of 30°S, the Andes above 1,000 meters in Venezuela, Colombia, and Ecuador, the eastern slopes of the Andes in Peru and Bolivia, the Brazilian Atlantic forest, Uruguay, Paraguay, northeastern Argentina, and the southwestern and Madeira–Tapajós Amazonian rainforests.
Currently, the effects of chytridiomycosis are most visible in Central America, eastern Australia, South America, and western North America.
Climate change
A study indicates that changes in global temperatures might be causing more cases of chytridiomycosis. Higher temperatures have increased evaporation in some forests, leading to more clouds forming. Scientists suggest that more clouds may be lowering daytime temperatures by blocking sunlight, while at night, clouds trap heat and raise temperatures. This pattern of cooler days and warmer nights could create ideal conditions for the Chytrid fungus, which grows best between 17° and 25 °C (63° and 77 °F). The fungus cannot survive at 30 °C or higher. Without the extra cloud cover caused by increased evaporation, temperatures may reach 30 °C more often, which can help control the fungus population.
Causative agents
Chytridiomycosis, caused by the fungus B. dendrobatidis, mainly affects the outer layers of skin that contain a protein called keratin. When most species reach a B. dendrobatidis level of 10,000 zoospores, they struggle to breathe, absorb water, balance water and salts in their bodies, or control body temperature. Blood tests show lower levels of certain electrolytes, such as sodium, magnesium, and potassium. B. dendrobatidis has two life stages. The first is the asexual stage where spores form. When a host becomes infected, spores enter the skin and attach using tiny root-like structures. The second stage occurs when the initial spores produce mobile zoospores. These zoospores need a wet surface to move and infect skin cells. A second species of Batrachochytrium, called B. salamandrivorans, was discovered in 2013 and causes chytridiomycosis in salamanders.
Disease transmission and progression
B. dendrobatidis is a waterborne pathogen that releases zoospores into the environment. Zoospores use flagella to move through water until they reach a new host and enter through the skin. The lifecycle of B. dendrobatidis continues when new zoospores are produced from the zoosporangium and released into the environment or reinfect the same host. Once a host is infected with B. dendrobatidis, it may develop chytridiomycosis, but not all infected hosts show symptoms. Scientists are still learning about other ways the disease spreads. It is believed that chytridiomycosis can spread through direct contact between hosts or through an intermediate host.
Much is unknown about how B. dendrobatidis successfully spreads between hosts. After being released into water, zoospores move less than 2 cm (0.8 in) in 24 hours before forming a protective covering. The limited movement of zoospores suggests that an unknown mechanism allows them to spread between hosts, which may involve the pet trade and the American bullfrog. Environmental factors such as temperature, pH, and nutrient levels influence the survival of B. dendrobatidis zoospores. These zoospores can survive in temperatures between 4–25 °C (39–77 °F) and pH levels between 6–7.
Chytridiomycosis is believed to occur in the following way: zoospores first contact amphibian skin and quickly form sporangia, which produce new zoospores. The disease then progresses as these new zoospores reinfect the host. Amphibians infected with the fungus may show physical changes, such as redness on the belly, seizures with stretched legs, skin peeling over the body, loss of skin on feet and other areas, rough skin with small bumps, and occasional sores or bleeding. Behavioral changes may include being inactive, not seeking shelter, not escaping danger, losing the ability to flip back to a normal position, and unusual postures, such as sitting with legs away from the body.
In addition to amphibians, chytridiomycosis also infects certain crayfish species (Procambarus alleni, P. clarkii, Orconectes virilis, and O. immunis) but does not infect mosquitofish (Gambusia holbrooki).
Clinical signs
Amphibians infected with B. dendrobatidis may display various symptoms. The earliest sign is often a loss of appetite, which can occur as soon as eight days after exposure. Infected amphibians are frequently found in a slow-moving state and may refuse to move when touched. Many frog species infected with B. dendrobatidis show excessive skin shedding. The shed skin is typically described as grayish-white or tan and may stick to the amphibian’s body. These symptoms are commonly observed 12–15 days after exposure. The most common symptom of chytridiomycosis is thickened skin, which can lead to death because the amphibians cannot absorb nutrients, release toxins, or, in some cases, breathe. Other signs include redness of the skin, seizures, and loss of the ability to flip back to the right side when turned over. A study found that even mild infections can cause skin damage, changes in hormone levels, and issues with water balance, while more severe infections are needed to affect reproduction. In tadpoles, B. dendrobatidis affects the mouthparts where keratin is present, leading to feeding problems or changes in the color of the mouth.
Research and impact
The amphibian chytrid fungus grows best in temperatures between 17 and 25 °C (63 and 77 °F). When infected frogs are exposed to high temperatures, the infection can be cured. In nature, frogs that stay in temperatures above 25 °C for longer periods are less likely to be infected by the fungus. This may explain why declines in amphibian populations caused by chytridiomycosis have mostly happened at higher elevations and during cooler months. Naturally produced skin peptides can stop the growth of B. dendrobatidis when infected amphibians are near 10 °C (50 °F). This allows some species, like the northern leopard frog (Rana pipiens), to clear the infection in about 15% of cases.
Although many amphibian population declines have been linked to the fungus B. dendrobatidis, this may be an overstatement in some cases. Some species resist the infection, and some populations can survive with a low level of the disease. In addition, some species that seem to resist the infection may actually carry a nonharmful form of B. dendrobatidis.
Some researchers argue that focusing too much on chytridiomycosis has made amphibian conservation efforts too narrow. A review of data from the IUCN Red List found that the threat of the disease was assumed in most cases, but there is no clear evidence that it is a major threat. In New Zealand, conservation efforts continue to target curing the critically endangered Archey's frog (Leiopelma archeyi) of chytridiomycosis, even though research shows these frogs are immune to B. dendrobatidis and are dying from other, still-unknown diseases in the wild. In Guatemala, thousands of tadpoles died from a pathogen that is not related to B. dendrobatidis.
A 2019 study in Science estimated that chytridiomycosis contributed to the decline of at least 501 amphibian species over the past 50 years. Of these, 90 species were confirmed or likely to have gone extinct in the wild, and another 124 had population declines of more than 90%. The study described the impact as the "greatest recorded loss of biodiversity caused by a disease." However, a later study in Science found that the 2019 research by Scheele et al. lacked enough evidence to support these conclusions and could not be repeated using the same data and methods. It is still unclear exactly how many species have been affected by chytridiomycosis, but there is strong data for a few species, such as the mountain yellow-legged frog in the Sierra Nevada mountains.
Immunity
Because the fungus has a big effect on amphibians, many scientists have studied ways to stop it from spreading in the wild. Amphibians that survive the chytrid fungus often have higher levels of a bacterium called Janthinobacterium lividum on their skin. This bacterium makes antifungal chemicals, such as indole-3-carboxaldehyde and violacein, which stop the growth of B. dendrobatidis, even in small amounts. Another bacterium, Lysobacter gummosus, found on red-backed salamanders (Plethodon cinereus), produces a chemical called 2,4-diacetylphloroglucinol that also stops B. dendrobatidis from growing. A 2021 study showed that many more antifungal bacteria live on amphibians than previously known.
Understanding how bacteria on amphibians' skin interact with B. dendrobatidis helps explain why some species, like the frog Rana muscosa, are harmed by the fungus, while others, like the salamander Hemidactylium scutatum, can live with it. The bacterium Janthinobacterium lividum, found on several amphibians, can prevent B. dendrobatidis from causing disease even when added to amphibians that do not naturally have it. Studies show that adding J. lividum, which makes violacein, to amphibians without enough of this chemical can help them resist infection. While the exact amount of violacein needed to stop B. dendrobatidis is not fully known, its presence or absence affects whether an amphibian survives the fungus. For example, Rana muscosa has very low levels of violacein on its skin, and J. lividum is not found on this species. In contrast, Hemidactylium scutatum has enough violacein from J. lividum to survive B. dendrobatidis.
One study suggested that the water flea Daphnia magna eats the spores of the fungus.
Interactions with pesticides
Scientists have suggested that the use of pesticides may be linked to the decrease in amphibian populations. In 2007, researchers studied how pesticides interact with a disease called chytridiomycosis. They found that exposure to a pesticide called carbaryl, which affects a chemical in the body called cholinesterase, made foothill yellow-legged frogs (Rana boylii) more likely to get sick from chytridiomycosis. Specifically, the frogs' natural defenses on their skin, which help protect against disease, were reduced after exposure to carbaryl. This suggests that pesticides might weaken these natural defenses, making amphibians more vulnerable to illness.
Evolution
Scientists found signs that some frogs might be developing resistance to a disease in a population of Mixophyes fleayi, a type of frog living in subtropical Australia. This frog species was once in danger of dying out, but its numbers are now increasing again. In Panama, a similar situation occurred when a frog species declined and then recovered. Researchers believe the recovery was not because the disease became weaker, but because the frogs developed a trait that helps them survive the infection. This trait could be a genetic change that makes them resistant to the fungus or another characteristic they gained over time, such as a helpful type of bacteria living on their skin.
Treatment options
The use of antifungal medicines and heat treatment has been suggested as a way to treat B. dendrobatidis. However, some antifungal medicines may cause skin problems in certain frog species. Although these treatments are used for frogs infected with chytridiomycosis, the infection is not always completely cured. A study by Rollins-Smith and others found that itraconazole is the preferred antifungal for treating Bd. This is because other options, like amphotericin B and chloramphenicol, can be harmful. Chloramphenicol, in particular, has been linked to leukemia in toads. This creates a challenge because untreated frogs may develop limb deformities or die, but treatment can also cause skin issues. "Treatment is not always fully successful, and not all amphibians handle treatment well. Therefore, chytridiomycosis should always be treated under a veterinarian's guidance."
Frogs infected with B. dendrobatidis are often soaked in itraconazole solutions. After a few weeks, tests using PCR assays show they no longer have the infection. Heat treatment is also used to eliminate B. dendrobatidis. In controlled experiments, the temperature of infected frogs is raised above the range where B. dendrobatidis grows best (25 to 30 °C). When the temperature exceeds this range, the infection disappears within weeks, and the frogs recover. Formalin and malachite green have also been used to treat chytridiomycosis. A species of Archey's frog was cured by applying chloramphenicol directly to its skin. However, using antifungal drugs can carry risks for the animals.
Bioaugmentation is another possible treatment for B. dendrobatidis. This involves adding probiotic bacteria to frogs or their environment. These bacteria produce substances that fight B. dendrobatidis. For example, in Rana muscosa frogs in Sierra Nevada, those treated with the probiotic J. lividum had higher survival rates and lower infection levels than untreated frogs. Similar results were seen in Beyşehir frogs (Pelophylax caralitanus) in Turkey.