varies considerably, and there are marked disparities between individuals and geographic localities. This suggests that genetic differences on the parts of both the parasite and the host influence the manifestation of disease. There are two phases of the disease: an acute phase and a chronic phase. Initial parasite invasion may cause an acute infection or symptoms so general that it is not obvious that infection has occurred. The acute phase is characterised by high levels of parasitaemia and in a small percentage of cases proves fatal. There is often an initial localised inflammatory response with swelling of the nearest lymph node. If the infection starts at an insect bite wound, a raised red nodule develops called a ‘chagoma’. If the infection occurs via the eye, it induces a condition called Romaňa’s sign in which the eyelid and preauricular lymph node swell so much that the eye becomes closed. As the acute phase of the disease progresses, the parasites invade all organs of the body. However, the most severe consequences arise from the parasite’s tendency to localise within and destroy heart muscle and cardiac ganglion cells. The pathological mechanisms are uncertain. However, damage to cardiac muscle during chronic Chagas disease may have an autoimmune basis. As he became older, Charles Darwin suffered from chronic ill health, the symptoms of which were consistent with him suffering from Chagas disease. Obviously, it is impossible to confirm this, but in his South American journals he recorded being bitten by reduvidid bugs. If the parasites invade the brain, meningoencephalitis can develop with potentially fatal or long‐term damage as a result. The patient often develops a fever and their liver and spleen become enlarged; they may also suffer from diarrhoea and exhibit evidence of respiratory infection. The acute phase occurs most commonly in children less than 5‐years‐old but unless their heart or nervous tissues are severely damaged, most of them recover even without adequate medical treatment.
4.3 Phylum Chlorophyta
Commonly known as the green algae, the Chlorophyta is a paraphyletic phylum – that is, the species within it derive from several different ancestors. Because most of them contain chloroplasts, they are often referred to as plants. Furthermore, these chloroplasts are similar in appearance to those in multicellular plants, such as wheat and roses, have a very similar physiology, and contain both chlorophyll a and chlorophyll b. However, the Chlorophyta are single‐celled organisms (although some are colonial) and are usually classed within the Protista rather than Plantae – although this remains a source of debate. Several species have close symbiotic relationships with invertebrates. For example, Chlorella spp. lives in association with the cnidarian Hydra viridis, and some sea slugs extract the chloroplasts from their algal food and utilise them as photosynthetic organelles within their own cells. Although various algae grow on the pelage of sloths and the skin of certain lizards, there are few reports of them becoming intracellular symbionts of vertebrates. An instance where it does occur is between the alga Oophila amblystomatis and the egg masses of certain amphibia. This alga enters the embryos of the spotted salamander Ambystoma maculatum and is maternally transmitted (Kerney et al. 2019). The alga utilises nitrogenous waste generated by the host cells and undertakes photosynthesis; the relationship therefore appears to be beneficial to both organisms. The alga Nannochloris eukaryotum will enter an endosymbiotc relationship with human cells under in vitro culture conditions. However, this is mainly of interest for the development of molecular machines (Black et al. 2014) and not something that happens naturally outside the laboratory.
There are isolated case reports of Chlorella spp. infecting wounds in humans and other mammals. There are also accounts of fatal disseminated infections in sheep that were presumably acquired via the digestive tract after consuming contaminated drinking water (Ramírez‐Romero et al. 2010). These, presumably, represent rare opportunistic infections. Some species of algae lost their chloroplasts during evolution. Amongst these are members of the genus Prototheca, which includes species that parasitize mammals and the genus Helicosporidium that are parasitic in insects.
4.3.1 Genus Prototheca
Members of this genus are closely related to the well‐known alga Chlorella, but they lack chloroplasts, and most species survive as saprophytes feeding on dead organic matter in a similar manner to free‐living fungi. They are found throughout the world and can be isolated from the soil, slime, sludge, gut contents, faeces, marine and freshwater, swimming pools, and virtually anywhere which has high organic matter content (Kano 2020). Some species are facultative parasites that infect various animal species with consequences that range from mild disease to fatalities. Prototheca wickerhamii and Prototheca zopfii are responsible for most human infections. These are usually associated with patients who are immunocompromised through disease (e.g., HIV infection) or medical treatment (e.g., chemotherapy/ corticosteroid therapy). A new species, Prototheca cutis, was described from a patient in Japan (Satoh et al. 2010) and further species will probably be discovered in the future now that the genus is receiving more attention. In 2018, an outbreak occurred in a cancer chemotherapy unit in India that resulted in 12 patients becoming infected with P. wickerhamii (Khan et al. 2018).
The algae gain entry to the body via the skin – usually through an existing wound – and cause a localised cutaneous infection. This often manifests as dermatitis with the formation of pustules, ulcers, and erythematous plaques. Occasionally, the infection becomes disseminated throughout the body and causes potentially fatal meningitis (Joerger et al. 2020).
There are isolated but increasing case reports of dogs and cats suffering from illnesses caused by Prototheca. These often take the form of gastrointestinal infections that cause diarrhoea, but they can become disseminated elsewhere in the body with often fatal results. In cows, P. wickerhamii, P. zopfii, and Prototheca blaschkeae are responsible for sporadic cases of mastitis in many parts of the world. Protothecosis is not a commonly recognised cause of mastitis, and therefore, it often remains undiagnosed because vets do not think to test for it. This can cause problems because the algae do not respond to normal treatments for mastitis. Indeed, at the time of writing, there was no effective treatment available. Consequently, the course of the disease can be prolonged, and there is a potential for severe economic losses in dairy herds (Jagielski et al. 2019).
4.4 Kingdom Fungi
Some estimates suggest that there may be over a million species of fungi although less than 10% of these have so far been described. Unlike plants, fungi are heterotrophs – that is, they cannot make their own food and must gain their nutrients by breaking down existing organic matter. Most fungi do this by acting as saprophytes, that is, they break down dead organic matter. In addition, many species are in symbiotic relationships with plants and invertebrates, whilst some are parasites of other fungi, plants, and invertebrate and vertebrate animals. Some of these parasitic species are important in human and veterinary medicine, as well as wildlife ecology. For example, Pneumocystis (which was once thought to be a protozoan) is a major cause of morbidity and mortality in AIDS patients (Gilroy and Bennett 2011), the skin disease ‘ringworm’ in cattle is caused not by a helminth but fungi such as Trichophyton verrucosum (Pier et al. 1994), and chytridiomycota fungi are responsible for widespread and catastrophic levels of mortality among amphibians in many parts of the world (Fisher and Garner 2020). However, only the Microsporidia will be covered here.
4.4.1 Phylum Microspora
The Microsporidia are a cosmopolitan group of obligate intracellular parasites that infect many invertebrates and vertebrates. There are even accounts of them infecting protozoa but apparently not plants or fungi. Over 1,200 species have been described, but the majority of these are parasites of invertebrates and fish. Several species are of medical, veterinary, and commercial importance. For example, Nosema apis and Nosema ceranae are major causes of disease in honeybees whilst several species such as Nosema locustae (vs locusts) and Nosema algerae (vs mosquitoes) have potential as biological control agents.
Up until the AIDS epidemic, there were few accounts of human infections by microsporidian parasites. However, they subsequently became identified as important causes of morbidity and mortality