Among the parasites known to elicit morphological changes in their ant hosts, surely the longest research tradition and most extensive body of work surrounds the nematode family Mermithidae (Fig. 1). Mermithid nematodes occur world-wide and are common macroscopic endoparasites of arthropods, including most subfamilies of the Formicidae. To date, six extant genera of the family Mermithidae are known to parasitize ants . The first published scientific record of ants parasitized by mermithid nematodes dates back to Gould , who described long, white worms from “large and small ant-flies” (i.e. alate gynes and males) as early as 1747. Later, especially researchers of the early twentieth century (Fig. 1d) showed a growing scientific interest in these parasites and the often bizarre morphologies produced in their ant hosts (e.g., [30, 36, 37, 50, 55,56,57,58,59,60,61,62,63,64,65,66,67]).
Many studies have investigated parasitogenic effects in the Formicinae and Myrmicinae, especially the genera Lasius (e.g., [30, 37, 51, 55, 64, 65, 68, 69]) and Myrmica (e.g., [33, 70,71,72,73,74]). While these taxa may be among the most ubiquitous and commonly infected, other accounts report mermithid infections of Ponerinae, Ectatomminae and Dorylinae [50, 57, 60, 66, 75] as well as of charismatic groups like the Southeast-Asian “exploding ants” (Colob-opsis spp., [52, 53]) or invasive species like Solenopsis invicta [76, 77].
In the few well-studied cases, mermithids develop in an indirect life-cycle involving paratenic (intermediate) hosts in moist environments (e.g., oligochaetes or aquatic insect larvae in Pheromermis spp.), which contain the infective nematode juveniles and are fed to ant larvae as a protein source [68, 78]. Subsequently, the nematode and the infected ant larva develop in synchronicity until eclosion of the ant imago. One ant host usually contains a single mermithid, but up to nine nematodes per host have been reported . When the mermithid has reached maturity, it will eventually alter the infected ant’s behaviour, leading to host suicide by drowning, to release the parasite [42, 55, 68, 79].
Parasitized individuals can present with a wide range of aberrant characters and proportions: while male hosts may exhibit slight shifts in size, allometry and gonad development [30, 33, 37, 69, 76], mermithid nematodes are known to cause intercaste or “mosaic” (sensu ) phenotypes in female ants: these may present anywhere on a wide spectrum of possible morphologies and can resemble workers, soldiers, gynes, possess combinations of the healthy castes’ characters or exhibit entirely novel traits [33, 50, 52, 68, 80, 81]. In comparison to the respective original host caste, characteristic changes may include altered body size, elongated or shortened extremities, physogastry (enlarged gaster, distended by the parasite), reduced size of head, deviations in pilosity and sculpture, as well as reduction of all sexual characters (wings, thoracic sclerites, ovaries, and ocelli; Fig. 1a, b) (e.g., [31, 33, 42, 50,51,52, 55, 67,68,69,70,71, 74]).
The extent of morphological alterations induced by mermithid infections can thus range from no observable changes apart from slight physogastry (e.g., in Solenopsis spp., [76, 77, 82]) to aberrations extreme enough to render morphology-based caste or even species assignment impossible (e.g., in Myrmica spp. or Colobopsis sp., [33, 52]. Unsurprisingly, mermithogenic phenotypes have led to instances of taxonomic confusion in the past, because parasitized individuals were mistakenly described as new taxa on several occasions [70,71,72,73].
This diversity of phenotypes has led to the use of specialized terminology, such as “intermorph/intercaste”, “mermithogyne” (infected gyne or queen), “mermithergate” (infected worker), “mermithostratiote” (infected soldier), or “mermithaner” (infected male) to describe these specimens [32, 50, 81]. Originally, these categories were based on the assumption that mermithogenic phenotypes develop directly from the caste they are morphologically most similar to . In contrast, newer studies on Myrmica spp. have proposed a common origin of all aberrant morphologies from larvae destined to become gynes or males  or opted to omit caste assignment of the host in light of unclear morphology . Accounts of “workers” and “soldiers” exhibiting gigantism or gyne-like traits [32, 36, 83] or infection of adult ants [63, 67] are currently considered doubtful and are in need of further investigation.
Mermithids themselves are only reliably identifiable morphologically in their rarely encountered mature stage [84, 85]. Attempts to recreate their life-cycles under controlled laboratory conditions in order to rear mature specimens have been largely unsuccessful . Many hitherto published studies have therefore had to forgo identifying parasites to species or even genus level and settle for a family-level identification (Mermithidae) (e.g., [52, 76, 83]) or the largely outdated genus name “Mermis” instead (e.g., [50, 73, 79]). Due to this often unresolved parasite taxonomy but comparable variability of morphological syndromes across identified taxa, Mermithidae are summarized at the family level in Table 2.
The mechanisms whereby mermithid nematodes influence host phenotypes have long been a matter of speculation; historical hypotheses range from larval hypertrophy by overfeeding ([36, 83], now considered outdated, see [30, 33]) to hormonal or chemical influences [60, 69]. The currently most common hypothesis assumes nutrient depletion through metabolic competition between host’s and parasite’s tissues during preimaginal development [30, 33, 37, 60, 70, 71, 86]. This model considers the importance of timing and severity of infection and interprets morphological changes as results of metabolic disturbances during ontogeny. For gynes of Myrmica and Lasius, Kloft  describes a consistent sequence, in which mermithids deplete pupal energy reserves of their hosts via hydrolysis of tissues: first, the flight musculature is replaced by loose fatty tissue, followed by depletion of the gastral fat body and, finally, the gonads.
Whether the extent of the changes to host morphology mainly depends on timing of infection, size, and number of the parasites, or whether combinations of different host and parasite taxa result in different levels of developmental robustness or plasticity [11, 33, 53] must be further investigated. Thus, despite the plethora of literature available on the ant–mermithid system, it still offers numerous open questions and opportunities for further research (see “Discussion”, Outlook).
From the family of tetradonematid nematodes, only two species are known to cause morphological aberrations in ants:
Tetradonema solenopsis, the first tetradonematid parasite to be discovered in ant hosts, was described from the host ant Solenopsis invicta in Brazil . Infected workers were reported to have enlarged gasters and scalloped gastral tergites. Due to the role of S. invicta as an agricultural pest, T. solenopsis has been discussed as a possible biological control agent . However, as the parasite’s life-cycle and the timing of infection are unstudied in this case, it is unknown whether the observed changes in morphology represent the results of developmental disturbances or are simply due to the presence of the parasite in the adult host [22, 42].
Myrmeconema neotropicum is perhaps one of the most charismatic parasites known from ants: in its only known hosts, workers of the neotropical arboreal ant Cephalotes atratus, it causes a conspicuous change in the colour of the gaster from black to shiny red (Fig. 2a) [88, 89]. This parasite-induced colour morph has been known for more than 100 years, but was erroneously described as the separate taxon C. atratus var. rufiventris . The nematode infects the ant host at the larval stage via eggs or larvae of the parasite contained in bird faeces . Developmental stages of M. neotropicum can thus be found in all life stages of the ant, with mating adult parasites (Fig. 2b) present in callow workers and fertilized females in adult ants exhibiting a red gaster . The reddish colour of the gaster can extend to the femoral integument in late stages of infection and is thought to be caused by a parasite-induced thinning of the cuticle, which reaches its most noticeable appearance when the eggs mature and the parasite is most infective . In addition to this eye-catching colour change, infected ants also exhibit atrophy of the ventral nerve cord , a weakened attachment of the gaster at the postpetiole, reduction of head size by an average of 10%, an increase of gastral mass and a decrease in overall body mass (excluding gaster) [88, 92]. Interestingly, despite the increase in gastral weight, studies found a decrease in metabolic rate of the gastral tissue in parasitized ants . Apart from these morphological changes, infected C. atratus ants show altered behavioural patterns, acting more sluggish and less aggressive than their healthy nestmates—which has been attributed to lower levels of alarm pheromones [23, 88]—as well as a peculiar gaster-flagging display. These behavioural traits combined with the red, berry-like, and weakly attached gaster have led to the hypothesis of “fruit mimicry” , whereby the parasite-induced changes to the phenotype serve to attract birds, which devour the infective gasters and thus complete the parasite’s life-cycle. The M. neotropicum–C. atratum system has thus become one of the textbook examples of the so-called extended phenotype concept, wherein changes to the host phenotype may serve to increase parasite fitness [38, 92] (see also “Discussion”).
Apart from the occurrences of the relatively well-studied mermithid and tetradonematid nematodes described above, members of three other families of the Nematoda are mentioned sporadically as parasites with possible phenotypic effects on their ant hosts (reviewed in ):
Within the Allantonematidae, Formicitylenchus oregonensis is reported as a parasite of queens of Camponotus vicinus from Oregon, USA (Fig. 3a). Poinar  reports one adult female and 120 juveniles of the parasite found in the body cavity of the dealate gyne host. The infected ant exhibited reduced, abnormally formed ovaries and eggs. While the parasite’s life-cycle remains unknown, the author hypothesizes infection through the host larva’s cuticle and a possible dispersal of the parasite during the nuptial flight of winged Camponotus queens.
A case of ant parasitism by a nematode of the family Physalopteridae is illustrated by Lee , who first reported Skrjabinoptera phrynosoma from Pogonomyrmex barbatus occurring in Texas, USA. Infected worker ants are recognizable by their enlarged, light-coloured gaster. In the complex cycle, the ants represent the intermediate host for this nematode parasite of the Texas horned toad (Phrynosoma cornutum): dead, gravid female nematodes expelled by the final host are an attractive food source for the ants and are fed to ant larvae. During the ants’ larval and pupal stage, the juvenile nematodes develop and eventually encyst in the host’s fat body (up to 75 cysts per host). When infected ants are eaten by the final host lizards, parasite development is completed.
A single questionable case of parasite-induced host phenotype is reported from the Seuratidae, with Rabbium paradoxus infecting Camponotus castaneus workers in Florida, USA (Fig. 3b) . While no infection of juvenile ants is known, infected workers exhibit an enlarged gaster and behavioural shifts to more diurnal activity, possibly facilitating vertebrate predation. Interestingly, this host–parasite pair may be currently in transition between an indirect cycle involving a final vertebrate host and reproduction of the parasite entirely within the infected ant .
Tapeworms of the davaineid genera Cotugnia and Raillietina are known to utilize ants and other arthropods as intermediate hosts before infecting their final hosts, several species of birds and mammals, e.g., grouse, chickens, turkeys, emus, and rabbits [97,98,99,100,101,102,103,104,105,106]. Workers, soldiers, gynes, and males of the myrmicine genera Pheidole, Tetramorium, Monomorium, Leptothorax, Pachycondyla, and Myrmica [97,98,99,100, 102, 104, 107, 108] have been identified as intermediate hosts containing cystercercoids. Formica rufa, reported to harbour Raillietina friedbergeri and thereby the sole published formicine host of davaineid cestodes, is listed as “not experimentally verified” .
The role of these cestodes as parasites of economically important animals has contributed to the rather extensive body of literature surrounding them. However, detailed investigations of morphological aberrations in ant hosts are extremely sparse: apart from cystercercoids (up to 50 per host, see ) visible though the gastral integument , only a darker colour of the cuticle has been reported as a suspected parasite-induced alteration of the host phenotype. An account of this phenomenon along with a hypothesis for its origin in Myrmica rubra and M. scabrinodis infected with Raillietina urogalli is provided by Muir (: 689): “The cysticercoids have been found in males, queens and workers of both species, the infected ants being detected by an unnaturally dark chocolate colouration affecting the whole cuticle, compared with the dark reddish-brown tint of non-infected individuals. This colour difference may be due to the formation of a melanoid pigment from the excretions of the parasite.”
Among cestodes as parasites of ants, the greatest number of publications treats the family Dilepididae (Cestoda, Cyclophyllidea). The species Choanotaenia unicoronata  and—more commonly—Anomotaenia brevis [110,111,112,113,114] have been identified as parasites of ants, while in several cases in the literature, the parasites remain determined only to the generic or family level (e.g., [40, 115, 116]). Cestode eggs are taken up by ant larvae, presumably from the faeces of several bird species (e.g., woodpeckers, quail), which represent the final hosts (see Fig. 1 in ).
Infected ants reported from throughout Europe, northern Africa and the USA  belong exclusively to the subfamily Myrmicinae, comprising several species of Temnothorax, as well as Leptothorax acervorum and its slavemaker Harpagoxenus sublaevis (see Table 2).
The majority (up to 90% ) of infected ants were identified as workers (but see “Discussion”), with several authors also reporting lower rates of infection in gynes and males, and the occurrence of presumably parasite-induced intercaste phenotypes [40, 111, 112]. The number of cystercercoids found in the gaster of each parasitized individual varied greatly from one to over 100 .
Infection coincides with certain characteristic morphological changes in the host (Fig. 4): a yellowish and unusually soft cuticle, widening of the petiole and postpetiole, shortened antenna, tibia and femur, reduction of head size and overall body size, and atrophy of mandibular muscles in workers, as well as lowered fertility and intercaste morphology in presumptive gynes [40, 109,110,111,112,113,114,115,116,117,118,119,120]. While the exact developmental mechanisms underlying these changes are unknown, authors have hypothesized disruptions of imaginal disks and hormone levels, depletion of melanin precursors, and malnutrition during the larval or pupal phase as possible causes [40, 110, 111, 118].
In addition to morphological alterations, some studies report increased longevity  and changes in behaviour, especially sluggish movement, increased begging for food and reduced aggression in workers, and less flight activity in gynes [40, 110, 112, 116, 118]. These alterations to social and overall behaviour of infected ants are thought to be connected to observed changes in the ants’ cuticular hydrocarbon (CHC) profile [111, 113, 114]. Interestingly, infection of some individuals within a colony seems to have an effect on uninfected nestmates as well: even though infected colonies do not seem to suffer significant production or fitness losses, they may produce fewer eggs while investing in more or bigger males, while uninfected workers display reduced aggression and increased mortality rates during periods of colony stress [112, 113, 121]. Upon removal of the queen, infected Temnothorax nylanderi workers showed increased reproductive potential compared to their healthy nurse sisters . These complex interactions of parasitism, behaviour, reproduction and colony composition have been interpreted as mechanisms of colonial buffering [11, 112, 113, 122].
Recent studies comparing gene expression in T. nylanderi parasitized by A. brevis to healthy conspecifics [114, 123] found differences in expression patterns of over 400 genes, many linked to cuticular hardening, CHCs, metabolism, lifespan, fertility, and muscle function, and found no evidence of neurochemical influences on host behaviour by the parasite. The authors interpret this parasitogenic syndrome—particularly cuticular softening, altered colouration and reduced activity—as traits that may facilitate parasite transmission to the final woodpecker host, interpreted as an example of the extended phenotype concept (sensu , but see “Discussion”).
Apicomplexa: Neogregarinorida: Mattesia spp.
Parasitic unicellular organisms of the genus Mattesia (Order Neogregarinorida, Family Lipotrophidae), were first described from ants in 1979, upon identifying the infection in the fire ant Solenopsis geminata . The parasite Mattesia geminata described in this study destructively invades oenocytes of the hypodermis and causes disruptions in the hosts’ preimaginal development, leading to melanization of the cuticle, reduced or discoloured compound eyes, and pupal death. Subsequent studies on multiple myrmicine host species from the USA, Canada, Brazil, and Europe (Table 2) yielded similar results, adding reduction of mandibular dentition to the characteristic syndrome and identifying preimaginal workers, gynes, and males as hosts [125,126,127,128]. A detailed account of the parasite’s complex life-cycle in hosts of the genus Leptothorax is provided in Kleespies et al. , showing characteristic tissue tropism: briefly, infective spores are ingested by host larvae; subsequent stages of the parasite develop extracellularly in the haemocoel, especially beneath the hypodermis and between lobes and cells of the fat body. In later stages, macronuclear merozoites invade the hypodermis and the fat body or settle extracellularly in the haemocoel. Upon maturity, two characteristic lemon-shaped spores (Fig. 5b, c) are developed in each gametocyst. In a laboratory setting, feeding infected pupae to ant larvae resulted in successful transmission of the parasite.
In contrast, the first described host, S. geminata, only presented with a limited range of infected tissues and parasite transmission in the lab was unsuccessful , leading to the assumption that it may not actually be a suitable host for M. geminata .
In the abovementioned cases, hosts were unable to attain imaginal maturity and died in the pupal stage. However, two cases of infection with Mattesia spp. of hitherto unresolved species identity are known to have produced aberrant adult ant phenotypes: the only published case of non-myrmicine hosts, namely workers of the Australian bull-ants Myrmecia pilosula and M. rufinodis, presented with a softer and lighter coloured exoskeleton, and increased mortality . In workers and gynes of the invasive fire ant Solenopsis invicta, an infection with Mattesia-like spores resulted in the so-called “yellow-head disease” [130, 131]: host ants were recognizable by a yellow-orange discolouration of their head and parts of the thorax (Fig. 5a). Large workers were preferentially infected, though it is unknown whether the infection itself may alter imaginal size.
As some of the known hosts, e.g., S. invicta and Monomorium pharaonis, are known pest species of agricultural or medical importance, M. geminata has also received attention as a possible biological control agent [28, 127, 130].
Fungi: Myrmicinosporidium durum
A recent surge of studies has dealt with investigating the phylogeny and effects of behaviourally manipulative fungal parasites in ants (e.g., Ophiocordyceps [29, 41], Pandora ). Despite the extensive literature on these so-called “zombie-fungi” and other fungal pathogens found in ant hosts (e.g., [133,134,135]), a review of hitherto published studies has yielded only one candidate putatively fitting the criteria of this publication: the enigmatic generalist fungal parasite Myrmicinosporidium durum.
First described by Karl Hölldobler from workers of Solenopsis fugax, the parasite was hypothesized to be of protozoan, perhaps haplosporidian origin [136,137,138]. Only in 1993 was it recognized as a fungal parasite and tentatively placed close to the order Chytridiomycetes , though newer studies place it within the Entomophthorales [140, 141]. Its true phylogenetic placement thus remains unresolved.
The parasite exhibits a remarkably generalist host range and wide distribution (see Table 1 in  and Table 2 for a complete list): cases have been reported from Central, southern and eastern Europe, the southern USA, the Galapagos Islands, and East Asia . Ant hosts have been assigned to 40 species from three different subfamilies (Myrmicinae, Formicinae, Dolichoderinae) and may be queens, workers, soldiers, or males [136, 138, 141, 143,144,145,146]. While the details of its life-cycle remain elusive, previous authors have identified the ant host’s fourth larval instar as probable time of infection .
Infected ants with a light-coloured cuticle  are recognizable in the field by visible dark spores filling their gaster and—at later stages of infection—the entire body, even to the tips of the extremities (Fig. 6), though never the vital organs [136, 146, 147]. Spores are approximately 0.45 mm in diameter, lentil-shaped, and take on a characteristic bowl-like appearance when stored in alcohol, which inspired the German term “Näpfchenkrankheit” (lit. “little bowl disease”, Fig. 6b) . Apart from the visible presence of the parasite, some authors have reported a distended, shiny, and darkened gaster in ant hosts [136, 138, 144, 147, 148], while others recorded no change in the appearance of infected ants [141, 149]. Increased mortality during hibernation or stress, depletion of fat reserves, and potential sterility of queens have been discussed as possible detrimental effects of the infection [136, 137, 146, 147], though other studies found no obvious negative influences and even reported a remarkable longevity of infected ants [133, 139].
This apparent lack of any strong detrimental effect on its diverse hosts has led to the hypothesis that M. durum may be a true generalist parasite with a long co-evolutionary history linking it to its hosts [133, 146, 148]. However, whether the observed morphological aberrations are truly the result of parasitic influence on host development and whether the occurrences reported from a wide range of different habitats and host taxa all represent the same parasitic species [141, 150] remains to be investigated in the course of further molecular and taxonomic studies.
Viruses (?): “labial gland disease”
This chapter is concluded by a hitherto unsolved mystery: in several species of formicine ants from Europe, the USA and Japan, the occurrence of individuals with characteristically malformed, enlarged mesosomas (Fig. 7) has been reported. Affected ants are known from at least ten species of Formica, as well as from two species, respectively, of Camponotus and Prenolepis [151,152,153,154,155,156,157].
The condition has been termed “labial gland disease”, as the swollen thorax is caused by the swelling of labial glands during the pupal phase . Apart from the enlarged glands, the resulting workers (often termed “pseudogynes” sensu , or “secretergates” sensu ) are of normal size  or slightly smaller , exhibit a domed, gyne-like meso- and metanotum with variably defined sclerites, coupled with pale cuticle patches and increased pilosity on the affected regions, as well as increased mortality [153,154,155,156, 160]. Gynes (“secretogynes”) and males (“secretaners”) have also been reported to suffer from the condition. Secretogynes also show enlarged pronotums with lighter colouration and may have reduced wings and flight ability , but can mate normally and produce viable offspring with or without the disease .
As the causative agent remains unknown, the transmission of the disease can only be speculated about: the term “secretomorphs” for all affected individuals stems from the observed trophallaxis behaviour, whereby the sugary secretions of the enlarged labial glands are distributed to larvae and nestmates , which may transmit the disease to preimaginal stages. In Formica fusca, dead secretergates were found with holes bitten into their thorax and the labial glands removed, pointing to cannibalism as a potential mode of transmission . Alternatively, accounts of secretergates developing from eggs of mated secretogynes without any observed feeding behaviour suggests a possible direct transmission from queen to offspring .
While earlier studies hypothesized the disease’s origin to be connected to the presence of myrmecophile beetles  or “erroneous” creation of intercastes by differential rearing conditions , the current—albeit unconfirmed—assumption is that of a viral pathogen . If so, this would not be the first virus found to infect ants [22, 162]—a recently published review article reports 87 viruses found within 38 ant species across 15 viral families —but hitherto the only one to cause such drastic and distinct morphological changes in its hosts.