Trichuris: A Critical Review

Abstract

Trichuris (whipworms) is a type of roundworm that is responsible for trichuriasis in human beings. Globally, 600–800 million people are infected by this helminthic worm per year. Trichuris is more prevalent in some tropical and sub-tropical areas such as East Asia, China, Sub-Saharan Africa, and the Americas. These parasitic nematodes affect the small intestines of mammals, causing a great deal of discomfort. Their life cycle is completed in two stages; mammals and the external environment. The zoonotic transmission of the disease is responsible for huge infections and deaths around the world. In recent times, researchers have gained a lot of understanding about the genetics and parasitology of Trichuris. In this chapter, we will discuss the origin, phylogeny, life cycle, diagnosis, and zoonotic transmission of the parasite. At the same time, the chapter discusses the genomics of the parasite and the future directions that can help us contain this parasitic nematode.

1. Introduction

Soilborne helminths affect roughly a quarter of the world’s population or 1.5 billion people. Especially prevalent in East Asia, sub-Saharan Africa, the Americas, and China, soilborne helminthiasis is found across the tropics and sub-tropics. More than 568 million school-aged children and 267 million preschoolers need treatment and prevention measures because they reside in locations with high rates of these parasites’ spread. Humans are most commonly infected with Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), Necator americanus, and Ancylostoma duodenale, all of which are soil-dwelling helminths (hookworms) [1]. The nematode parasite Trichuris trichiura is responsible for causing trichuriasis, a condition that is often overlooked despite its pathogenicity. Trichuriasis, caused by T. trichiura, is the second most prevalent helminth infection in humans and is found in every region of the world. The incidence rate is greater in areas with tropical climates where proper sanitary facilities are lacking. The greatest parasite burden and the most noticeable symptoms are seen in children, who account for 30–80% of cases [2]. This parasite is spread through the oral consumption of its embryonic eggs. New hosts can contract the disease from infected hands, food, soil, or water. These then develop into L1 larvae, which are passed out of the body after hatching in the intestine. The larvae eat their way through the large intestine’s epithelial lining and mature into adults. The females lay their unfertilized eggs into the environment after mating, and the eggs once again enter the environment via the excrement of their hosts. To this day, T. trichiura has remained the species of choice for describing whipworms found in primates [3, 4, 5]; Trichuris suis refers to those found in domestic pigs and wild boars [6, 7]. The phenotypic flexibility of the organisms, variation generated by the host, a lack of morphological traits, and the overlapping of morphological characteristics across closely related species of Trichuris make accurate identification of one species from another a formidable challenge [8, 9, 10, 11]. Because of their molecular differences but comparable morphologies, T. trichiura and T. suis have been the focus of numerous Trichuris-related investigations [7, 12, 13, 14].

Trichuris is a protozoan parasite that has been found in humans and nonhuman primates (NHP), although the genetic and evolutionary ties between the two are unclear. Whether or not Trichuris species are shared by humans and NHP has been the subject of some recent publications. Due to its widespread distribution and ability to infect a wide variety of hosts, the genus Trichuris is an excellent candidate for hiding cryptic species [15]. Recent research has shown that more than one taxon of T. trichiura is able to infect humans and other primates, including captive animals, suggesting that this species is more complicated than previously thought [16, 17]. Trichuris rhinopiptheroxella, discovered in the golden snub-nosed monkey (Rhinopithecus roxellana), Trichuris colobae from Colobus guereza kikuyuensis, and Trichuris ursinus from Papio ursinus have all been reported based on morpho-biometric and molecular data [18, 19, 20]. As a result of these findings, T. trichiura is not the only whipworm discovered in primates. The systematics of the genus Trichuris currently have substantial gaps. This is due to two major factors: i) a lack of comparative morpho-biometric data obtained through the application of multiple parameters and statistical tests to the taxonomic study of these species, and (ii) a scarcity of published research on the genetics of the various Trichuris species in humans, NHP, and pigs. Researchers have yet to determine the degree of divergence between the several genetic lineages that appear to exist in Trichuris species that parasitize these hosts. We shall try to understand the morphological and biometric properties of T. trichiura isolated from people in this chapter. Moreover, molecular data (mitochondrial and nuclear markers) are used to describe the molecular phylogenetic relationships between these populations. Furthermore, we shall attempt to comprehend the origin, life cycle, taxonomy, transmission, and resistance of the Trichuris spp.

2. The origin of the species

Whipworms are parasitic nematodes that inhabit the intestines of mammals. Due to their distinctive form, which comprises of a long, thin front end (the stichosome) that embeds in the intestinal epithelial cells of its host, and a bulbous rear end, all whipworm species share the generic name Trichuris, meaning “hair tail.” In 1761, Roederer gave the parasite the name Trichuris after mistaking its head for its tail. There are more than seventy different species of Trichuris, and a number of these parasites have significant roles in medicine, veterinary science, and fundamental research. The human whipworm is an example of a parasite that co-evolved with humans, earning it the moniker “heirloom parasite.” Due to the discovery of whipworm eggs in both Old and New World archeological sites, evidence of a link between the whipworm and prehistoric man dates back more than 6000 years [21]. Mice infected with Trichuris were first studied by parasitologists curious about the parasite, its life cycle, and parasite biology. Eventually, parasite immunologists took use of T. muris infections in laboratory mice to investigate host–parasite interactions immunologically, with the ultimate goal of developing vaccines to increase resistance to infection. The value of intestinal worm infections as tools for testing the immune system and addressing fundamental immunological topics has also been recognized by immunologists who study more advanced immunological concerns. Parasite biology and the roles that parasite chemicals play in disease have received fresh attention in recent years. This renaissance is due to the desire to find parasite immunomodulatory chemicals that may have therapeutic applications for inflammatory diseases of the developed world and the scarcity of lead antigens for use in vaccines. From a parasitological perspective, characterizing the full life cycle of the Trichuris parasite required a long time (Table 1).

Year	Researcher	Findings	Ref.
1761	Roederer et al.	He gave the parasite the name Trichuris after mistaking its head for its tail	[21]
1858	Davaine et al.	Described the process of embryonation in Trichuris Spp	[23]
1954	Fahmy et al.	Defined the environmental requirements for the first stage of larval development within the egg	[22]
1989	Panesar et al.	Defined the complete sequence of larval molts from L1 through L4 to adult	[24]
2008	Araujo et al.	Discovery of whipworm eggs in both Old and New World archeological sites	[21]

Table 1.

The people involved in the identification of Trichirus trichiura.

Davaine initially described the process of embryonation in Trichuris spp. Eggs and Fahmy defined the environmental requirements for the first stage of larval development within the egg [22, 23]. Recently, it was discovered by accident that slightly acidic water hinders embryonation and results in failure in egg cultures in laboratories throughout the world that maintain the Trichuris life cycle. These discoveries are still relevant today because of this thing. Before Fahmy outlined a more accurate direct life cycle involving two larval molts and fecund adult parasites emerging around day 34, there were early misconceptions regarding the life cycle, including descriptions of migratory phases [22]. The complete sequence of larval molts from L1 through L4 to adult was not determined until the 1980s [24].

2.1 Taxonomy and Phylogenetics

Trichuris is a genus of the worm family Enoplea, in the suborder Trichinellida, together with Trichinella spiralis. There are 16 recognized species of Trichuris, which live in a wide variety of mammalian hosts, according to the NCBI Taxonomy Browser. Although Trichuris suis in pigs is the closest relative of Trichuris trichiura, it is still unclear whether Trichuris in dogs and rodents (Trichuris vulpis, Trichuris arvicolae, Trichuris muris) or ruminants (Trichuris ovis, Trichuris discolor, Trichuris skrjabini) diverged before or after Trichuris trichiura [25, 26, 27, 28]. Trichuris trichiura is the scientific name for human whipworms. At the same time, it was previously considered that just one species of whipworm infected humans, but recent articles have begun to study the potential that numerous species exist in the human population. Because of its extensive distribution and ability to infect a wide variety of host species, the Trichuris genus is a likely candidate for cryptic species, which are parasites that cannot be identified as species by standard approaches such as morphological research (Figure 1) [29]. For a more in-depth look at the taxonomic relationship between Trichuris parasites in humans and NHP, as well as the potential for cross-species transmission, Trichuris parasites were sampled from a wide range of wild and captive NHP host species and then sequenced their nuclear and mitochondrial markers. Internal transcribed spacer (ITS) sequences were compared between Trichuris from baboons in the wild on the Cape Peninsula of South Africa and Trichuris from humans and pigs [30]. Trichuris in humans was found to be divided into two clades (DG and CP-COB), both of which were also found in baboons. Full mitochondrial DNA (mtDNA) genome study of worms from humans in China and Uganda, as well as baboons in the United States and Denmark, produced comparable results [31]. Genetic divergence between these worms reached as high as 20%, suggesting that Trichuris in humans consists of multiple species and that parasite transmission between humans and baboons is possible. Trichuris samples collected from baboons in captivity in Denmark and the United States were revealed, through sequence analysis of the conserved beta-tubulin gene, to be members of the same evolutionary group as human Trichuris samples from Uganda [32]. An examination of Trichuris samples from humans and a variety of NHP species in and around Kibale National Park in Uganda revealed a similar separation of primate Trichuris into separate clades as documented by Ravasi et al. [33].

Figure 1.

Life cycle of Trichuris.

The clade CP-GOB was further separated into two groups, one with Trichuris from colobus and yellow-cheeked gibbon and the other with Trichuris from eight primate host species, including humans [33]. Trichuris mitochondrial and nuclear marker sequencing on the critically endangered Francois’ leaf monkey indicated the possibility of a new Trichuris species. A recent in-depth study has added new, never-before-seen evidence to the phylogeny given by Callejon et al. [27, 34, 35]. The authors proposed that there are two subclades within clade 2 (baboon and human Trichuris and macaque Trichuris), and at least two subclades within clade 1 (Trichuris from a range of primate species including humans) and SUIS (Trichuris from pigs and occasionally humans), with Trichuris from black-and-white colobus and gibbons falling into subclade CA or a separate grouping depending on the phylog Trichuris colobae, a new Trichuris species based on morphological criteria, was recently reported from black and white colobuses [36]. Similar to the work of Cavallero et al., this study determined that François’ leaf-monkey Trichuris belongs to a distinct subclade based on its ITS sequences. It’s probable that the whipworms that plague people are actually different species of the nematode parasite Trichuris, some of which are also seen in ungulates [27, 31].

Because current studies have been limited by a small number of human samples from only a few sites, and because different researchers have used different genetic markers, it is possible that more species or subspecies will be identified in the future. Recently, the rrnL gene of the mtDNA of Trichuris from persons in China (n = 7) and Ecuador (n = 15) was sequenced and compared genetically [37]. Worms from the same geographical location tended to cluster together, showing a phylogeographic pattern; nonetheless, it is unclear whether these worms are distinct subspecies. Further investigation of the taxonomic relationship between worms necessitates the collection of more worm samples from humans and NHPs all over the world, as well as the use of various genetic markers.

The ITS region has been the primary focus of previous studies; however, because of its high repetition content, even alignments of closely related worm sequences would include gaps. This complicates worm phylogenetic studies. Hence it’s recommended that additional genetic markers, including mitochondrial DNA genes, be used [27, 30, 33, 35, 38, 39].

3. Life cycle, development, and diagnosis

T. trichiura eggs have a unique barrel shape and measure 50–54 lm in length and 22 lm in breadth when oviposited in the large intestine. Before hatching into infectious larvae, the eggs must spend around 3 weeks in the soil at the proper temperature and humidity. As a result, the optimal circumstances are shady, warm, and wet soil. Eggs will not grow in direct sunlight and will perish if the temperature falls below 9 degrees Celsius or rises beyond 52 degrees Celsius. It is unknown what happens to the larvae in the first 5–10 days after they are consumed by humans (Figure 2). The larvae first enter the duodenum, where they stay for about a week before reentering the intestinal lumen and moving to the caecum, where they burrow into the mucosal surface via their anterior ends, according to most parasitology textbooks. However, there are contradictory findings from animal research and no human studies of the duodenal phase [40]. After hatching in the duodenum, T. vulpis larvae have been shown to develop in the caecum, piercing the mucosal epithelium and re-emerging into the lumen 8–10 days later. The major evidence for this approach comes from serial necropsies of diseased dogs performed for up to 10 days [41]. A dose of this magnitude could have stimulated migration to abnormal locations. Due to insufficient histological monitoring of the caecal mucosa over the course of 10 days, it is possible that all larvae identified there first entered the mucosa.

Figure 2.

The classification of Trichuris.

There needs to be more investigation into whether or not the duodenum phase of Trichuris spp. is an experimental artifact or an actual stage in the life cycle. Investigations using pigs infected with physiological doses of T. suis eggs may serve as the most accurate model for human infection and provide valuable background for future studies on humans. Adult T. trichiura appears 30–90 days after infection, and after mating, the females start laying eggs. All researchers agree that it is common to find adult worms in the epithelium lining the caecum and colon. In severe infections, worms may also be found in other parts of the gastrointestinal tract, including the appendix, rectum, and distal ileum. Like a whip, an adult worm’s body is divided between a thicker, more rounded section at the back (the handle) and a thinner, more tapered section up front (the lash). The length of an adult worm is between 3 and 5 centimeters, with females being somewhat longer. Laboratory investigations of T. muris have revealed that the worm’s anterior segment is ensconced in a syncytium (or mass of cytoplasm) generated from enterocytes [42]. It appears that the parasite is using its anterior stylet to burrow inside this tube.

Cytolytic enzymes are secreted from the mouth and the bacillary band on the ventral cuticle. This thicker rear end stretches into the caecal lumen, making mating and oviposition much easier. If the worms are able to penetrate the basement membranes of the enterocytes, they will be able to ingest not only the syncytium but also the erythrocytes, leucocytes, mucosaluids, and cells that are present in the gastrointestinal tract [43]. The Kato-Katz thick smear is the gold standard for this purpose; it is used in field surveys to identify hookworm and A. lumbricoides and to assess the degree of infection in eggs per gramme of feces (EPG) [44]. Some hospital-based researchers have used anoscopy to see adult worms in the rectum to diagnose severe trichuriasis, as the worm population extends all the way down to the lower colon in cases of severe trichuriasis [45]. In extreme cases, the worm population can extend as far down the lower colon as the rectum. Hence some hospital-based researchers have used anoscopy to detect adult worms in the rectum to diagnose severe trichuriasis [46]. A total of 187 people of varying ages in a St. Lucian village and 120 schoolchildren in the Tanga region of Tanzania were used for the study. Anti-T. trichiura salivary IgG responses were higher in children with active Trichuris infection compared to children without infection, and the age associations of parasite-specific salivary IgG antibodies mirrored those of infection severity in the general population. This method may be used as a community-wide gauge of transmission ferocity; however, its widespread adoption will depend in part on its suitability for in-house use and per-case cost.

3.1 Zoonotic transmission

Many people believe that Trichuris trichiura is the sole causative agent of human trichuriasis; however, there is evidence of infection with additional Trichuris species in humans and of zoonotic transmission of Trichuris parasites. The dog- and wolf-infecting parasite Trichuris vulpis has been hypothesized to be transmitted to humans due to the identification of its unusually large eggs in human feces [47].

Trichuris trichiura eggs can be little or large, and females may deposit eggs that are similar in size to Trichuris vulpis eggs [47, 48]. Eleven percent of Trichuris-positive kids in Thailand were found to have Trichuris vulpis eggs in their poop when tested using molecular markers, highlighting the parasite’s zoonotic potential in the area [49]. Because Trichuris suis is more closely related to Trichuris trichiura, it is assumed that this parasite, which naturally infects pigs and can cause significant economic losses in pig production, is more likely to be transmitted to humans. Morphological analysis, however, cannot tell Trichuris trichiura eggs, larvae, and adults from Trichuris suis [25]. This means that traditional parasitological methods are useless for detecting probable cases of host–host cross-transmission. Recently, there have been endeavors to use genetic approaches to better understand Trichuris suis’s zoonotic potential. Three out of a total of 29 worms collected from people in Uganda who shared their environment with pigs were positive for Trichuris suis, as reported by Nissen et al. [14]. They sequenced the beta-tubulin gene and analyzed the ITS-2 region using PCR-RFLP. Nuclear and mitochondrial markers were not able to detect Trichuris suis in either people or pigs in rural Ecuador [50]. This genetic exchange between Trichuris trichiura and Trichuris suis was detected in two pig Trichuris samples, which had a Bheterozygous-type PCR-RFLP pattern. However, the sample size (n = 16) was too small to draw any firm conclusions on the possibility of cross-species transmission based on sequencing of the ITS region and the rrnL gene of Trichuris from pigs and humans in China [26, 51]. To assess the scope and significance of Trichuris transmission between domestic animals and humans, more sympatric sampling of Trichuris from humans, dogs, or pigs in various geographic locations, together with DNA analysis, is recommended and required. Several wild NHP species, including colobus monkeys, macaques, baboons, and chimps, have tested positive for Trichuris infections [27, 28, 29]. The aforementioned molecular studies suggest that certain Trichuris species are restricted to certain NHPs, while other Trichuris species are genetically identical to humans and could therefore spread across the two groups. This has crucial consequences for human health and wildlife conservation when NHPs and people coexist, as is increasingly the case as humans encroach onto pristine ecosystems and NHPs gain access to gardens and farms in search of food.

3.2 Anthelmintic resistance

By 2020, the World Health Organization (WHO) hopes to provide preventative chemotherapy to 75 percent of all preschool and school-age children who are at risk. This goal can be met by regularly distributing benzimidazole anthelminthic medicines to school-aged children, such as single-dose albendazole or mebendazole (Table 2) [30, 31, 52]. Treatment of Trichuris with a single dosage of albendazole or mebendazole has a low success rate (between 30 and 70 percent) [53]. Some people are worried about the rise of drug resistance [32, 33, 54, 55]. Due to their widespread usage, anthelmintics have bred resistance in nematodes of veterinary importance, including those that cause gastrointestinal parasitism in ruminants and horses [34, 35, 36, 37]. A single nucleotide polymorphism (SNP) in the parasite beta-tubulin gene that causes phenylalanine to be substituted by tyrosine at codon 200 is a common source of benzimidazole drug resistance [38]. Resistance is sometimes also associated with nonsynonymous SNPs at codons 167 and 198 [39, 56]. An early investigation of sequence variation in the beta-tubulin gene of 72 Trichuris trichiura isolates from seven countries identified no alterations linked with benzimidazole resistance [57]. It was projected that antihelmintic resistance would arise more slowly in Trichuris trichiura than in trichostrongyles from domesticated animals due to its lower genetic diversity and smaller population size. Recently, pyrosequencing techniques have been developed to detect nonsynonymous SNPs at codons 167, 198, and 200 in Trichuris trichiura and other soil-transmitted helminths [58, 59]. These SNPs are present naturally in whipworm populations since 2.6% of Trichuris samples from Kenyan newborns who were assumed to have not had benzimidazole treatment were homozygous for the resistance mutation at codon 200. Furthermore, the codon 200 mutation associated with resistance was present in five out of eight Trichuris trichiura egg pools collected from children treated with a single dose of albendazole [58].

Treatment	Mechanism of action	Egg reduction rate (%age)	Cure rate (%age)
Albendazole	β- Tubulin binding	64.3	32.1
Mebendazole	β- Tubulin binding	80.7	44.4
Pyrantel pamoate	L- subtype nAChR agonist	62.3	28.5
Levamisole	L- subtype nAChR agonist	41.8	23.4
Albendazole–; ivermectin	N/A	95.5	60.0

Table 2.

The drugs used in the treatment and their mechanism of action [53].

In Trichuris trichiura samples from Kenya and Haiti that were collected before and after treatment with albendazole, there was a significant increase in the homozygous resistance genotype at codon 200 of beta-tubulin, and this was associated with low rates of egg reduction [59]. It was also discovered that Trichuris from Panama had polymorphisms at codons 198 and 167. By contrast, Hansen et al. detected no SNPs in Trichuris from captive baboons, Ugandan people, wild animals, and domestic animals at beta-tubulin codons 167, 198, or 200 [60, 61]. However, 41 percent of human Trichuris samples were collected via mebendazole chemoexpulsion, which may explain why no resistance SNPs were detected. Because only worms without the resistance marker are ejected, it stands to reason that resistance markers are less common when using DNA retrieved from evicted worms. The beta-tubulin genotypes of eggs found in feces can be used to learn more about the resistant and non-resistant mother worms that lay them. More research is needed to prove that benzimidazole treatment increases the frequency of these mutations and that these SNPs are responsible for the reduced efficacy of albendazole and mebendazole in treating human trichuriasis, but existing data show that SNPs in the beta-tubulin gene are present in whipworms and are associated with anthelmintic resistance in other nematodes. The fact that the adult form of Trichuris trichiura dwells in the large intestine may explain why anthelmintics are ineffective, but it is far from the only explanation. The Trichuris trichiura worm’s front segment is embedded in the intestinal mucosa, which may contribute to poor treatment outcomes. As a result, even though the anthelmintic momentarily paralyzes the worms, the worms remain attached to the host and can recover if the therapy is stopped. Trichuris may be able to excrete the medication via P-glycoprotein-mediated transport [62], despite the fact that the drug is thought to enter the worms by passive diffusion [63].

3.3 Ancient DNA

Evidence of human Trichuris infection dating back thousands of years have been discovered through paleoparasitological studies, even in regions where the parasite is now uncommon, such as Europe and North America. Eggs of the parasitic worm Trichuris have been found in a variety of artifacts from the ancient world, including human feces, feces from other animals, coprolites, and latrines [64, 65]. Paleoparasitological research has traditionally relied on morphological analyses of parasite eggs, which only allow for genus-level identification. When working with old samples, the fundamental problem is the degradation of DNA into minute bits that are not amplifiable using traditional PCR. Recent advances in DNA extraction technology, as well as the amplification and sequencing of small species-specific amplicons, have enabled the identification of ancient DNA from parasite eggs [66, 67]. To this end, longer sequences homologous to Trichuris trichiura have been reconstructed from archeological finds in Denmark (1030 AD) and Korea (1755 AD) by focusing on tiny overlapping portions of Trichuris 18S SSUrRNA [67]. As science and technology advance, it may be possible to obtain more in-depth genomic insights from ancient parasites, shining a light on their distributions and migration patterns throughout history.

3.4 Genomics and transcriptomics

The advancement of high-throughput genomic and transcriptomic technologies has ushered in a new era in which a wholly novel technique can give extraordinary insights into parasite molecular biology [68]. The recent publication of the genomes of Trichuris trichiura, Trichuris muris, and Trichuris suis marks a major milestone in Trichuris studies [69]. Furthermore, transcriptome analysis confirmed the genomes of Trichuris suis and Trichuris muris, providing a thorough understanding of the chemicals and genes expressed by these parasites during invasion, survival, and interaction with their hosts. Trichuris trichiura has a smaller genome (75.2 MBin) and fewer genes (9650) than Trichuris suis (male: 83.6 MB; female: 87.2 MB; 14,781 genes) and Trichuris muris (85.0 MB; 11,004 genes), although many of these genes are preserved [69]. There are two sets of autosomes and one set of X and Y sex chromosomes in Trichuris muris (2n = 6), and it appears that Trichuris trichiura has the same karyotype. Numerous genes in the genomes have been predicted to play a role in parasite–host interactions and immuno-regulation (or immunological modulation) of the infected host.

There are 618 predicted excretory-secretory proteins in Trichuris suis, and while secretory proteins only make up about 4% of the gene set, they are responsible for 10% of the genes that are actually transcribed [70]. Furthermore, both Trichuris muris and Trichuris suis overexpressed proteases and protease inhibitors, showing that these molecules play an important role in host-tissue disintegration and in regulating protein activities relevant to immunomodulation [70]. Genome-guided drug development [71] uses information from genomes and transcriptomes to identify potential therapeutic compounds with high parasite specificity. Hundreds of proteins were identified as potential pharmacological targets for Trichuris suis and Trichuris trichiura. However, Foth et al. narrowed the list down to 29 top protein choices that were homologs to targets for currently available drugs [69]. Jex et al. investigated the significance of short non-coding RNAs in gene regulation, and their central role as gene regulators suggests that these RNA species could be novel therapeutic targets [70, 72].

4. Future research directions

Because of decreasing assay costs and simpler implementation of B-omic-based techniques, including genomic, transcriptomic, epigenomic, and proteomic research, novel insights into Trichuris biology are predicted in the future years. Advances have paved the path for population-level comparative investigations of whole genome sequencing [73], which have the potential to completely alter Trichuris phylogenetic and evolutionary investigations. This will lead to a much more precise understanding of distribution patterns and the discovery of new subspecies and hybridization occurrences between existing species. Since anthelmintic therapies are generally ineffective, the lack of readily available worms will continue to be a significant barrier to genetic research on Trichuris. The proteome of the non-embryonated eggs of T. trichiura as a unique source of data on prospective targets for immunodiagnostics and immunomodulators from a neglected tropical disease was investigated by Cruz et al. and a list of T. trichiura non-embryonated egg proteins (proteome and antigenic profile) was provided which can be used in future research into the pathophysiology and immunobiology of human trichuriasis, as well as the management of disorders of the human intestinal immune system [74]. A number of potential new drugs have been found thanks to the whole-genome sequencing of Trichuris trichiura, which may make worm collection less of a hassle in the future [69]. However, as the necessary input sample for comparative studies decreases fast, it is expected that widely available feces samples containing Trichuris eggs will become crucial to large-scale studies. Single cells have yielded whole genome sequences and even transcriptomes [75], which allows similar experiments on embryonated eggs containing hundreds of cells could be possible in the near future. Micromanipulation, which has allowed researchers to pick individual helminth eggs for subsequent PCR-based amplification, could be a first step [76]. While there does appear to be a pattern of infection with distinct Trichuris species infecting distinct host species, there are still a number of questions that require answering. To what extent can pathology, epidemiology, and drug susceptibility vary across Trichuris spp. that infect humans, and can numerous Trichuris spp. be found in the same area? In what ways, if any, do NHPs naturally transmit Trichuris to humans? Can Trichuris from one clade infect hosts from another clade, or are the various Trichuris species in primates host specific? These mysteries have only recently begun to be unveiled, and additional research is needed that employs multiple genetic marker manufacturers to analyze Trichuris samples from people and NHPs from sympatric regions and around the world. This will shed light on the pathways through which parasites are transmitted between these monkeys, paving the way for more effective measures of control and prevention to be put in place.

Another important topic for future study is the dissection of host–parasite interactions; this is a goal shared by the “50 Helminth Genomes project” and the “959 Nematode Genomes” initiative [77]. These genomes will shed new light on the molecular biology and evolutionary history of helminth parasites, a field that has been largely overlooked until now. The host stimulus-induced hatching of Trichuris eggs during transit through the small intestine is a poorly understood mechanism in Trichuris development. Trichuris suis eggs require a different set of stimuli for hatching than Trichuris muris eggs do, demonstrating the extreme host–parasite specificity of this phenomenon [78]. Genome and transcriptome data from the protozoan parasites Trichuris suis and Trichuris muris have improved our understanding of other mechanisms, such as the parasites’ ability to establish themselves in the host and to avoid the host immune system [69, 70]. Unpublished transcriptome data from Trichuris trichiura will also definitely contribute new insights. Exosomes are tiny microvesicles (about 30–100 nm in size) that are employed for intercellular communication in complex organisms. Interesting new research shows that parasites also make and discharge exosomes containing microRNA that can be absorbed by host cells. Intriguingly, exosomes released by the gastrointestinal worm Heligmosomoides polygyrus have been found to inhibit type 2 innate response in mice and activate certain immune genes in vitro [79]. Similarly, it was demonstrated that Trichuris suis, like other protozoa, secretes vesicles of exosome size that contain RNA, although the function of these vesicles is still a mystery [80]. Future research should define the contents of these exosomes and investigate their role in the host–parasite interaction, such as whether Trichuris uses exosomes to manipulate the host’s immune response in order to decrease inflammation and optimize its survival. Genotyping of ancient Trichuris eggs is anticipated to become more common in paleoparasitology. Because Trichuris spp. has a limited host range, genotyping a specific egg discovery has been suggested as a suitable approach to determine the host of origin, which gives paleoparasitologists a tool for studying prehistoric host–parasite interactions. In addition, investigations of historical migration patterns can benefit greatly from the information provided by genotyping Trichuris eggs. The question of how Trichuris trichiura got to the Americas is still up for grabs. The problem, however, is that Trichuris trichiura, like other STH infections, probably cannot be maintained in Arctic conditions, which is exactly what the human journey through the Beringian Land Bridge into the Americas would have required [81]. Point-of-care molecular diagnostics for human trichuriasis are on the horizon, and they may be used in tandem with other STH illnesses. It is critical that testing can be carried out in low-resource and low-cost situations common in developing countries. Loop-mediated isothermal amplification (LAMP) and its derivatives have been found to be a promising technology in early research. Strongyloides stercoralis [82] and Opisthorchis viverrine [83]. DNA has been detected using LAMP after being isolated from human feces samples. The current greatest challenge is sample preparation and how it connects to DNA extraction and detection. This has been done in one device for testing gastroenteric infections, but not for any STHs as of yet [84]. The zoonotic potential of Trichuris spp. might be addressed, and the degree and species of human infection revealed through widespread point-of-care testing of stool samples for STHs using molecular-based approaches.

5. Conclusion

In recent years, scientists have increased their knowledge of the genetics of trichuriasis and the parasite Trichuris. Their genomes have been made public for Trichuris trichiura, Trichuris suis, and Trichuris muris. Important potential mechanisms of host–parasite interaction and immunomodulation, as well as new treatment targets, have been found in this research. In research on human Trichuris trichuira isolates, beta-tubulin gene variants associated with resistance in veterinary-important nematodes have been found infrequently. Recent advances have been made in the phylogeny of Trichuris. Infections with Trichuris appear to take different forms depending on the host. Infections with Trichuris trichiura in nonhuman primates, Trichuris suis in pigs, and Trichuris vulpis in dogs have all been linked to zoonotic transmission. Future research should concentrate on several genetic marker studies of Trichuris gathered from humans, nonhuman primates, pigs, and dogs in sympatric and geographical areas in order to understand more about parasite transmission between host species. The development of sensitive molecular diagnostics that can be employed at the point of care will be supported by new technologies for monitoring the spread of anthelmintic resistance. Any advancement in these domains will be incredibly beneficial for preventing and treating this parasitic sickness.

Conflict of interest

The author(s) declare no conflict of interest.