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Strongyloides

Strongyloides is a of parasitic nematodes belonging to the family Strongyloididae within the order , comprising approximately 50 species that primarily infect the small intestines of vertebrates, including mammals, , reptiles, and amphibians. These thread-like are notable for their unique biphasic life cycle, which alternates between free-living adults in the soil and parasitic females in the host's , with the parasitic generation reproducing parthenogenetically to produce eggs that develop into either infectious filariform larvae or free-living adults. The most significant species for human health is , a soil-transmitted helminth that causes , an infection affecting an estimated 300–600 million people worldwide (as of 2024), particularly in tropical and subtropical regions with poor . occurs when filariform larvae in contaminated soil penetrate the skin, typically of the feet, migrate through the bloodstream to the lungs, and are swallowed to reach the , where they mature; autoinfection—where larvae reinfect the host internally—allows chronic infections to persist for decades, often asymptomatically, but can lead to hyperinfection syndrome in immunocompromised individuals, with mortality rates up to 90% if untreated. Another zoonotic species, S. fuelleborni, primarily affects but can cause infections in humans in parts of and . Recognized as a neglected by the , is diagnosed through stool examination for larvae or serological tests, and treated with antiparasitic drugs like . The genus's , including its compact genome and high host specificity, makes it a valuable model for studying nematode and evolution.

Taxonomy and etymology

Classification

The genus Strongyloides is classified within the kingdom Animalia, phylum Nematoda, class , order , family Strongyloididae. This placement reflects its position among the chromadorean nematodes, which are characterized by their diverse parasitic and free-living lifestyles. Phylogenetically, Strongyloides resides in the Rhabditina (clade IVa) of the , showing close relationships to other rhabditid nematodes such as genera Rhabditis, Rhabdias, and its sister genus Parastrongyloides. Molecular analyses, particularly of the small subunit (18S rRNA) , support this positioning, revealing two distinct clades within Strongyloides that do not align perfectly with traditional morphological species boundaries. These genetic studies highlight its evolutionary ties to soil-dwelling microbivores while underscoring adaptations for parasitism. Historically, the genus was formalized by Giovanni Battista Grassi in 1879, who unified several species previously described under the genus Anguillula based on shared morphological and biological traits; was designated as the . This establishment distinguished Strongyloides from superficially similar strongylid s, emphasizing its unique facultative free-living phase in the life cycle. The family Strongyloididae was subsequently recognized to accommodate these distinguishing features. Currently, approximately 50 species are recognized in the genus Strongyloides, primarily obligate gastrointestinal parasites of vertebrates, though molecular phylogenetic revisions continue to refine species delineations and uncover cryptic diversity.

Etymology

The genus name Strongyloides derives from the Greek words strongylos (round) and eidos (form or resemblance), alluding to the nematodes' slender yet rounded, thread-like body morphology. This nomenclature was established by Italian parasitologist Grassi in 1879, who recognized the parasitic and free-living stages as belonging to a single species rather than distinct entities. Prior to this, French physician Arthur Bavay had described the free-living adult and parasitic generations separately as species within the Anguillula in 1876 and 1877, based on specimens from human hosts in (modern-day ). Common names for Strongyloides species include "threadworm," emphasizing their thin, elongated appearance, and "anguillula," a diminutive form of the Latin anguilla (eel), which highlights their serpentine, eel-like shape in early observations. These terms reflect the 19th-century focus on the parasite's distinctive morphology during its initial discovery and classification in tropical regions.

Morphology and biology

Physical characteristics

Strongyloides nematodes are slender, thread-like worms characterized by their cylindrical bodies and smooth cuticles. Adult females, which are the primary reproductive form in the parasitic stage, measure approximately 2 to 3 mm in length and are about 50 to 70 µm in diameter, with a pointed and a filariform occupying roughly one-third of the body length. The parasitic females embed in the of the host's and produce eggs parthenogenetically, as males are absent in this stage. Free-living adult females are smaller, reaching up to 1.0 mm in length, with a rhabditiform and a positioned near the midpoint of the body. Males are rare and occur only in the free-living stage, measuring up to 0.75 mm long, with a ventrally curved and spicules for . This sexual underscores the predominance of parthenogenetic reproduction in females across Strongyloides species. Larval stages exhibit distinct morphologies adapted to their roles. Rhabditiform larvae (L1 and L2), which are 180 to 380 µm long, feature a short buccal , a rhabditoid comprising about one-third of the body length, and a prominent genital . In contrast, infective third-stage filariform larvae (L3) are longer, up to 600 µm, with a filariform about half the body length, a notched or forked , and no surrounding . Diagnostic features include a thin anterior end, smooth without striations prominent enough for easy visualization, and posterior phasmidial pores. Unlike hookworms, Strongyloides lacks an oral capsule, and its filariform larvae have a characteristic forked tail.

Life cycle

The life cycle of Strongyloides species is heterogonic, featuring both free-living and parasitic generations that alternate depending on environmental and host conditions. In the free-living phase, eggs deposited in the environment hatch into rhabditiform first-stage larvae (L1), which develop into free-living adults (males and females) in moist . These adults mate, and the females produce eggs that hatch into rhabditiform first-stage larvae (L1). The L1 larvae undergo further development: some molt through four stages to become free-living adults, perpetuating the cycle for a single generation, while others molt into infective third-stage filariform larvae (L3), which are capable of penetrating host tissues. Upon host contact, the infective filariform larvae (L3) initiate the parasitic phase by penetrating the skin or mucosal surfaces. These larvae migrate through the bloodstream to the lungs, where they ascend the trachea, are swallowed, and reach the . There, they mature into parthenogenetic females that embed in the intestinal mucosa and produce eggs asexually. The eggs hatch directly into rhabditiform larvae (L1) within the host's gut, which are then excreted in the feces to continue the free-living cycle or, in some cases, undergo further development internally. A distinctive feature enabling chronic infections is autoinfection, where rhabditiform larvae in the intestine molt into filariform larvae (L3) without exiting the host. These internal L3 larvae can reinvade the intestinal wall or migrate through tissues back to the , perpetuating the parasitic cycle indefinitely and allowing infections to persist for decades in immunocompetent hosts. In certain conditions or species, a homogonic variant occurs, bypassing the free-living adult stage. Here, rhabditiform L1 larvae from eggs develop directly through molts into infective filariform L3 larvae, facilitating rapid parasitic transmission without an environmental phase. Free-living adults live 2–4 days, with the external cycle completing in up to 3 weeks under optimal conditions (e.g., 20–28°C and high moisture), while the parasitic phase can last from weeks to over 60 years via autoinfection mechanisms.

Species diversity

Species infecting humans

The primary species of Strongyloides infecting humans is S. stercoralis, the type species of the genus, which has a in tropical and subtropical regions and is the causative agent of . This soil-transmitted helminth is estimated to infect around 600 million people globally, with prevalence rates varying from 1.4% in to 7.8% in based on recent surveys. Although primarily anthropophilic, S. stercoralis exhibits zoonotic potential, with transmission occurring between humans, dogs, and non-human , and it can lead to rare but severe hyperinfection syndromes in immunocompromised individuals. Genetic analyses of S. stercoralis reveal significant diversity, including distinct multilocus genotypes such as A (associated with human and infections) and B (more dog-specific), alongside novel haplotypes that highlight geographic variation and historical events. This diversity, evidenced by over 15,000 single nucleotide polymorphisms across sampled populations, has implications for transmission dynamics. A second species infecting humans is S. fuelleborni, which encompasses subspecies such as S. f. fuelleborni (found in and ) and S. f. kellyi (endemic to ), both of which are neglected causes of human . Unlike S. stercoralis, S. fuelleborni is predominantly zoonotic, spilling over from non-human primates to humans via skin penetration by filariform larvae, though evidence of limited interhuman transmission exists. Parasitic females reproduce parthenogenetically in the human , shedding larvated eggs in feces rather than rhabditiform larvae. In , infections with Strongyloides fuelleborni (including those historically attributed to S. f. kellyi) are particularly significant among infants. Historical reports indicate prevalence reaching up to 60% in the first year of life, with detections as early as 18 days of age, and suggest potential transmammary transmission, though recent studies have not detected larvae in and transmission remains unconfirmed. Recent phylogenetic analyses using markers like cox1 and 18S rRNA indicate that many such infections are due to S. f. fuelleborni rather than S. f. kellyi, which appears rare, confirming S. f. kellyi as part of the clade of S. f. fuelleborni, genetically distinct from S. stercoralis. Overall human prevalence remains underreported but is increasing in recognition across , , and .

Species infecting animals

The genus Strongyloides encompasses approximately 50 species of parasitic nematodes that primarily infect vertebrates, with the majority exhibiting strict host specificity, though some demonstrate broader compatibility across related hosts. These animal-infecting species play significant roles in , often targeting specific taxa and contributing to health challenges in and populations. Among ruminants, Strongyloides papillosus is a prominent infecting , sheep, and worldwide, residing in the and known to induce particularly in young animals. This parasite has a global distribution in domesticated and wild ruminants, with prevalence varying by region and host age. In equines, Strongyloides westeri serves as the primary intestinal threadworm, mainly affecting and donkeys, with concentrated in foals up to several months of age. It inhabits the proximal and is prevalent in warm, humid environments conducive to larval development. Other mammalian hosts harbor distinct species, such as Strongyloides procyonis in raccoons (Procyon lotor), where it is a common intestinal parasite with notable prevalence in wild populations. Strongyloides dasypodis specifically infects armadillos ( novemcinctus), targeting the in these xenarthrans. In pigs, Strongyloides ransomi is the key species, primarily affecting piglets through transmammary or environmental transmission. Non-mammalian vertebrates also host Strongyloides species, including Strongyloides ardeae in birds such as (Ardea herodias), where it occupies the . In reptiles, Strongyloides serpentis and Strongyloides gulae infect , with S. serpentis found in the intestine of various colubrids and S. gulae in the of multiple snake species. Among primates, Strongyloides cebus parasitizes , such as capuchins (Cebus spp.) and woolly monkeys (Lagothrix cana), often leading to intestinal infections in captive and wild settings.

Pathogenicity

Disease in humans

Strongyloidiasis, the disease caused by infection with in humans, typically begins with acute symptoms following larval penetration of , leading to a pruritic known as ground itch at the site of entry. As larvae migrate through the bloodstream to the lungs, they induce a , wheezing, and resembling Loeffler's , often accompanied by transient pulmonary infiltrates and . Upon reaching the , larvae cause , , and diarrhea, with rhabditiform larvae detectable in stool samples. In the chronic phase, infections often persist asymptomatically for years due to the parasite's unique autoinfection cycle, where rhabditiform larvae in the intestines develop into infective filariform larvae that reinvade the host mucosa or perianal skin. Symptomatic cases may present with mild, intermittent gastrointestinal issues such as epigastric pain, bloating, alternating with constipation, and , alongside dermatological manifestations like urticaria or the fast-moving larva currens rash. is common but variable in this stage. Hyperinfection syndrome arises in immunocompromised individuals, such as those receiving corticosteroids, with , or undergoing , where suppressed allows massive larval proliferation and dissemination beyond the gut and lungs. This leads to severe complications including from gram-negative bacteremia (e.g., ), (ARDS), , and multi-organ failure, with larvae invading distant sites like the or . Mortality rates in hyperinfection cases exceed 80%, often approaching 100% in disseminated forms without prompt intervention. Infections with Strongyloides fuelleborni, particularly subspecies kellyi, cause similar symptoms to S. stercoralis but are more frequently associated with pulmonary involvement in infants, especially in . Heavy infections manifest as swollen belly syndrome, characterized by , , respiratory distress, and due to intestinal villus atrophy and , leading to high infant mortality rates of up to 8% in affected villages prior to treatment. Pathophysiologically, Strongyloides larvae invade the intestinal mucosa, causing ulcerations, inflammation, and crypt in the duodenum and , which disrupts nutrient absorption and elicits a Th2 . This response features peripheral and elevated serum IgE levels in 38-59% of cases, promoting larval expulsion but also contributing to allergic symptoms like pruritus and wheezing during migration. In hyperinfection, mucosal barrier breakdown facilitates bacterial translocation, exacerbating and .

Disease in animals

In ruminants, Strongyloides papillosus primarily affects young calves and , causing hemorrhagic , , and due to intestinal damage from larval and adult worms. Heavy infections can lead to hyperinfection syndromes, including sudden cardiac death from larval invasion of the heart and lungs, as observed in outbreaks affecting over 150 weaned dairy calves in , over 50 in , USA, and 150 in , where affected animals exhibited weakness, , and . These cases are exacerbated by high stocking densities and poor management, though the parasite is often considered of minor concern at low levels. In equines, Strongyloides westeri infects foals up to about four months of age, typically via transmammary transmission from mares, resulting in , , acute , and from small intestinal and villous . High egg counts exceeding 2000 eggs per gram of correlate with clinical signs, but infections are generally self-limiting and sporadic, with below 10% in young horses. In pigs, Strongyloides ransomi causes nodular in piglets through prenatal and transmammary transmission, leading to anorexia, , , growth retardation, and intestinal nodules from chronic inflammation. Severe experimental can result in up to 30% mortality, though subclinical predominate under modern husbandry practices with low prevalence rates of 2-3.3%. Among wildlife, Strongyloides procyonis infections in raccoons are typically asymptomatic, though heavy larval burdens may cause mild gastroenteritis without significant clinical impact. Similarly, S. dasypodis in armadillos is often incidental and detected postmortem without associated disease syndromes. Zoonotic risks arise from potential spillover of Strongyloides fuelleborni from nonhuman primates, such as macaques and vervet monkeys, where human infections have been documented in Africa and Asia, occasionally causing mild intestinal symptoms. Rare reports suggest S. stercoralis transmission from dogs or cats to humans, though molecular evidence indicates host-specific strains with limited cross-infection potential. In birds and snakes, Strongyloides spp. can induce respiratory issues through larval migration to the lungs, manifesting as distress, anorexia, and pneumonia in colubrid snakes, while intestinal involvement leads to diarrhea and weight loss in both groups.

Epidemiology and transmission

Global distribution

Strongyloides stercoralis, the primary species infecting humans, is endemic in tropical and subtropical regions worldwide, including parts of Asia, sub-Saharan Africa, Latin America, the Caribbean, and Oceania, but is notably absent in colder climates such as northern Europe and high-altitude areas. The parasite's global burden is estimated at 300–600 million infections, with the highest prevalence in Southeast Asia, Africa, and the Western Pacific regions, which account for over 75% of cases. Additionally, approximately 2.6 billion people are at risk of infection due to suitable environmental conditions in these areas. The 2024 WHO guideline on strongyloidiasis recommends mass drug administration with ivermectin in endemic areas with prevalence ≥5%. Strongyloides fuelleborni, another human-infecting species, has a more restricted distribution, primarily in Central and and , often linked to reservoirs in forested regions. Among animal species, S. papillosus is globally distributed in , particularly ruminants like , sheep, and , with widespread occurrence in both tropical and temperate farming areas. In contrast, S. westeri predominantly affects young horses in temperate regions, such as parts of and , where breeding farms are common. infections, exemplified by S. procyonis in raccoons, are localized mainly to . The distribution of Strongyloides species is heavily influenced by environmental factors, with warm, moist soils favoring the and of free-living larval stages, thereby promoting in humid tropical and subtropical zones. prevalence is further exacerbated by socioeconomic conditions, including and inadequate , which facilitate in endemic areas. Recent trends show increasing cases in non-endemic regions among migrants and refugees from high-prevalence countries, highlighting the role of human mobility in expanding the parasite's footprint.

Modes of transmission

The primary mode of transmission for Strongyloides species, particularly S. stercoralis in humans, occurs through penetration of the by infective third-stage filariform (L3) larvae present in contaminated with containing rhabditiform larvae. These larvae actively seek out and invade exposed , such as bare feet or hands, facilitating entry into the host's bloodstream and initiating to the lungs and intestines. Oral ingestion represents a rarer transmission route, potentially occurring through consumption of contaminated water, food, or via (soil-eating behavior), which can introduce larvae directly into the . This pathway is less efficient than skin penetration and is more commonly associated with poor or cultural practices involving soil contact. Zoonotic transmission from animal reservoirs to humans has been documented, primarily involving S. stercoralis from dogs and nonhuman , where shared environments enable larval . Evidence supports bidirectional between humans and dogs in endemic areas, though (e.g., transplacental or transmammary) remains unconfirmed in humans despite observations in models. A unique feature of Strongyloides is autoinfection, where rhabditiform larvae in the host's intestines develop into filariform larvae that penetrate the intestinal mucosa or perianal skin, re-entering the circulation and perpetuating the without external environmental exposure. This internal recycling mechanism allows chronic, asymptomatic infections lasting decades and prevents natural clearance by the host . Filariform larvae exhibit limited environmental survival, remaining viable for up to three weeks in moist under optimal conditions of 20–30°C and high humidity, during which they can develop from free-living stages. Survival is significantly reduced by dryness, extreme temperatures, or (UV) exposure, which disrupt larval and , thereby limiting transmission potential in arid or sanitized environments.

Diagnosis, treatment, and prevention

Diagnostic approaches

Diagnosis of Strongyloides stercoralis infection primarily relies on laboratory methods to detect larvae, antibodies, or parasite DNA, as clinical symptoms alone are nonspecific. The gold standard remains parasitological examination of stool samples, which identifies rhabditiform larvae, though intermittent shedding necessitates multiple specimens—often up to seven—for adequate . Specialized techniques enhance detection, including the Baermann concentration , culture, and plate cultures, which can increase yield fourfold compared to direct smears or formal-ether concentration techniques. Duodenal aspirates or biopsies may also reveal larvae in gastric crypts or infiltration, offering higher than stool in some cases, particularly for immunocompromised patients. Serological tests, such as enzyme-linked immunosorbent assay () detecting anti-Strongyloides IgG, provide high sensitivity (70–95%) for chronic infections and are useful when parasitological methods fail, but they exhibit with other helminths like filariae, schistosomes, and . More specific assays, including those using recombinant antigens like NIE in immunoprecipitation system (LIPS) or , achieve specificities up to 100% with minimal (0–11.3%), though persistent antibodies post-treatment can indicate historical rather than active infection. The Centers for Disease Control and Prevention (CDC) offers reference serologic testing to confirm equivocal results. Molecular methods, particularly (PCR) targeting genes such as 18S rRNA or cox1 on stool or duodenal aspirates, offer high specificity (93–95%) and are especially valuable for detecting low-burden or hyperinfection cases, with real-time PCR sensitivities ranging from 64–72% against composite references as of 2024. These assays address limitations of microscopy but face challenges from PCR inhibitors in stool and irregular larval output, requiring optimization for routine use. Emerging molecular tools, such as species-specific PCR assays developed in 2025, enable differentiation between S. stercoralis and S. fuelleborni, enhancing surveillance in zoonotic contexts. The (WHO) notes PCR as more efficient than traditional stool culture, though no standardized diagnostic protocol exists. In cases of complications like hyperinfection syndrome, imaging such as or can visualize worms or larvae, while peripheral supports suspicion but is not diagnostic. Key challenges include low sensitivity of parasitological tests (often <50% in light infections), serologic , and the need to distinguish Strongyloides larvae from those of hookworms based on , such as the prominent genital in rhabditiform stages. Overall, combining methods—e.g., with —improves accuracy in endemic or high-risk settings.

Therapeutic options

The primary treatment for chronic strongyloidiasis in humans is , administered orally at a dose of 200 μg/kg as a single dose or repeated for 1–2 days, achieving cure rates exceeding 90% in most cases. Alternative options include at 400 mg twice daily for 3–7 days, though it demonstrates lower efficacy, with cure rates around 45–86% depending on the regimen and population. Thiabendazole, historically used at 25 mg/kg twice daily for 2–3 days, has comparable efficacy to but is associated with more frequent side effects such as gastrointestinal upset and vertigo, and it has been largely discontinued in favor of . Emerging treatments include emodepside, an investigational that showed high efficacy in a 2025 phase 2 trial, with cure rates up to 96% at doses of 15–30 mg, positioning it as a promising alternative to due to its broad-spectrum activity and safety profile. In cases of hyperinfection or disseminated , particularly in immunocompromised patients, treatment involves higher-dose oral (200 μg/kg daily) continued until stool or sputum examinations are negative for larvae for at least two weeks; rectal or may be used if oral intake is not possible, and broad-spectrum antibiotics are added to address secondary bacterial infections due to larval migration through the intestinal wall. Reducing or discontinuing immunosuppressive therapy is also critical to improve outcomes. For animal infections, similar anthelmintics are employed, with at 200 μg/kg administered every four days for three to four doses or at 50 mg/kg daily for 7–14 days showing high efficacy against Strongyloides species in dogs and other hosts. Ivermectin resistance in Strongyloides is rare, with isolated reports of treatment failures attributed to high parasite burdens or reinfection rather than true , necessitating post-treatment via serial examinations 2–4 weeks after to confirm parasitological cure.

Preventive measures

Preventing Strongyloides transmission requires multifaceted strategies at individual, community, and global levels, focusing on interrupting the parasite's fecal-oral cycle through . At the individual level, basic practices are essential, including the use of proper to avoid direct skin contact with contaminated in endemic regions and improved fecal disposal to reduce environmental . Avoiding walking in areas with poor , such as tropical and subtropical zones where the parasite thrives, significantly lowers infection risk, as larvae penetrate the skin primarily through the feet. Community-level interventions emphasize mass drug administration () programs, particularly in high-risk populations. The recommends annual with a single dose of (200 μg/kg) for individuals aged 5 years and older in endemic areas where among school-aged children is ≥5% as part of neglected control efforts, which has demonstrated substantial reductions in Strongyloides . Studies in regions like and have shown that ivermectin-based , often combined with other anthelmintics, effectively targets Strongyloides alongside soil-transmitted helminths, achieving long-term decreases of up to 50% in treated communities. campaigns promoting , such as handwashing and safe water use in tropical settings, further support these efforts, while routine screening for immigrants and refugees from endemic zones helps prevent importation and hyperinfection in vulnerable hosts. Veterinary measures are crucial to curb zoonotic potential, as Strongyloides species can infect animals like , , and , potentially serving as reservoirs. Regular of companion animals and using or , combined with protocols for , reduces animal-to-human transmission risks. Environmental management in veterinary settings, including prompt feces removal and disinfection of kennels or stables, prevents larval persistence in . Despite these approaches, challenges persist in fully controlling Strongyloides spread. is expanding suitable habitats for the parasite by warming temperatures and altering patterns, potentially increasing distribution into previously non-endemic temperate areas. Incomplete coverage in remote or underserved communities further hinders progress, underscoring the need for integrated and resource allocation.

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