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Strongyloidiasis

Strongyloidiasis is a parasitic disease caused by infection with the soil-transmitted helminth Strongyloides stercoralis, a nematode that penetrates the skin of humans, typically through contact with contaminated soil, and migrates to the small intestine where it can establish chronic infection via its unique autoinfection mechanism.^[1] This allows the parasite to persist for decades in the host without external reinfection, leading to a spectrum of clinical manifestations from asymptomatic carriage to life-threatening hyperinfection syndrome, particularly in immunocompromised individuals.^[2] Globally, strongyloidiasis affects an estimated 30–100 million people, predominantly in tropical and subtropical regions of Southeast Asia, sub-Saharan Africa, Latin America, and the Pacific Islands, though underdiagnosis means the true burden may be higher, with some studies suggesting up to 600 million infections.^[3] The infection is more prevalent in areas with poor sanitation and where people walk barefoot on fecally contaminated soil, including rural communities, agricultural workers, and migrants from endemic zones.^[4] In non-endemic areas like the United States, cases occur among immigrants, travelers, or veterans from affected regions, and it remains a neglected tropical disease without a dedicated global control program.^[3] Most infections are asymptomatic or cause mild, intermittent gastrointestinal symptoms such as abdominal pain, bloating, diarrhea, or constipation, alongside possible respiratory issues like cough or skin rashes including larva currens—a fast-moving urticarial eruption.^[5] However, in about 75% of chronic cases, peripheral eosinophilia is observed, serving as a diagnostic clue.^[2] Severe forms, known as hyperinfection or disseminated strongyloidiasis, arise when immunosuppression—often from corticosteroids, HIV, or organ transplantation—triggers massive larval dissemination to organs like the lungs, brain, and bloodstream, resulting in complications such as respiratory failure, bacterial sepsis, or meningitis, with mortality rates exceeding 80% if untreated.^[2] Diagnosis relies on detecting larvae in stool samples via microscopy, though multiple serial examinations are needed due to intermittent shedding; serological tests like enzyme immunoassays offer higher sensitivity (up to 96%) but may cross-react with other helminths.^[1] Molecular methods such as PCR are increasingly used for confirmation.^[1] Treatment is primarily with oral ivermectin at 200 µg/kg for 1–2 days in uncomplicated cases, achieving cure rates over 90%, while albendazole serves as an alternative; in hyperinfection, prolonged daily dosing is required until larvae are cleared.^[6] Prevention focuses on avoiding skin contact with contaminated soil by wearing shoes and improving sanitation to prevent soil contamination and break the transmission cycle, with screening recommended for at-risk populations before immunosuppressive therapy.^[4] Despite its potential severity, strongyloidiasis remains underrecognized, emphasizing the need for heightened awareness in clinical practice, especially amid rising global migration and immunosuppression.^[3]

Etiology and Pathogenesis

Causative Agent

Strongyloides stercoralis is a soil-transmitted helminth belonging to the family Strongyloididae, classified as a small, thin nematode parasite primarily affecting humans. Adult parasitic females measure 2.0 to 3.0 mm in length and are slender in body form, while free-living adult males, which are rare in human infections, reach up to 0.75 mm. The parasite's morphology includes rhabditiform larvae (180–380 µm long) with a rhabditoid esophagus comprising about one-third of the body length and a prominent genital primordium, and filariform larvae (infective stage, up to 600 µm) distinguished by a notched tail and a 1:1 ratio of esophagus to intestine length.^[1] Although Strongyloides stercoralis is the predominant species causing human strongyloidiasis, other congeners such as the zoonotic Strongyloides fuelleborni can occasionally infect humans, particularly in Africa and Papua New Guinea, but are far less common and typically associated with primate hosts. The S. stercoralis genome is compact at approximately 43 Mb. Transcriptome analyses of infective third-stage larvae (L3i) have assembled approximately 11,250 contigs encoding over 8,000 putative proteins, many of which are homologs to those in related nematodes like Caenorhabditis elegans (42%) and Strongyloides ratti (48%). Notably, the transcriptome of infective larvae (L3i) expresses a high proportion of excretory/secretory (ES) proteins (about 15%), including galectins, heat shock proteins (HSPs), and proteases such as cathepsins and metalloproteinases, which facilitate immune modulation by inhibiting host cytokine signaling, suppressing T-cell proliferation, and detoxifying reactive oxygen species. Improved genome assemblies using long-read sequencing have been reported as of 2023.^[1]^[7]^[8]^[9] These antigenic features, including stage-specific ES products like tropomyosin and immunodominant metalloproteases (e.g., strongylastacin), enable immune evasion through mechanisms such as induction of regulatory T and B cells that produce IL-10, thereby dampening Th2 responses and promoting chronic persistence. The parasite's capacity for autoinfection—wherein rhabditiform larvae within the host transform into filariform larvae that reinvade the intestinal mucosa or perianal skin—allows for lifelong infection without external re-exposure, a trait uniquely supported by its parthenogenetic reproduction in the human host.^[10]^[7]^[1]

Life Cycle

The life cycle of Strongyloides stercoralis, the causative agent of strongyloidiasis, is unique among soil-transmitted helminths due to its alternation between free-living and parasitic phases, as well as its capacity for autoinfection, which enables chronic infections without external reinfection.^[1] Rhabditiform larvae (L1 stage), approximately 200–300 µm in length with a short buccal cavity, are released into the host's feces following egg production by parthenogenetic females in the intestinal mucosa.^[1] Once excreted into the environment, these larvae can develop in one of two ways: directly into infective filariform larvae (L3 stage, up to 600 µm long with a notched tail) or into free-living adult males (up to 0.75 mm) and females (up to 1.0 mm) that mate and lay eggs, which hatch into additional rhabditiform larvae that then mature into filariform larvae.^[1]^[11] The free-living phase occurs in warm, moist soil, typically under optimal conditions of 20–28°C and high humidity, where filariform larvae can survive for up to two weeks and free-living adults for 2–4 days.^[11] This environmental dependence favors transmission in tropical and subtropical regions with poor sanitation, though the larvae's limited viability underscores the parasite's reliance on close proximity to human hosts.^[1] In contrast to many other nematodes, such as hookworms, S. stercoralis requires no intermediate host and features only a single generation of free-living adults, simplifying its external cycle while enhancing its adaptability through the parasitic route.^[11] Upon penetrating human skin, filariform larvae enter the bloodstream or lymphatic system and migrate to the lungs, where they are coughed up, swallowed, and reach the small intestine.^[1] There, they molt twice to become adult parthenogenetic females (2.0–3.0 mm long), which embed in the intestinal submucosa and produce eggs parthenogenetically; these eggs hatch into rhabditiform larvae that migrate into the intestinal lumen.^[1] A hallmark of the cycle is the autoinfection mechanism, where some rhabditiform larvae in the gut convert directly to filariform larvae without exiting the host; these penetrate the intestinal mucosa or perianal skin, re-entering the circulation to perpetuate infection endogenously and potentially leading to hyperinfection in immunocompromised individuals.^[1]^[11] This internal reinfection cycle distinguishes S. stercoralis from other helminths lacking such a facultative mechanism, allowing persistent infections lasting decades.^[11]

Transmission and Risk Factors

Modes of Transmission

The primary mode of transmission for Strongyloidiasis involves percutaneous penetration of the skin by infective third-stage filariform larvae of Strongyloides stercoralis, typically occurring when individuals come into contact with contaminated soil, such as through walking barefoot in endemic areas with warm, moist conditions conducive to larval survival.^[1]^[3] This route is facilitated by the parasite's free-living stage in the environment, where larvae develop from eggs passed in human feces.^[12] Soil contamination arises from the deposition of feces containing rhabditiform larvae, which hatch and mature into filariform larvae in soil, thereby perpetuating transmission cycles in regions with inadequate sanitation and hygiene practices.^[3]^[1] Rare alternative routes include ingestion of filariform larvae through contaminated food or water, though this is far less common than skin penetration.^[12] Vertical transmission from mother to child has been documented, particularly for S. fuelleborni subspecies via breastfeeding, but it is not established for S. stercoralis in humans.^[1] There is no direct person-to-person spread under normal circumstances, except in exceptional cases of organ transplantation from an infected donor, which can lead to donor-derived infection in recipients.^[13]^[12]

At-Risk Populations

Strongyloidiasis predominantly affects populations in tropical and subtropical regions, including sub-Saharan Africa, Southeast Asia, Latin America, and the Pacific islands, where poor sanitation and hygiene facilitate ongoing transmission. The highest burdens occur in rural and socioeconomically disadvantaged communities in these areas. Certain occupational groups face elevated risks due to frequent soil contact, such as farmers, agricultural workers, and miners in endemic zones. For instance, individuals engaged in farming or coal mining activities, particularly in regions with inadequate protective measures, exhibit higher infection rates owing to repeated exposure to contaminated environments. Migrant and refugee populations from endemic areas represent a significant at-risk group, with infection rates often exceeding 75% among certain refugee cohorts resettling in non-endemic countries.^[14] Veterans and travelers who have resided in these regions also carry latent infections that may persist for decades. ^[15] Immunocompromised individuals are particularly vulnerable to severe outcomes, including hyperinfection syndrome, which carries a case-fatality rate over 60%. This includes patients with HIV/AIDS, though observational data indicate lower rates of hyperinfection in this group compared to others; recipients of solid organ transplants; and those on long-term immunosuppressive therapies such as corticosteroids. Notably, the widespread use of glucocorticoids in COVID-19 management has heightened risks. ^[6]

Clinical Features

Uncomplicated Infection

In uncomplicated strongyloidiasis, the acute phase typically occurs shortly after larval penetration of the skin and is characterized by a localized pruritic, erythematous rash at the site of entry.^[1] As larvae migrate through the bloodstream to the lungs, patients may experience transient pulmonary symptoms, including dry cough, dyspnea, wheezing, and occasionally Loeffler-like syndrome with migratory pulmonary infiltrates.^[12] A distinctive cutaneous manifestation during this phase is larva currens, a rapidly advancing (up to 10 cm per hour), pruritic, serpiginous urticarial rash often appearing on the trunk, thighs, buttocks, or perineum, resulting from dermal migration of larvae.^[1]^[16] Upon reaching the gastrointestinal tract, larvae mature into adults, leading to the chronic phase, which is often asymptomatic in immunocompetent individuals and may go undetected for years.^[12] When symptoms occur, they are typically intermittent and mild, involving gastrointestinal disturbances such as abdominal pain, diarrhea (often watery or alternating with constipation), nausea, anorexia, and bloating.^[1]^[17] Peripheral eosinophilia is a frequent laboratory finding in chronic uncomplicated infection, observed in up to 75% of cases, often mild or with increased total IgE levels, though it may diminish or fluctuate in long-term carriage.^[16]^[17] In some cases, chronic infection can cause malabsorption of nutrients, potentially resulting in weight loss, vitamin deficiencies, or protein-losing enteropathy, though these are less common in otherwise healthy hosts.^[16]^[12] Due to the parasite's unique autoinfection cycle, where rhabditiform larvae in the intestines develop into infective filariform larvae that reinvade the host's tissues, uncomplicated infections can persist asymptomatically for decades in immunocompetent persons.^[12]^[1]

Hyperinfection and Disseminated Disease

Hyperinfection syndrome and disseminated strongyloidiasis represent the most severe manifestations of Strongyloides stercoralis infection, occurring almost exclusively in individuals with impaired immunity and often arising from underlying chronic infection. These conditions involve an unchecked acceleration of the parasite's autoinfection cycle, leading to massive larval proliferation and systemic spread, which can result in life-threatening complications. Unlike uncomplicated cases, these forms are characterized by rapid deterioration and high lethality, particularly in the presence of immunosuppression. Unlike in uncomplicated infection, peripheral eosinophilia is typically absent or suppressed in hyperinfection and disseminated disease due to the underlying immunosuppression.^[18] The primary triggers for hyperinfection and disseminated disease are various forms of immunosuppression, including high-dose corticosteroids, chemotherapy for malignancies, and co-infection with human T-lymphotropic virus type 1 (HTLV-1), which impairs Th2-mediated immune responses against the parasite. Other risk factors include solid organ or bone marrow transplantation, hematologic malignancies such as leukemia or lymphoma, and conditions like HIV/AIDS in advanced stages, all of which disrupt the host's ability to control larval replication. In hyperinfection syndrome, this leads to an overwhelming increase in larval burden within the gastrointestinal and pulmonary tracts, manifesting as severe watery diarrhea, abdominal pain, and respiratory distress including pneumonitis or acute respiratory failure; additionally, larval migration facilitates bacterial translocation from the gut, causing polymicrobial sepsis with enteric pathogens like Escherichia coli or Klebsiella species.^[2]^[19]^[18] Disseminated strongyloidiasis extends beyond hyperinfection by involving larval invasion of extraintestinal sites outside the parasite's normal migratory pathway, such as the central nervous system (e.g., meninges causing aseptic meningitis), heart, liver, kidneys, and endocrine organs, resulting in widespread multi-organ dysfunction and failure. This systemic dissemination often culminates in complications like disseminated intravascular coagulation, renal failure, and shock, with reported mortality rates reaching up to 85% even with intervention, primarily due to delayed diagnosis and overwhelming parasitic load.^[19]^[18] Post-2020, the global use of corticosteroids like dexamethasone for severe COVID-19 treatment has heightened awareness of strongyloidiasis risks, as these agents can rapidly precipitate hyperinfection in undiagnosed carriers from endemic areas, with cases of fatal dissemination reported despite short-term therapy. The World Health Organization highlighted this concern in 2020, noting that such immunosuppression in the context of the pandemic could exacerbate parasitic reactivation, underscoring the need for preemptive screening in at-risk populations.^[20]^[21]

Diagnosis

Clinical Assessment

Clinical assessment of strongyloidiasis begins with a detailed patient history to identify risk factors and potential exposure. Clinicians should inquire about travel or residence in endemic regions, such as tropical and subtropical areas of sub-Saharan Africa, Southeast Asia, and Latin America, where contact with contaminated soil through barefoot walking or poor sanitation is common.^[2] Immunosuppression status is critical to evaluate, including use of corticosteroids, HIV infection, HTLV-1 seropositivity, or other conditions like malignancy that impair immune function, as these increase the risk of severe disease.^[22] Patterns of eosinophilia, often noted incidentally in prior blood work, may suggest chronic infection, though this finding can be absent in immunocompromised individuals.^[12] Physical examination may reveal characteristic findings, particularly in symptomatic cases. A pathognomonic rash known as larva currens, presenting as a pruritic, linear or serpiginous urticarial eruption that migrates rapidly (5-15 cm per hour) across the trunk, buttocks, or thighs, strongly indicates active larval migration through the skin.^[22] Abdominal tenderness, often diffuse and associated with pain, bloating, or episodic diarrhea, points to gastrointestinal involvement from larval penetration of the intestinal mucosa.^[2] Respiratory signs such as wheezing or cough may occur due to larval transit through the lungs, mimicking asthmatic episodes.^[12] Differential diagnosis requires considering conditions that overlap with strongyloidiasis symptoms, such as other helminthiases (e.g., hookworm or ascariasis), irritable bowel syndrome (IBS), inflammatory bowel disease, or bacterial colitis for gastrointestinal complaints; asthma, pneumonia, or acute respiratory distress syndrome for pulmonary features; and drug-induced or idiopathic eosinophilia for hematologic clues.^[23] In patients with relevant history, exclusion of these mimics relies on the combination of exposure risk and specific findings like larva currens, which are uncommon in alternative diagnoses.^[22] Suspected hyperinfection syndrome demands urgent clinical assessment due to its life-threatening potential, particularly in immunosuppressed patients. Rapid evaluation for signs of sepsis, such as fever, hemodynamic instability, or disseminated rash, is essential, as hyperinfection can lead to bacterial superinfection, respiratory failure, or multiorgan involvement with case-fatality rates approaching 90% if untreated.^[2] Prompt recognition through history and exam facilitates immediate intervention to prevent progression.^[23]

Laboratory and Imaging Methods

Diagnosis of strongyloidiasis is not standardized globally.^[3] Laboratory diagnosis primarily relies on detecting Strongyloides stercoralis larvae or specific antibodies, as the infection can be chronic and low-burden, often evading routine screening.^[12] These methods are essential when clinical suspicion arises from symptoms or risk factors, including peripheral eosinophilia noted in patient history.^[2] Stool examination remains the cornerstone for confirming active infection, though its limitations necessitate complementary approaches. Stool microscopy for rhabditiform larvae is the traditional direct method, but it has low sensitivity of approximately 25-50% in single samples due to intermittent larval shedding.^[12] Sensitivity improves to up to 50% with examination of three consecutive stool samples and can reach 72% using concentration techniques like the Baermann method, which exploits larval motility to concentrate them from fecal matter.^[24] Despite these enhancements, multiple samples—sometimes up to seven—may be required for near-100% detection in low-intensity infections, making it labor-intensive and prone to false negatives.^[2] Serological tests, particularly enzyme-linked immunosorbent assay (ELISA) for anti-Strongyloides IgG antibodies, offer high sensitivity, often exceeding 90% in validated assays, though performance varies by test and population (ranging from 46% to 93.9% in recent studies); they detect past or current exposure even in light infections where parasitological methods fail and are recommended for screening at-risk groups such as immigrants and refugees from endemic areas.^[25]^[26]^[27] For instance, commercial ELISAs like the IVD Strongyloides ELISA achieve 91.2% sensitivity, while indirect fluorescent antibody tests (IFAT) reach 93.9%.^[25] However, cross-reactivity with other helminths, such as filarial nematodes, can lead to false positives, reducing specificity in endemic areas or co-infection scenarios, and serology cannot distinguish active from resolved infections.^[28] In cases of low parasite burden or negative stool exams, duodenal aspiration or biopsy provides a more invasive but targeted approach to sample the primary site of larval maturation.^[29] Techniques like the Entero-Test (string test) or direct aspiration during endoscopy yield larvae in duodenal fluid, with biopsy confirming parasites in up to 71% of histopathologically examined cases showing mucosal inflammation or larval invasion.^[30] These methods are particularly useful for immunocompromised patients but carry procedural risks and are not routinely recommended as first-line due to their invasiveness.^[31] Imaging modalities support diagnosis indirectly by revealing complications, especially in hyperinfection syndrome. Upper endoscopy may visualize duodenal mucosal changes, such as edema, erythema, or nodular lesions harboring larvae, aiding biopsy procurement.^[32] Computed tomography (CT) scans of the abdomen detect nonspecific bowel wall thickening in the small intestine, while chest CT identifies pulmonary infiltrates or nodules indicative of larval migration in disseminated disease.^[29] These findings, such as diffuse ileal wall thickening on abdominal CT, correlate with heavy larval loads but lack specificity for strongyloidiasis alone.^[33] Molecular methods, including polymerase chain reaction (PCR) targeting S. stercoralis DNA in stool, represent an emerging diagnostic tool with superior specificity over microscopy and serology, enabling detection in formalin-fixed samples and monitoring treatment response.^[1] Real-time PCR assays achieve high analytical sensitivity for copro-DNA, outperforming traditional methods in low-prevalence settings, though they require specialized equipment and are not yet widely standardized.^[34] Loop-mediated isothermal amplification (LAMP) offers a field-friendly alternative with comparable accuracy to PCR.^[1]

Management

Pharmacological Treatment

The primary pharmacological treatment for uncomplicated strongyloidiasis is ivermectin, administered orally at a dose of 200 µg/kg daily for 1 to 2 days.^[6] This regimen achieves cure rates exceeding 80%, with studies reporting up to 93% efficacy for a two-dose course given two weeks apart.^[35] Albendazole serves as an alternative when ivermectin is unavailable or contraindicated, dosed at 400 mg orally twice daily for 7 days, though it demonstrates lower efficacy of approximately 70%.^[6]^[35] In cases of hyperinfection or disseminated disease, particularly in immunocompromised patients, ivermectin treatment is prolonged to 200 µg/kg orally daily until larvae are absent from stool or sputum for at least two weeks, often requiring courses extending beyond 7 days.^[6] Concurrent broad-spectrum antibiotics are recommended to address secondary bacterial infections arising from larval migration through the intestinal wall and lungs.^[31] Relapse is common in immunocompromised individuals, such as those with HTLV-1 co-infection, where ivermectin efficacy may drop to 50% or less, necessitating repeated dosing and close monitoring.^[35]

Supportive Care and Monitoring

Supportive care for strongyloidiasis primarily focuses on managing complications in severe cases, such as hyperinfection syndrome, where the infection can lead to life-threatening dissemination and secondary bacterial infections. In hyperinfection, patients often require intensive care unit (ICU) admission due to risks of respiratory failure, septic shock, and multi-organ dysfunction. Mechanical ventilation is frequently necessary to support patients with acute respiratory distress or pneumonia caused by larval migration through the lungs, as seen in cases where invasive ventilation was weaned after antiparasitic therapy initiation. Fluid resuscitation and vasopressor support are essential to stabilize hemodynamics in distributive shock, while broad-spectrum antibiotics address concurrent bacteremia from enteric flora translocated by migrating larvae. Nutritional support plays a key role, particularly in malnourished or chronically infected individuals, to bolster immune recovery and prevent further deterioration, though specific regimens are tailored to the patient's overall status. Addressing underlying immunosuppression is a cornerstone of supportive management, as corticosteroids and other agents can exacerbate hyperinfection by promoting autoinfection cycles. Clinicians should aim to reduce or discontinue immunosuppressive therapy whenever feasible, weighing the risks against the underlying condition, such as in transplant recipients or those with autoimmune diseases. This adjustment has been shown to improve outcomes by allowing partial immune reconstitution to aid parasite clearance. Post-treatment monitoring is crucial to verify cure and detect relapse, given the potential for persistent infection despite therapy. Serial stool examinations for larvae or serologic testing for anti-Strongyloides IgG antibodies are recommended at 2-4 weeks and 6 months after treatment, with extended follow-up up to 1-2 years in high-risk cases to account for delayed serologic decline. Trends in eosinophil counts provide additional insight, as normalization often correlates with successful eradication, though persistent eosinophilia may signal ongoing infection. In hyperinfection scenarios, daily clinical surveillance, including vital signs and laboratory markers for secondary infections, is advised until stabilization. Relapse prevention emphasizes long-term vigilance, particularly in endemic regions or among immunocompromised patients. High-risk individuals, such as those from tropical areas or undergoing immunosuppression, benefit from periodic screening and follow-up in non-endemic settings to mitigate autoinfection risks. Community-level hygiene measures, including sanitation improvements, complement individual monitoring to reduce reinfection potential.

Prevention and Control

Individual Prevention Strategies

Individuals at risk of strongyloidiasis, particularly those in or traveling to endemic areas, can reduce infection risk through targeted behavioral measures. The primary mode of transmission involves percutaneous penetration of infective larvae from soil contaminated with human feces, so wearing shoes or protective footwear when walking or working in potentially contaminated soil is a key preventive strategy. This practice significantly lowers the odds of infection, as barefoot contact facilitates larval entry through the skin. Additionally, avoiding direct skin contact with untreated sewage or fecal-contaminated water during bathing or recreation helps prevent exposure to larvae in aquatic environments. Hygiene practices further support prevention by minimizing secondary transmission routes, such as fecal-oral spread in settings with poor sanitation. Regular handwashing with soap and clean water, especially after soil contact, before eating, and after using latrines, reduces the potential for ingesting larvae. Safe food preparation, including thorough washing of produce with safe water and cooking vegetables to eliminate any contaminants, addresses risks from contaminated sources, though percutaneous transmission remains predominant. For travelers or expatriates planning extended stays in endemic regions, pre-travel serological screening for Strongyloides stercoralis antibodies is recommended for those with prior residence or frequent visits to high-prevalence areas, allowing early detection and treatment to prevent chronic infection. Serology, such as enzyme-linked immunosorbent assay (ELISA), offers high sensitivity for identifying latent infections in asymptomatic individuals. In immunocompromised individuals, such as those anticipating corticosteroid therapy or organ transplantation, prophylactic treatment with ivermectin (200 μg/kg orally for 1-2 days) is advised if screening indicates exposure risk or if empirical therapy is warranted before immunosuppression begins, to avert hyperinfection syndrome. This approach has demonstrated efficacy in preventing severe dissemination in high-risk scenarios.

Public Health Interventions

Public health interventions for strongyloidiasis focus on population-level strategies to reduce transmission and disease burden in endemic areas, primarily through integrated neglected tropical disease (NTD) programs. Mass drug administration (MDA) using ivermectin is a cornerstone approach, recommended by the World Health Organization (WHO) for endemic settings where prevalence exceeds defined thresholds. In these campaigns, single-dose ivermectin (200 μg/kg orally) is administered to individuals aged 5 years and older, targeting both school-aged children and adults to interrupt transmission and lower infection rates. ^[36] Studies in endemic communities, such as rural Cambodia, have demonstrated that ivermectin MDA achieves high cure rates, exceeding 96% shortly after treatment, with sustained reductions in prevalence when repeated annually. ^[37] This strategy leverages existing MDA platforms for other NTDs like lymphatic filariasis and onchocerciasis, enhancing cost-effectiveness and coverage in resource-limited settings. ^[38] Sanitation improvements play a critical role in breaking the fecal-oral transmission cycle of Strongyloides stercoralis by preventing soil contamination with human feces. Community-wide efforts, including latrine construction and improved wastewater management, have been shown to significantly lower infection risk at the population level. For instance, in rural Cambodian villages, increasing sanitation coverage through latrine provision reduced reinfection odds by nearly 1% per percentage point increase in community access, highlighting the protective effect of collective infrastructure over individual behaviors. ^[37] The WHO emphasizes that enhanced sanitation and human waste disposal have led to near-elimination of strongyloidiasis in regions with improved infrastructure, underscoring its integration into broader environmental health initiatives. ^[3] Combining sanitation upgrades with ivermectin MDA yields synergistic benefits, as evidenced by over 85% of treated individuals remaining infection-free one year post-intervention in high-burden areas. ^[37] Surveillance for strongyloidiasis is increasingly integrated into routine health screening programs, particularly for high-risk groups such as migrants and refugees from endemic regions in sub-Saharan Africa, Southeast Asia, and Latin America. The U.S. Centers for Disease Control and Prevention (CDC) recommends serologic testing (e.g., Strongyloides IgG) and presumptive ivermectin treatment for refugees not treated overseas, with additional screening for Loa loa co-infection in those from central African countries to avoid severe adverse reactions. As of January 2025, CDC overseas presumptive treatment guidelines have been updated to include refugees from Latin America and the Caribbean, implement a screen-and-treat approach for Loa loa-endemic areas, standardize single-dose ivermectin at 200 mcg/kg orally, and discontinue presumptive albendazole during pregnancy.^[39]^[40] Systematic reviews support this approach, showing that targeted screening and treatment in migrant populations reduce morbidity and prevent hyperinfection in immunocompromised individuals. ^[41] These efforts facilitate early detection and contribute to global surveillance by monitoring prevalence trends and treatment outcomes in mobile populations. Global goals for strongyloidiasis control are embedded in the WHO's NTD Roadmap for 2021–2030, which aims to reduce the need for interventions against soil-transmitted helminths (including strongyloidiasis) by 90% and achieve elimination as a public health problem in 100 countries. ^[42] Key milestones include accelerating programmatic action through MDA expansion, cross-sectoral integration of water, sanitation, and hygiene (WASH) measures, and enhancing surveillance to track progress toward universal access to prevention and treatment. ^[42] The 2024 WHO guideline on strongyloidiasis control aligns with these targets, promoting ivermectin-based preventive chemotherapy in endemic areas to support Sustainable Development Goal 3 on health and well-being. ^[38]

Epidemiology

Global Distribution and Burden

Strongyloidiasis, caused by the soil-transmitted helminth Strongyloides stercoralis, is endemic in tropical and subtropical regions worldwide, with an estimated 300–600 million people infected globally according to the World Health Organization. A comprehensive modeling study from 2020 further refined this to approximately 613.9 million cases, corresponding to a global prevalence of 8.1%, though these figures are likely underestimates due to the high proportion of asymptomatic infections and diagnostic challenges in endemic areas. The disease's neglected status contributes to underreporting, as many cases remain undetected without routine screening. Geographic hotspots for strongyloidiasis are concentrated in areas with warm, humid climates conducive to the parasite's free-living stages, including parts of sub-Saharan Africa and Southeast Asia where prevalence often exceeds 40% in certain communities. For instance, studies in Ethiopia have reported rates up to 41.8% in semi-highland regions, while in Southeast Asia, pooled prevalence reaches 12.7% regionally but climbs to 45.9% in high-risk areas of Laos and Cambodia. In contrast, prevalence in the Americas, particularly Latin America, tends to be lower, typically ranging from 10% to 20% in endemic foci, reflecting differences in sanitation, soil conditions, and population density. The global burden of strongyloidiasis manifests primarily through chronic infections leading to malnutrition, anemia, and impaired growth, particularly in resource-limited settings, though precise disability-adjusted life years (DALYs) estimates are limited due to the disease's exclusion from many standard burden calculations. As part of soil-transmitted helminthiases, it contributes to the overall 1.38 million DALYs lost annually from these infections, with strongyloidiasis exacerbating chronic undernutrition that hinders child development and adult productivity. In agriculture-dependent economies of sub-Saharan Africa and Southeast Asia, the economic impact is significant, as infected individuals experience reduced work capacity and agricultural output, perpetuating cycles of poverty and food insecurity. Climate change poses risks for the expansion of strongyloidiasis into previously unaffected regions by altering temperature and precipitation patterns that favor the parasite's survival and transmission. Warmer, wetter conditions could extend suitable habitats northward and to higher elevations, potentially increasing the population at risk beyond the current 2.6 billion people in endemic zones.

Prevalence Trends and Risk Groups

Mass drug administration (MDA) campaigns using ivermectin have contributed to declining prevalence of strongyloidiasis in several endemic regions since the early 2010s. For instance, in a remote Australian Aboriginal community, seroprevalence dropped from 21% at baseline to 5% six months after the first ivermectin MDA round and further to 2% 18 months after the second round, demonstrating sustained reductions through community-wide interventions. Similarly, on Pemba Island, Tanzania, MDA for lymphatic filariasis led to a sharp decline in strongyloidiasis prevalence among schoolchildren from 41% in 1998 to 7% by 2013, following multiple ivermectin treatments. These examples illustrate how targeted MDA post-2010 has achieved notable reductions, often exceeding 80% in monitored populations, though rebound can occur without ongoing efforts.^[43]^[44] Despite these advances, strongyloidiasis persists at high levels in conflict-affected areas where sanitation infrastructure and control programs are disrupted. In Venezuela, amid ongoing socioeconomic crisis and conflict, prevalence exceeds 20%, highlighting challenges in maintaining intervention coverage in unstable regions. Such persistence underscores the need for resilient public health strategies in zones with limited access to diagnostics and treatment. Certain subgroups face elevated risks due to migration patterns and comorbidities. Immigrants and refugees from endemic areas represent a key vulnerable population, with screening programs implemented in countries like Australia and European nations to detect chronic infections upon arrival. For example, serological screening in Spain from 2009 to 2014 identified strongyloidiasis in a significant proportion of immigrants, informing targeted treatment. Co-infections with HIV or HTLV-1 further amplify prevalence and severity; among people living with HIV in endemic settings, strongyloidiasis rates reach up to 24.2%, while HTLV-1 co-infection increases the likelihood of hyperinfection by impairing immune responses.^[45]^[39]^[46]^[47] Post-2020, surveillance data indicate rises in hyperinfection cases, particularly linked to corticosteroid use in COVID-19 management, which can reactivate latent infections in immunocompromised individuals from endemic regions. A multicenter analysis reported that widespread steroid administration during the pandemic precipitated severe strongyloides reactivation, with multiple cases documented globally from 2020 onward. Modeling projections under WHO's 2030 targets suggest that integrating ivermectin into preventive chemotherapy in at least 96 endemic countries could avert millions of infections and reduce prevalence to below 5% in school-aged children, provided diagnostic and supply chain challenges are addressed.^[48]^[20]^[36]^[49]

History

Discovery and Early Descriptions

The nematode parasite Strongyloides stercoralis, the primary causative agent of strongyloidiasis, was first identified in 1876 by French physician Louis Normand, who detected larvae in stool samples from soldiers returning from French Cochinchina (present-day Vietnam) to the naval hospital in Toulon, France.^[50] Normand, along with Arthur Bavay, initially classified the parasite as Anguillula stercoralis, noting its association with diarrhea among the troops but not yet establishing its pathogenic role.^[51] Subsequent reports emerged in Europe during the late 1870s and 1880s, expanding recognition beyond Asia. In 1879, Italian parasitologist Giovanni Battista Grassi and colleague Corrado Parona described the parasite in fecal samples from Italian prisoners of war, formally naming the genus Strongyloides (from Greek terms meaning "round-like") and the species S. intestinalis, distinguishing it as a threadworm residing in the human intestine.^[52] These findings marked the parasite's entry into European medical literature, though early observers like Grassi initially viewed it as a benign commensal rather than a significant pathogen.^[53] Early characterizations were hampered by diagnostic challenges, particularly the morphological similarity of Strongyloides larvae to those of hookworms (Ancylostoma and Necator species), leading to frequent misidentifications in stool examinations.^[11] This confusion delayed accurate differentiation until improved microscopy techniques in the late 19th century clarified the distinct esophageal structures and life cycle stages. By the early 1900s, accumulating case reports from colonial expeditions linked Strongyloides infections predominantly to tropical and subtropical environments, where warm, moist soils facilitated larval transmission through skin penetration.^[54]

Modern Research and Guidelines

In the mid-20th century, particularly during the 1940s to 1960s, researchers built upon earlier descriptions to further elucidate the complex life cycle of Strongyloides stercoralis, highlighting its unique features such as facultative free-living stages and autoinfection mechanisms that enable chronic persistence in hosts.^[11] This period also marked a significant advancement in treatment, with thiabendazole introduced in the early 1960s as the first effective oral anthelmintic for strongyloidiasis, demonstrating cure rates of around 80-90% in initial clinical trials despite associated gastrointestinal side effects.^[55]^[56] The 1980s brought further progress with the establishment of ivermectin's efficacy against S. stercoralis, showing high parasitological cure rates exceeding 80% in early studies and positioning it as a safer alternative to thiabendazole for both uncomplicated and hyperinfection cases.^[57]^[58] By the 2000s, strongyloidiasis gained formal recognition as a neglected tropical disease (NTD) by the World Health Organization, emphasizing its underdiagnosis and potential for severe outcomes in immunocompromised individuals, which spurred inclusion in broader NTD control frameworks.^[3]^[17] In the 2010s, mass drug administration (MDA) trials using ivermectin demonstrated substantial reductions in S. stercoralis prevalence, with community-level seroprevalence dropping by up to 75% in some endemic settings after multiple rounds, though complete elimination proved challenging due to the parasite's autoinfection cycle.^[59]^[60] The COVID-19 pandemic prompted a 2020 WHO alert highlighting the risks of strongyloides hyperinfection syndrome in undiagnosed carriers receiving corticosteroids, reporting cases of dissemination and mortality in co-infected patients from endemic regions.^[61] Ongoing research into PCR-based diagnostics has improved detection sensitivity to 89-100% in stool and serum samples, enabling better surveillance and early intervention in low-burden settings.^[62]^[63] In 2024, the WHO published its first guideline on the public health control of human strongyloidiasis, recommending ivermectin-based preventive chemotherapy for at-risk populations and improved diagnostics. Current guidelines from the CDC (updated 2025) and WHO (updated 2024) recommend routine screening for strongyloidiasis among immigrants and refugees from endemic areas using serology or stool examination, followed by ivermectin treatment for positive cases to prevent chronic infection and complications in at-risk populations.^[39]^[64]^[36]

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