Helminth infections are considered neglected diseases of poverty, more prevalent in developing countries. However, these parasitic infections continue to be transmitted in areas of the United States, which is why all health-care providers need to recognize, diagnose, manage, and prevent endemic helminth infections to avoid adverse consequences on cognitive and growth development in children.After completing this article, readers should be able to: Recognize the most common helminth infections encountered in clinical practice.Understand the distribution of helminth infections based on their prevalence according to geographic distribution in the United States and globally.Describe the specific clinical manifestations caused by soil-transmitted helminths, Toxocara species, and other helminthiases of clinical significance.Identify community-based approaches for the prevention, diagnosis, and treatment of helminthic infections.Helminths (derived from the Greek Helmins, which means worms) (1) are large, multicellular parasites that can infect humans and have severe health repercussions. Helminth infections are considered by the World Health Organization (WHO) to be part of the neglected tropical diseases (NTDs), a diverse group of widespread debilitating infectious diseases that are prevalent in tropical and subtropical countries and occur in the setting of poverty impeding economic and educational development. (2)In the United States, helminthiases have propagated to some areas due to international migration; in other areas they are an endemic underrecognized public health problem affecting mainly socially disadvantaged areas. (3)(4) The importance of these infections lies in their long-term consequences on the health of children, whose cognitive and physical development can be severely affected. (5)We aimed to review the most common helminth infections that are encountered in clinical practice and provide guidance for the initial diagnostic approach.Helminths is an umbrella term for human multicellular parasites. (6) They can be classified into 2 major phyla: Nematodes (or roundworms) and Platyhelminthes (flatworms). The nematodes include soil-transmitted helminths (STHs) and filarial worms. The platyhelminthes include flukes, or trematodes (Schistosoma, Fasciola, Paragonimus), and tapeworms, or cestodes (Fig 1). Roundworms are the most common helminth infections in children in the United States of public health importance, causing significant morbidity at a young age.Nematodes (roundworms) can be classified into 3 groups based on their life cycle.Embryonated eggs are ingested from contaminated soil. They hatch and mature only in the gastrointestinal tract. This can be seen in Enterobius vermicularis and Trichuris trichiura. (7)Eggs passed in feces undergo a period of development in the soil before being ingested. The larvae migrate to the upper and lower respiratory tract and then return to the small intestine, where they develop into adult worms. This is seen in Ascaris lumbricoides in humans and in Toxocara species in animals. (7)Eggs pass via feces to the soil and hatch into larvae, which undergo further development before penetrating the human skin. They migrate to the upper and lower respiratory tract and then return to the small intestine to complete their development. Necator americanus and Ancylostoma duodenale are part of this group, along with Strongyloides stercoralis. (7)STHs, or geohelminths, are human infections by nematodes that require a period of development in the soil before they become infective. STHs are considered major NTDs occurring worldwide, and not just limited to tropical and subtropical areas.As reported by the WHO, more than 1.5 billion people are infected with STHs worldwide, mainly affecting impoverished communities. According to the Global Burden of Disease Study 2017, NTDs collectively caused 1 billion disability-adjusted life-years worldwide, with intestinal worms contributing significantly to the burden of 900 million disability-adjusted life-years. It is estimated that there were 450 million cases of ascariasis, 300 million of trichuriasis, and 200 million of hookworm worldwide in 2017. (8)(9)(10) The geographic burden of helminths varies considerably, with the most significant impact occurring in Sub-Saharan Africa and South Asia, particularly involving those aged 1 to 9 years. (9)The risk of acquiring an STH is influenced by environmental and socioeconomic factors; warm and moist soil facilitates transmission. Although more prevalent in rural areas in developing countries, some urban and suburban areas in the United States have reported a high prevalence for these infections. (11)The large increase in extreme poverty among US households since 1996 has made conditions suitable for persistence and transmission of parasites. Children experiencing 7 or more months of residential instability, food insecurity, and delayed medical care because of cost increases the risk of living in unsanitary conditions with poor waste removal and incomplete plumbing. (12) These diseases limit children from achieving their economic and educational potential, promoting the vicious cycle of poverty (Fig 2). (11)(13) In recent field surveys from 2017 and 2020, individuals living in impoverished areas in Alabama and Texas were found to have stool samples positive for N americanus (hookworm), polyparasitism, and positive serology for S stercoralis. (14)(15)Historically, the southern United States had a high prevalence of STH infection in 1914, after which the Rockefeller Sanitary Commission invested in screening and eradication programs to eliminate these infections. (11) However, the current US surveillance of STHs in the United States is unknown, with the most recent systematic review of the southern states and Appalachia from 1942 to 1982 reporting school-age children being affected by hookworms (19.6%), T trichiura (55.2%), A lumbricoides (49.4%), and S stercoralis (3.8%). (16) Reliable and recent prevalence studies are lacking, overlooking the health and economic consequences that these infections represent.Although the mortality attributed to helminth infections is minimal, the morbidity is considerably high, and it is related to the burden of infection. Most infected adults harbor a few worms and have some or no manifestations of clinical disease. This is not the case in children, where a moderate to severe STH infection will negatively affect growth and development during early childhood. (7)(17)(18)(19)The age patterns of infection prevalence display a rise in childhood. For helminths such as A lumbricoides and T trichiura, infections are common in children aged 5 to 15 years, with minimal infections seen in adulthood. On the contrary, hookworm infections show a steady increase with age, with cases peaking in adulthood. (1)(20)STHs affect overall nutritional status, by local and systemic mechanisms. Helminths feed on the host’s blood and tissues, leading to iron and protein-energy malnutrition. Direct mucosal damage causes loss of enzymes at the brush border and reduces the area available for nutrient digestion and absorption. (21) Systemic inflammation and activation of the immune system lead to cytokine release, which induces anorexia, impairment of nutrient storage, and increased basal energy expenditure. Polyparasitism, the concurrent infection with multiple intestinal parasites, and co-infections with other micro-organisms (eg, S stercoralis is associated with tuberculosis and human immunodeficiency virus) may have additional adverse effects on the health of the host. (17)(22)(23) The main outcome is impaired growth and neurologic function over the long-term. On average, children infected with helminths have lower cognitive and verbal scores. (24) Women who harbor hookworms are at risk for severe anemia during pregnancy, which might cause prematurity, low birthweight, and impaired lactation. (25)STHs have developed multiple strategies to evade host immune response. Mechanisms include encapsulation within fibrous tissue (Toxocara), their intraluminal location and size (A lumbricoides), and via immune modulation, which allows their long-term survival. (18)(26) Due to the inability to phagocytose these large extracellular parasites, there is no significant macrophage or natural killer cell activation. Mast cells and eosinophils produce interleukin (IL)-4 to drive the differentiation of the naive Th0 cells into CD4+ T-helper cells (Th2). In addition, IL-4 causes B cells to isotype switch to immunoglobulin (Ig) E and, in combination with IL-10, IL-13, and IL-5, promote Th2 response, recruiting eosinophils while downregulating the Th1 response. (26) This explains the peripheral blood, bone marrow, and tissue eosinophilia associated with the presence of worms in tissues. It is not observed in intraluminal infections or when the parasites are enclosed in cystic structures. (27)Most patients are asymptomatic; when symptoms are present, they depend on the phase of the parasite’s life cycle and the intensity of infection. (6)Early-phase infection presents with pulmonary manifestations 10 to 14 days after egg ingestion. The larvae may cause variable respiratory symptoms ranging from cough, wheezing, dyspnea, and hemoptysis to severe Loeffler syndrome, a type 1 hypersensitivity eosinophilic pneumonitis with lung infiltrates on radiographs associated with parasitic infections. (28) Ascaris increases susceptibility to asthma in children and is associated with increased allergic skin test reactivity during this phase. (29)(30)Late-phase infection presents with nonspecific gastrointestinal symptoms such as anorexia, abdominal discomfort, nausea, and vomiting caused by adult Ascaris worms that reside in the jejunum. (6)(31)Adult worms do not replicate in the human host, so the worm burden is related to the continued exposure to infectious eggs over time. Ascaris bolus can cause the intraluminal obstruction volvulus, the lead point for intussusception, commonly seen in children aged 4 to 8 years. Intestinal perforations occur with obstruction of the lumen of blind-ending structures, such as Meckel diverticulum and the appendix. Migration of the larvae can also cause surgical complications of the hepatobiliary or pancreatic system. (6)(31)(32)A duodenale and N americanus infections usually course unnoticed due to mild to no symptoms. The percutaneous entry of larvae can lead to the local pruritic vesicular rash “ground itch,” which typically appears in the extremities. Although not as common as with ascariasis, some hosts might exhibit transient Loeffler syndrome during larval pulmonary migration. (33) After 1 to 3 weeks, the larvae reach the small intestine, where they reside and attach to the intestinal mucosa to extract blood from the host, secreting anticoagulants so that lesions continue to bleed even between feeds. (30)(31)(33)A duodenale can be orally ingested, resulting in Wakana syndrome, an immediate type 1 hypersensitivity reaction characterized by pharyngeal irritation, cough, and dyspnea. (31)(33) In the small intestine, nonspecific gastrointestinal symptoms may be present. Hookworms attach to the host’s gut, causing occult gastrointestinal bleeding, leading to iron deficiency anemia, hypoalbuminemia, and anasarca, considered hookworm disease. N americanus is more predominant and remains the leading cause of hookworm disease globally. (31)(33)The most frequently encountered zoonotic hookworm, particularly among the canine and feline parasites, is A braziliense. The percutaneous entry of A braziliense can cause cutaneous larva migrans (or “creeping eruption”) generated by the migration of the larva through the epidermis when it penetrates the human skin within a week. (34) A braziliense initially presents as a papule that progresses to a long serpiginous intensely pruritic rash, which is self-limiting (Fig 3A). (33)(34)(35) Cutaneous larva migrans is commonly encountered in travelers returning from tropical locations having frequented beaches in regions where A braziliense is endemic, including Southeast Asia, Africa, South America, the Caribbean, and the southeastern parts of the United States. In some instances, A braziliense larvae may migrate to the lungs, causing pneumonitis. They can also cause folliculitis, myositis, and, occasionally, eosinophilic enteritis. (33)(34)(35)Most larvae move to the cecum and penetrate the mucosa using the “whiplike” anterior end, causing chronic colonic mucosal damage leading to chronic abdominal pain and diarrhea. Heavily infected children may develop Trichuris dysentery syndrome, which resembles inflammatory bowel disease, presenting with tenesmus, rectal prolapse, and malnutrition. Bloody stools can cause severe anemia, leading to clubbing, impaired growth, and developmental and cognitive deficits. (6)(31)(37)E vermicularis, the most common helminth infection in the United States, transmits by close person-to-person contact, via ingestion or inhalation of eggs. The gravid worm migrates to the perianal area at night and releases its eggs. The eggs create a local inflammatory reaction perceived as pruritus by the host, leading to scratching, cutaneous trauma, superimposed bacterial infection, and contamination, especially underneath the fingernails and surrounding surfaces. Autoinfection occurs from scratching the perianal area and then putting contaminated hands to the mouth, especially in children aged 4 to 11 years because of close social contact, putting toys in the mouth, or nail biting. (30)(38) Occasionally, the parasite’s erratic migration is associated with recurrent urinary tract infections and vulvovaginitis in girls. (30)(39) The association between E vermicularis infection and appendicitis is controversial, with no conclusive evidence to date. (40) In adolescence, sexual transmission is possible in partners engaging in oral-anal sex.S stercoralis infects humans through contact with soil containing the larvae. This parasite has a characteristic ability to undergo persistent replication in the host or “autoinfection,” leading to an ongoing chronic infection in immunocompetent individuals and an acute systemic infection in the immunocompromised. (31)(41)Skin penetration is characterized by a linear urticarial rash that expands serpiginously for several weeks. In chronic infections, S stercoralis larvae can also migrate under the dermis, causing intense linear itchy red tracts known as “larva currens” (Fig 3B). (41)(42) During lung migration, it can cause Loeffler syndrome. Once the adult worms reach the small intestine, they can cause nonspecific gastrointestinal symptoms such as enteritis in the immunocompetent host. Rarely, immune-mediated diseases such as reactive arthritis can occur. (41)(42)In the immunocompromised patient, accelerated autoinfection can lead to Strongyloides hyperinfection syndrome due to the immune system’s inability to control larvae replication. This results in dissemination to end organs, including the brain, lungs, and liver. Septic shock is a complication due to translocation of the enteric bacteria during larval migration, with potentially life-threatening consequences and mortality greater than 85%. (41)(42) High-risk individuals include patients taking immunosuppressants and chemotherapeutics, as well as patients with hypogammaglobulinemia, malignancies, human T-cell lymphotropic virus type 1, and coronavirus disease 2019 infection. (31)(44)Recognition of helminth infections requires knowledge of their clinical presentation according to the different stages of their life cycle, worm burden, geographic distribution, and epidemiological risk factors. Persons with light-intensity infection might have no or few symptoms, the only evidence being a history of traveling to an endemic region or consumption of undercooked food (Table 1). (45)The diagnosis of most STHs is established by identifying the characteristic eggs by microscopic examination of several stool specimens (≥3), which have been collected daily or on alternate days to maximize the testing sensitivity. (45) The Kato-Katz thick smear method is the gold standard of the WHO. However, it often misses low-intensity infections and is less valuable for eradication. (46)(47) Other commonly used methods include FECPAKG2 and Mini-FLOTAC, which show sensitivity comparable with Kato-Katz to diagnose first-time moderate- and heavy-intensity infections but tends to underestimate the average egg count. (46)(48)(49) Molecular methods such as quantitative real-time polymerase chain reaction (PCR) have improved the detection of enteric helminthiasis. (50) They are more sensitive and can detect multiple parasites in one go. Unfortunately, quantitative real-time PCR is yet to be standardized and is not easily accessible globally. (47)(51)(52)S stercoralis is the exception, as using microscopy is challenging due to its variable larval output and it requires visualization of larvae (not eggs) in stools. Other approaches have been used to increase yield, including stool concentration techniques, examination of duodenal content using the string test or direct aspirate from endoscopy, and culture methods to visualize characteristic larval tracks in agar. However, serology is a more consistent and available diagnostic method. (37)(53)Serology for S stercoralis and A lumbricoides is diagnostic when larvae migrate through tissues and is beneficial when larval output is inconsistent. The lack of specificity and the inability to differentiate current and past infections are significant limitations of this test. (52)(54) Recently, using recombinant antigens is proposed, which shows higher sensitivity and specificity. (31)E vermicularis eggs are identified by microscopic examination of cellophane tape placed on the perianal skin first thing in the morning (sensitivity of 3 samples is approximately 90%). (55)These dog and cat roundworms are the cause of the zoonotic parasitic disease toxocariasis. Due to widespread soil contamination with their eggs, humans can become accidental hosts.The main route of infection to humans is via the ingestion of contaminated soil where dogs, cats, or foxes defecate. (56) Highest worm burden tends to be in stray dogs younger 6 months of age, and in cats 2 to 6 months old. A 2020 surveillance study performed on soil samples from New York City public parks through microscopy and quantitative PCR detected Toxocara egg contamination in all 5 boroughs, with the highest prevalence in poorer neighborhoods (Bronx, 66.7%), posing a potential health risk to young children with pica locally because they spend time in sandpits and recreational areas contaminated by stray animals, especially cats. (57)(58)Estimated serological prevalence in the United States for Toxocara species ranges from 5.1% to 13.9%. (11) The most recent National Health and Nutrition Examination Survey (2011–2014) tested sera from participants using a sensitive and specific recombinant antigen for IgG antibodies for Toxocara species. The prevalence remained elevated in the minority ethnic groups (10% Hispanic), in those with medical hardships, and in those with low education and socioeconomic status. (11)(59)After ingestion, the larvae usually hatch in the small intestine. They then migrate to various organs, inciting a strong eosinophilic inflammatory response giving rise to multiple clinical syndromes. (60) The larvae fail to develop into adult worms in humans and can remain in an arrested state in organ tissues for years, inducing a strong CD4+ T-helper cell immune response characterized by elevated IgG, IgM, IgE, IL-4, and IL-5 levels and significant eosinophilia, resulting in encapsulation of the larvae. (60)(61)(62) Risk factors for human toxocariasis include geophagia; consumption of contaminated raw/undercooked meat, fruits, or vegetables; exposure to dogs; poverty; and rural residence. (63)Infections are usually asymptomatic; nevertheless, the migrating larvae can give rise to various clinical syndromes; in pediatrics, the most relevant are visceral larva migrans, ocular larva migrans (OLM), and covert (or subclinical) toxocariasis in children. (62)Visceral larva migrans classically presents with fever, severe eosinophilia, and hepatomegaly, affecting children 2 to 7 years of age. Other symptoms are associated with hepatic and pulmonary larval migration, presenting with hepatosplenomegaly, abdominal pain, loss of appetite, wheezing, coughing, hypergammaglobulinemia, skin allergic reactions, and vasculitis. (60)(61)(62)(63)OLM is commonly reported at 3 to 16 years of age. It is characterized for unilateral vision loss, strabismus, and leukocoria, but it can present with a variety of pathologies. The larva migrates into the retina and vitreous, causing a granulomatous reaction and tractional retinal detachment. (60)(61)(63)(64)(65)Covert toxocariasis is a frequently undiagnosed condition in patients with nonspecific symptoms such as abdominal pain, nausea, headaches, and loss of appetite, with or without eosinophilia and reduced pulmonary function, including wheezing, acute bronchitis, and pneumonitis. (62) These patients have elevated Toxocara species antibodies, which is associated with a twofold increased risk of asthma and significant cognitive and developmental delays compared with noninfected children. (66)(67)Direct microscopic examination of tissues revealing eosinophilic granulomas surrounding larvae is the gold standard for toxocariasis. Nonetheless, this procedure is invasive and not routinely used, and the larvae are continuously migrating. (60)(61) Stool microscopy for eggs is not applicable because Toxocara species do not reach adulthood. Therefore, clinical history and physical examination, laboratory tests, and serological tests are used routinely.For serodiagnosis, 2 consecutive serum samples collected 2 weeks apart are indicated. Detection of IgG by indirect Toxocara excretory-secretory antigen-based enzyme-linked immunosorbent assay is commonly used as the initial diagnostic test. (64)(68) Western blot analysis should confirm positive serological findings to rule out cross-reactivity with other nematodes. (61)(65) It is important to keep in mind that serological findings may persist as positive for years; as a result, it cannot distinguish between a current or past infection.The following helminth infections are not endemic of the United States but are of clinical significance for the general pediatrician when assessing returning travelers, immigrants, or internationally adopted children. (4)Schistosomiasis is another NTD that causes acute and chronic organ dysfunction in 140 million people worldwide. (9) This is of particular importance in relocated refugees or adopted children from Southeast Asia and Sub-Saharan Africa because more than one-half of immigrants would be seropositive for schistosomiasis. (3) Clinical manifestations include a localized reaction after schistosomes enter the human skin, causing the pruritic maculopapular response called “swimmer’s itch” (Fig 3C). (69)(70)(71) Acute schistosomiasis (Katayama fever or syndrome) is a systemic hypersensitivity reaction characterized by sudden onset of serum sickness–like symptoms lasting 2 to 12 weeks after the first infection in returning travelers. (73) Chronic schistosomiasis can progress to hepatosplenic disease with portal hypertension, with Schistosoma mansoni and Schistosoma japonicum, and to obstructive uropathy, infertility, and an increased risk of squamous cell carcinoma of the bladder with Schistosoma haematobium. (69) Chronic disease usually develops 5 to 15 years after the first infection in adults; however, in children, the pathologic process can start as young as 6 years of age. In children, early treatment can completely resolve the granulomatous inflammation, which is why it is important to refer to an infectious disease specialist on suspicion. (69)(70)Neurocysticercosis (NCC) results from accidentally ingesting the eggs of Taenia solium, excreted from direct contact with infected households. (74)(75)(76) NCC is classified into parenchymal and extraparenchymal, which includes ventricular, subarachnoid, ocular, or spinal. (74)(77)(78) Approximately 80% of NCC initially presents as new-onset seizure disorder, epilepsy, and other neurologic deficits in children older than 5 years. (74) Immigrants acquired it more commonly from their country of origin; however, NCC is now transmissible within the United States at the US-Mexico borderlands. (3) Among internationally adopted children, seroprevalence ranges between 1.7% and 8.9%. (74)(79) NCC is a complex helminth infection managed between infectious diseases and neurology/neurosurgery specialists. Initial evaluation should include neuroimaging, preferably magnetic resonance imaging, to determine the number and stage of the disease, which would dictate the antiparasitic treatment. (78)Cystic echinococcosis is the zoonosis caused by the larvae of Echinococcus granulosus (most common in pediatrics) via the ingestion of eggs from food contaminated with feces of dogs, foxes, and other canids. (80)(81) These eggs hatch in the human intestines, and the larvae migrate, affecting mainly the liver and the lungs, where it encapsulates, developing the characteristic cysts. In the United States, cases have been reported in immigrants and on lands specifically designated for Native Americans, where there is a high prevalence of child poverty, overcrowding, and lack of adequate in-house plumbing among these tribes. (3)Almost 80% of patients demonstrate single-organ involvement and usually have a solitary cyst, but all organs can be affected. Cysts that are acquired in childhood remain asymptomatic for 10 to 12 years in the early stages and grow gradually. They are often well tolerated until they start exerting pressure and damage adjacent tissues and organs during later stages. (82) Clinical complications include formation of fistulas or cyst rupture resulting in anaphylactic shock, superinfection, dissemination, and acute abdomen.Diagnosis relies on a stage-specific management approach based on the ultrasonography findings. Cysts not visualized on ultrasonography can be detected using computed tomography or magnetic resonance imaging. (82)(83) Because this zoonosis is a chronic and complex helminth infection, referral to an infectious disease specialist is recommended once imaging findings are suggestive of cystic echinococcosis.Albendazole, ivermectin, and praziquantel (PZQ) are commonly used drugs that are preferred due to their efficacy, affordability, and safety profiles. (84)(85) Recently, there is increasing concern about anthelmintic drug resistance. Amidst decreasing effectiveness and drug failures with some anthelmintic drugs, efforts are being made to develop new therapies, such as vaccines against hookworms and intestinal schistosomiasis to combat these NTD. (30)(86) Doses and suggested regimens of commonly used anthelmintics are described in Tables 2 and 3.Albendazole inhibits microtubule synthesis, leading to disruption of cytoskeleton and energy pathways. (86) Commonly seen adverse effects with these drugs are tolerable, but physicians should monitor complete blood cell counts and liver function tests during long-term therapy. (70) Albendazole is taken on an empty stomach when used against intraluminal parasites and is taken with a fatty meal when used against tissue parasites to increase absorption. (90)(91) Single-dose albendazole has the highest cure rates and egg reduction rates against A lumbricoides and is efficacious against hookworms. (91) For trichuriasis, a combination of either albendazole or mebendazole with ivermectin or oxantel pamoate has improved treatment outcomes without compromising efficacy against other STHs. (92) In pinworm infections, the entire family, should be treated with 1 of the antihelminthic agents listed in Table 2. In addition, other control measures include personal hygiene and separate washing of bed linens and underwear of infected children.Albendazole is also the drug of choice for Toxocara species, and mebendazole is an appropriate alternative therapy. The inflammation and secondary damage caused by OLM can be mitigated by conjunctive therapy with corticosteroids. (87) The transmission of this zoonotic disease can be interrupted by additional preventive measures, such as reducing the direct contact with contaminated soil by using gloves during gardening and washing hands thoroughly, washing fresh produce before eating, avoiding undercooked meat, covering sandpits at night, and not allowing animals at playgrounds have showed reduction in transmission. (63)Ivermectin is the preferred therapy in strongyloidiasis and is also used to treat onchocerciasis, lymphatic filariasis, and cutaneous larva migrans. (93)(94) It causes flaccid paralysis in the parasite by intensifying γ-aminobutyric acid–ergic neuromuscular inhibition. In immunocompromised patients with disseminated strongyloidiasis infection, repeated and suppressive treatment is often needed, and subcutaneous injections of a parenteral preparation may be required. (86) Physicians should screen for Strongyloides to avoid hyperinfection syndrome before beginning corticosteroid therapy or other immunosuppressants.The most effective drug against schistosomiasis is PZQ. In the parasite, it increases the cell membrane’s permeability to calcium, inducing paralysis and death. (70)(95) Most typical adverse effects in children after PZQ treatment include dizziness, headache, gastrointestinal discomfort, and night fevers, which are related to the antigenic release from dying worms. (69)(70)(71)(89) Management of cercarial dermatitis is supportive to prevent secondary bacterial infection. (20)The 3 main interventions for preventing and controlling helminth infections in developing countries are anthelmintic drug treatment, sanitation, and health education. (85)(96)Preventive chemotherapy (PC) is the foundation of helminth control established by the WHO since 2001 to reduce morbidity from moderate to high worm burdens. In 2005, the “rapid-impact” package was proposed to deliver a combination of drugs directed against STHs (albendazole or mebendazole), schistosomiasis (PZQ), filarial diseases and onchocerciasis (ivermectin or diethylcarbamazine), and trachoma (azithromycin), with the additional benefit of covering other NTDs by cross-reaction of medications. (97)(98) The justification for incorporating these programs is based on the observation of polyparasitism due to the geographic overlap of NTDs. However, there is an ongoing debate as to whether PC confers any health benefit to the population. (99) Experts claim that available data might not reflect the actual benefits of PC for 2 main reasons. First, the short duration of follow-up might fail to detect the long-term benefits of PC. Second, the large numbers of lightly infected or uninfected individuals in the population being studied might weaken the statistical significance of the benefits observed in patients with moderate to severe infections after PC. (100)Periodic PC in preschool-age children (aged 1–4 years) and school-age children (aged 5–14 years) without a previous diagnosis of helminthiasis can ensure that the infection levels are kept below those associated with morbidity and transmission. (85) For instance, for STHs, the WHO recommends a case-by-case treatment if the prevalence of STH is less than 20%, PC once a year if prevalence is 20% to less than 50%, and twice a year where the prevalence is 50% or greater. (88) Between 2010 and 2018, PC coverage in preschool- and school-age children steadily increased, and the 75% target of global coverage seems within reach by the end of 2020. Currently, newly established goals for 2030 are to achieve and maintain less than 2% prevalence of STH infections in high-risk groups, progressively reduce the cost of the PC interventions, allow country ownership, and establish an efficient strongyloidiasis control program. (97) Although PC alone is unlikely to eliminate helminthiasis, it is a bridge until other more sustainable measures can be reached.Complementary strategies, including sanitation and health education, are pivotal in prevention. However, to be effective, they should be implemented at the community level and cover a high population percentage, making these projects burdensome in resource-limited areas. (101) Water, sanitation, and hygiene practices reduce the transmission of STH infections by improving access to clean water, safe disposal of fecal sludge, and hygiene. (101) Another practical approach is the “One Health” concept, which tries to connect human, animal, and environmental health. (102)(103)(104) Interventions such as livestock vaccination and regular anthelmintic treatment in puppies and kittens to stop the Echinococcus and Toxocara life cycle or environmental control of snails to prevent schistosomiasis transmission can be useful tools.You can find the teaching slides that accompany this article on the Views>Supplementary Data option in the online article toolbar.