Hookworm Infections

Intestinal hookworm infections that affect humans are caused mainly by Necator americanus and Ancylostoma duodenale. Millions of people are infected around the world, mainly in tropical regions, where warm and moist environments facilitate larva survival in the soil. Transmission is via dermal penetration by the larvae. From entry, the parasite undergoes a transpulmonary passage, reaching the trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea and pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx, where it is swallowed. In the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine, worms mature and attach to the duodenum. Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, nausea, and vomiting are GI symptoms. Blood loss (leading to anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview) and subsequent malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries are complications. Diagnosis is by stool microscopy showing the hookworm eggs and by PCR. Management targets prevention through proper sanitation and regular deworming of high-risk groups. Treatment involves the use of anti-parasitic medications, with iron supplements for anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview.

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Overview

General characteristics

  • Hookworms:
    • Average length of adult worm: 10 mm
    • Head is often curved in the opposite direction of the body: worms have a “hooked” appearance.
    • Male worms have a unique copulatory bursa instead of the curved, pointed tail seen in other intestinal nematodes.
  • Major species of hookworms that cause human infections:
    • Ancylostoma duodenale:
      • 4 sharp tooth-like structures
      • Life span: 1 year
    • Necator americanus (New World hookworm):
      • Dorsal and ventral cutting plates
      • Life span: 3–5 years
  • Other species: 
    • A. ceylanicum: 
      • Infects dogs and cats
      • Cause of zoonotic infections in Asian and South Pacific regions
    • A. caninum
    • A. braziliense

Epidemiology

  • Approximately 500 million people are infected by hookworm around the world every year.
  • N. americanus is the causative agent worldwide.
  • A. duodenale is usually found in:
    • Mediterranean region
    • Northern India
    • China
  • Preference for tropical climates

Host risk factors

  • Children
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Low socioeconomic background
  • Walking barefoot
  • Poor sanitation
  • Poor personal hygiene

Pathogenesis

Reservoirs and transmission

  • Reservoirs: 
    • A. duodenale and N. americanus: human
    • A. ceylanicum: dogs and cats
    • A. caninum: dogs
  • Modes of transmission:
    • Direct penetration of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin
    • Ingestion of larvae (e.g., contaminated water supply)
  • Factors facilitating transmission:
    • Fecal contamination of the soil
    • Moist, warm, and shady environment in which the larvae survive
    • Human skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin contact

Life cycle

  • External environment:
    • Hookworm eggs contaminate soil.
    • Eggs hatch in moist soil → rhabditiform larvae (live for 3–4 weeks) → mature into filariform larvae (can penetrate skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin)
  • Humans:
    • Larvae penetrate the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin (typically on the feet) and enter the bloodstream.
    • Enter right side of the heart → pulmonary vessels → alveoli → bronchial tree Bronchial tree The collective term "bronchial tree" refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further. Bronchial Tree trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx → swallowed into the intestine
    • Attach onto duodenal mucosa → adult hookworms mature
    • Adult females → lay up to 30,000 eggs per day → fecal ejection

Disease process

  • Dermal penetration and migration by proteolytic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes:
    • N. americanus → protease → break down elastin and collagen
    • A. duodenale → Ancylostoma–secreted proteins (development of parasite) + hyaluronidase enzyme (breach dermal integrity)
    • Penetration leads to skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin irritation.
  • Transpulmonary passage: can cause respiratory symptoms including pharyngeal/airway irritation and eosinophilic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
  • Duodenal attachment and blood consumption:
    • Teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth or cutting plates on buccal capsule → attaches to the host’s intestinal mucosa
    • Metalloprotease and anticoagulant peptides (inhibit activated factor X and factor VIIa/tissue factor complex) aid in digesting blood.
    • Blood consumption by worms and blood leakage → anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview (blood loss) and hypoalbuminemia/ malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries (loss of albumin)
      • N. americanus consumes 0.3 mL/day.
      • A. duodenale consumes 0.5 mL/day.
  • Immunosuppression: 
    • Parasite protease inhibitors → neutralize host proteolytic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes and reduce host nutritional absorption
    • Parasite induces apoptosis of T lymphocytes T lymphocytes T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells → T cell hyporesponsiveness

Clinical Presentation

Dermal penetration

  • At time of penetration → localized reaction (“ground itch”)
    • Often affects area between the toes
    • Resolves within a few days
  • Cutaneous larvae migrans: erythematous papule → characteristic serpiginous pattern (tunnels beneath the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin)

Pulmonary stage

  • Symptoms:
    • Can be asymptomatic
    • Cough or sneezing
    • Bronchitis
    • Hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis
    • Loeffler syndrome: eosinophilic pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Usually self limiting

Gastrointestinal stage

  • Abdominal cramps or pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Nausea, vomiting, diarrhea
  • Flatulence
  • GI bleeding in severe cases (melena or fecal occult blood)

Nutritional impairment

  • Failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive (mental and physical development of children adversely affected)
  • Iron deficiency anemia Iron Deficiency Anemia Iron deficiency anemia is the most common type of anemia worldwide. This form of anemia is caused by insufficient iron due to a decreased supply, an increased loss, or an increased demand. Iron deficiency anemia is seen across all ages, sexes, and socioeconomic strata; however, children, women of childbearing age, and patients from lower socioeconomic strata are at higher risk. Iron Deficiency Anemia (dependent on worm burden)
  • Edema/anasarca (due to hypoalbuminemia)
  • Chronic infection in pregnant women: low birth weight

Diagnosis and Management

Diagnosis

  • Stool microscopy: 
    • Identify eggs.
    • Fecal eggs are detectable about 8 weeks (in N. americanus infection) and up to 38 weeks (in A. duodenale infection) after skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin penetration.
    • Prior to the GI stage, stool studies are not helpful.
  • PCR of stool
  • CBC:
    • Eosinophilia: a major finding suggestive of parasitic infection
    • Microcytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview (from iron deficiency)
    • Low albumin
Hookworm egg

Diagnostic characteristics of hookworm eggs include a thin shell, which is oval or ellipsoidal in shape.

Image: “4825” by CDC. License: Public Domain

Management

Medical management:

  • Antiparasitic medication:
    • Mebendazole (multiple dose)
    • Albendazole (single dose)
    • Pyrantel pamoate
  • Anemia
    • Iron supplement (especially for pregnant or lactating women)
    • Blood transfusion when indicated
  • Nutritional support

Prevention:

  • Key, as reinfection is common
  • Hygiene (proper handling of food, safe drinking water, handwashing)
  • Use of appropriate footwear
  • Sanitary disposal of human feces
  • Regular deworming of high-risk groups

Differential Diagnosis

  • Malabsorption Malabsorption Malabsorption involves many disorders in which there is an inability of the gut to absorb nutrients from dietary intake, potentially including water and/or electrolytes. A closely related term, maldigestion is the inability to break down large molecules of food into their smaller constituents. Malabsorption and maldigestion can affect macronutrients (fats, proteins, and carbohydrates), micronutrients (vitamins and minerals), or both. Malabsorption and Maldigestion: the inability of the intestinal wall to absorb the broken-down products of food. Manifestations include weight loss, diarrhea, weakness, anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview, and fatigue. Hookworm infections cause malabsorption, usually presenting with nutritional deficiencies due to iron and protein loss. Other malabsorptive disorders that should be considered include celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease and inflammatory bowel disease. Differentiation of other causes is important, as treatment is specific to the underlying cause.
  • Ascariasis Ascariasis Ascariasis is most often caused by A. lumbricoides. If symptomatic, characteristics typically follow 2 phases, which correlate with the migration of the parasite through the body. The early phase may include cough, dyspnea, and wheezing. The late phase typically includes abdominal discomfort, bloating, nausea, and intermittent diarrhea. Ascaris/Ascariasis: an infection caused by the parasitic roundworm Ascaris Ascaris Ascaris is a genus of parasitic nematodes. The infection, ascariasis, is most often caused by A. lumbricoides. Transmission occurs primarily via ingestion of water or food contaminated with Ascaris eggs. Most patients with ascariasis are asymptomatic. Ascaris/Ascariasis lumbricoides. Transmission occurs via ingestion of contaminated water or food. Most patients are asymptomatic. If symptoms do occur, they can be mild, with only abdominal discomfort, or severe, causing intestinal obstruction. Other symptoms, such as cough, are due to the migration of the worms through the body.
  • Trichinellosis Trichinellosis Trichinellosis is an illness caused by infection with Trichinella. The most common causative parasite is Trichinella spiralis, which is usually found in pigs and transmitted to humans through the ingestion of undercooked meat. Once ingested, the parasite grows and matures within the intestinal walls. Symptoms occur during larval migration. Trichinella/Trichinellosis: caused by a Trichinella Trichinella Trichinellosis is an illness caused by infection with Trichinella. The most common causative parasite is Trichinella spiralis, which is usually found in pigs and transmitted to humans through the ingestion of undercooked meat. Once ingested, the parasite grows and matures within the intestinal walls. Symptoms occur during larval migration. Trichinella/Trichinellosis infection, commonly due to T. spiralis (found in pigs). Transmission is through the ingestion of undercooked meat. Once ingested, the parasite moves to the intestine. Patients may have GI symptoms similar to hookworm infections. Spread through the bloodstream follows, and larvae reach striated muscles. Systemic symptoms include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, chills, myalgias, and periorbital edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. Diagnosis is by serological examination and is confirmed by muscle biopsy. Systemic disease is treated with antiparasitic medications and corticosteroids.
  • Strongyloidiasis Strongyloidiasis Strongyloidiasis is a common parasitic disease caused by infection with the roundworm Strongyloides stercoralis. Transmission occurs through skin penetration. Strongyloides has a unique life cycle that can be entirely completed in the human host, migrating from the skin to the pulmonary system and then to the GI system. Strongyloidiasis: a disease caused by the roundworm (nematode) Strongyloides. Strongyloidiasis Strongyloidiasis Strongyloidiasis is a common parasitic disease caused by infection with the roundworm Strongyloides stercoralis. Transmission occurs through skin penetration. Strongyloides has a unique life cycle that can be entirely completed in the human host, migrating from the skin to the pulmonary system and then to the GI system. Strongyloidiasis has various clinical manifestations including GI symptoms and eosinophilia. Diagnosis is via serology.

References

  1. Feldmeier, H., Schuster, A. (2012). Mini review: Hookworm-related cutaneous larva migrans. Eur J Clin Microbiol Infect Dis. 31(6),915–918. https://pubmed.ncbi.nlm.nih.gov/21922198/
  2. Ghodeif, A.O., Jain, H. (2021). Hookworm. StatPearls. Retrieved April 3, 2021, from: https://www.ncbi.nlm.nih.gov/books/NBK546648/
  3. Loukas, A., et al. (2016). Hookworm infection. Nat Rev Dis Primers. 2(16088). https://pubmed.ncbi.nlm.nih.gov/27929101/
  4. Jiraanankul, V., et al. (2011). Incidence and risk factors of hookworm infection in a rural community of central Thailand. Am J Trop Med Hyg. 84(4),594–598. https://pubmed.ncbi.nlm.nih.gov/21460016/
  5. Riedel, S., et al. (Eds.). (2019). Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28e. McGraw-Hill.
  6. Speich, B., et al. (2016). Efficacy and reinfection with soil-transmitted helminths 18-weeks post-treatment with albendazole-ivermectin, albendazole-mebendazole, albendazole-oxantel pamoate and mebendazole. Parasit Vectors. 9(123). https://pubmed.ncbi.nlm.nih.gov/26935065/
  7. Weller, P., Leder, K. (2019). Hookworm infection. UpToDate. Retrieved April 3, 2021, from https://www.uptodate.com/contents/hookworm-infection

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