Helminthiasis

Etiology

Intestinal parasite infections often cause morbidity and mortality, especially in children. The major risk factors of helminthiasis are rural areas, low socioeconomic status, poor sanitation, poor availability of clean water, poor personal hygiene, lack of nail trimming, crowded living conditions, lack of education, lack of access to health care, and inadequate dwelling conditions.

• A. lumbricoides and T. trichiura are transmitted through the fecal-oral route. Adult Ascaris is a long cylindrical worm, and its larvae can migrate into the pulmonary circulation, but T. trichiuria can not.
• A. duodenale and N. americanus are transmitted by penetration of the skin from where it goes into the lungs and crosses pulmonary capillaries to penetrate into alveolus and then to the intestine through the passing of larynx. N americanus is globally predominant compared to A. duodenale. S. stercoralis can infect percutaneously and orally.[4][7][9][10]
• Poor hygiene of mother or caregiver is also one of the most important risk factors for soil-transmitted helminths infection in preschool children.[4]
• Schistosomiasis infection is usually transmitted from contact with freshwater snails during swimming or washing. Schistosomiasis causes chronic inflammation that produces oxygen-free radicals. These free radicals are responsible for different mutations and the formation of carcinogenic N-nitrosamines that cause bladder carcinoma and portal tract fibrosis.[11][12]
• Diphyllobothriasis is most commonly occurs by species being D. latum from the ingestion of larva of the fish tapeworm.[13]

Epidemiology

Studies have suggested that within the USA, approximately 1.3 to 2.8 million people have serological evidence with Toxocara species, 4 million with soil-transmitted helminths, 41,400 to 169,000 with cysticercosis, and approximately 8000 with schistosomiasis. A recent study was done in Chicago shows that approximately 12% of subjects providing samples which were recent immigrants were found to have evidence of current or prior infection with a pathogenic parasite species where most common infections were Toxocara (6.4%), followed by S. stercoralis (4%).

The affected rate in females was 8% and males was 7%.[14] Global prevalence is greatly reduced in the comparison between 1990 and 2016, such as the prevalence of ascariasis was 1089.36 million in 1990 and 799.68 million in 2016, Trichuriasis was 524.62 million and 435.09 million, Hookworm was 497.52 million and 450.68 million, schistosomiasis was 195.36 million and 189.77 million, Lymphatic filariasis was 44.14 million and 29.38 million, Onchocerciasis was 24.13 million and 14.65 million.[15] Approximately more than 2 billion people have soil-transmitted helminthiasis.[5]

Pathophysiology

Direct damage:

Direct damage is done by worm activity itself, such as internal organ blockage or direct pressure effects by growing parasites.

• Adult Ascaris blocks the intestine that leads to small bowel obstruction, volvulus, or intussusception, especially in children, or can invade orifices leading to appendicitis, cholecystitis, pancreatitis, and gastric ascariasis. Migrating Ascaris can also block the bile duct and may also alter the intestinal microbiota. Mucosal bleeding from the upper gastrointestinal tract or generalized inflammation leads to anemia.
• Trichuris lies in intestinal mucosa and can cause petechial lesions, blotchy mucosal hemorrhage, oozing, and colonic inflammation. It can also cause severe anemia in pregnant women.[3][16]
• Schistosomiasis infection is acquired by contact with contaminated freshwater, especially during swimming or washing.[11][17] Deposition of schistosome eggs within the liver and bladder may form granulomas around these eggs that can block blood flow in the liver that leads to pathological changes like periportal fibrosis and have been linked with neoplasia. Interestingly, this periportal fibrosis has retained hepatocellular function that is different from other causes of cirrhosis. These liver flukes can also cause bile duct hyperplasia.[16][18][19][20]
• Wuchereria bancrofti causes lymphatic obstruction leads to elephantiasis[16][1] Hydatid cyst caused by the larval tapeworm infections (Echinococcus granulosus) leads to pressure atrophy.
• Taenia solium, the pork tapeworm, frequently develops in the intestine leads to taeniasis, and in the central nervous system leads to cysticercosis.[16][18][21]
• Ancylostoma and Necator burrow their teeth into mucosa and submucosa, create negative pressure by contracting their muscular esophagi that lead to rupture of the capillaries and arterioles and actively sucks blood. Blood vessels are ruptured by both mechanical compressions and hydrolytic enzymes secreted by these hookworms. These worms also secrete anticoagulants that lead to prolonged bleeding and, ultimately, significant blood loss. They can cause significant anemia, especially in children and pregnant women, along with schistosomiasis, these can increase neonatal prematurity and maternal morbidity and mortality, also causes protein loss by inflammation.
• Diphyllobothrium latum causes vitamin B12 deficiency through interfering with the absorption through the intestine. Migration through body tissue, many helminths cause direct tissue damage and also by hypersensitivity reactions, whereas most affected organs are skin, lungs, liver, and intestines.[16][3][18][22]

Indirect damage:

Indirect damage is done by the host immune response against helminth.

• All helminths are antigenic to the body because they are foreign bodies and stimulate the immune response. Lymphatic blockage by W. bancrofti and granuloma formation by schistosomes in the liver and bladder are associated with hypersensitivity reaction against these helminths.
• Strongyloides and Trichinella may induce prolonged inflammation of the intestine that causes villous atrophy; in severe cases, it may cause protein-losing enteropathy.
• S stercoralis can cause Loeffler syndrome by type 1 hypersensitivity reaction.
• Trichuris, which is also known as whipworm, can cause inflammation of the colon that leads to blood loss and rectal prolapse.
• Indirect damage depends on the severity of the inflammation and the duration of inflammation. If the duration is prolonged, many worms produce extensive inflammatory damage to tissues that is an irreversible and functional loss of the tissues, such as bile duct hyperplasia by long term infection with liver flukes, fibrosis caused by schistosomiasis and skin atrophy caused by onchocerciasis.[3][16]

History and Physical

Most of the patients with helminthiasis are from developing countries, especially from rural areas with poor sanitation and poor hygiene maintenance. Most are also preschool and school-aged. In most cases, clinical presentation depends on the burden of helminth infection because some patients may be mildly infected. In contrast, others may be heavily infected and harbor almost all of the worms.

Patients with adult ascariasis may also have an acute abdominal presentation like upper gastrointestinal bleeding, acute cholecystitis, acute pancreatitis, biliary colic, acute cholangitis, and hepatic abscess for which patient may present with anemia, fever, jaundice, abdominal pain and tenderness. The heavy burden may present as small bowel obstruction with abdominal distension, tenderness, and increased bowel sound. Volvulus, intussusception, gastric perforation, and peritonitis are a very critical presentation of adult ascariasis. Vomiting (may contain long cylindrical worm), weakness, loss of appetite, weight loss, diarrhea, or altered bowel habit are also common in intestinal ascariasis. Pleuritis or pleural effusion may occur in rare cases. Diminished physical fitness, growth stunting, memory, and cognitive impairment is seen in young patients. Eosinophilic pneumonia (Loeffler syndrome) that occurs by A. lumbricoides may present with urticaria, cough, dyspnea, hemoptysis, and abnormal breath sound on auscultation.[1][3][18] Intestinal parasitic infections have also been shown to impair micronutrient digestion and absorption of vitamin A, zinc, and selenium, which leads to malnutrition and decreases immune function.[4][23]

Patients with A. duodenale and N. americanus infections commonly remain asymptomatic. After penetration of the skin, migrating larvae may cause intensely pruritic, tortuous, and vesicular lesions. These worms can also cause eosinophilic pneumonia that presents with cough, respiratory distress, and hemoptysis. Wakana syndrome occurs in the perioral infection that presents as a constellation of symptoms such as pharyngeal irritation, cough, nausea, vomiting, and respiratory distress. Intestinal infection can cause various presentations like weakness, fatigue, abdominal pain, tenderness or discomfort, tachycardia, tachypnea, anemia, and edema due to extensive blood loss and protein loss respectively through the gastrointestinal tract, joint pain and sternal pain, headache, and impotence.[3][22]

S. stercoralis infection is commonly asymptomatic, although it may present with eosinophilic pneumonia just like hookworms and A. lumbricoides. Chronic strongyloidiasis might present with anorexia, nausea, weakness, abdominal pain, tenderness, and diarrhea. Larva currens is present as serpiginous urticaria due to chronic infection, mostly over the abdomen, torso, groin, and buttocks. Rarely, reactive arthritis may occur by the immune-mediated mechanisms. Strongyloides hyper-infection syndrome occurs by autoinfection in immunosuppressed individuals who present with intestinal failure or pulmonary failure. If untreated, the mortality ratio is approximately 100%. When large numbers of parasites spread into the different organs of the body, it leads to disseminated strongyloidiasis that present with catastrophic clinical manifestations such as meningitis, disseminated intravascular coagulation, shock, and renal failure. Those who are taking immunosuppressive drugs such as corticosteroid and vincristine, hematological malignancies, hypogammaglobinaemia, and human T-cell lymphotropic virus type 1 infection are vulnerable to develop disseminated strongyloidiasis.[3][24][25]

T. trichiura infection is asymptomatic in most cases. Loeffler syndrome does not develop in trichuriasis. Symptomatic individuals may present with weakness, abdominal pain. Patients may also present with iron deficiency anemia, finger clubbing, abdominal tenderness, mucoid diarrhea, rectal bleeding, rectal prolapse, this syndrome has traditionally named Trichuris dysentery syndrome (TDS). Children with severe T. trichiura infection can cause growth stunting, mental retardation, and decrease cognitive function.[3][26][27]

Schistosomiasis can be classified as an acute and chronic infection. Acute schistosomiasis also is known as Katayama syndrome and typically presents with sudden onset of fever, fatigue, malaise, myalgia, rash (generally urticarial), wheeze, headache, abdominal pain, eosinophilia, it may also present with hepatosplenomegaly.[19][11]

In the case of chronic schistosomiasis, intestinal schistosomiasis may present with intermittent abdominal pain, chronic diarrhea, and rectal bleeding. Some people with S. mansoni and S. japonicum infection may develop the hepatosplenic disease with periportal fibrosis, upper abdominal discomfort, palpable nodular, and hard hepatomegaly, splenomegaly, and portal hypertension. Ascites and haematemesis may occur from esophageal varices. The chronic form of the disease may also present as pulmonary hypertension.[11][19][28] Urogenital schistosomiasis may present with haematuria, increased urinary frequency, dysuria, and suprapubic discomfort. Urinary tract fibrosis may lead to obstructive uropathy (hydroureter and hydronephrosis), which can cause bacterial superinfection and renal dysfunction. S. hematobium infection also causes squamous-cell carcinoma of the bladder. Female genital schistosomiasis by S. hematobium may present with pain, stress incontinence, infertility, and increased risk of abortion. For men, urogenital schistosomiasis may present with oligospermia, hematospermia, orchitis, and prostatitis. Some non-specific but disabling systemic morbidities are associated with all Schistosoma species, including a pruritic rash that is commonly called ‘swimmers itch, other features include low-grade fever, anemia, and malnutrition with impaired childhood development. Ectopic eggs deposition can lead to very rare but important morbidities. The most common morbidities are spinal compression or encephalopathy. Cerebral schistosomiasis can also occur that may present with symptoms of meningoencephalitis such as headache, vomiting, blurred vision, high-grade fever, and altered sensorium or Jacksonian epilepsy. Spinal cord involvement can present as acute transverse myelitis or subacute myeloradiculopathy, although it is more common in acute schistosomiasis that results in acute lower limb paraplegia or lumbar and leg pain, muscle weakness, sensory loss, and bladder incontinence.[11][17][19]

Elephantiasis mostly caused by filaria called Wuchereria bancrofti is asymptomatic in most of the case. Symptomatic patients may present fever, malaise, headache, and chills. The patient may present with swelling of the limbs or scrotum, also known as elephantiasis or hydrocele, respectively. Swelling is usually limited to single limbs. Red streaks present on the skin of the arms and legs, and lymphatic trunks become very painful. Tropical pulmonary eosinophilia also caused by this filaria that presents with asthma-like symptoms, restrictive lung disease, and high eosinophilia levels. In addition to these, extreme pain in the genital area may also develop as well as filarial abscesses.[29][30][31]

For echinococcosis, most of the patients remain asymptomatic unless complications occur and are diagnosed accidentally. During patient admission, the most common presentation is pain at the right hypochondrium. Mechanisms by which a cyst becomes symptomatic include rupture with resultant infections or anaphylaxis, development of fistula with surrounding structures such as biliary tract, intestine, and bronchus.[32][33]

Taeniasis may be asymptomatic in most of the cases. When present, it may be due to abdominal pain and abdominal distension for intestinal taeniasis. Neurocysticercosis may present with recurrent seizures, paresis, obstructive hydrocephalus, headache, features of intracranial hypertension, stroke, cognitive decline, and depression.[21][34][35][36]

Diphyllobothriasis causes a variety of symptoms in different organs such as the central nervous system is affected and manifested as paresthesia, subacute combined degeneration of spinal cord due to megaloblastic anemia as a cause of vitamin B12 deficiency. Long-standing Diphyllobothrium latum infection also causes gastrointestinal symptoms like diarrhea, constipation, abdominal pain, intestinal obstruction, cholecystitis, cholangitis, and also subacute appendicitis. Hematological manifestations include megaloblastic anemia, pancytopenia, pernicious anemia, and eosinophilia. Diphyllobothriasis may also cause dyspnea due to prolonged vitamin B12 deficiency.[13]

Evaluation

Ascaris lumbricoides can be diagnosed by the presence of eggs, larvae, or adult worms.

• The chest X-ray can show pulmonary infiltrates, bronchoscopy may show the evidence of bronchitis, and filariform larvae may also be found in sputum, bronchoalveolar lavage, or gastric aspirate in Loeffler syndrome that may also occur by A. duodenale, N. americanus, and S. stercoralis.
• Acute larval infections are associated with eosinophilia and increased IgE titers.
• Egg concentration techniques are commonly used in hospital-based laboratories, whereas the Kato-Katz technique, which is more simplified and field-friendly tests are used for public health control. There are some other techniques like McMaster, FLOTAC, and mini-FLOTAC; these techniques use the concentration of eggs that can be more sensitive than Kato-Katz.[3][37]
• Ultrasonography is one of the most important diagnostic tools for hepatobiliary and pancreatic ascariasis, although duodenoscopy and endoscopic retrograde cholangiopancreatography can also be used.[3][38][10]

Stool microscopy is sufficient in uncomplicated cases of trichuriasis. Colonoscopy can detect trichuriasis in severe cases, and sometimes biopsy also be needed to confirm the diagnosis. In trichuriasis dysentery syndrome, iron-deficiency anemia should be evaluated.[3][27] 

Loeffler syndrome can occur in A. duodenale and N. americanus infection, the diagnostic method is the same as Ascaris infection. In intestinal infection, the mainstay of diagnosis is stool microscopy. Capsule endoscopy can identify hookworms, although it is rarely used. Anemia should be evaluated in any case of hookworm infection as well as in hookworm infections.[3] 

S. stercoralis also causes Loeffler syndrome, and the diagnostic method is the same as Ascaris induced Loeffler syndrome. For intestinal infection, filariform larvae can be seen in a single wet mount stool preparation. Duodenoscopy with duodenal biopsies may also be used and shows eggs, larvae, and adult worms. If gut damage is being investigated, then plain X-ray of the abdomen, contrast-enhanced CT, and MRI can be used. If Strongyloides hyperinfection syndrome is suspected, targeted tissue such as lung, bronchial, and small bowel biopsies might identify eggs, larvae, and adult worms. Either IgE titers and eosinophils can be highly elevated or depleted.[3][24]

The gold standard method for the diagnosis of schistosomiasis is the microscopic examination of ova in urine (S. haematobium) or stool. Kato Katz technique may also be used to assess the intensity of infection. Schistosomiasis can also be diagnosed by the presence of eggs in tissue biopsy specimens that might be taken from rectum, bladder, intestine, and liver. The standard screening method is the serology for egg antigen. Some other nonspecific findings may also present in schistosomiasis, including eosinophilia, anemia, and thrombocytopenia (from splenic sequestration). Schistosomiasis tests are usually negative when Katayama fever develops because it occurs before maturation of schistosome flukes begin to lay eggs, but diagnostic tests for schistosomiasis detects eggs or serology for egg antigens. Hepatosplenic schistosomiasis may be diagnosed by abdominal ultrasonography.[20][11][19]

History of exposure in endemic areas is the first step for the diagnosis of lymphatic filariasis. Then serology testing of blood for microfilariae can be done. A skin biopsy can be performed but is usually reserved for tissue-dwelling nematodes such as Onchocerca volvulus infection. In the case of asymptomatic males with microfilaraemia, ultrasonography can be done to see scrotal lymphatics. PCR tests, lymphoscintigraphy, and immunochromatographic tests are can also be used.[29]

Hydatid cyst may reveal laboratory abnormalities, including elevated ALT, eosinophilia, and fibrinogen level. Elevated transaminases, bilirubin, and gamma-glutamyl transferase may signify the complication such as biliary obstruction. If cyst leaked into biliary structures or there is cyst rupture, gamma-glutamyl transferase and alkaline phosphatase may be significantly elevated along with eosinophilia; but these findings are usually absent in intact cysts. Imaging is the main diagnostic mode of a hydatid cyst, and the most commonly used method is ultrasonography. Other imaging modalities are CT scan, MRI, or MRI with MRCP.[32][33]

For intestinal taeniasis, enzyme-linked immunoelectrotransfer blot (EITB) for excretory-secretory antigens detection and enzyme-linked immunosorbent assays (ELISA) for coproantigen may be used. For neurocysticercosis, CT and MRI of the brain are the main modalities of neuroimaging tests. ELISA method is used as a serological test to detect the parasitic antigen in the serum and anticysticercal antibody in cerebrospinal fluid. Enzyme-linked immunoelectrotransfer blot (EITB) assay may also be a useful diagnostic test.[35][36][39][40]

Diphyllobothriasis is evaluated by appropriate clinical features and laboratory workup that may reveal megaloblastic anemia, pancytopenia, and eosinophilia. The presence of eggs or proglottids in the stool sample may use for diagnosis. Molecular methods such as PCR and restriction fragment length polymorphism are also an available method for diagnosis of D. latum.[13]

Treatment / Management

Proper hygiene maintenance is one of the most important measures to prevent helminth infection. For the treatment of A. lumbricoides, several drugs may be used, including albendazole, mebendazole, pyrantel pamoate, levamisole, and ivermectin. If patients develop intestinal obstruction, it requires proper treatment with intravenous support, anthelmintics, and antibiotic treatment. Laparotomy might be necessary in case of small bowel obstruction, intussusception, and volvulus. Hepatobiliary ascariasis can be treated with drug therapy. If conservative therapy fails, then endoscopic and surgical therapy may be required.[3][38][10]

Pharmacology

1. For trichuriasis, available drugs that might be used are albendazole, mebendazole, pyrantel pamoate, and ivermectin. If the symptom is severe or the patient develops anemia, iron therapy is provided, and supportive therapy is needed if a patient develops dysentery.[3][27][26][41]
2. For A. duodenale and N. americanus, recommended treatment options include albendazole or mebendazole. Iron supplementation is provided for additional nutritional support.[3][22]
3. For S. stercoralis treatment, benzimidazoles (thiabendazole, mebendazole, and albendazole) or ivermectin gives a very good response. In Strongyloides hyperinfection syndrome and disseminated strongyloidiasis, hydration, nutritional support, and antibiotics are needed as indicated; ivermectin should be continued for at least seven days or until sputum or stool samples are negative for the parasite for two weeks.[3][24]
4. For schistosomiasis, the drug of choice is praziquantel. Repeated treatment is needed in severe cases or if Katayama fever develops. Steroids may also be given during Katayama fever to decrease symptoms[19][20][11]
5. Lymphatic filariasis can be treated by several drugs, including ivermectin, suramin, mebendazole, flubendazole, and diethylcarbamazine. Other available options are surgical, thermal, and herbal treatment.[29][30]
6. Four different modalities are available for the management of cystic echinococcosis, which includes chemotherapy, percutaneous therapy, surgery, and observation without intervention. Benzimidazoles are the cornerstone of medical therapy.[32][33]
7. Treatment options for neurocysticercosis are symptomatic therapy such as anticonvulsants, analgesics, antihelminthic therapy, and surgery, which include worm removal surgery or shunt placement.[35][36]
8. Praziquantel is used for the treatment of diphyllobothriasis. Niclosamide is also another available drug.[13]
(B3)

Differential Diagnosis

• Nutritional deficiencies
• Anemia
• Asthma
• Cholecystitis
• Chron's disease
• Lymphedema
• Lymphogranuloma Venerum
• Tuberculosis
• Loffler syndrome
• Chronic obstructive pulmonary disease
• Inflammatory bowel diseases
• Acute bacterial gastroenteritis
• Amoebiasis
• Giardiasis
• Acute pancreatitis
• Biliary colic
• Intestinal volvulus
• Intussusception
• Encephalitis
• Meningitis
• Idiopathic epilepsy
• Biliary obstruction
• Biliary cirrhosis
• Portal hypertension
• Liver abscess
• Lung abscess
• Hepatic cyst
• Hypothyroidism
• Pernicious anemia
• Folic acid deficiency

Prognosis

Prognosis of helminthiasis depends on the extent of helminth infection. If the worm burden is high, ascariasis may produce some serious complications such as intestinal obstruction. Strongyloidiasis carries a good prognosis, although hyperinfection syndrome and disseminated strongyloidiasis carry a high mortality rate. For A. duodenale, and N. americanus infection, the prognosis is excellent, and appropriate anthelmintic treatment with iron and diet therapy completely cure the manifestations in most of the cases. The prognosis of echinococcosis mainly depends on the type of infestation.

Prognosis of cystic echinococcosis is generally good, and it may be cured completely if total surgical excision can be done without spillage. In alveolar echinococcosis, the prognosis is worse than cystic echinococcosis, and early detection with complete surgical excision can cure the disease. Diphyllobothriasis carries an excellent prognosis. Filarial diseases are rarely fatal, and the prognosis is generally good. In the case of schistosomiasis, hepatosplenic schistosomiasis carries a good prognosis because the hepatic function is preserved.

Patients with end-stage complications of portal hypertension, severe pulmonary hypertension, or cor pulmonale are much less likely to benefit from treatment. The prognosis of schistosomiasis is generally dependent on the worm burden. Prognosis of taeniasis is excellent who receives antihelminthic treatment, and it depends on the location of the cysts.

Complications

A lot of complications can occur in helminth infection, which may include:

• Anemia
• Malnutrition
• Growth retardation
• Developmental retardation
• Intestinal obstruction
• Gastrointestinal hemorrhage
• Cor pulmonale
• Portal hypertension
• Urinary bladder carcinoma
• Neurological complications such as seizure, myelopathy
• Primary and secondary infertility
• Ectopic pregnancy and tubal pregnancy
• Hypogonadism
• Systemic cysticercosis
• Cholangitis
• Cholecystitis
• Pancreatitis
• Cyst or Hydatid cyst rupture
• Chronic lymphatic damage
• Blindness