Continuing Education Activity

Giardiasis, caused by the protozoa Giardia duodenalis (also called Giardia intestinalis and Giardia lamblia), is a prevalent small intestinal infection marked by symptoms such as watery diarrhea and flatulence. This activity reviews the evaluation and treatment strategies for giardiasis, emphasizing the crucial role of the interprofessional healthcare team in enhancing patient care. 

Objectives:

• Differentiate giardiasis from other gastrointestinal infections and disorders, ensuring precise diagnosis and appropriate treatment.

• Implement evidence-based guidelines for treating giardiasis, selecting appropriate medications and dosages for optimal patient outcomes.

• Select suitable medications and treatment regimens based on the patient's age, comorbidities, and individual factors, ensuring personalized and effective care.

• Communicate clearly with patients and other healthcare providers, providing detailed information about giardiasis, treatment options, and preventive measures, fostering patient understanding and cooperation.

Introduction

Giardiasis, an enteric infection caused by the protozoan parasite Giardia duodenalis,  is a common condition, especially in low-resource settings. Individuals with giardiasis often present with complaints of flatulence and watery diarrhea. G duodenalis, the flagellated protozoan responsible for the infection, ranks as the most commonly found intestinal parasite in the United States and is also recognized as the most prevalent protozoal intestinal parasite globally.[1][2][3][4] Giardia infections are more widespread among children than adults.

International travelers, outdoor enthusiasts, and daycare workers in the United States are the primary groups susceptible to this disease. While some individuals may remain asymptomatic, others can experience severe manifestations leading to dehydration and weight loss. Treatment with nitroimidazole or antihelminthic medication can be highly effective and often leads to a rapid recovery.[5][6][7]

G duodenalis can cause asymptomatic colonization or a diarrheal illness, which can either be acute or chronic. Studies have revealed its presence in up to 80% of water supplies sourced from lakes, ponds, and streams and around 15% of filtered water samples.[8][9] In developing countries, this parasite often causes chronic diarrhea and growth impairment in children. High-risk groups susceptible to giardiasis include immunocompromised individuals, travelers visiting highly endemic regions, and certain sexually active homosexual men. Members of these groups are frequently symptomatic.[10]

Etiology

Giardiasis is caused by the protozoan G duodenalis, also known as G lamblia and G intestinalis. Infected animals excrete cysts into freshwater, which remain infective and viable for weeks to months. There are 7 distinct genetic assemblages (A to F), but only genotypes A and B have been found to infect humans.[11][12][13]

Human infection occurs through ingesting cysts via contaminated water or direct person-to-person contact, with transmission heavily influenced by inadequate hygiene and sanitation practices. Daycares have emerged as epicenters of infection due to insufficient handwashing protocols, especially during diaper handling and changing.[14] Within the intestinal system, cysts undergo excystation, giving rise to trophozoites. These trophozoites are identifiable as pear-shaped flagellated protozoa with 2 nuclei.

Epidemiology

Giardiasis is the most prevalent enteric protozoal infection globally, affecting nearly 2% of adults and 8% of children in developed countries. About 33% of individuals in developing countries have been infected with giardiasis. Giardiasis spans temperate and tropical regions, with prevalence rates between 4% and 42%. In industrialized countries, prevalence rates are 2% to 5%. Giardiasis constitutes a significant cause of epidemic diarrhea among children in the developing world, with prevalence rates reaching 15% to 20% in those under 10 years.[15][16] Giardia is among the most common gut parasites in the United Kingdom, with particularly high infection rates in Eastern Europe.

The estimated prevalence of giardiasis in the US is approximately 1.2 million cases, although most of these cases go unnoticed because carriers remain asymptomatic. According to data from the Centers for Disease Control and Prevention (CDC), 15,223 cases were reported in 2012. Children aged 0 to 4 years were the most affected demographic group, with the largest percentage of cases being reported from the northwest US. Notably, Yoder et al observed that the prevalence in northern states could be associated with variations in state-level surveillance systems and may not reflect a higher incidence.[17] Giardiasis exhibits peak incidence during late summer and early fall, correlating with increased outdoor water activities.[18]

Protozoa are transmitted via the fecal-oral route, primarily through consuming contaminated water or food. Person-to-person transmission is also standard, while animal-to-person transmission occurs less frequently. An infected individual can shed 1 million to 1 billion cysts daily, while the infectious dose can be as low as 10. People with subclinical disease can act as carriers, potentially infecting others. Within the US, populations at risk include international travelers, wilderness enthusiasts, daycare workers, certain men who have sex with men, and professionals who have contact with human waste.[19]

Pathophysiology

The lifecycle of Giardia is uncomplicated, consisting of only 2 stages: 

1. Trophozoite: This is the active feeding stage of the parasite, residing freely within the human small intestine.
2. Cyst: This is the dormant and hardy stage, passed into the environment.

Intermediate hosts are unnecessary in the Giardia lifecycle. Upon ingesting water or food contaminated with cysts, these cysts enter the stomach and duodenum. In this environment, they undergo excystation triggered by exposure to acid and pancreatic enzymes. Within minutes of infection, trophozoites can appear in the duodenum.[20] These trophozoites then multiply rapidly in the small intestine. Encystation occurs in a neutral pH environment with secondary bile components upon reaching the large intestine. Subsequently, cysts are released into the environment, restarting the cycle.

The exact mechanism behind the symptoms of giardiasis remains unclear. Trophozoites possess a ventral disk, which they use to attach themselves to the intestinal epithelium. Researchers theorize that these protozoa disrupt small intestine epithelial cell junctions and brush border enzymes. Consequently, infected patients might display altered gastrointestinal motility. The protozoa release thiol proteinases and lectins that have a cytopathic effect. The combination of these effects increases permeability and impairs the processing of saccharides.[21]

Histopathology

A biopsy is rarely necessary for suspected giardiasis evaluation. However, when obtained in the evaluation of chronic diarrhea, the histopathological analysis may reveal normal to subtotal villous atrophy, with the degree of atrophy corresponding to the disease's severity. After treatment and symptom improvement, a follow-up biopsy typically reveals the restoration of typical villous architecture.[22]

History and Physical

Nearly half of the individuals infected with giardiasis are asymptomatic. The onset of symptoms is typically 1 to 2 weeks after infection for those with symptoms. Typical symptoms include abdominal pain, nausea, and flatulence, accompanied by large volume, watery, foul-smelling, and greasy stools. Children may present with abdominal pain with minimal diarrhea. Due to frequent loose stools, infected individuals often suffer from dehydration.[23] Fever is a less common symptom but can occur. In rare cases, patients might exhibit skin lesions and joint pain due to reactive arthritis. Symptoms typically resolve on their own within 4 weeks of onset. Individuals may present with weight loss and show signs or symptoms of vitamin deficiency in chronic infections.

Several factors, including the virulence of the isolate, the parasite load, and the host's immune response, influence the clinical presentation of giardiasis. Diarrhea is the most predominant symptom in acute cases, affecting 90% of symptomatic patients. Additionally, 70% to 75% of symptomatic individuals experience abdominal cramping, flatulence, and bloating. Chronic giardiasis is characterized by persistent diarrhea, weight loss, nausea, malaise, and anorexia. Postinfection lactase deficiency is another common occurrence.[24]

Extraintestinal manifestations in giardiasis are rare and can manifest as allergic reactions like urticaria, bronchospasm, erythema multiforme, reactive arthritis, and biliary tract disease. These symptoms are likely a result of the activation of the host's immune system.

The CDC advises healthcare professionals to include giardiasis in the differential diagnosis for individuals experiencing diarrhea lasting more than 3 days. When assessing patients, healthcare professionals should inquire about specific risk factors, including recent international or wilderness travel, exposure to unsanitary water, employment in daycare settings, and sexual practices.[25] Additionally, women of reproductive age should be screened for pregnancy, as this information is vital for determining appropriate treatment options.[26]

Physical examination findings are typically unremarkable, with mild dehydration being a common observation. Fever is rare but can occur. Mild, diffuse abdominal tenderness might be present upon palpation, and borborygmi may be audible on auscultation. Healthcare professionals should also assess for possible skin manifestations such as hives or granuloma annulare.[27] Rectal examination should reveal heme-negative stools. In advanced cases, signs of dehydration or wasting could be present.

Evaluation

Traditionally, giardiasis diagnosis involved identifying Giardia trophozoites or cysts through stool studies. However, more objective techniques, such as nucleic acid amplification techniques (NAATs), are now widely used.[28] Stool antigen enzyme-linked immunosorbent assays are also available.[29] These tests benefit screening in high-incidence situations, such as during an epidemic or in daycare centers. However, they should not replace stool microscopy. Stool antigen detection assays and NAATs are typically quicker, more sensitive, and more specific than microscopy.[30] Detecting Giardia through microscopy can be challenging as the protozoa only intermittently shed. The sensitivity of microscopy can be increased by collecting 3 stool samples on different days.[31]

Polymerase chain reaction (PCR) techniques can identify Giardia in stool samples, even at low concentrations such as 10 parasites/100 microliter. PCR may also help screen water supplies for the presence of the parasite.[32] Real-time PCR is effective in detecting both mild and asymptomatic infections.[33]

Standard ova and parasite laboratory testing might not routinely include Giardia testing. Therefore, the CDC advises healthcare providers to make specific requests for Giardia testing when submitting stool samples. Additionally, given that the differential for giardiasis includes other parasitic diseases, microscopy should be performed even if antigen or NAAT tests are obtained.

Routine laboratory tests, including complete blood count and electrolyte levels, typically yield unremarkable results in cases of giardiasis. Eosinophilia is an infrequent finding.

Esophagogastroduodenoscopy (EGD) could be considered in cases where the diagnosis is suspected but not confirmed after stool microscopy and ELISA. It is also helpful for patients experiencing persistent malabsorption despite appropriate therapy. A biopsy obtained during EGD can provide visual insights into histologic changes, such as a flattened surface with mild lymphocytic infiltration and the presence of trophozoites.[34]

Treatment / Management

Most patients presenting with giardiasis are nontoxic and may necessitate only oral rehydration for initial fluid resuscitation. In severe cases, intravenous (IV) fluids might be necessary.[35][36] Proper fluid and electrolyte management is crucial, particularly in large-volume diarrheal losses.

The standard treatment for giardiasis involves antibiotic therapy, with metronidazole being the first-line treatment for this condition.[37][38] However, metronidazole has challenges, including significant failure rates in clearing protozoa from the intestine and issues related to patient compliance.[39] Moreover, an escalating incidence of nitroimidazole-refractory infection has been reported, especially among travelers from India and other Asian countries.[40][41] Determining an optimal treatment strategy for such cases of giardiasis remains an ongoing challenge.[41]

Real-time PCR can be valuable in evaluating treatment efficacy. Research by Van den Bijllaardt et al revealed that samples typically turned negative approximately 1 week after treatment, indicating rapid clearance following successful therapy.[42]

The standard dosing for metronidazole is as follows:

• 250 to 500 mg 3 times a day for 5 to 10 days

Research suggests that once-daily dosing could be equally effective. Caution is advised when administering metronidazole to pregnant women, especially during the first trimester, due to the potential risks of cleft lip formation. Patients should be counseled on avoiding alcohol consumption to prevent the disulfiram effect, which includes symptoms such as flushing, headaches, and nausea.

Metronidazole is safe for children, and a typical dose is 30 mg/kg to 50 mg/kg per day divided into 3 doses. It is recommended to treat children experiencing failure to thrive with acute or chronic diarrhea, malabsorption, or other GI symptoms when Giardia organisms have been identified.[43]

Alternative treatment regimens for giardiasis include tinidazole, nitazoxanide, mebendazole, albendazole, and paromomycin. Paromomycin, which has poor systemic absorption, could be considered for a pregnant patient during her first trimester.[44]

Conflicting data exists regarding the most effective treatment for giardiasis. A systematic review found that albendazole may be as effective as metronidazole with fewer side effects.[45] If patients experience persistent symptoms despite therapy, a medication from another class should be used.

Generally, asymptomatic individuals do not require treatment, except in cases where it is necessary to prevent household transmission, especially from toddlers to pregnant women or patients with cystic fibrosis. Treatment is also recommended for patients with malabsorption associated with G intestinalis who require oral antibiotics for other infections.[46] Close contacts of the infected individual for giardiasis should be assessed and treated if infected. 

Differential Diagnosis

The list of diseases that should be considered in suspected cases of giardiasis is as follows:

• Traveler's diarrhea
• Lactose intolerance
• Inflammatory bowel disease [47]
• Cryptosporidiosis
• Tropical sprue
• Irritable bowel syndrome [48]
• Strongyloidiasis
• Viral gastroenteritis

Prognosis

The prognosis for patients with giardiasis is generally excellent, as most infections are self-limited. The mortality risk associated with giardiasis is low, with infants or malnourished children facing a slightly higher risk in cases of extreme dehydration. Several antibiotics are available and are reasonably successful in shortening the illness duration, although drug resistance has been reported in clinical cases. If left untreated, giardiasis can persist for weeks, as the parasite stays in the stool, and reinfection is possible.

Potential complications include weight loss, disaccharidase deficiency, growth retardation, and malabsorption.[49][50] G intestinalis has been identified as the primary cause of growth retardation in affected children, even after other causes of diarrhea are controlled.

Complications

Giardiasis can lead to the following complications:

• Irritable bowel syndrome
• Chronic illness with weight loss
• Malabsorption syndrome
• Disaccharidase deficiency
• Chronic fatigue syndrome
• Food allergies
• Reactive arthritis [51]
• Zinc deficiency in school-aged children [52]
• Persistent GI symptoms [53]

Patients presenting with these conditions should be screened for possible Giardia exposure.

Deterrence and Patient Education

Patients and individuals at risk should receive advice on proper hygiene methods and recognize the signs of infection. Emphasis should be placed on thorough hand washing after changing diapers. Additionally, daycare workers should be meticulous about hand hygiene to reduce transmission between children and staff.

Pearls and Other Issues

The essential pearls about giardiasis to understand are as follows:

• Giardiasis is caused by the protozoan parasite G duodenalis (G lamblia or  G intestinalis).

• Giardia spreads through ingesting contaminated water or food, person-to-person contact, or, less commonly, animal-to-person contact.

• Common symptoms include abdominal pain, nausea, flatulence, and watery, foul-smelling diarrhea. Children might experience abdominal pain with minimal diarrhea. Some individuals, especially children, may be asymptomatic carriers.

• Diagnosis involves stool studies, including microscopy and antigen detection tests. Polymerase chain reaction (PCR) techniques offer accurate results.

• Metronidazole is the standard treatment, although alternative medications like tinidazole, nitazoxanide, mebendazole, albendazole, and paromomycin can be used.
• Complications can include weight loss, disaccharidase deficiency, growth retardation, and malabsorption, particularly in children.

• Proper hygiene practices, such as thorough handwashing after using the restroom or changing diapers, and safe water and food consumption are essential to prevent giardiasis. Close contacts of infected individuals should also be assessed and treated if infected.

• Most cases have an excellent prognosis. In severe cases, especially in infants or malnourished children, dehydration can be a concern.

Enhancing Healthcare Team Outcomes

Giardiasis is a prevalent enteric infection, typically characterized by watery diarrhea and abdominal cramps in affected patients. A collaborative healthcare approach involving emergency department providers, nurse practitioners, and primary caregivers emphasizes the crucial role of hydration in achieving positive patient outcomes. Antibiotic treatment is reserved for individuals with severe symptoms, and in cases of uncertainty regarding the diagnosis or management, consulting an infectious disease specialist is recommended. Following treatment, symptoms resolve quickly; however, a minority of patients may experience sensitivity to dairy products for several weeks or months.