Amoebic Liver Abscess: Potential Application of New Diagnostic Techniques for an Old Pathogen

Amoebiasis is a frequent infectious disease caused by the protozoan parasite Entamoeba histolytica and is one of the most common causes of infectious diarrhea among travelers returning from endemic areas (estimated incidence of 14 patients in every 1000 returning travelers) [1]. Most infections are asymptomatic (luminal amoebiasis) and less than 20% of patients develop symptomatic infection. When E. histolytica disseminates, it can cause more severe infections such as watery or bloody diarrhea, which can ultimately result in massive bowel necrosis with perforation and peritonitis, or toxic megacolon [2,3,4]. Among extraintestinal manifestations (pneumonia, pericarditis, cerebral amoebiasis), liver abscess is the most common manifestation and develops more commonly in men than women, even more than 20 years after the last visit to an endemic area [5,6,7,8].

As a result of the fecal–oral route transmission, amoebiasis is distributed worldwide, especially in areas with poor sanitation such as the tropics; areas with the highest rates of infection include India, Africa, and Central and South America. The prevalence in the Americas between 1990 and 2022 ranged from 0.08% to 82.6%, being more frequent in Venezuela, Colombia, and Mexico [9]. However, the exact burden of amoebiasis is difficult to quantify because of the heterogeneity of studies, and the scarce diagnostic tools and screening programs in endemic countries [4].

Categories at higher risk for exposure are humanitarian aid workers, immigrants, and long-term travelers. It has been estimated that up to 50 million people are affected, mostly in developing countries, causing over 100,000 deaths every year [3, 4].

Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii, Entamoeba bangladeshi, Entamoeba coli, Entamoeba hartmanni, and Entamoeba polecki are seven species that infect the human intestinal lumen, although the last two are rare and considered nonpathogenic [3, 10].

After ingestion of mature cysts from contaminated food, water, or sexual contact, motile trophozoites are released in the small intestine and can pass through the colonic epithelium spreading to the peritoneum, liver, lungs, or brain. Symptoms may occur within weeks after ingestion but may develop even years after infection [9]. Amoebic liver abscess is caused by the unbalanced host’s immune response after the invasion of E. histolytica trophozoites in tissues with the recruitment of immune cells such as monocytes, neutrophils, and macrophages forming a capsule. The massive necrosis of hepatocytes causes the typical “anchovy paste” aspect of the fluid, when aspirated [11, 12].

Traditionally, the diagnosis and characterization of Entamoeba spp. have been based mainly on microscopy examination of protozoan morphology. However, this technique is time consuming, heavily affected by the operator’s skills, and is unable to differentiate among protozoa with similar morphological features. More recently, other research tools have become available, such as antigen and antibody detection. Since most people in endemic areas have been exposed to E. histolytica, antibody detection, mainly conducted by ELISA, is unable to distinguish past from current infection, and consequently needs a combination of antigenic test or PCR detection to confirm active disease. Moreover, serology may be falsely negative early in the course of the disease. Antigen detection, mainly performed on stools, has several advantages compared to other methods: it can differentiate between different species, it has a good specificity and sensitivity, and it can be carried out by non-experienced personnel [13]. A limitation of this method, however, is the ease of denaturation, which makes it possible to test only fresh or frozen samples and that an important reduction in sensitivity was observed when the patient had been exposed to antibiotic therapy [13, 14]. Molecular assays such as DNA detection by real-time PCR showed an impressive sensitivity and specificity (around 100%), an optimized turnaround time, and the ability to differentiate between different species. Therefore, PCR should be preferred when available and affordable over antigen detection and microscopy for definitive identification of E. histolytica. In fact, PCR-based assays avoid not only misdiagnosis but also overtreatment [15,16,17].

The FilmArray gastrointestinal panel has recently become available in some hospitals and can detect several gastrointestinal pathogens, including Clostridioides difficile toxin A/B, six diarrheagenic Shigella spp./E. coli, four parasites including E. histolytica, and five viruses. The results are available in 1 h and it has an overall 98.5% sensitivity and 99.2% specificity [18,19,20].

All patients with clinical disease need to be treated with a tissue-active agent (metronidazole or tinidazole) and a luminal cysticidal agent (paromomycin) [2, 4, 7, 17].

Here we present a clinical case of a patient with amoebic liver abscess promptly diagnosed by FilmArray gastrointestinal panel performed on liver drainage fluid.

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