Amebiasis

The following sections are included:

• List of Contributors

• Contents

Study of the biology of Entamoeba histolytica has a long history but the organism has not yet yielded all of its secrets. However, in the past several years significant advances have been made in our understanding of the parasite. This chapter briefly summarises our knowledge of the basic biology of E. histolytica, concentrating on the more recent discoveries.

The following sections are included:

• Introduction

• Historical Background

• The Strains of E. histolytica and E. dispar

• Parasite and Disease Distribution

• Epidemiological Indices
  • Frequency of invasive amebiasis
  • Stool microscopy and serology
  • Isoenzyme electrophoresis
  • Antigen capture tests
  • Nucleic acid studies

• References

Tissue invasion by E. histolytica stimulates cell-mediated and humoral immune responses. Although innate defences may retard amebic invasion, acquired immunity is required for host defence and resistance to reinfection. Antigen-specific T cells directly lyse amebas in vitro and produce cytokines such as Interferon-γ that activate macrophages for in vitro amebicidal activity. Killing of E. histolytica by activated macrophages appears to be a major mechanism involved in anti-amebic defence. Depletion of macrophages in vivo allows or exacerbates amebic liver abscess development. In vitro, macrophages activated by recombinant cytokines exhibit potent amebic killing by a nitric oxide-dependent mechanism. Activated neutrophils and eosinophils express in vitro amebicidal activity and possibly contribute to control of infection in vivo. Antibody production does not correlate with protection against E. histolytica; ameba can cap and ingest or proteolytically degrade antibodies attached to its surface. In a primary invasive infection, acute disease is associated with suppression of cell-mediated immunity (CMI). In contrast, drug-cured patients and animals as well as immunized animals, which are resistant to challenge infection, displayed potent CMI responses in vitro. Hence, development of effective CMI appears key in controlling or resisting invasive amebiasis.

The ability of the E. histolytica trophozoite to invade the colon and other tissues, and to persist in the face of the host immune response depends upon adaptation and expression of pathogenic factors. These pathogenic factors control the capabilities for extracellular matrix destruction, contact-dependent cytolysis of host tissue, and development of complement resistance, which are important aspects of invasion. Transcriptional regulation of virulence factors may be an important mechanism for modulating the pathogenic potential of the parasite. This chapter presents the known molecular aspects of transcription and pathogenesis, focusing on the best characterized virulence factors of E. histolytica.

An estimated 10% of the world's population is infected with E. histolytica and E. dispar with associated mortality rates that are second only to malaria and schistosomiasis (1). International travel and large immigrant populations have caused infection with E. histolytica to emerge as a problem in industrial nations as well. The diagnosis of intestinal and extraintestinal amebiasis can be challenging to western physicians as symptoms mimic many other diseases. Recent advances in our understanding of the pathogenesis of amebiasis however, have had a significant impact on the early diagnosis and treatment of amebic infection (Reviewed in (2–4)). Furthermore, separation of Entamoeba into E. histolytica, which can cause invasive disease, and E. dispar, which cannot, allows the clinician to focus on early identification and treatment of E. histolytica infection in the minority of patients who are at highest personal risk and pose a major public health problem.

The treatment of amebiasis has two fundamental objectives: (i) to cure invasive disease at both intestinal and extra-intestinal sites and (ii) to eliminate the passage of cysts from the bowel lumen. Metronidazole has emerged as the drug of choice for the treatment of invasive disease. Other 5-nitroimidazole derivatives such as tinidazole, ornidazole, and secnidazole, available outside of North America, may be equally efficacious. Several lumenal agents are available to eradicate cyst passage. Diloxanide furoate is the preferred agent but is not readily available. Other effective agents include paromomycin and iodoquinol. One complicating factor in the use of these agents has been the overwhelming evidence that there exists a morphologically identical but genetically distinct non-pathogenic species, Entomoeba dispar. This organism does not cause disease and therefore requires no chemotherapy. Controlled trials with antigen detection kits and PCR-based assays that can distinguish E. histolytica from E. dispar are in progress. However, until these techniques are fully evaluated and widely available, treatment of asymptomatic cyst passers in non-endemic is suggested. Treatment of asymptomatic cyst passers in areas where E. histolytica is endemic remains a futile public health policy due to high rates of re-infection. In addition to chemotherapy, drainage of amebic liver abscesses using fine needle aspiration, guided by ultrasound or computed tomography, is a useful therapeutic intervention when (i) abscesses are extremely large and there is danger of imminent rupture, (ii) medical therapy has failed, (iii) a left lobe abscess threatens to rupture into the pericardium, or (iv) immediate symptomatic relief is required. Surgical intervention is reserved for toxic megacolon complicating amebic colitis or in cases where hepatic abscesses have ruptured into the peritoneal cavity.

The persistence of amebiasis as a global health problem, despite the availability of effective treatment, has led to the search for vaccines to prevent amebiasis. Recent progress in this area has been facilitated by the application of recombinant technology. Recombinant vaccines containing epitopes derived from the serine rich E. histolytica protein (SREHP), the 170 kDa subunit of the galactose-inhibitable lectin, and a 29 kDa cysteine rich protein, have been tested and found to be protective in animal models of amebic liver abscess. Oral vaccines, utilizing amebic antigens either co-administered with some form of cholera toxin, or expressed in attenuated strains of Salmonella or Vibrio cholera, have also been developed and tested in animals for mucosal immunogenicity. These new vaccine preparations show promise, but there are unanswered questions regarding the duration of immunity, and, as yet, the safety, immunogenicity, and efficacy of these vaccines in humans has not been established.

Controversial issues in management of patients with amebiasis include whether to treat asymptomatic Entamoeba infection, how to best use serology and newer diagnostic tests, when to aspirate an amebic liver abscess, and what is the optimal, most efficacious, and least toxic therapy for amebic liver abscess. These issues are discussed, evidence is presented, and expert opinions are provided.

The following sections are included:

• Introduction

• Pathogenicity in Amebiasis: Is it genetic or acquired

• Virulence of E. histolytica: Is it responsible for symptomatic and asymptomatic infections?

• Infections of E. dispar and E. histolytica in the same host

• Mysteries of the ameba genome

• Acknowledgments

• References