Giardia Lamblia (Giardiasis)

Giardia lamblia is an enteric flagellated protozoan of the Hexamitidae family, considered to be one of the most primitive eukaryotes based on rRNA sequence.(1) No giardial virulence factor is known and its ability to survive in diverse, hostile environments may be a key to its pathophysiology. Since G. lamblia is one of the few microbes to colonize the normal human small intestine, it may provide clues to physiologic host barrier functions and how the parasite avoids them. G. lamblia has two life cycle stages that adapt remarkably well to survival in different and inhospitable environments. The dormant, quadrinucleate, ovoid cyst form, which is responsible for transmitting giardiasis, persists in fresh water at 4°C.(2)

The parasite divides into two equivalent binucleate trophozoites that attach and specifically colonize the human small intestine.(4) Protective variant-specific surface proteins (VSPs) cover exposed surfaces of trophozoites and allow G. lamblia to survive in the small intestine, protecting the trophozoite surface from immunologic and environmental attack.(5,6) Trophozoites can change the VSP expressed on surface, expressing a single vsp at a time. Note: lowercase (vsp) = gene, uppercase (VSP) = protein. Variations of expressed VSP can occur spontaneously in vitro and in vivo every 6 to 13 generations.(7) Trophozoites use four pairs of flagella to “swim” in lumenal fluid and adhere to mucous strands in vivo and in vitro.(3)

VSPs differ in size and are rarely immunologically cross-reactive, suggesting that antigenic variation may be immune evasion.

Few microbes can colonize this complex and variable environment. Investigators have reproduced the G. lamblia life cycle in vitro by inducing encystation and excystation, enabling cell biologic and molecular studies of these important differentiation processes.(8,9) We must gain an understanding of the cellular pathways that enable this parasite to survive in the host small intestine and secrete the resistant cyst wall that protects it from the environment and gastric acid when infecting a new host. Figure 2-6 provides details on the clinical, biological weapon, and public health features of G. lamblia.

Clinical Features

Use as Biological Weapon

Public Health Issues

The basic biology of this parasite is not well understood

Cysts ingested in fecal-contaminated water or food;(3) gastric acid triggers excystation, but trophozoite is killed if it emerges from cyst before entering small intestine(4)

Trophozoites colonize below bile duct entrance, bathed in hydrogen ions, bile, proteases, digestive enzymes, and ingested food

Penetrate mucous layer and attach to intestinal epithelial cells via ventral adhesive disc

Chronic symptoms may last for months, as trophozoites may stay in small intestine for weeks or years

Trophozoites do not naturally survive outside the host

Can lead to diarrhea, bloating, dehydration, weight loss, and abdominal cramps

Antibiotic treatments: metronidazole (Flagyl), atabrine, or furazolidone

Some people asymptomatic; infections may resolve spontaneously

NIAID Biodefense Research initiative classifies G. lamblia as a Category B priority pathogen

Natural history of Giardia and 3- to 25-day delay before onset of symptoms render it a potential “natural” weapon

Frequent occurrence in United States makes it difficult to recognize as bioterrorism agent

Ingestion of 10–25 cysts resistant to standard chlorination is sufficient to initiate infection

The NIH supports a genome project on this water-borne parasite because of relevance to human health and early diverging position in molecular phylogenetic analyses

Current genome coverage is 7.6X and assembles into an 11.3 megabase genome that minimally accounts for 96% of its coding capacity

Although there is antigenic variation, there is little evidence of stable strain differences in virulence(2,5)

Although rarely fatal in the United States, diarrheal diseases cause infant death and malnutrition in less developed countries

Trophozoites can cause severe and protracted diarrhea in children that can lead to malabsorption and failure to thrive

One of most frequently identified causes of water-borne intestinal disease in the United States and worldwide

Persistent cause of diarrhea among daycare centers, hikers, and campers

Duration and symptoms of infection highly variable in immunocompetent people

References

1. Mandell GL, Douglas RG, Bennett JE, Dolin R, eds Principles and Practice of Infectious Diseases. (ed 4th). New York, Edinburgh, London, Madrid, Melbourne, Milan, Tokyo: Churchill Livingstone; 1995.
2. Nash TE, Aggarwal A, Adam RD, Conrad JT, Merritt JW, Jr. Antigenic variation in Giardia lamblia. J Immunol. 1988;141:636–641.
3. Adam RD. The biology of Giardia spp. Microbiol Rev. 1991;55:706–732.
4. Smith PD, Gillin FD, Spira WM, Nash TE. Chronic giardiasis: studies on drug sensitivity, toxin production, and host immune response. Gastroenterology. 1982;83:797–803.
5. Adam RD, Aggarwal A, Lal AA, de La Cruz VF, McCutchan T, Nash TE. Antigenic variation of a cysteine-rich protein in Giardia lamblia. J Exp Med. 1988;167:109–118.
6. Aley SB, Gillin FD. Specialized surface adaptations of Giardia lamblia. Infect Agents Dis. 1995;4:161–166.
7. Nash TE, Banks SM, Alling DW, Merritt JW Jr, Conrad JT. Frequency of variant antigens in Giardia lamblia. Exp Parasitol. 1990;71:415–421.
8. Boucher SE, Gillin FD. Excystation of in vitro-derived Giardia lamblia cysts. Infect Immun. 1990;58:3516–3522.
9. Gillin FD, Reiner DS, Boucher SE. Small-intestinal factors promote encystation of Giardia lamblia in vitro. Infect Immun. 1988;56:705–707.