**6. Diagnostics**

The two assemblages (A and B) are composed of genetically distinguishable isolates, which may vary in infectivity, antigenicity, and virulence. In addition, human hosts vary in susceptibility to infection and disease and in the response to tolerance to infection. In this way, *Giardia* is an intraluminal parasite that adheres to the epithelium by way of an adhesive or sucking disk, although invasion of the epithelium either does not occur or is rare. Meanwhile, the number of trophozoites in the intestine can be so large that adherent organisms cover much of the epithelial surface. This could disrupt the epithelial brush border and contribute to lack

The clinical manifestations, course, and duration of *Giardia* infections are variable. In that way, infections may be self-limited or persistent, asymptomatic, or symptomatic. Usually, most patients remain asymptomatic, but when signs and symptoms occur and acute disease is established, manifestations happen normally in travelers and in outbreaks, and they are characterized by diarrhea, nausea, anorexia, dehydration, flatulence, eructation, distention, abdominal cramping, and weight loss. Contradictorily, fever and vomiting are uncommon

The first signs of infection appear after 6–15 days. Most symptomatic infections resolve spontaneously; however, sometimes, hospitalization is required when infections have longterm consequences and do not respond to the normal treatment. Chronic *Giardia* infections are reported frequently in nonendemic areas and also could result in irritable bowel syndrome, food allergies, arthritis, aphthous ulcers, or chronic fatigue syndrome after resolution

In some cases, if acute symptoms are not treated on time, they can develop into a chronic stage, which can affect all age groups but children are at higher risk, in whom *Giardia* infections have been associated with lower serum level of zinc, iron, and vitamins (A, B12, and folate); despite similar anthropometric indicators among infected and uninfected individuals in early childhood, the failure to thrive and poor cognitive function are characteristics in them. Furthermore, the loss of lactose is common and can persist for some weeks after treatment, which is why it is necessary to be distinguished in symptomatic patients from relapse or reinfection. In extreme cases, malabsorption and weight loss are severe and mimic sprue

A typical scenario is a mildly to moderately ill person who grumbles of a raised number of urgent loose stools, with flatus, cramping, anorexia, and weight loss. There may even be periods when the person feels better only to relapse and then become noticeably worse. Finally, after some days to several weeks, the person will seek medical help. Similar to other causes of infectious diarrheas, symptoms can carry on after successful treatment and evolve into irritable bowel syndrome and chronic fatigue, even 6 years after the infection. Infrequently, *Giardia* is also found in biliary and pancreatic ducts and can cause cholecystitis and pancreatitis, and other localizations reported are the urinary tract, gastric mucosa, and colonic and ileal

of disaccharidase as could be seen in some patients [8, 14, 15].

**5. Clinical aspects**

6 Current Topics in Giardiasis

[7, 13, 20].

[3, 10–12].

[1, 2, 8].

The diagnosis of giardiasis is based on the detection of cysts, trophozoites, or parasite-specific antigens in fecal microscopic examination, complemented with microscopic examination of duodenal fluids or in other biological samples. Polymerase chain reaction has been largely experimental, but it is being increasingly used in field and laboratory settings; considering that excretion of cysts may be variable or in low concentrations (50–80% sensitive), two or three checkups may be necessary, leading to a late diagnosis (>2 weeks) [3]. Stool antigen tests are standard in most laboratories and are highly sensitive (>90%), specific (~100%), and relatively inexpensive and do not require a trained microscopist [2, 9, 13, 18].

The observation of small intestine biopsy specimens or intestinal contents for trophozoites was the previous "gold standard" for diagnosis, but now, it is uncommonly needed to establish or to confirm the diagnosis. A number of morphological characteristics of the trophozoite can be used for the initial diagnostic, but it is not possible to identify which specific species by light microscopy, the reason why another type of test could be used in the medical approach. Electron microscopy might be useful for the identification of some *Giardia* species, but it is not applicable for screening or routine use [15, 18].

The use of immunological methods offers an important alternative for the diagnosis. The use of fluorescence microscopy and the direct fluorescence antibody test, which recognizes surface epitopes on cysts, has been reported to achieve relatively high specificity (99.8–100%) and sensitivity (93–100%) for the detection. The detection of *Giardia* antigens in fecal samples is another approach. Various enzyme-linked immunoassays have been used and report specificities of 87–100% and sensitivities of 63–100%. Flow cytometry is another technique to identify the *Giardia* cysts when immunofluorescent staining and microscopic examination and/or enumeration report unsatisfactory results [15, 18].

In some cases, the laboratory findings are nonspecific, and in low-intensity infections, testing methods can be false negative for which it is required to repeat the test. On the other hand, the white blood cell count and liver function test results used to be normal. The electrolyte disturbances could be present if diarrhea and vomiting are severe. White blood cells, lactoferrin, blood, and mucus are not found in stools. Immunoglobulin levels are usually normal but usually low or absent in susceptible hypogammaglobulinemic individuals [2, 3].

## **7. Treatment**

During the last 60 years of the past century, the arsenal of antigiardial drugs has been increasing, and they still are in use. Before the introduction of quinacrine, these infections were treated with mercury, carbon tetrachloride, arsenicals, and bismuth; at present, an important number of agents have shown to be efficacious against *Giardia* in vitro and clinically. Nevertheless, current investigations try to establish an appropriate treatment regimen in giardiasis, but none of them appear to fulfill most of the criteria for an ideal drug. In fact, giardiasis is regularly considered an easily treated infection, but at times, due to treatment failure, re-infection or postinfection syndromes can have a huge impact on quality of life of the patient, which is why it is important to know at least six different classes of drugs, with different mechanisms, indication, and contraindications [1, 2, 21].

The 5-nitroimidazole (5-NI) derivatives remain the most frequently prescribed drugs, as well as metronidazole, tinidazole, and secnidazole. In spite of their efficacy, the treatment with these drugs is associated with several adverse effects, which are not always tolerable such as headache, metallic or bitter taste in mouth, nausea, vomiting, diarrhea, dizziness, general body discomfort, loss of appetite, etc. Whereas medical opposition may limit the use of some of them in singular cases, as in pediatrics, where their dose requirements make difficult the administration of tablet formulations to children. Finally, in the follow-up of some patients after treatment to evaluate the response to antigiardial drugs, a therapeutic failure is identified [4, 7, 21, 22].

Nitazoxanide is a new very broad spectrum 5-nitrothiazolyl derivative with a potentially useful activity against a range of biological agents. The effect of nitazoxanide in *Giardia* trophozoite includes ultrastructural changes in the cell morphology, swelling, and the formation of large empty areas in the cytoplasm and the disruption of the plasma membrane. An overall response rate of 75–94%, usually well tolerated, and a few adverse effects are the reason to choose this medicament [1, 22].

Some patients, who are being treated with the standard treatment that cures other patients, can continue with symptoms. In these cases, there are possibilities of different situations, including drug resistance, cure followed by reinfection, and also noncompliance and post*-Giardia* lactose intolerance, because when a drug-resistant giardiasis is identified, the stage changes and it is necessary to use another antigiardial compound with a different mechanism of action or a drug combination [1, 2, 4].

When there is a resistant *Giardia*, some therapeutic strategies could be used, since increasing the alternative dose and/or duration of the same one, changing another antigiardial, or using a drug combination might exert the synergistic effects. For this reason, the combination of the therapy should be reserved when single primary agents have failed to clear the infection. However, it also should be considered that administration of two or three drugs may have more profound physiological consequences, alter the intestinal microbiota, and increase the drug-related adverse events and health care costs [8, 9, 22].
