Giardia Infection: Causes and Treatment
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Published: Wed, 30 May 2018
Giardiasis is the widespread infection of the small intestine. It is caused by a flagellate protozoan Giardia lamblia in humans. It is also known as Giardia intestinalis or Giardia duodenalis. It occurs all over the world but is more common in places where hygienic environment is insufficient and where drinking water are not treated properly and also among people using common swimming pools, travellers, and those who are in close contact with infected individuals, Giardiasis is more prevalent. Its highest prevalence occurs in tropical and subtropical regions. It is acquired by ingestion of contaminated food and water. It spreads through fecal-oral route. It is occasionally associated with disorders of gastrointestine such as irritable bowel syndrome, dysfunction of biliary tract. It may sometimes also involve with reactive arthritis, pruritus and few other health complications as indicated by case reports of few patients.
Giardiasis is infection of small intestine caused by Giardia lamblia in humans. Its life cycle has two stages: trophozoite and cysts. The clinical features are low grade fever and diarrhoea. Other symptoms are malabsorption and anorexia. The cysts are ingested and the gastric acid in the intestine stimulates the excystation and trophozoites, the active forms of the parasite are released. They reproduce by binary fission and attaches to the mucosal epithelium but do not invade it. They move down into the large intestine where they are encysted and are released out through feces. Highly prevalent in developing countries, travellers and people at day care centres are at higher risk of acquiring the infection. It is also common in tropics and subtropics. Gene sequencing and identification of restriction enzymes can be done in order to investigate the epidemiology. Immune evasion is done by the surface antigen variation during encystation and excystation. Incubation period is 9 to 15 days and appears of symptoms varies from person to person depending on factors like inoculums size, exposure time etc,. Few individuals remain asymptomatic and few develop symptoms. It causes lactase deficiency syndrome in few individuals after the treatment. It can be diagnosed by multiple stool tests, needle aspiration and immunological tests which can reveal the presence of the parasite. Few drugs are very effective in treating this infection and they are metronidazole, tinidazole , nitazoxanide. There is no vaccination and chemoprophylaxis to prevent this infection, so good hygiene conditions are to be maintained and only filtered water should be taken.
CAUSAL ORGANISM: The causal organism is Giardia lamblia. In 1859, it was first named as Cercomonas intestinalis by Lambl and later it was renamed by Stiles in 1915 as Giardia lamblia . It was first discovered by Antony van leeuwenhoek in 1681 while examining his own stool sample.
Genome structure: its genome contains five chromosomes with near about 12 million base pairs. The sizes of the chromosomes range from 0.7 to 3Mb. http://microbewiki.kenyon.edu/index.php/Giardia
CELL STRUCTURE: It has an oval shape and is 10-15 µm in length. It has two nuclei and a disk that helps in adhesion. It has 4 pairs of flagella, one at anterior end , two are posterior pairs and one caudal pair. Other cell organelles like mitochondria, lysosomes, golgi complex and endoplasmic reticulum are absent.
LIFE CYCLE: Its life cycle has two stages, they are trophozoite and cyst stages. Life cycle begins in the duodenum by the ingestion of cysts, from which the trophozoites are released .the sucking disk present on the ventral side helps in attaching it to the epithelial surface of the intestine. They swim freely in spiral motion while they are attached to epithelium . There reproduction occurs by binary fission. They undergo encystment and resistant, inactive cysts which are released into the surroundings through feces.
SURFACE ANTIGEN VARIATION: For surviving outside the host body, Giardia lamblia undergoes encystation. It is considered to be an adaptation to survive in the external atmosphere and these dormant cysts can pass through the stomach. Previously it was known that trophozoites which did not undergo encystment after the lifecycle , switched TSA417 which is a major variant surface protein (VSP) . this protein predominates in the cysts. And during the process of excystation it is down regulated. During the late encystation, during and after excystation new transcripts of the VSPs appear. While the VSPs present on the cell surface diminishes and they are internalised in vacuoles similar to lysosomes, the trophozoites appear to switch during the encystation. The switching of the VSPs of giardiasis is similar to switching of glycoproteins on surface of African trypanosomes. In all the VSP transcripts there is a polyadenylation signal that is extended for 15 nucleotides and this signal is unique as this does not occur in the other genes of giardia. These antigenic variations that occur during encystment and excystment ia an important form of immune evasion that is explaining the infection by Giardia. (Nash TE, 2002) http://www.ncbi.nlm.nih.gov/pubmed/12139606
CLINICAL FEATURES: symptoms differ in different persons infected and the appearance of symptoms depends on the individual host variability, parasite factors, and size of inoculum and duration of infection. Incubation period is 9 to 15 days. Symptoms may not appear in many of the infected adults and infected children and they remain asymptomatic. In others symptoms appear and remain for different time periods. Symptoms of the acute stage are low fever, chills, uneasiness of intestine, nausea and anorexia. Later symptoms such as watery diarrhoea with foul smell, belching with foul taste, gurgling in the abdomen and cramps in the upper and mid-epigastric regions also appear. In the stool, blood and mucus are rare. The symptoms of acute stage as similar to that of traveller’s diarrhoea.
Chronic infection which is long-standing may develop in few cases and intermittent diarrhoea is involved for two or more years. The symptoms that appear during the chronic phase are loss in weight which is continuous, anorexia, malabsorption along with lassitude, headache and also myalgia. Few other symptoms are uncommonly associated with giardiasis, and they are arthritis, retinal arteritis and iridocyclitis.
Normal hemogram and rare eosinophilia are seen in patients infected with giardiasis. Fat, glucose, lactose, xylose, vitamin A, vitamin B12 are the metabolites which are malabsorbed in some patients. Intolerance to lactose is frequently present during the infection and it persists for variable time periods and treatment against Giardia should be considered carefully.(Martin S.Wolfe,1992)
PATHOGENESIS: The specific mechanism of causing the disease is not clearly known and the virulence factors responsible for this are not identified. Ingestion of the cysts from the contaminated food and water can cause the infection .They transform into the trophozoites stage, which is the active form in the stomach and enter duodenum. Binary fission of trophozoites occurs and a number of trophozoites are produced in the duodenum.
Disease is caused due to the following reasons:
- The intestinal mucosa is blocked by the large number of parasites.
- The parasite develops competition with the normal cells of the intestine for the required nutrients.
- In the intestine the secretary antibody IgA may be deficient.
- Intestinal mucosal inflammation.
- Crypts of the intestinal wall are elongated called as crypt cell hypertrophy and microvillus are shortened(atrophy).
Deficiency of lactase and few other enzymes can also be caused as a result of Giardia infection in the microvillus. The malabsorption syndrome of giardiasis can be explained by the osmotic diarrhoea which occurs due to the reduced digestion and less absorption of solutes. Therefore, there is no unifying mechanism which can explain its pathogenesis. During active stage of infection of Giardia some individuals may be intolerant to lactose and this may persist even after the clearance of parasite by using anti-giardia drugs. This is due to the deficiency of lactase induced by the parasite. Lactose is broken down into absorbable monosaccharide by an enzyme called lactase. Persons with no detectable parasites but with mushy stools and excess gas after the treatment can be considered to have this syndrome.
LABORATORY DIAGNOSIS: Giardia lamblia is many times wrongly diagnosed to normal diarrhoea. Multiple stool tests are recommended to diagnose it correctly because of the reason that the cysts may not be shed continuously and many a times the result can be negative although the person is infected. giardiasis can be diagnosed in humans by performing some of the clinical examinations. They are:1. Stool examination: Ova and parasite exam (o+p) of one to three specimens on non-consecutive days, this is done to improve sensitivity. It is done to look for the presence of ova or parasite in the stool sample that can infect the intestine, by examining the slides of the stool samples from the patients suffering from diarrhoea.
Duodenal drainage examination: This is the technique used to reveal the presence of parasites which are not usually detected using the regular stool examinations. The causal organism is generally trapped in the mucus strands and their flagella may not move freely. The duodenal fluid consists of mucus with the organisms trapped in it. The specimen is collected and is centrifugated, so that the mucus that is sedimented can be examined . light intensity should be kept low for this microscopic examination. Fluorescent antibody can be used with formalised material. If it is presumptively diagnosed as giardiasis, it can be further fixed with poly vinyl alcohol and stained subsequently with iron hematoxylin or trichrome. If the amount of specimen available is small, rather than the wet preparations, permanent slides can be prepared, which give a better approach in diagnosing the disease by observing the stained slides under oil immersion at a magnification of X1000.( Weissfeld, A S, et al 2007)
Collection of duodenal fluid with the string test (Entero test): This duodenal capsule test or the entero test is the simple and convenient method that helps in diagnosing giardiasis without the need of intubation of intestine. In this technique a gelatine capsule in which a length of nylon cord is coiled is used. The one end of this cord is taped to the patients face and the capsule is then swallowed. In the stomach, gelatine is dissolved and the weighted cord is carried into the duodenum by the peristaltic movements. The cord is retrieved after 4 hrs and is released out through stool. Examining the mucus that is collected from the cord for the presence of parasites is done with a microscope. .( Weissfeld, A S, et al 2007)
Immunologic tests: certain immunologic tests such as counter current immuno-electrophoresis, enzyme immunoassay, immuno-chromatographic assay and indirect immuno fluorescent staining are available commercially. ( Weissfeld, A S, et al 2007)
Needle aspiration: Needle aspiration is done into the gastrointestine to detect the parasite in the intestine. The needle aspiration is guided by the endoscopic ultrasound. .( Weissfeld, A S, et al 2007)
EPIDEMIOLOGY: In the most developing countries the prevalence of giardiasis is about 20 to 30 % and in the developing countries it is 2 to 7%. Many cases of giardiasis are reported in the United states every year. Nearly 2.5 million cases are being reported annually in United states. Epidemiological rates of infection with cysts are not investigated thoroughly but there are about two-thirds of asymptomatic infected people. It is more common to occur in tourists who travel to the developing countries. A number of studies also revealed the prevalence of the disease in the homosexual males involving the fecal and oral activities of sex. The day care centres with young children and the nursing homes are at high risk of spreading the disease. Most of the cases of giardiasis are reported in summer as the climate is suitable and the public swimming pools are more at usage by large groups of people. In the untreated sewage levels of giardia are ranged between 10,000 and 100,000 cysts/L , in the treated sewage its range is between 10 and 100 cysts/L and in tap water 10 or few cysts/L. The giardiasis outbreak in United states is generally reported due to the contamination of drinking water by improper handling of food, child-care workers and also by maintaining other unhygienic cconditions. http://en.wikipedia.org/wiki/Giardiasis#Physical
Giardia lamblia isolates are classified effectively which can possibly facilitate a better understanding of its epidemiology. From the origins of various hosts, a number of G.lamblia are isolated and the particular gene that encodes an enzyme triose phosphate isomerise, which is a metabolic enzyme was sequenced in order to develop a classification system that is sequence based. Later on, without the requirement of gene sequencing, the isolates are then distinguished among themselves by the identification of the restriction enzymes .This further simplified the investigation of epidemiology . The utility of this technique was verified by measuring the accuracy of the epidemic results of the gene sequenced isolates to this.(Baruch AC et al, 1996)
IS GIARDIASIS IN HUMANS CAUSED BY TWO DIFFERENT SPECIES OF GIARDIA? : Genome sequencing was carried out in the isolates of assemblages A and B .These two genotypes assemblages A and B are known to cause giardiasis in humans. Assemblage A WB parasites genome was sequenced and it has 11.7 Mbp, which contains all the required cell machinery. The sequencing of the assemblage B GS was also carried out and and this was the only isolate of Giardia which was effective in infecting humans and also other animals. The similarity in genomes of these isolates is 77% in nucleotides and in amino acids it is 78%. Of these two isolates, variable surface proteins, 28 of unique GS , and 3 unique genes that code for proteins in WB isolate are different entirely. The GS genome is tetraploid and it has allelic sequence polymorphism which is of higher level. Between the two isolates WB and GS, there are differences both clinically and biologically which are explained by the differences in the genome and thus both assemblage A and B are the species of Giardia which can infect humans.(Oscar F, etal, 2009)
MICROBIAL RISK ASSESSMENT: There is a quantitative risk of Giardia in water supplies that are extremely small. And water borne diseases are out broken from such small supplies of water. Regression equations were derived using the existing data, these equations give the relation between the concentrations of the pathogen and E.coli in these small supplies and is compared to that of the national surveillance data and found to contain more concentrations of pathogens and it may increase in more poorer supplies of water. These concentrations are more than the tolerable limit. And there are more chances of people acquiring this infection.( Hunter PR , et al,2010) http://www.ncbi.nlm.nih.gov/pubmed/20880218
EFFECT OF GIARDIAIS ON STATUS OF VITAMIN A: A persons predisposition to an infectious disease is increased by the compromised natural and acquired immunity. This compromised immunity can be caused due to vitamin A deficiency(VAD). In giardiasis, the architecture of the intestine is changed, and it malabsorption of vitamin A occurs. And therefore giardiasis is related to the deficiency of vitamin A. Its relation was studied in school children of Mexico, who were affected by giardiasis. Levels of vitamin A were recrded during infection and after the treatment. They had nutrition that is normal and vitamin A was adequate. Only 22 of thirty children had adequate amount of vitamin A daily. After the treatment of giardiasis, levels of serum retinol were improved and sub clinical VAD was reduced. Hence, vitamin A status had a negative effect by Giardia lamblia and their predisposition was increased, to infectious diseases.( Veronica LT. Et al, 2010) http://www.fasebj.org/cgi/content/meeting_abstract/24/1_MeetingAbstracts/716.8
TREATMENT: Giardiasis can be treated by giving suitable drugs to the infected patients and also to the people who are in close contact with the infected individuals, as they may be infected but remain asymptomatic in the early stages of infection. Several medicines are prescribed for treating giardiasis, which can cure about 80% of the infected people. The same medicine is recommended for a longer period of time or a different medication may be recommended if the symptoms of giardiasis do not disappear with the treatment of a particular drug. In the patients with chronic giardiasis, parasite may be killed by the treatment, but the improvement of the symptoms is delayed. Even after the treatment with several medicines, if a patient do not recover from the symptoms of the infection, causes of reinfection are explored. http://diarrhea.emedtv.com/giardia/giardia-treatment.html
The medicines which can treat the giardiasis in humans are metronidazole, tinidazole , nitazoxanide. Metronidazole is avoided during the pregnancy due to its mutagenecity in bacteria and carcinogenic nature in mice. Though it is the first line of treatment. It is carcinogenic in other mammals but It does not cause cancer directly in the humans and can be used safely. Another common treatment used as an alternate is berberine sulphate and it has antimicrobial and antipyretic effects. This should be also avoided during the time of pregnancy as it may cause uterine stimulation. It may lead to hypotension in few individuals when used continuously. There are possible side effects with each of these drugs. They are listed as follows:
Treatment duration: 5-7 days
Possible Side Effects: Metallic taste; nausea; vomiting; dizziness; headache; disulfiram-like effect; neutropenia
Treatment duration: Single dose
Possible Side Effects: Metallic taste; nausea; vomiting; belching; dizziness; headache; disulfiram-like effect
Treatment duration: 3 days
Possible Side Effects: Abdominal pain; diarrhea; vomiting; headache; yellow-green discolouration of urine
Treatment duration: 5 days
Possible Side Effects: Dizziness; headache; fever; nausea; vomiting; temporary hair loss
PREVENTION: No vaccine is developed for the prevention of giardiasis and no chemoprophylaxis is recommended. So maintaining good hygienic conditions like washing hands every time before eating and after using bathroom is the best way to prevent the disease. Consumption of contaminated water and untreated water should be avoided, water from the public swimming pool should not be swallowed. Only bottled water and clean food has to be taken. One should be very careful about the intake of food and water when travelled to the developing countries. and avoid fecal exposure during the sexual activity.
CONCLUSION: Giardiasis in humans caused by two assemblage isolates A and B of Giardia is a water borne disease and transmits through fecal- oral route. It has no vaccination, so it can be prevented only by maintaining hygienic surroundings and by practising hygienic food habits.
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