Protozoal Infections

Protozoal infections are disorders caused by a variety of different organisms affecting multiple systems, causing a variety of many different signs and diseases. Amebiasis Because of its worldwide distribution and serious gastrointestinal manifestations, amebiasis is one of the most important parasitic diseases of humans. The major causative organism in amebiasis is Entamoeba histolytica, which inhibits the colon, and must be differentiated from the E. dispar, which is associated with an asymptomatic carrier state and is considered nonpathogenic. It is estimated that 50 million cases of invasive disease result each year worldwide, leading to an excess of 100,000 deaths. Pathology E. histolytica invades mucosal cells of colonic epithelium producing the classic flask-shaped ulcer in the submucosa. The trophozoite has a cytolethal effect on cells through a toxin. If the trophozoite gets into the portal circulation, it will be carried to the liver where it produces abscess and periportal fibrosis. Amebic ulcerations can affect the perineum and genitalia, and abscesses may occur in the lung and brain. Causes Amebiasis is caused by Entamoeba histolytica, a microscopic one-celled parasite. Amebiasis is most prevalent in tropical and subtropical countries where standards of public hygiene and sanitation may be low. People get amebiasis when they swallow Entamoeba histolytica cysts. This can happen by putting anything into the mouth that has touched the stool of an infected person. Trophozoites often live in the large intestine without causing any symptoms, but sometimes they invade the lining of the large intestine, causing intestinal disease called intestinal amebiasis. E. histolytica exists in two forms:

A cyst: which may be survived outside the body. A trophozoite: which may not be survived outside the body.

Transmission generally occurs through ingestion of cysts from food or water contaminated by feces. All household members should have their stools examined, because person to person transmission can occur. Humans are the principal reservoir of infection. Clinical Presentation The moat frequent clinical manifestations of the disease are gastrointestinal, with vague complaints of abdominal discomfort and malaise to severe abdominal cramps, flatulence, and bloody diarrhea with mucus. Right upper quadrant pain, hepatomegaly, and liver tenderness, with referred pain to the left or right shoulder, usually suggest an amebic liver abscess. Liver abscesses that are located in the right lobe can spread to the lungs and pleura. Pericardial infection, although rare, may be associated with extension of the amebic abscess from the left lobe of the liver. Erosion of liver abscesses also present as peritonitis. Eosinophilia is usually absent, although mild leukocytosis is not unusual in intestinal amebiasis. A patient with liver abscess, whoever, will usually present with left shift, elevated alkaline phosphate, and liver tenderness on palpitation. Complications Amebiasis Amebic colitis - Electrolyte imbalance and dehydration Necrotizing colitis - Intestinal perforation leading to peritonitis, septicemia leading to shock Ameboma - Intestinal obstruction Extraintestinal amebiasis Liver abscess (most common complication, associated with high morbidity rates) - Rupture to pleura, pericardium (leading to tamponade), bronchia, or peritoneal cavity (leading to peritonitis); amebic hepatitis Perianal perirectal abscess

Abscesses in other organs (eg, brain, kidney) Prognosis

Intestinal infections due to amebiasis generally respond well to appropriate therapy. The severity of amebiasis is increased in the following individuals: o Children, especially neonates o Pregnant and postpartum women o Those using corticosteroids o Those with malignancies o Malnourished individuals Mortality rate in patients with uncomplicated amebic liver abscess is less than 1%. Fulminant amebic colitis has a mortality rate of more than 50%. Pleuropulmonary amebiasis has a 15-20% mortality rate. Amebic pericarditis has a case fatality rate of 40%. Cerebral amebiasis is highly fatal with a 90% death rate.

Treatment In amebiasis, the goals of therapy are initially oriented to eradicate the parasite by use of specific amebicides and then to render supportive therapy. Metronidazole, tetracycline, dehydroemetine, and chloroquine are tissueacting agents, whereas iodoquinol, diloxanide furoate, and paromomycin are luminal amebicides. A systemic agent may be so well absorbed that only small amounts of the drug stays in the bowel, which might prove ineffective as a luminal agent. A luminal-acting agent, on the other hand, may be too poorly absorbed to be effective in the tissue. In the asymptomatic cyst-passer, it is necessary to eradicate the causative agent from lumen to prevent intestinal amebiasis or the development of amebic liver abscess. Drug effectiveness must be monitored by stool examination; that is, from one to three negative specimens from 1 to 3 months after treatment. Asymptomatic cyst passers and patients with mild intestinal amebiasis should receive one of the following luminal agents: paromomycin 25-30 mg/kg/day three times daily for 7 days, or iodoquinol 650 mg three times daily for 20 days, or diloxanide furoate 500 mg three times daily for 10 days. These regimens have cure rates between 85% and 94%. The pediatric dose for paromomycin is the same as in adults, whereas the dose of iodoquinol is 30-40 mg/kg/day in 3 doses for 20 days and the dose of diloxanide furoate is 20

mg/kg/day in 3 doses for 10 days. Paromomycin is the preferred luminal agent in pregnant patients. Patients with severe intestinal disease or liver abscess should receive Metronidazole 750 mg three times daily for 10 days, followed by a course of one of the luminal agents indicated above. An alternative regimen of Metronidazole 2.4 g/day for 2 days has been suggested to treat intestinal amebiasis. In the pediatric patients, the dose of Metronidazole 50 mg/kg/day in divided doses to be folloed by a luminal agent. Patients who are too ill to take oral Metronidazole should receive the drug in equivalent doses by IV route. Giardiasis Giardia lambila, an enteric protozoan, is the most common intestinal parasite responsible for diarrheal syndromes throughout the world. G. lambila has been identified as the first enteric pathogen seen in children in developing countries with prevalence rates between 15% and 30%. Pathophysiology Giardiasis is caused by ingestion of Giardia cysts. The infective dose is low in humans; 10-25 cysts are capable of causing clinical disease. Ingestion of more than 25 cysts results in a 100% infection rate. After ingestion of cysts, excystation, trophozoite multiplication, and colonization of the upper small bowel occur. The exact pathophysiology of giardiasis is unclear. Postulated mechanisms include damage to the endothelial brush border, enterotoxins, immunologic reactions, and altered gut motility and fluid hypersecretion via increased adenylate cyclase activity. Adhesion of trophozoites to the epithelium has been demonstrated to cause increased epithelial permeability. Giardia-induced loss of intestinal brush border surface area, villus flattening, inhibition of disaccharidase activities, and eventual overgrowth of enteric bacterial flora appear to be involved in the pathophysiology of giardiasis but have yet to be causatively linked to the disease's clinical manifestations. Most infections result from fecal-oral transmission or ingestion of contaminated water. Contaminated food is a less common etiology. Causes Giardiasis is caused by the ingestion of infective cysts.

Person-to-person transmission and poor hygiene are the primary means of infection. Giardiasis also may be contracted through the ingestion of contaminated water, a mechanism responsible for a significant number of epidemics in the United States. Giardia was implicated in 90 waterborne outbreaks in the United States from 1964-1984, affecting 23,500 persons. Venereal transmission occurs through direct fecal-oral transmission.

Complications Development of chronic illness with weight loss Malabsorption syndrome in adults Failure to thrive in children Symptoms Giardiasis can show itself in different ways. Some people can be carriers of the parasite and have no symptoms of the disease. A mild infection may not produce intestinal symptoms. In untreated giardiasis, symptoms wax and wane, with treatment, recovery is complete. Symptoms may include: diarrhea nausea rash vomiting headache constipation abdominal pain abdominal fullness abdominal cramps abdomen swollen loss of appetite low grade fever Prognosis Prognosis is generally excellent. Giardiasis is usually a self-limited acute disease, and several antibiotic agents are available with good efficacy rates to shorten the disease course.

Untreated, giardiases lasts for weeks.

Treatment Desired outcomes in the treatment of giardiasis include reducing morbidity and avoidance of complications in patients identified with prolonged diarrhea and malabsorption. All symptomatic adults and children older than 8 years of age should be treated with Metronidazole 250 mg three times daily for 7 days. The alternative drugs include Furazolidone 100 mg four times or Paromomycin 25-30 mg/kg/day in divided doses daily for 1 week. Paromomycin or Bacitracin or Bacitracin zinc may be safe agents in pregnancy. The pediatric dose for Metronidazole is 15 mg/kg/day three times daily for 5-7 days. Furazolidone suspension (50 mg per 15 ml) is an alternative drug for pediatrics. Special Concerns Pregnant patients No consistent recommendations exist for the treatment of pregnant patients because of the potential adverse effects of anti-Giardia agents on the fetus. If possible, treatment should be avoided during the first trimester. o Mildly symptomatic women should have treatment delayed until after delivery. o If the patient is left untreated, adequate nutrition and hydration maintenance are paramount. Failed treatment o Documenting the continued presence of Giardia in patients who appear unresponsive to treatment is important. o A significant number of patients develop post-Giardia lactose intolerance and present with symptoms consistent with persistent infection. These patients usually improve with time and the institution of a lactose-free diet. o If Giardia is present in the patient, a careful history should indicate whether this is a reinfection or a treatment failure. A second course of the same drug should be effective in reinfections, whereas the use of an alternative drug should be effective in true treatment failures.

 Trichomoniasis Trichomoniasis is a common sexually transmitted disease (STD) that affects both women and men, although symptoms are more common in women. Worldwide, approximately 180 million infections occur yearly. Prevalence of trichomoniasis was found to range from 5% in patients at family planning clinics to 75% in prostitutes. Pathophysiology In prepubertal girls, the healthy vaginal wall is thin and hypoestrogenic, the healthy vaginal pH is greater than 4.7, and culture of the vagina demonstrates a number of organisms. As the girl enters adolescence, the vagina thickens, and lactobacilli become the predominant species. The pH of the vagina decreases to less than 4.5. Lactobacilli are important in protecting the vagina from infection, and they remain the dominant, but not the only, flora of the vagina. The range of the incubation period, before symptoms of trichomoniasis develop, is 3-28 days. During infection with the protozoan Trichomonas vaginalis, jerky motile trichomonads may be observed on wet mount. The vaginal pH increases, as does the number of polymorphonuclear (PMN) leukocytes. PMN leukocytes are the predominant host defense mechanisms, and they respond to chemotactic substances released by trichomonads. T vaginalis destroys epithelial cells by direct cell contact and by release of cytotoxic substances. It also binds to host plasma proteins, thus preventing recognition by the alternative complement pathway and by host proteinases. Causes T vaginalis is a flagellated single-celled protozoan parasite. Incubation period averages 1 week but can have a range of 3-28 days. Trichomoniasis is predominantly an STD. The risk of acquiring this infection is based on the patient's level of sexual activity. Risk factors for T vaginalis include the following: o Number of lifetime sexual partners o Recent sexual partners o Not using barrier contraception o Using oral contraception

Signs and Symptoms Most men with trichomoniasis do not have signs or symptoms; however, some men may temporarily have an irritation inside the penis, mild discharge, or slight burning after urination or ejaculation. Some women have signs or symptoms of infection which include a frothy, yellow-green vaginal discharge with a strong odor. The infection also may cause discomfort during intercourse and urination, as well as irritation and itching of the female genital area. In rare cases, lower abdominal pain can occur. Symptoms usually appear in women within 5 to 28 days of exposure. Complications

Pelvic inflammatory disease Pregnancy o Premature rupture of membranes o Premature birth o Posthysterectomy cellulitis o Low birth weight infants

Prognosis

Metronidazole produces a 95% cure rate. Cure rate is even higher if sexual contacts are treated.

Treatment Metronidazole is the treatment of choice for Trichomonas vaginalis infection. In only few cases have T. vaginalis isolates been resistant to standard metronidazole doses. In theses instances, longer courses of therapy or doses higher than those routinely recommended as initial therapy usually produces a cure.
Type Symptomatic and asymptomatic infections Treatment in pregnancy Neonatal infections Recommended Regimen Metronidazole 2 g po in a single dose Metronidazole 2 g po in a single dose Metronidazole 10-30 mg/kg Alternative Regimen Metronidazole 500 mg po twice daily for 7 days

daily for 5 to 8 days