JV Anandan
KEY CONCEPTS
The drug of choice for giardiasis in a first-term pregnant patient is paromomycin 25 to 35 mg/kg/day in divided doses for 5 to 10 days.
Stool samples for amebiasis may not be ideal for differential diagnosis of species and the specific antigen test for definitive diagnosis of Entamoeba histolytica is the ELISA (Entamoeba histolytica II Kit) test.
Asymptomatic cyst passers and patients with mild intestinal amebiasis should receive one of the following luminal agents: paromomycin 25 to 35 mg/kg/day three times daily for 7 days, iodoquinol 650 mg three times daily for 20 days, or diloxanide furoate 500 mg three times daily for 10 days.
With the unavailability of pyrantel pamoate, either mebendazole (Vermox) or albendazole (Albenza) is the drug of choice for hookworm, ascariasis, enterobiasis, and trichuriasis.
Administration of corticosteroids or other immunosuppressive drugs to an infected individual with strongyloidiasis can result in hyperinfections and disseminated strongyloidiasis.
The most serious complication of cysticercosis is invasion of the CNS, which results in neurocysticercosis. Neurocysticercosis can cause obstructive hydrocephalus, strokes, and seizures; antihelminthic treatment for these conditions remains controversial.
When IV quinidine is not readily available, IV artesunate (available under an investigational new drug (IND) from the CDC at www.cdc.gov/malaria/features/artesunate_now_available.htm), a water-soluble artemisinin derivative, administered at 2.4 mg/kg/dose for 3 days at 0, 12, 24, 48, and 72 hours is the recommended drug if severe Plasmodium falciparum is suspected.
Because falciparum malaria is associated with serious complications, including pulmonary edema, hypoglycemia, jaundice, renal failure, confusion, delirium, seizures, coma, and death, careful monitoring of fluid status and hemodynamic parameters is mandatory. Either hemofiltration or hemodiafiltration is indicated in renal failure.
The two drugs that are available in the United States (obtained from CDC) to treat Trypanosoma cruzi infections are nifurtimox (Lampit) and benznidazole (Rochagan). Benznidazole is used as the drug of choice in South America.
Permethrin (1% and 5%) for pediculosis and scabies, respectively, is the preferred agent and remains the safest agent, especially in infants and children. Spinosad crème rinse 0.9% and benzyl alcohol 5% are new agents for head lice.
Parasitic diseases continue to receive increasing attention from clinicians in the United States because of the high frequency of travel, deployment of personnel for humanitarian and military missions (e.g., Peace Corps volunteers), inflow of immigrants from a wider geographic distribution, and the presence of immunosuppressed populations (e.g., acquired immunodeficiency syndrome [AIDS] and transplant patients). Migrant farm workers who work and live in substandard hygienic conditions, the large and growing Central and South American immigrant population, and other inadequately screened immigrants from Asia represent significant sources of parasitic infections in the United States.1–9 Clinicians need to have a heightened awareness of parasitic diseases and how to treat them. Clinical signs and symptoms, together with the patient’s travel history, should be used with other diagnostic aids in the identification of parasitic diseases. Parasitic infections caused by pathogenic protozoa or helminths affect more than 3 billion people worldwide and impose tremendous health and economic burdens on developing countries.9
This chapter discusses the major parasitic diseases, including protozoan diseases (giardiasis, amebiasis, malaria, and Chagas disease), helminthic infections (ascariasis, enterobiasis, hookworm, strongyloidiasis, and cestodiasis), and ectoparasitic infestations (head and body lice). Emphasis is placed on diseases seen more frequently in the United States. World distribution of parasites depends on the presence of suitable hosts, habitats, and environmental conditions.9 A human parasite that does not use an intermediate host is likely to be found in any inhabited region of the world as long as the environmental conditions are suitable. Ascaris (roundworm) and Trichuris (whipworm) require carelessness of habits for transfer and require time outside the human body, where they are exposed to heat and dryness, to reach the infective stage. The distribution of the hookworm is more limited because the free-living forms are unprotected by resistant shells or cysts. African trypanosomiasis never occurs outside the range of the tsetse fly; malaria normally never occurs beyond the range of the infective Anopheles mosquito; and schistosomiasis never occurs in the absence of a specific water snail. The prevalence of clonorchiasis (Chinese liver fluke) is an example of the impact of both environmental and geographic factors. Clonorchiasis requires the simultaneous presence of not only humans, specific snail species, and certain fish, but also unsanitary conditions that make the eggs accessible to the snails, an association of the snail and fish, and the established local habit of eating raw fish. The ability of some parasites to infect hosts other than humans may perpetuate an infection even when human habits preclude the possibility of more than occasional access to the human body. In North America, the broad tapeworm (Diphyllobothrium latum) would perish if it were not that dogs and other carnivores, such as the brown bear, serve as reservoir hosts.
HOST–PARASITE RELATIONSHIP
Symbiosis is the association of two species for the purpose of obtaining food for either one or the other. Parasitism is a symbiotic relationship in which one species, the host, is injured through the activities of the other. Through evolution, parasites have made specific morphologic adaptations. Adaptation to the host has taken a number of forms: loss of locomotor organelles in the protozoan Sporozoa; partial and complete lack of digestive systems in the trematodes and cestodes, respectively; elaboration of proteolytic enzymes to penetrate the host intestinal mucosa by Entamoeba histolytica; the cercariae of the blood fluke that penetrate the skin of the host by elaborate enzymes; and, finally, the ability to infect an intermediate host to increase reproductive capacity, as seen among the cestodes and trematodes.9
Parasites normally inflict some degree of injury to the host, the extent of which depends on such factors as parasite load, nutritional status, and immunologic competence of the host. Entamoeba coli is considered commensal because it subsists on the bacterial flora of the gut and does not cause any harm to the host. Unlike Entamoeba coli, Fasciolopsis buski, the giant intestinal fluke, can produce severe local damage to the intestinal wall. Ascaris, the roundworm, can perforate the bowel wall, cause intestinal obstruction, and invade the appendix and bile duct. Malarial parasites destroy red blood cells by multiplying inside them. D. latum, or the broad fish tapeworm, removes vitamin B12 from the GI tract, resulting in megaloblastic anemia.9
PROTOZOAN DISEASES
Giardiasis
Epidemiology and Etiology
Giardia lamblia (also known as Giardia intestinalis or Giardia duodenalis), an enteric protozoan, is the most common intestinal parasite responsible for diarrheal syndromes throughout the world.10–13 Giardiais the most frequently identified intestinal parasite in the United States, with a prevalence rate of 15% in some areas. G. lamblia is the first enteric pathogen seen in children in developing countries, with prevalence rates between 15% and 30%.12
There are two stages in the life cycle of G. lamblia: the trophozoite and the cyst. G. lamblia, which is found in the small intestine, gallbladder, and biliary drainage, is a pear-shaped trophozoite with four pairs of flagella. Two nuclei lie in the area of the sucking disk, giving the protozoan a characteristic face-like image.
The distribution of giardiasis is worldwide. Children seem to be affected more frequently than adults. Children in day care centers may infect parents and other family members.12 In less developed countries, fecal contamination of the environment and lack of potable water, education, and housing continue to be risk factors for giardiasis among children.
Pathology
Giardiasis results from ingestion of G. lamblia cysts in fecally contaminated water or food. The protozoan excysts under the stimulus of low gastric pH to release the trophozoite.12 Colonization and multiplication of the trophozoite lead to mucosal invasion, localized edema, and flattening of the villi, resulting in malabsorption states in the host.10,12
Lactose intolerance precipitated by giardiasis and iron deficiency can persist even after eradication of the protozoan. Achlorhydria, hypogammaglobulinemia, or deficiency in secretory immunoglobulin A (IgA) are predispositions for giardiasis.10,12,14 Table 93–1 describes the clinical presentation of giardiasis.
TABLE 93-1 Clinical Presentation of Giardiasis
Diagnosis of giardiasis is made by examination of fresh stool or a preserved specimen during the acute diarrheal phase. Fresh stool specimens may show the trophozoites, whereas preserved specimens usually yield the cysts. Three stool specimens for ova and parasites (O&P) will yield up to 90% of the parasites.10 Since detection of the trophozoites or cysts in fecal samples by enzyme-linked immunosorbent assay (ELISA) or immunofluorescence or identification of the Giardia antigen by counterimmunoelectrophoresis are readily available in most laboratories, and these tests are frequently utilized to identify Gardiabefore initiating therapy.10,12,15
TREATMENT
Desired Outcome
To reduce morbidity and to avoid complications in patients identified with prolonged diarrhea and malabsorption and who have a recent history of travel to an endemic area, rapid identification by the O&P examination or by the antigen detection test should be used to institute appropriate therapy.10,12
Pharmacologic Therapy
All symptomatic adults and children older than 8 years of age with giardiasis can be treated with metronidazole 250 mg three times daily for 5 to 10 days, or tinidazole 2 g once, or nitazoxanide 500 mg twice daily for 3 days.16 The alternative drugs include furazolidone 100 mg four times daily or paromomycin 25 to 35 mg/kg/day in divided doses daily for 1 week.10,12,16,17 Paromomycin 25 to 35 mg/kg/day in three doses for 5 to 10 days is a safe agent in pregnancy.10,12,16 The pediatric dose for metronidazole is 15 mg/kg/day three times daily for 5 to 7 days.16 The pediatric dose of tinidazole is 50 mg/kg (maximum 2 g) once while nitazoxanide (Alinia) suspension is dosed at 100 mg every 12 hours (1 to 3 years), 200 mg every 12 hours (4 to 11 years), and the adult dose is recommended for children older than 12 years; all are administered for 3 days.12,16 Quinacrine, which was the drug of choice in giardiasis, has been discontinued by the manufacturer but is obtained in the United States from a specialized pharmacy (see Appendix 93–1). Albendazole 400 mg daily for 5 days has variable cure rates (55% to 95%). Tinidazole (50 mg/kg—single dose) and metronidazole regimen may be considered equivalent in children.10,13,17
Evaluation of Therapeutic Outcomes
Patients with symptomatic giardiasis, positive stool samples, or the detection of Giardia antigen by counterimmunoelectrophoresis or ELISA should be treated with metronidazole for 5 to 7 days. Metronidazole produces cure rates of between 80% and 90%.10,17 Diarrhea will stop within a few days, although in some patients it may take 1 to 2 weeks. Cyst excretion will cease within days; however, intestinal dysfunction (manifested as increased transit time) and radiologic changes (irregular thickening of the folds in the upper small intestine) may take a few months to resolve.10 Patients who fail initial therapy with metronidazole should preferably be treated with a drug from a different class. Nitazoxanide (500 mg twice daily for 3 days) is effective in patients who are not responding to metronidazole.12Pregnant patients can receive paromomycin 25 to 35 mg/kg/day in divided doses for 7 days. Metronidazole has been used in the second and third trimesters of pregnancy.12 Giardiasis can be prevented by good personal hygiene and by caution in food and drink consumption.
Amebiasis
Epidemiology and Etiology
Because of its worldwide distribution and serious GI manifestations, amebiasis is one of the most important parasitic diseases of humans.9,18–21 The major causative organism in amebiasis is E. histolytica, which inhabits the colon and must be differentiated from the Entamoeba dispar and a recently identified species, Entamoeba moshkovskii that are associated with an asymptomatic carrier state. E. dispar is considered nonpathogenic, while the status of E. moshkovskii remains to be defined.19 Although E. histolytica and E. dispar are indistinguishable morphologically, monoclonal antibodies have been used to separate the two.20,21 The E. histolytica II kit (TechLab, Blacksburg, VA) remains the most specific antigen test for E. histolytica.19 Invasive amebiasis is almost exclusively the result of E. histolytica infection. Approximately 50 million cases of invasive disease result each year worldwide, leading to an excess of 100,000 deaths.21 The incidence of amebiasis is estimated at approximately 1% in the general U.S. population.21 The highest incidence is found in institutionalized mentally retarded patients, sexually active homosexuals, patients with AIDS, and new immigrants from endemic areas (e.g., Mexico, India, West and South Africa, and portions of Central and South America).19,21
Pathology
E. histolytica invades mucosal cells of colonic epithelium, producing necrotizing ulcers in the submucosa.19–21 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.19–24 Amebic ulcerations can affect the colon, perineum, and genitalia, and abscesses may occur in the lung and brain.20–24
Clinical Presentation
The most frequent clinical manifestations of the disease are GI (Table 93–2).
TABLE 93-2 Most Common Manifestations of Amebiasis
Amebic liver abscesses can spread to the lungs and pleura.20,21 Pericardial infections, 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.19–22
Review of the patient’s history and recent travel should be strongly emphasized. Intestinal amebiasis is diagnosed by demonstrating E. histolytica cysts or trophozoites (may contain ingested erythrocytes) in fresh stool or from a specimen obtained by sigmoidoscopy. 
Stool samples are insensitive and do not distinguish between E. histolytica and the nonpathogenic E. dispar or E. moshkovskii. Sensitive techniques are available to detect E. histolytica in stool (these are rapid tests within 2 hours) including ELISA, antigen detection (E. histolytica II kit), and polymerase chain reaction (PCR).19–21,23 Endoscopy with scraping or biopsy may provide more definitive diagnosis where stool examinations do not provide adequate evidence.19,21
When amebic liver abscess is suspected from initial physical examination and history, confirmatory diagnostic procedures will include serology and liver scans (using isotopes by ultrasound or computed tomography) or magnetic resonance imaging.20,21 Leukocytosis (>10,000/mm3 [>10 × 109/L]) and an elevated alkaline phosphatase concentration (>75%) are common findings. In rare instances, needle aspiration of the hepatic abscess may be attempted using ultrasound guidance.22,24
TREATMENT
Desired Outcome
In amebiasis, the goals of therapy are initially to eradicate the parasite by use of specific amebicides and then to render supportive therapy.
Treatment Regimens
A number of different regimens have been suggested depending on the category of amebiasis: asymptomatic cyst passers, intestinal amebiasis, and amebic liver abscess.16,19–22 Electrolyte replacement, antibiotic therapy, and nutritional support are essential adjunctive treatment modalities. Large hepatic abscess or amebic pericarditis may require needle aspiration, percutaneous catheter drainage, or, rarely, surgery before drug therapy.20–22 Most regimens require a combination of drugs administered concurrently or sequentially.19,21,24
A careful history to exclude concurrent bacterial infection and other tissue complications of E. histolytica should be part of consideration when planning therapy for amebiasis.
Pharmacologic Therapy
Metronidazole (Flagyl), dehydroemetine, and chloroquine (Aralen) are tissue-acting agents, whereas iodoquinol (Yodoxin), diloxanide furoate (Furamide), and paromomycin (Humatin) are luminal amebicides. A systemic agent may be so well absorbed that only small amounts of the drug stay in the bowel, which might prove ineffective as a luminal agent.20–23 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 the lumen to prevent intestinal amebiasis or the development of amebic liver abscess. Drug effectiveness may be monitored by stool examination, although the ELISA test should be used to verify eradication of E. histolytica.19,21
Asymptomatic cyst passers and patients with mild intestinal amebiasis should receive one of the following luminal agents: paromomycin 25 to 35 mg/kg/day three times daily for 7 days, iodoquinol 650 mg three times daily for 20 days, or diloxanide furoate 500 mg three times daily for 10 days.16 Diloxanide furoate is available only from Panorama Compounding Pharmacy (6744 Balboa Blvd., Van Nuys, CA 91406, (800) 247–9767; or Medical Center Pharmacy, New Haven, CT, (203) 688–6816).16 The pediatric dose for paromomycin is the same as in adults, whereas the dose of iodoquinol is 30 to 40 mg/kg/day (maximum: 2 g) in three doses for 20 days, and the dose of diloxanide furoate is 20 mg/kg/day in three doses for 10 days.16 Paromomycin is the preferred luminal agent in pregnant patients.16,21
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 earlier.16,20–21 Tinidazole 2 g mg once daily for 5 days has been suggested for amebic liver abscess.16 In the pediatric patient, the dose of oral metronidazole is 50 mg/kg/day in divided doses to be followed by a luminal agent.16Patients who are too ill to take oral metronidazole should receive the drug in equivalent doses by the IV route.21
Evaluation of Therapeutic Outcomes
Followup in patients with amebiasis should include repeat stool examination, serology, colonoscopy (for colitis), or computed tomography (CT) (for liver abscess) between days 5 and 7, at the end of the course of therapy, and a month after the end of therapy. Most patients with either intestinal amebiasis or colitis will respond in 3 to 5 days with amelioration of symptoms. Patients with liver abscesses may take from 7 to 10 days to respond; patients not responding during this period may require aspiration of abscesses or exploratory laparotomy. Serial liver scans have demonstrated healing of liver abscesses over 4 to 8 months after adequate therapy.21
Sanitation and Preventive Measures
Travelers and tourists visiting an epidemic area should avoid local tap water, ice, salads, and unpeeled fruits. Water can be disinfected by the use of iodine (tincture of iodine or commercial sources: Potable Aqua tablet [Wisconsin Pharmacal] or 5% to 10% acetic acid), but boiled water is probably the safest. An alternative or additional measure may be to carry a portable water purifier (such as MSR Mini Works Ex Water Filter. www.backcountry.com). Because food handlers in Asia and Latin America may be a source of amebiasis, travelers should avoid eating at food stalls and open markets.
HELMINTHIC DISEASES
Most intestinal helminthic infections may not be associated with clearly defined manifestation of disease, but they can cause significant pathology.9,25–33 One factor that determines the pathogenicity of helminths is their population density. Light infections may be fairly well tolerated, whereas high populations of intestinal helminths can result in predictable disease presentations. In the United States, these infections are seen most frequently in recent immigrants from Southeast Asia, the Caribbean, Mexico, and Central America.2,26,27 Other populations that have a high risk of infestation include institutionalized patients (both young and elderly), preschool children in daycare centers, residents of Indian reservations, and homosexual individuals. Certain conditions and drugs (fever, corticosteroids, and anesthesia) can cause atypical localization of worms.34–38 Immunocompromised hosts can be overwhelmed by some helminthic infections, such as strongyloidiasis.34
Nematodes
Hookworm Disease
This is an infection of the small intestine caused by either Ancylostoma duodenale or Necator americanus. N. americanus is found in the southeastern United States, where the temperature and humidity provide the proper environment. Ancylostoma is seen rarely in the United States.25
The life cycles of both species of hookworm are similar. The adult worms live in the small intestine attached to the mucosa. The females liberate eggs, which are eliminated in the feces and develop into larvae. Infective larvae enter the host in contaminated food or water or penetrate the skin, where a papular eruption with localized edema and erythema can result.
In the small intestine, where the adult worm lives attached to the mucosa, injury is usually caused by mechanical and lytic destruction of tissue. The loss of blood can lead to anemia and hypoproteinemia (Table 93–3).26–29
TABLE 93-3 Clinical Presentations of Nematode Infections and Cysticercosis
Stool should be examined for eggs and the rhabditiform larvae. Eosinophilia (30% to 60%) may be present in patients during early infection.
TREATMENT
Mebendazole (Vermox), an oral synthetic benzimidazole, is the agent of first choice in hookworm. It is also effective against ascariasis, enterobiasis, and trichuriasis.16,25 The adult dose for treatment of hookworm infestation is 100 mg twice daily for 3 days. Pediatric patients older than 2 years of age should receive the same dose as adults.16 Albendazole is an alternative agent.16
Ascariasis
Ascariasis is caused by the giant roundworm Ascaris lumbricoides. Female worms range from 20 to 35 cm in length. The worm is found worldwide but more commonly in areas where sanitation is poor. In the United States, endemic areas include southeastern parts of the Appalachian range and the Gulf Coast states.
During migration of the larvae through the lungs, patients can present with pneumonitis, fever, cough, eosinophilia, and pulmonary infiltrates.9,25 Other symptoms of ascariasis include abdominal discomfort, abdominal obstruction, vomiting, and appendicitis (see Table 93–3).9,25,31,32 Diagnosis is made by demonstrating the characteristic egg in the stool.
TREATMENT
In both adults and pediatric patients older than 2 years of age, the treatment for ascariasis is mebendazole (Vermox) 100 mg twice daily for 3 days.16 An alternative drug for ascariasis is albendazole 400 mg as a single dose.16
Enterobiasis
Enterobiasis, or pinworm infection, is caused by Enterobius vermicularis. The pinworm is a small, thread-like, spindle-shaped worm about 1 cm in length. It is the most widely distributed helminthic infection in the world. There are estimated to be 42 million cases in the United States.25 The majority of those infected are children.
The most common problem with enterobiasis is cutaneous irritation in the perianal region, made by the migrating females or the presence of eggs. However, there are reports of other complications, including appendicitis and intestinal perforation.25,33 The intense pruritus and scratching can cause dermatitis and secondary bacterial infections. In children, the itching can cause loss of sleep and restlessness (see Table 93–3).
The most effective method of diagnosing pinworm infections is by the use of perianal swab using adhesive Scotch tape. The Scotch tape, which is applied to the perianal region with a tongue depressor, is examined microscopically for eggs.9,25
TREATMENT
The common agents for treatment include pyrantel pamoate, mebendazole, or albendazole (Albenza). The dose of pyrantel pamoate is 11 mg/kg (maximum 1 g) as a single dose that can be repeated in 2 weeks. The dose of mebendazole for adults and children older than 2 years of age is 100 mg as a single dose; this may be repeated in 2 weeks.16,25 The dose of albendazole for adults and children older than 2 years of age is 400 mg, and should be repeated in 2 weeks.25 Following treatment, all bedding and underclothes should be sterilized by steaming or washing in the hot water cycle of a regular washing machine; this will eradicate the eggs. Bathroom rugs and toilet accessories also should be cleaned in a similar way.
Strongyloidiasis
Strongyloidiasis is caused by Strongyloides stercoralis, which has a worldwide distribution and is predominantly prevalent in South America (Brazil and Columbia) and in Southeast Asia. Strongyloidiasis is primarily seen among institutionalized populations (mental homes, mentally disabled children’s homes) and immunocompromised individuals (patients with human immunodeficiency virus [HIV], AIDS, and hematologic malignancies).34–38 The worm is usually found in the upper intestine where the eggs are deposited and hatch to form the rhabditiform larvae. The rhabditiform larvae (male and female) migrate to the bowel where they may be excreted in the feces. If excreted in the feces, the larvae can evolve into either one of two forms after copulation: (a) free-living noninfectious rhabditiform larvae or (b) infectious filariform larvae. The filariform larvae can penetrate host skin, travel to the lungs via the bronchi and glottis, and make their way to the small intestine. At times, the filariform larvae may not pass out in the feces but instead migrate to the lungs and produce progeny, a process called autoinfection. This can result in hyperinfection (i.e., increased number of larvae in intestine, lungs, and other internal organs), especially in immunocompromised hosts.34–36
Symptoms with acute infection may appear with localized pruritic rash, but heavy infestations can produce eosinophilia (10% to 15%), diarrhea, abdominal pain, and intestinal obstruction (see Table 93–3).37–39
Administration of corticosteroids or other immunosuppressive drugs to an infected individual can result in hyperinfections and disseminated strongyloidiasis.34,36,38 Diagnosis of strongyloidiasis is made by identification of the rhabditiform larvae in stool, sputum, duodenal fluid, and cerebrospinal fluid, by small bowel biopsy specimens, or by antigen testing (ELISA assay).37
TREATMENT
The drug of choice for strongyloidiasis is oral ivermectin 200 mcg/kg/day for 2 days and the alternative is albendazole 400 mg twice daily for 7 days.16,34,39,40 In a patient with hyperinfection or disseminated strongyloidiasis, immunosuppressive drugs should be discontinued and treatment initiated with ivermectin 200 mcg/kg/day until all symptoms are resolved (duration, 5 to 14 days). Patients should be tested periodically to ensure the elimination of the larvae.39 Individuals from endemic areas, who are candidates for organ transplantation, must be screened for S. stercoralis.
Taenia solium: Cysticercosis and Neurocysticercosis
Tapeworm infection caused by T. solium is a result of ingestion of poorly cooked pork that contains the larvae or cysticercus.41,42 Cysticercus, when released from the contaminated meat by host digestive juices, matures into the adult tapeworm and attaches to the host jejunum. Cysticercosis is a systemic disease caused by the larva of T. solium (oncosphere) and is usually acquired by ingestion of eggs in contaminated food or by autoinfection.41–44 The larvae can penetrate the bowel and migrate through the bloodstream to infect different organs including the CNS (neurocysticercosis).43,44,46 The larvae matures in about 8 weeks and remain as a semitransparent, oval-shaped, fluid-filled bladder in tissues. In the United States, the highest incidence of cysticercosis has been reported in immigrants from Mexico.41–43 Cysticercosis in most tissues may not produce major symptoms and usually manifest as subcutaneous nodules, primarily in the arms, legs, and chest. However, penetration of the larval stage (cysticercus) into the CNS can produce hydrocephalus, intracranial hypertension, stroke, and seizure activity.42 Epileptic seizures (50% to 80%) may be the presenting symptoms in patients with neurocysticercosis (see Table 93–3).42,45 Clinical presentation, primarily seizure history, together with radiographic demonstration (CT and magnetic resonance imaging) of the cysticercus within the bladder or calcified cysts in the CNS, is diagnostic for neurocysticercosis.41,42 Serologic diagnosis is made by the use of an enzyme-linked immunoelectrotransfer blot assay, which is considered highly sensitive and specific for cysticercosis.41,42,45,46
TREATMENT
Evaluation of Therapeutic Outcome
Morbidity and disease with intestinal nematodes are related to the intensity of infection or worm burden; subjects with transient exposure have less severe disease. The major adverse effects of intestinal nematodes are malnutrition, fatigue, and diminished work capacity. Treatment with antihelminthic agents results in complete eradication and significant change in the well-being of patients. Unlike other nematode infections, strongyloidiasis can perpetuate itself by autoinfection, and in the immunosuppressed host, the filariform larvae can invade various organs (e.g., lungs, CNS, and the like) to produce disseminated infection that can be fatal.9,43–47
The most serious complication of cysticercosis is invasion of the CNS, which results in neurocysticercosis. Neurocysticercosis can cause obstructive hydrocephalus, strokes, and seizures; antihelminthic treatment for these conditions remains controversial.42,45,46
Clinical Controversy…
Cysticercosis (excluding neurocysticercosis) is normally not treated. The management for neurocysticercosis remains controversial but may include surgery, anticonvulsants (neurocysticercosis-induced seizures), and antihelminthic therapy.42,45,46 Antihelminthic therapy, if one decides this is an option, is albendazole 400 mg twice daily for 8 to 30 days and this regimen can be repeated if necessary.16However, the dose and duration of therapy with albendazole is not clearly defined.42,46
MALARIA
Malaria represents the most devastating disease in terms of human suffering and economics. It affects the largest number of people (between 300 and 500 million new infections are reported annually) in the world, and between 1 and 2 million deaths worldwide.5,48–50 In the United States, deaths from malaria are preventable. The primary reasons for deaths are failure to take chemoprophylaxis, inappropriate chemoprophylaxis, delay in seeking medical care, and misdiagnosis.5,7,50
Epidemiology
The exact geographic distribution of the various species is not well documented; it is reported that Plasmodium vivax is more prevalent in India, Pakistan, Bangladesh, Sri Lanka, and Central America; whereas P. falciparum is predominant in Africa, Haiti, Dominican Republic, the Amazon region of South America, and New Guinea. Most of the infections with Plasmodium ovale occur in Africa, and the distribution of Plasmodium malariae is considered worldwide.5,49,60
In the United States, most cases of malaria are reported in immigrants from endemic areas and in American travelers. Blood transfusion also has been cited as a cause of malarial infection.48,51
Etiology
Malaria is transmitted by the bite of an infected Anopheles mosquito that introduces the sporozoites (tissue parasites) of the plasmodia (P. falciparum, P. vivax, P. malariae, and P. ovale) into the bloodstream. The asexual reproduction stage develops in humans, whereas the sexual stage occurs in the mosquito.9,48,49 The sporozoites invade parenchymal hepatocytes, multiply in stages referred to as exoerythrocytic stages, and become hepatic vegetative forms or schizonts. Schizonts rupture to release daughter cells, or merozoites, that then infect erythrocytes.
P. falciparum and P. malariae remain in the primary exoerythrocytic stage in the liver for about 4 weeks before invading erythrocytes, whereas P. vivax and P. ovale can exist in the liver in the latent exoerythrocytic form for extended periods, and, therefore, infected subjects can experience relapses. The merozoites that invade the erythrocytes develop sequentially into ring forms, trophozoites, schizonts, and finally, merozoites, which can invade other erythrocytes or can develop into gametocytes, which undergo the sexual stage in the Anopheles vector. Because erythrocytic forms never reinvade the liver without developing into sporozoites in the vector, malaria infections from transfusion never result in the exoerythrocytic, or “liver,” form.9,49 P. falciparum can result in high levels of parasitemia because of its ability to invade erythrocytes of all ages, unlike P. vivax and P. ovale, which only invade young cells.48,49
Pathology
The erythrocytic phase causes extensive hemolysis, which results in anemia and splenomegaly. The most serious complications usually are associated with P. falciparum infections.48–50,52–60 Infants and children younger than 5 years of age and nonimmune pregnant women are at high risk for severe complications from falciparum malaria.52–56 The complications associated with falciparum malaria are primarily a result of the high parasitemia and the ability of the parasites to sequester in capillaries and postcapillary vessels of organs such as the brain and the kidney. It has been postulated that tissue hypoxia from anemia, together with P. falciparum-parasitized red blood cell adherence to endothelial cells in capillaries, contribute to extensive vascular disease and severe metabolic effects.52,53 P. malariae is implicated in immune-mediated glomerulonephritis and nephrotic syndrome (Table 93–4).49,52
TABLE 93-4 Clinical Presentation of Malaria
To ensure a positive diagnosis, blood smears should be obtained every 12 to 24 hours for three consecutive days.9,49,52 The presence of parasites in the blood 3 to 5 days after initiation of therapy suggests drug resistance. Recent advances for detecting malaria parasite have included DNA or RNA probes by PCR and rapid dipstick tests (ParaSight F, Becton-Dickinson, Cockeysville, MD) and OptiMAL.48,49,52 The dipstick is reported to have a sensitivity of 88% and a specificity of 97%; however, microscopy is still considered the optimal test.
TREATMENT
Desired Outcome
The primary goal in the management of malaria is the rapid diagnosis of the Plasmodia spp. by blood smears (repeated every 12 hours for 3 days) so as to initiate timely antimalarial therapy to eradicate the infection within 48 to 72 hours and to avoid complications such as hypoglycemia, pulmonary edema, and renal failure that are responsible for increased mortality in malaria.49
Pharmacologic Therapy
In adults (including pregnant women), the chemoprophylaxis for all species of Plasmodium is chloroquine phosphate 300 mg (base) once weekly beginning 1 to 2 weeks prior to departure and continued for 4 weeks after leaving an endemic area.16,48,49,52,61–63 The pediatric dose of chloroquine phosphate is 5 mg (base) per kilogram of body weight (maximum 300 mg). When departing an area endemic for P. vivaxor P. ovale, primaquine phosphate 30 mg (base) daily for 14 days beginning the last 2 weeks of chloroquine prophylaxis should be added to the regimen. The pediatric dose of primaquine is 0.6 mg (base) per kilogram of body weight per day for 14 days. The pediatric doses of chloroquine can be calculated based on body weight, and the tablets can be pulverized and placed in gelatin capsules. Parents can be instructed to suspend the dose in food, simple syrup, chocolate milk, or in a drink.61
In areas where chloroquine-resistant P. falciparum (CRPF) strains exist, travelers should receive mefloquine (Lariam) for prophylaxis. The adult dose of mefloquine is 250 mg once weekly beginning 1 week prior to departure and continuing for the full period of exposure, followed by 250 mg for 4 weeks after last exposure.16,48,49 The pediatric dose of mefloquine for prophylaxis is based on body weight.16
For travelers who are at immediate risk for drug-resistant falciparum malaria, a loading dose of mefloquine may be considered (except for travel to Thailand, Myanmar, Vietnam, Laos, and Cambodia, where atovaquone–proguanil combination, one tablet daily 2 days prior to departure and through the stay and 1 week after leaving area, may be an alternative).49 Mefloquine is administered at 250 mg daily for 3 days before travel, followed by 250 mg once weekly while in the endemic area and continued for 4 weeks after last exposure.48,49 All patients receiving mefloquine should receive the FDA Medication Guide, and the drug should be avoided in patients with a history of cardiac conduction problems.48 Patients may experience neuropsychiatric reactions (seizures, psychosis, anxiety, sleep disturbances, insomnia, and dizziness) from mefloquine and may need to be monitored closely.16,62,63
An alternative regimen for prophylaxis in chloroquine-resistant areas for those who cannot tolerate mefloquine or Malarone, is to take oral doxycycline 100 mg daily starting 1 to 2 days prior to departure, during the exposure period, and continuing for 4 weeks after leaving the endemic area.16 Children older than 8 years of age should receive 2 mg/kg/day (up to 100 mg) of doxycycline. Doxycycline is contraindicated in children younger than 8 years of age, in pregnant women, and during breastfeeding.16,49,63,65
In an uncomplicated attack of malaria (for all plasmodia except CRPF), the recommended regimen is chloroquine 600 mg (base) initially, followed by 300 mg (base) 6 hours later, and then 300 mg (base) daily for 2 days. In severe illness or when oral therapy is not tolerated or parenteral quinine is not available, quinidine gluconate 10 mg/kg as a loading dose (maximum 600 mg) in 250 mL normal saline should be administered slowly over 1 to 2 hours, followed by continuous infusion of 0.02 mg/kg/minute until oral therapy can be started.16,48,49 In patients who have received either quinine or mefloquine, the loading dose of quinidine should be omitted. Oral quinine (650 mg every 8 hours) together with doxycycline 100 mg twice daily should follow the IV dose of quinidine to complete a total of 7 days of therapy.16,48,60The pediatric dose of IV quinidine gluconate is the same as the dose for adults.16 The pediatric dose of quinine is 30 mg/kg/day in three divided doses for 7 days. Children younger than age 8 years and pregnant women should get clindamycin 20 mg/kg/day in divided doses for 7 days instead of doxycycline.16,49,60
When IV quinidine is not readily available, IV artesunate (available under an IND from the CDC at www.cdc.gov/malaria/features/artesunate_now_available.htm), a water-soluble artemisinin derivative, administered at 2.4 mg/kg/dose for 3 days at 0, 12, 24, 48, and 72 hours is the recommended drug if severe P. falciparum is suspected.16,58
In P. falciparum (chloroquine-resistant) infections, a dose of 750 mg mefloquine followed by 500 mg 12 hours later is recommended. The pediatric dose of mefloquine is 15 mg/kg (<45 kg body weight) followed by 10 mg/kg 8 to 12 hours later.16 IV quinidine gluconate (or IV artesunate) followed by oral quinine plus doxycycline to complete a total of 7 days of therapy should follow in a severe illness, as already indicated.16,49 An alternative oral treatment for CRPF infection in adults, especially in those with a history of seizures, conduction problems, or psychiatric disorders to mefloquine, is the combination of atovaquone 250 mg and proguanil 100 mg (Malarone) (four tablets daily for 3 days).16,48,49 An alternative to Malarone is the combination product of artemether 20 mg and lumefantrine 120 mg (Coartem) recently approved by the FDA in the United States (for regimen, see http://www.cdc.gov/malaria/pdf/treatmenttable.pdf). The IV quinidine regimen requires close monitoring of the electrocardiogram and other vital signs (e.g., hypotension, QT interval prolongation, and hypoglycemia).16,49,55,60
Because falciparum malaria is associated with serious complications, including pulmonary edema, hypoglycemia, jaundice, renal failure, confusion, delirium, seizures, coma, and death, careful monitoring of fluid status and hemodynamic parameters is mandatory.48,49,55,60 Either hemofiltration or hemodiafiltration is indicated in renal failure.
Malarial infection does not produce immunity in patients, and active research has been initiated to develop a malaria vaccine.66–68 A vaccine that blocks the entry of sporozoites into the liver cells will prevent malaria at this stage. However, immunity to sporozoites does not protect the host against parasites in the erythrocytic cycle. Infective sporozoites of P. falciparum are covered by a polypeptide, circumsporozoite protein. Isolation and identification of the gene encoding for this circumsporozoite protein have led to the development of a monoclonal antibody by recombinant DNA technology; P. falciparum sporozoite vaccine is now under investigation.68
Evaluation of Therapeutic Outcomes
When advising potential travelers on prophylaxis for malaria, be aware of the incidence of CRPF malaria and the countries where this is prevalent.16,62,63 Detailed recommendations for prevention of malaria may be obtained by checking the website www.cdc.gov/travel/ or www2.cdc.gov/mmwr/63,69 or calling the U.S. Centers for Disease Control and Prevention (CDC) (see Appendix 93–1). In view of the increasing incidence of P. falciparum resistance to antimalarials, newer drugs are under active study and include the water-soluble artesunate and the oil-soluble artemether and combinations with other agents.16,49,63,64,70–75
Acute P. falciparum malaria resistant to chloroquine should be treated with IV quinidine or artesunate.16,58 Patients receiving IV quinidine should have a central venous catheter to follow fluid status, and the electrocardiogram should be monitored closely. Hypoglycemia that is associated with P. falciparum should be checked and corrected with dextrose infusions.48,49,55 Quinidine infusion should be slowed temporarily or stopped if electrocardiogram shows a QT interval of greater than 0.6 seconds, an increase in the QRS complex to greater than 50%, or hypotension unresponsive to fluid challenge results. The suggested quinidine levels should be maintained at 3 to 7 mg/L (9 to 22 μmol/L).49 Blood smears should be checked every 12 hours until parasitemia is less than 1%. Resolution of fever should take place between 36 and 48 hours after initiation of the IV quinidine therapy and the blood should be clear of parasites in 5 days.48,49,52 If parenteral therapy is required for more than 48 hours, the dose of quinidine should be lowered by half.16
Travelers to endemic areas for malaria should be advised to remain in well-screened areas, to wear clothes that cover most of the body, and to sleep in mosquito nets.7,49,71 It is prudent to carry the insect repellent DEET (N, N-diethyl-metatol) or Picaridin (Cutter Advanced) insect spray for use in mosquito-infested areas. Readers are urged to check publications from the CDC for the list of countries where CRPF exist.16,69
Clinical Controversy…
Because there remains public concern with mefloquine chemoprophylaxis, primarily about its neuropsychiatric effects and cardiac conduction problems,16,62 an alternative regimen for chemoprophylaxis may be the combination of atovaquone and proguanil (Malarone): one tablet daily beginning 1 to 2 days prior to travel and continuing for the duration of stay and 1 week after leaving the area.16,62 Daily primaquine 30 mg (base) also has been suggested for prophylaxis for both P. vivax and P. falciparum malaria.16 However, these alternative agents compared to mefloquine, remain less than ideal choice for high CRPF malaria regions.62
AMERICAN TRYPANOSOMIASIS
Etiology
Two distinct forms of the genus Trypanosoma occur in humans. One is associated with African trypanosomiasis (sleeping sickness) and the other with American trypanosomiasis (Chagas disease).76–79Trypanosoma brucei gambiense, T. brucei, and T. brucei rhodesiense are the causative organisms for the African trypanosomiasis. T. brucei rhodesiense causes the acute disease and is the more virulent of the three species. African trypanosomiasis is transmitted by various species of tsetse fly belonging to the genus Glossina. Further discussion of this subject will focus on American trypanosomiasis.
Trypanosoma cruzi is the agent that causes American trypanosomiasis. American trypanosomiasis is transmitted by a number of species of a reduviid bug (Triatoma infestans, Rhodnius prolixus) that live in wall cracks of houses in rural areas of North, Central, and South America. The reduviid bug is infected by sucking blood from animals (e.g., opossums, dogs, and cats) or humans infected with circulating trypomastigotes (Table 93–5).
TABLE 93-5 Clinical Presentation of South American Trypanosomiasis
In chronic trypanosomiasis, patients present with cardiomyopathy and heart failure. Electrocardiograms are usually abnormal, demonstrating extrasystoles, first-degree heart block, right bundle-branch block, and other serious conduction disturbances.77–79 Degeneration of the autonomic ganglia in the smooth muscle of the esophagus and colon leads to uncoordinated peristalsis. The end result has been reported to be “megasyndromes” of affected organs.78,79 Penetration of the CNS results in meningoencephalitis, strokes, seizures, and focal paralysis.78–80
A history to verify the possible exposure to T. cruzi should be an important initial diagnostic workup. Recovery of T. cruzi is definitive, but this is not always possible, especially in chronic disease. Positive serologic tests using the indirect immunofluorescent antibody test and ELISA (Chagas’ EIA, Abbott Laboratories, Abbott Park, IL) may be diagnostic for the disease. The only serologic test available in the United States is Chagas’ Kit (Hemagen Diagnostics, Inc., Columbia, MD).78 A PCR test has also been used for diagnosis of T. cruzi76,81 Specimens may be sent to the CDC for testing. All candidates from an endemic area for Chagas disease who are candidates for transplantation should be tested for T. cruzi.82
TREATMENT
Desired Outcome
The primary goal of drug therapy in trypanosomiasis is to reduce the duration and severity of the illness and to decrease mortality.
Pharmacologic Therapy
The drugs that have been used to treat T. cruzi infections include nifurtimox (Lampit, Bayer 2502) and benznidazole (Rochagan).16,78,79,83 Both oral nifurtimox and benznidazole are available from the CDC. Oral benznidazole is the drug of choice for T. cruzi in South America.16 Neither of the agents are optimal therapy and there is ongoing search for newer agents.76,78 The adult oral dose of nifurtimox is 8 to 10 mg/kg/day in divided doses for 30 to 120 days. The pediatric dose (1 to 10 years of age) is 15 to 20 mg/kg/day in four divided doses and children (11 to 16 years) should receive 12.5 to 15 mg/kg/day in four divided doses for 30 to 120 days.16 Symptomatic treatment for heart failure includes digitalis and diuretics; the GI complications, however, may require surgical revisions and reconstruction.78,79
Evaluation of Therapeutic Outcomes
American trypanosomiasis (Chagas disease), which is endemic in all Latin American countries, can be transmitted congenitally, by blood transfusion, and by organ transplantation.78,79 Treatment with nifurtimox of the acute phase (i.e., fever, malaise, edema of face, generalized lymphadenopathy, and hepatosplenomegaly) produces between 30% and 70% cure rates.78 Treatment of chronic infection with nifurtimox is not recommended. It is essential to identify T. cruzi-infected patients by serology and to monitor the cardiovascular status of these patients by electrocardiogram periodically. The congestive failure of cardiomyopathic Chagas disease is treated the same way as cardiomyopathies from other causes.76,78
ECTOPARASITES
A parasite that lives on the outside of the body of the host is called an ectoparasite. Millions of people become infested with pediculosis yearly in the United States.84 Pediculosis usually is associated with poor personal hygiene, and infections are passed from person to person through social and sexual contact. The three types of human lice belong to two genera: Pediculus, including the head and body lice, and Phthirus, with only one species, the crab louse.9,84,85 The human louse is detectable to the human naked eye and measures approximately 2 to 3 mm in length.
Lice
The two species that belong to this group include Pediculus humanus capitis (head louse) and Pediculus humanus corporis (body louse). Female lice deposit eggs on the hair. The eggs (or nits) remain firmly attached to the hair, and in about 10 days, the lice hatch to form nymphs, which mature in 2 weeks. Using both their piercing mouthparts and a pumping device, the larva and adults feed on the blood of the host. The body louse and head louse are essentially identical, although they live on different parts of the body. Unlike the head louse, which lives on the hair, the body louse is more frequently found on clothing of the infected host.
Pubic or crab lice are found on the hairs around the genitals, although they can occur in other areas of the body (e.g., eyelashes, beards, and axillae). Patients usually complain of severe pruritus from papular lesions produced by the bite of the louse. Hypersensitivity to foreign material injected by the lice can produce macular swellings and occasionally can lead to secondary bacterial infections.84
TREATMENT
The goal of therapy is to eradicate the causative organisms and provide symptomatic relief to patients. The agent of choice for all three infections (body, head, and crab lice) is 1% permethrin (Nix).84–88Permethrin is a derivative of the flowers of the plant Chrysanthemum cinerariifolium. The term pyrethrin is usually applied to several esters of chrysanthemic acid and pyrethric acid. Permethrin has both pediculicidal and ovicidal activity against P. humanus var capitis. The cure rate is reported to be in the range of 85% to 95%.84 Individuals who have a history of ragweed or chrysanthemum allergy should use this compound with caution. The side effects reported with permethrin products include itching, burning, stinging, and tingling. Permethrin 1% is applied to the scalp after the hair has been dried following a shampooing. The scalp should be saturated with permethrin liquid, and a towel should be wrapped around the scalp to allow the application to stay on for 10 minutes. The hair then should be rinsed thoroughly. A cream rinse of permethrin 1% (Nix-Creme Rinse) is also available. To ensure complete eradication, especially of newly hatched lice, it may be necessary to repeat the application. Recently, the FDA approved benzyl alcohol 5% (Ulesfia; Sciele Pharma Inc., Atlanta, GA) as an alternative therapy for head lice.86
There is increasing lice resistance to permethrin 1%.85,88,89 Alternative preparations for lice are 0.5% malathion (Ovide), Spinosad 0.9% crème rinse (which is equally effective as permethrin89), and benzyl alcohol 5% (Ulesfia).16,86,89 To ensure complete eradication of lice infestation, the malathion application should be left on the scalp for about 90 minutes.87 For the relief of pruritus, a soothing lotion of calamine liniment or lotion with 0.1% menthol may be used. Other members of the family or sexual partners also should be treated. All bedding and clothes should be sterilized by boiling or washing in the hot water cycle of the washing machine to avoid reinfections. Seams of clothes should be examined to verify that all organisms are eradicated. An ocular lubricant (e.g., Lacri-Lube S.O.P.) applied twice daily may be used to remove crab louse infection of the eyelids.
Scabies
Scabies is caused by the itch mite Sarcoptes scabiei, which affects both humans and animals. Mange in domestic animals is caused by the same organism. Infection usually affects the interdigital and popliteal folds, axillary folds, the umbilicus, and the scrotum.90–92
Patients will complain of severe itching and an inability to sleep and may have excoriations in the interdigital web spaces, wrists, elbows, buttocks, groin, and scalp. Excoriations may lead to secondary bacterial infections. The diagnosis is made by looking for burrows formed by the mite and taking skin scrapings, which will demonstrate the mite on a wet mount.
TREATMENT
Because these infections cause a great deal of discomfort and distress to patients and families, the goals of therapy are to eradicate the infestations rapidly, to institute symptomatic treatment, and to provide counseling and reassurance. The treatment of choice is permethrin 5% (Elimite) cream.16,90–92 To initiate the treatment, the skin should be scrubbed thoroughly in a warm soapy bath using a soft brush to remove all scabs. The lotion is then applied to the whole body, avoiding the face, mucous membranes, and eyes. The application should be left on for 8 to 14 hours before bathing. A single application eradicates 97% of scabies in subjects.90 All close contacts should be checked and treated appropriately.
Other agents used to treat scabies include topical crotamiton 10% (Eurax) and oral ivermectin (Stromectol) 200 mcg/kg as a single dose, which may be repeated in 2 weeks.16,92 Crotamiton and oral ivermectin may be used in patients who have hypersensitivity to permethrin preparations. Topical corticosteroids and antihistamines may be used to decrease pruritus.
Permethrin (1% and 5%) for pediculosis and scabies, respectively, is the preferred agent and remains the safest agent, especially in infants and children.84,92 One application of permethrin is consistently effective in eradicating more than 90% of all infections. However, pruritus may persist for 2 to 4 weeks because of the remnants of mite parts in the skin. Ivermectin is an alternative therapy for scabies. Spinosad 0.9% and benzyl alcohol 5% are new agents approved for head lice.86,89
ABBREVIATIONS
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Appendix 93–1
Antiparasitic Drugs
