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.
Clinicians need to have a heightened awareness of parasitic diseases and how to treat them. Clinical
signs and symptoms, together with the patients 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.
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.. 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.

HOSTPARASITE 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.
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. Diphyllobothrium latum , or the broad fish tapeworm, removes
vitamin B 12 from the gastrointestinal tract (GI) tract, resulting in megaloblastic anemia.

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. Giardia
is 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%. 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, the 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. 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. Colonization and
multiplication of the trophozoite lead to mucosal invasion, localized edema, and flattening of the
villi, resulting in malabsorption states in the host.
Lactose intolerance precipitated by giardiasis can persist even after eradication of the protozoan.
Achlorhydria, hypogammaglobulinemia, or deficiency in secretory immunoglobulin A (IgA) are
predispositions for giardiasis. describes the 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. If both the stool examination and string test prove unsuccessful, it may be necessary
to attempt duodenal aspiration and biopsy to confirm the diagnosis; this may be more important in AIDS
patients and in patients with hypogammaglobulinemia. Most clinicians advocate a clinical trial of the
standard therapy before undertaking invasive diagnostic tests. Detection of the trophozoites or cysts
in fecal samples by enzymelinked immunosorbent assay (ELISA) or immunofluorescence or identification
of the Giardia antigen by counterimmunoelectrophoresis are alternative ways for diagnosis of
giardiasis.

TREATMENT
Giardiasis
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 ova
and parasite examination or by antigen detection test should be used to institute appropriate therapy.

PHARMACOLOGIC THERAPY
All symptomatic adults and children older than 8 years of age with giardiasis can be treated with
metronidazole 250 mg 3 times daily for 5 to 10 days, or tinidazole 2 g once, or nitazoxanide 500 mg
twice daily for 3 days. The alternative drugs include furazolidone 100 mg 4 times daily or paromomycin
25 to 35 mg/ kg/day in divided doses daily for 1 week. Paromomycin 25 to 35 mg/kg/day in three doses
for 7 to 10 days is a safe agent in pregnancy. The pediatric dose for metronidazole is 15 mg/ kg/day
3 times daily for 5 to 7 days. 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 (13 years), 200 mg every 12 hours
(411 years) and the adult dose is recommended for children older than 12 years; all are administered
for 3 days. 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 1241 ).
Albendazole 400 mg daily for 5 days has been cited to produce cure rates of 97% and as being equivalent
to metronidazole in children. However, other investigators have disputed the efficacy of this agent.

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 85% and 95%. 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. Patients who
fail initial therapy with metronidazole should receive a second course of therapy. Nitazoxanide (500
mg twice daily for 3 days) is effective in patients who are not responding to metronidazole. Pregnant
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. 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 gastrointestinal manifestations, amebiasis is one
of the most important parasitic diseases of humans. 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, E moshkovskii which are associated with an asymptomatic carrier state.
E dispar is considered nonpathogenic, while the status of E moshkovskii remains to be defined. Although
E histolytica and E dispar are indistinguishable morphologically, monoclonal antibodies have been used
to separate the two. The Entamoeba histolytica II kit (TechLab, Blacksburg, VA) remains the most
specific test for E histolytica . 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. The incidence of amebiasis is estimated at approximately 4% in the general
U.S. population. 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).

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 colon, perineum, and genitalia, and abscesses
may occur in the lung and brain.

Clinical Presentation
The most frequent clinical manifestations of the disease are gastrointestinal .Amebic liver abscesses
can spread to the lungs and pleura. 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. Review of the patients 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. Three
stool samples obtained 24 to 36 hours apart will produce a 60% to 90% yield for E histolytica.
Microscopy may not differentiate between the pathogenic E histolytica and the nonpathogenic E dispar
in stools. Sensitive techniques are available to detect E histolytica in stool, including ELISA and
antigen detection. Endoscopy with scraping or biopsy may provide more definitive diagnosis where stool
examinations do not provide adequate evidence.
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. Leukocytosis (>10,000/mm 3 ) 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.

TREATMENT
Amebiasis
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. 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. Most regimens require a combination of drugs administered concurrently
or sequentially.
A careful history should be taken when one of the differential diagnoses is ulcerative colitis because
corticosteroid administration has the potential to unmask amebiasis and produce toxic megacolon.

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. 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 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 to 35 mg/kg/day 3 times daily for 7 days, iodoquinol 650 mg
3 times daily for 20 days, or diloxanide furoate 500 mg 3 times daily for 10 days. These regimens have
cure rates of between 84% and 96%. Diloxanide furoate is available only from Ponorama Compounding
Pharmacy (6744 Balboa Blvd., Van Nuys, CA 91406, (800) 2479767; or Medical Center Pharmacy, New
Haven, CT, (203) 6886816]. 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. Paromomycin is the preferred luminal
agent in pregnant patients.
Patients with severe intestinal disease or liver abscess should receive metronidazole 750 mg 3 times
daily for 10 days, followed by a course of one of the luminal agents indicated earlier. Tinidazole 2
g mg once daily for 5 days has been suggested for amebic liver abscess. In the pediatric patient, the
dose of oral metronidazole is 50 mg/kg/day in divided doses to be followed by a luminal agent. Patients
who are too ill to take oral metronidazole should receive the drug in equivalent doses by the
intravenous route.

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.

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 Safewater, Durango, CO, www.outgear.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. 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. 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. Immunocompromised hosts
can be overwhelmed by some helminthic infections, such as strongyloidiasis.
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.
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 larva 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
.
Stool should be examined for eggs and the rhabditiform larvae. Eosinophilia (30%60%) may be present
in patients during early infection.

TREATMENT
Hookworm Disease
Mebendazole (Vermox), an oral synthetic benzimidazole, is the agent of first choice in hookworm. It
is also effective against ascariasis, enterobiasis, trichuriasis. 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. Albendazole is an alternative agent.

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.
Clinical Manifestations During migration of the larvae through the lungs, patients can present with
pneumonitis, fever, cough, eosinophilia, and pulmonary infiltrates. Other symptoms of ascariasis
include abdominal discomfort, abdominal obstruction, vomiting, and appendicitis .Diagnosis is made by
demonstrating the characteristic egg in the stool.

TREATMENT
Ascariasis
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.

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. 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. The intense pruritus and scratching can cause dermatitis and
secondary bacterial infections. In children, the itching can cause loss of sleep and restlessness .
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.

TREATMENT
Enterobiasis
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. The dose of albendazole for adults and children older than 2 years
of age is 400 mg, and should be repeated in 2 weeks. 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 childrens
homes) and immunocompromised individuals (patients with human immunodeficiency virus [HIV], AIDS, and
hematologic malignancies).
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.
Symptoms with acute infection may appear with localized pruritic rash but heavy infestations can
produce eosinophilia (10%15%), diarrhea, abdominal pain, and intestinal obstruction. Administration
of corticosteroids or other immunosuppressive drugs to an infected individual can result in
hyperinfections and disseminated strongyloidiasis. 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).

TREATMENT
Strongyloidiasis
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. 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 Taenia solium is a result of ingestion of poorly cooked pork that contains
the larvae or cysticercus. 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. The larvae can penetrate the bowel and migrate through the
bloodstream to infect different organs including the central nervous system (neurocysticercosis). 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. 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 central nervous system can produce hydrocephalus, intracranial hypertension,
stroke, and seizure activity. Epileptic seizures (50% to 80%) may be the presenting symptoms in
patients with neurocysticercosis . 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 central nervous system, is diagnostic for neurocysticercosis. Serologic
diagnosis is made by the use of an enzyme-linked immunoelectrotransfer blot assay, which is considered
highly sensitive and specific for cysticercosis.
TREATMENT
Helminthic Diseases
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, central
nervous system, and the like) to produce disseminated infection that can be fatal.
The most serious complication of cysticercosis is invasion of the central nervous system which results
in neurocysticercosis. Neurocysticercosis can cause obstructive hydrocephalus, strokes and seizures;
antihelminthic treatment for these conditions remains controversial.

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 to 2 million deaths worldwide. 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.

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.
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.

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. 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. 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.

PATHOLOGY
The erythrocytic phase causes extensive hemolysis, which results in anemia and splenomegaly. The most
serious complications usually are associated with P falciparum infections. Infants and children younger
than 5 years of age and nonimmune pregnant women are at high risk for severe complications from
falciparum malaria. 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 endotheial cells in
capillaries, contribute to extensive vascular disease and severe metabolic effects. P malariae is
implicated in immune-mediated glomerulonephritis and nephrotic syndrome
To ensure a positive diagnosis, blood smears should be obtained every 12 to 24 hours for 3 consecutive
days. 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
polymerase chain reaction (PCR) and rapid dipstick tests ( Para Sight F, Becton-Dickinson,
Cockeysville, MD) and OptiMAL. The dipstick is reported to have a sensitivity of 88% and a specificity
of 97%; however, microscopy is still considered the optimal test.

TREATMENT
Malaria
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.

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. 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 vivax or 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.
In areas where chloroquine-resistant P falciparu m 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. The pediatric dose of mefloquine for prophylaxis is based on body weight.
Body Weight (kg) Dose
5 to 10 kg one-eighth tablet/week
11 to 20 kg one-quarter tablet/week
21 to 30 kg one-half tablet/week
31 to 45 kg three-quarters tablet/week
>45 kg 1 tablet/week
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). 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.
Patients may experience neuropsychiatric reactions from mefloquine and may need to be monitored
closely.
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.
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.
In an uncomplicated attack of malaria (for all plasmodia except chloroquine-resistant P falciparum ),
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. 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 intravenous dose of quinidine
to complete a total of 7 days of therapy. The pediatric dose of intravenous quinidine gluconate is
the same as the dose for adults. 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.
When intravenous quinidine is not readily available, intravenous artesunate (available under an IND
from the CDC at www. cdc.gov/malaria/features/artesunate_now_available.htm ), a watersoluble
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.
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. Intravenous quinidine gluconate (or intravenous 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. An alternative oral treatment for chloroquine-resistant P falciparum
infection in adults, especially in those with a history of seizures or psychiatric disorders, is the
combination of atovaquone 250 mg and proguanil 100 mg (Malarone) (4 tablets daily for 3 days). 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 intravenous quinidine regimen requires close
monitoring of the electrocardiogram and other vital signs (e.g., hypotension, QT interval prolongation,
and hypoglycemia).
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.
Malarial infection does not produce immunity in patients, and active research has been initiated to
develop a malaria vaccine. 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.

EVALUATION OF THERAPEUTIC OUTCOMES

When advising potential travelers on prophylaxis for malaria, be aware of the incidence of chloroquine-
resistant P falciparum malaria and the countries where this is prevalent. Detailed recommendations
for prevention of malaria may be obtained by checking the websites w ww.cdc.gov/travel/ or w
ww2.cdc.gov/mmwr/ or calling the U.S. Centers for Disease Control and Prevention (CDC) (see Appendix
1241). 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.
Acute P falciparum malaria resistant to chloroquine should be treated with intravenous quinidine or
artesunate. Patients receiving intravenous 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. 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. 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 intravenous quinidine therapy and the blood should be clear
of parasites in 5 days. If parenteral therapy is required for more than 48 hours, the dose of quinidine
should be lowered by half.
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. 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
chloroquine-resistant P falciparum exist.
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).
Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense are the causative organisms for the
East African and West African trypanosomiasis, respectively. T brucei rhodesiense causes the acute
disease and is the more virulent of the two species. Both East and West African trypanosomiasis are
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 1245 ).
In chronic trypanosomiasis, patients present with cardiomyopathy and heart failure. Electrocardiograms
are usually abnormal, demonstrating extrasystoles, first-degree heart block, right bundlebranch block,
and other serious conduction disturbances. 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. Penetration of the central nervous system results in
meningoencephalitis, strokes, seizures, and focal paralysis.
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 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). A PCR test
has also been used for diagnosis of T cruzi. 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 .

TREATMENT
American Trypanosomiasis
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). Oral nifurtimox is available from the CDC, whereas benznidazole is only
available in Brazil. Neither of these agents are optimal therapy and there is ongoing search for newer
agents. The adult dose of nifurtimox is 8 to 10 mg/kg/day in divided doses for 120 days. Because
pediatric patients tolerate the drug better than adults, the dose for children age 1 to 10 years is
15 to 20 mg/kg/day, and for children age 11 to 16 years it is 12.5 to 15 mg/kg/day in divided doses.
Symptomatic treatment for heart failure includes digitalis and diuretics; the gastrointestinal
complications, however, may require surgical revisions and reconstruction.

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. Treatment with nifurtimox
of the acute phase (i.e., fever, malaise, edema of face, generalized lymphadenopathy, and
hepatosplenomegaly) produces between 10% and 30% cure rates. 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.
ECTOPARASITES
A parasite that lives on the outside of the body of the host is called an ectoparasite. Approximately
6 to 12 million people become infested with pediculosis yearly in the United States. 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. 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 mouth parts 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.

TREATMENT
Lice
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).
Permethrin 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%. Individuals who have a history of ragweed or chrysanthemum allergy
should use this compound with caution. The side effects reported with permethrin productsinclude
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% (NixCreme 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.
There is increasing lice resistance to permethrin 1%. An alternative preparation for lice is 0.5%
malathion (Ovide), which is very effective. To ensure complete eradication of lice infestation, the
malathion application should be left on the scalp for about 90 minutes. 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.

Clinical Presentation
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
Scabies
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. 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. 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. 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. sOne 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 therapyfor
scabies.

ABBREVIATIONS
AIDS: acquired immunodeficiency syndrome
ELISA: enzyme-linked immunosorbent assay
PCR: polymerase chain reaction