1692 PART 5 Infectious Diseases

Pneumocystis. Among PLWH, the incidence of PCP is inversely related

to the CD4+ T-cell count: at least 80% of cases occur at counts of <200/μL,

and most of these cases develop at counts of <100/μL. HIV viral load

is another factor that predisposes patients to PCP. CD4+ T-cell counts

are less useful in predicting the risk of PCP in patients who are immunosuppressed for reasons other than HIV infection. Clinicians must

recognize that PCP can occur at CD4+ T-cell counts >200/μL in any

immunosuppressed population including persons with HIV infection.

Such occurrences are especially common in patients who are immunosuppressed due to causes other than HIV infection, especially among

patients who have undergone solid-organ transplantation, since CD4+

T-cell counts are not as sensitive and specific indicators of PCP as they

are in PLWH.

Lung Pathology Pneumocystis has a unique tropism for the lung.

Organisms are presumably inhaled into the alveolar space after being

exhaled by another human. Clinically apparent pneumonia occurs only

if an individual is immunocompromised. Pneumocystis proliferates in

the lung, provoking a mononuclear cell response. The alveoli become

filled with proteinaceous material, and alveolar damage results in

increased alveolar-capillary injury and surfactant abnormalities. Stained

lung sections typically show foamy, vacuolated alveolar exudates composed largely of viable and nonviable organisms (Fig. 220-1A). Interstitial edema and fibrosis may develop, and organisms can be seen in the

alveolar space with silver or other stains. Moreover, the organisms can

be seen when tissue is subjected to colorimetric or immunofluorescent

staining (Fig. 220-1B–1D).

■ CLINICAL FEATURES

Clinical Presentation PCP presents as acute or subacute pneumonia that may initially be characterized by a vague sense of dyspnea

alone but that subsequently manifests as fever and nonproductive

cough with progressive shortness of breath. Patients may ultimately

progress to respiratory failure and death. Extrapulmonary manifestations of PCP are rare but can include involvement of almost any organ,

most notably the lymph nodes, spleen, and liver.

Physical Examination, Oxygen Saturation, and Imaging The

physical examination findings in PCP are nonspecific. Patients have

decreased oxygen saturation—at rest or with exertion—that, without

treatment, progresses to severe hypoxemia. Patients may initially have

a normal chest examination and no adventitious sounds, but later

develop diffuse rales and signs of consolidation.

Laboratory Findings The results of routine laboratory tests are

nonspecific in PCP. Serum levels of lactate dehydrogenase (LDH) are

often elevated as a result of pulmonary damage; however, a normal

LDH level does not rule out PCP, nor is an elevated LDH value specific

for PCP. The peripheral white blood cell count may be elevated in relation to the patient’s baseline values, but the increase is usually modest.

Hepatic and renal function are typically normal.

Radiographic Findings Although the initial chest radiograph

may be normal when patients have mild symptoms, the classic radiographic appearance of symptomatic PCP consists of diffuse bilateral

interstitial infiltrates that are perihilar and symmetric (Fig. 220-2A)—

yet another finding that is not specific for PCP. The interstitial infiltrates can progress to alveolar filling (Fig. 220-2B). High-resolution

chest CT shows diffuse ground-glass opacities in virtually all patients

with PCP, often before a routine chest radiograph becomes abnormal

(Fig. 220-2C). A normal chest CT essentially rules out the diagnosis

of PCP. Pneumatoceles and pneumothoraces are characteristic chest

radiographic findings, especially in patients with HIV infection

(Fig. 220-2D). A wide variety of atypical radiographic findings have

been described, including asymmetric patterns, upper-lobe infiltrates,

mediastinal adenopathy, nodules, cavities, and effusions.

■ DIAGNOSIS

The optimal sample for a specific microbiologic diagnostic examination depends on how ill the patient is and what resources are

recognized as the first presentations of what came to be known as the

acquired immunodeficiency syndrome (AIDS) (Chap. 202).

The incidence of PCP increased dramatically as the AIDS epidemic

grew: without chemoprophylaxis or antiretroviral therapy (ART),

80–90% of patients with HIV/AIDS in North America and Western

Europe ultimately developed one or more episodes of PCP. While its

incidence declined with the introduction of anti-Pneumocystis prophylaxis and combination ART, PCP has continued to be a leading cause of

AIDS-associated morbidity in the United States and Western Europe,

particularly in individuals who do not know they are infected with HIV

until they are profoundly immunosuppressed and in people living with

HIV (PLWH) with CD4+ T lymphocyte counts of <200/μL who are not

receiving ART or PCP prophylaxis.

PCP also develops in HIV-uninfected patients who are immunocompromised secondary to hematologic or malignant neoplasms, stem

cell or solid-organ transplantation, and treatment with immunosuppressive medications. The incidence of PCP depends on the degree and

duration of immunosuppression. PCP is increasingly reported among

individuals receiving tumor necrosis factor α inhibitors and immunosuppressive monoclonal antibodies for autoimmune, rheumatologic,

or neoplastic diseases. While clinical disease due to Pneumocystis in

immunocompetent hosts has not been clearly documented, studies

have shown that Pneumocystis organisms can colonize the airways

of children and adults who are not immunocompromised. The relevance of these organisms to acute or chronic syndromes, such as

chronic obstructive pulmonary disease (COPD), in immunocompetent

patients is being investigated.

In some developing countries, the incidence of PCP among PLWH

has been reported to be lower than that in industrialized countries.

This lower incidence may be due to competing mortality from infectious diseases such as tuberculosis and bacterial pneumonia, which

typically occur before patients become immunosuppressed enough

to develop PCP. Geographic variations in Pneumocystis exposure and

underdiagnosis attributable to lack of diagnostic resources also may

explain the apparent lower frequency of PCP in some countries.

■ PATHOGENESIS AND PATHOLOGY

Life Cycle and Transmission The life cycle of Pneumocystis

likely involves both sexual and asexual reproduction. The organism

exists as a trophic form, a cyst, and a precyst. Studies in rodents show

that immunocompetent animals can serve as reservoirs for respiratory

transmission of P. carinii (the infecting species in rodents) to immunocompetent and immunosuppressed animals. Human Pneumocystis

is thought to be transmitted by a respiratory route as well. P. jirovecii,

like all pneumocystis species, is host-specific. Thus, humans are not

infected, for example, by P. carinii (rodents) or P. oryctolagi (rabbits),

but are only infected by P. jirovecii.

Serologic and molecular studies have demonstrated that most

humans are exposed to P. jirovecii early in life. It was historically

thought that Pneumocystis pneumonia usually developed from reactivation of latent infection. However, molecular evidence makes it

clear that children and adults can develop PCP from primary infection

or reinfection. It is difficult to prove whether reactivation of latent

infection in fact occurs. The source of infection is thought to be either

healthy or immunosuppressed individuals who themselves experienced recent infection or reinfection, or immunosuppressed persons

with clinical PCP. Nosocomial outbreaks occur in inpatient and outpatient settings. The utility of droplet or airborne isolation for preventing

transmission from patients with PCP to other immunosuppressed

individuals has been debated; no clear evidence exists, although it

seems prudent to isolate patients with active PCP from other immunosuppressed patients using at least droplet precautions.

Role of Immunity Defects in cellular and/or humoral immunity

predispose to development of PCP. Such defects may be congenital,

or they may be acquired as a result of HIV infection or of treatment

with immunosuppressive drugs such as glucocorticoids, fludarabine, temozolomide, temsirolimus, cyclophosphamide, rituximab,

or alemtuzumab. CD4+ T cells are critical in host defense against

1693CHAPTER 220 Pneumocystis Infections

available. Before the 1990s, diagnoses of PCP were usually established

by open lung biopsy; later, transbronchial lung biopsy was employed.

Hematoxylin and eosin staining of pulmonary tissue demonstrates

a foamy alveolar infiltrate and a mononuclear interstitial infiltrate

(Fig. 220-1A). This appearance is pathognomonic for PCP even though

the organisms cannot be specifically identified with this stain. The

diagnosis is typically established in lung tissue or pulmonary secretions

by staining of the cyst—e.g., with methenamine silver (Fig. 220-1B),

toluidine blue O, or Giemsa (Fig. 220-1C)—or by staining with a specific immunofluorescent antibody (Fig. 220-1D).

The demonstration of organisms in bronchoalveolar lavage (BAL)

fluid is almost 100% sensitive and specific for PCP in patients with HIV

infection and is almost as sensitive in patients with immunosuppression due to other processes. The organisms are identified in pulmonary

secretions with the specific stains indicated above for lung biopsy.

While expectorated sputum or throat swabs have very low sensitivity,

an induced sputum sample obtained and interpreted by an experienced

provider can be highly sensitive and specific; however, the sensitivity is

dependent on both the characteristics of the patient and the experience

of the center conducting the test and is widely variable (55–90%).

Many laboratories now offer polymerase chain reaction (PCR) testing of respiratory specimens for Pneumocystis in preference to direct

microscopy of appropriately stained respiratory secretions. However,

these PCR tests are so sensitive that it is difficult to distinguish patients

with colonization (i.e., those whose acute lung disease is due to some

other process but who have low levels of Pneumocystis DNA in the

lungs) from those with acute pneumonia due to Pneumocystis. Such

PCR tests on appropriate samples may be more useful for ruling out a

diagnosis of PCP if they are negative than for definitively attributing

the disease to Pneumocystis.

There has been considerable interest in serologic tests, such as assays

for (1→3)-β-d-glucan, a component of the fungal cell wall. These

levels are frequently elevated in patients with PCP. However, serum or

BAL (1→3)-β-d-glucan levels are not perfectly sensitive or highly specific for PCP. There are increasing numbers of reports of serum PCR

tests for Pneumocystis, but such tests are still in preliminary stages of

development.

■ COURSE AND PROGNOSIS

Untreated, PCP is invariably fatal. Patients with HIV infection often

have an indolent course that may present early as mild exercise intolerance or chest tightness without fever or cough and a normal or nearly

normal posterior–anterior chest radiograph but progresses over days,

weeks, or even a few months to fever, cough, diffuse alveolar infiltrates,

and profound hypoxemia. Some patients with HIV infection and most

patients with other types of immunosuppression have more acute

disease that progresses over a few days to respiratory failure. Rare

patients also develop distributive shock. A few unusual patients present

with extrapulmonary manifestations in the skin or soft tissue, retina,

brain, liver, kidney, or spleen. Extrapulmonary disease is nonspecific

in presentation and can be diagnosed only by histology. When there

is extrapulmonary clinical disease in a patient with PCP, the priority

is to determine what other concurrent infectious or neoplastic process

might be present, given the rarity of extrapulmonary pneumocystosis.

Factors that influence mortality risk of PCP include the patient’s age

and degree of immunosuppression as well as the presence of preexisting lung disease, a low serum albumin level, the need for mechanical

ventilation, and the development of a pneumothorax. With advances

in supportive critical care, the prognosis for patients with PCP who

require intubation and respiratory support has improved and now

A B

C D

FIGURE 220-1 Direct microscopy of Pneumocystis pneumonia. A. Transbronchial lung biopsy stained with hematoxylin and eosin shows eosinophilic alveolar filling.

B. Methenamine silver–stained bronchoalveolar lavage (BAL) fluid. C. Giemsa-stained BAL fluid. D. Immunofluorescent stain of BAL fluid.

1694 PART 5 Infectious Diseases

depends to a large extent on comorbidities and the prognosis of the

underlying disease. Since patients typically do not respond to therapy

for 4–8 days, supportive care for a minimum of 10 days is a reasonable

consideration if such support is compatible with the patient’s wishes

and the prognosis of comorbidities. Patients whose condition continues to deteriorate after 3 or 4 days or has not improved after 7–10 days

should be reevaluated to determine whether other infectious processes

are present (either having been missed on initial evaluation or having

developed during treatment), whether initial anti-Pneumocystis treatment has failed, or whether noninfectious processes (e.g., congestive

heart failure, pulmonary emboli, pulmonary hypertension, drug toxicity, or a neoplastic process) are causing pulmonary dysfunction.

TREATMENT

P. jirovecii Pneumonia

The treatment of choice for PCP is trimethoprim-sulfamethoxazole (TMP-SMX), given either IV or PO for 14 days to non-HIVinfected patients with mild disease and for 21 days to all other

patients (Table 220-1). TMP-SMX, which interferes with the organism’s folate metabolism, is at least as effective as alternative agents

and is better tolerated. TMP-SMX can cause leukopenia, hepatitis,

rash, and fever as well as anaphylactic and anaphylactoid reactions.

Patients with HIV infection have an unusually high incidence of

hypersensitivity to TMP-SMX. Monitoring of serum drug levels is

useful if renal function or toxicities are issues in order to enhance

the likelihood that therapy will be effective and toxicity will be

avoided. Maintenance of a 2-h post-dose serum sulfamethoxazole

level of 100–150 μg/mL has been associated with a successful outcome. Resistance to TMP-SMX cannot be measured by organism

growth inhibition in the laboratory because Pneumocystis cannot

be cultured. However, mutations in the target gene for sulfamethoxazole that confer in vitro sulfa resistance when found in other

organisms have been recognized in Pneumocystis. The clinical relevance of these mutations for the response to therapy is unknown.

Sulfadiazine plus pyrimethamine, an oral regimen more often used

for treatment of toxoplasmosis, also is highly effective.

Intravenous pentamidine or the combination of clindamycin plus

primaquine is an option for patients who cannot tolerate TMP-SMX

and for patients in whose treatment TMP-SMX appears to be failing.

Pentamidine must be given IV over at least 60 min to avoid potentially lethal hypotension. Adverse effects can be severe and irreversible and include renal dysfunction, dysglycemia (life-threatening

hypoglycemia that can occur days or weeks after initial infusion

and be followed by hyperglycemia), neutropenia, and torsades des

pointes. Clindamycin plus primaquine is effective, but primaquine

can be given only by the oral route—a disadvantage for patients

who cannot ingest or absorb oral drugs. Oral atovaquone is also

a reasonable option for patients with mild disease who have no

A B

C D

FIGURE 220-2 Radiographs in Pneumocystis pneumonia. A. Posterior–anterior chest radiograph showing symmetric interstitial infiltrates. B. Posterior–anterior

chest radiograph showing symmetric alveolar infiltrates (courtesy of Alison Morris). C. CT image demonstrating symmetric interstitial infiltrates and ground-glass opacities.

D. CT image showing symmetric interstitial infiltrates, ground-glass opacities, and pneumatoceles.

1695CHAPTER 220 Pneumocystis Infections

TABLE 220-1 Treatment of Pneumocystis pneumoniaa

DRUG(S) DOSE, ROUTE ADVERSE EFFECTS

First-Choice Agent

TMP-SMX TMP (5 mg/kg) plus SMX

(25 mg/kg) q6–8h PO or

IV (i.e., 2 double-strength

tablets tid or qid)

Fever, rash, cytopenias,

hepatitis, hyperkalemia

Alternative Agents

Atovaquone 750 mg bid PO Rash, fever, hepatitis

Clindamycin

plus

Primaquine

300–450 mg q6h PO or

600 mg q6–8h IV

15–30 mg qd PO

Hemolysis (G6PD deficiency),

methemoglobinemia,

neutropenia, rash

Pentamidine 3–4 mg/kg qd IV Hypotension, azotemia,

cardiac arrhythmias (torsades

des pointes), pancreatitis,

dysglycemias, hypocalcemia,

neutropenia, hepatitis

Adjunctive Agent

Prednisone or

methylprednisolone

40 mg bid × 5 d, 40 mg qd ×

5 d, 20 mg qd × 11 d; PO

or IV

Peptic ulcer disease,

hyperglycemia, mood

alteration, hypertension

a

Treatment can be administered for 14 days to non-HIV-infected patients with mild

disease and for 21 days to all other patients.

Abbreviations: G6PD, glucose-6-phosphate dehydrogenase; TMP-SMX,

trimethoprim-sulfamethoxazole.

impediments to absorbing an oral drug that requires a high-fat

meal for optimal absorption. There is some evidence for activity of

echinocandins against the cyst form (but not the trophozoite form)

of pneumocystis, but the role for echinocandins as part of combination therapy is currently uncertain.

A major advance in therapy for PCP was the recognition that glucocorticoids could improve survival rates among PLWH with moderate to severe disease (room air PO2

 <70 mmHg or alveolar–arterial

oxygen gradient ≥35 mmHg). Glucocorticoids appear to reduce

the pulmonary inflammation that occurs after specific therapy is

started and organisms begin to die, eliciting inflammation. Therapy

with glucocorticoids should be the standard of care for patients with

HIV infection and probably is also effective for patients with other

immunodeficiencies. This treatment should be started for moderate or severe disease when therapy for PCP is initiated, even if the

diagnosis is suspected but has not yet been confirmed. If PLWH or

HIV-uninfected patients are receiving high-dose glucocorticoids

when they develop PCP, there are theoretical advantages to either

increasing the steroid dose (to reduce the inflammatory response

to the dying organisms) or decreasing the steroid dose (to improve

immune function), but there is no convincing evidence on which to

base any specific strategy.

No definitive trials have defined the best therapeutic algorithm

for patients in whom TMP-SMX treatment for PCP is failing. If no

other treatable infectious or noninfectious processes are detected

and pulmonary dysfunction appears to be due to PCP alone, many

authorities would switch from TMP-SMX to either IV pentamidine

or IV clindamycin plus oral primaquine. Some authorities would

add the second drug or drug combination to TMP-SMX rather

than switching regimens. If patients are not already receiving them,

glucocorticoids should be added to the regimen; the dosage and

regimen, which are usually chosen empirically, depend on what

glucocorticoid regimen (if any) the patient was receiving when PCP

therapy was begun.

For patients with HIV infection who present with PCP before the

initiation of ART, ART should be started within the first 2 weeks of

therapy for PCP in most situations. Immune reconstitution inflammatory syndrome (IRIS) can occur, and the decision to initiate ART

thus requires considerable expertise in optimal timing relative to

PCP recovery as well as for the other factors that are relevant when

ART is initiated in any patient.

■ PREVENTION

The most effective method for preventing PCP is to eliminate the cause

of immunosuppression by withdrawing immunosuppressive therapy

or treating the underlying cause (e.g., HIV infection). Patients who are

susceptible to PCP benefit from chemoprophylaxis during the period

of susceptibility. For patients with HIV infection, CD4+ T-cell counts

are a reliable marker of susceptibility, and counts below 200/μL are an

indication to start prophylaxis (Table 220-2).

For patients who are immunosuppressed as a result of factors other

than HIV infection, there is no laboratory parameter, including the

CD4+ T-cell count, that predicts susceptibility to PCP with adequate

positive and negative accuracy. The period of susceptibility is usually

estimated on the basis of experience with the underlying disease and

immunosuppressive regimen. Premature cessation of prophylaxis has

been associated with clusters of cases in certain patient populations,

such as solid-organ transplant recipients. Patients receiving a prolonged course of high-dose glucocorticoids appear to be particularly

susceptible to PCP. The glucocorticoid exposure threshold that warrants chemoprophylaxis is controversial, but such preventive therapy

should be strongly considered for any patient who is receiving more

than the equivalent of 20 mg of prednisone daily for 30 days or who is

receiving glucocorticoids in conjunction with other immunosuppressive agents. Clinical experience also suggests that chemoprophylaxis is

useful for patients receiving certain immunosuppressive agents (e.g.,

tumor necrosis factor inhibitors, antithymocyte globulin, rituximab,

and alemtuzumab). The duration of such chemoprophylaxis is empirically estimated based on prior clinical experience and immunologic

factors that would plausibly relate to immunity such as CD4+ T-cell

counts, recognizing that such estimates are not precise.

TMP-SMX is the most effective prophylactic drug; few patients

experience a PCP breakthrough when they are reliably taking a recommended TMP-SMX chemoprophylactic regimen. Several TMP-SMX

regimens have been used successfully. Regimens of one single-strength

or double-strength tablet daily are the regimens with which there

is the most experience, but one double-strength tablet two or three

times weekly also has been recommended for various PLWH and nonHIV-infected populations of patients.

TABLE 220-2 Prophylaxis of Pneumocystis pneumonia

DRUG(S) DOSE, ROUTE COMMENTS

First-Choice Agent

TMP-SMX 1 tablet (double- or

single-strength) qd PO

Incidence of hypersensitivity is

high. Rechallenge for nonlife-threatening hypersensitivity;

consider dose-escalation

protocol.

Alternative Agents

Dapsone 50 mg bid or 100 mg

qd PO

Hemolysis is associated with

G6PD deficiency.

Dapsone

plus

Pyrimethamine

plus

Leucovorin

50 mg qd PO

50 mg weekly PO

25 mg weekly PO

Leucovorin ameliorates

cytopenias due to pyrimethamine.

Dapsone

plus

Pyrimethamine

plus

Leucovorin

200 mg weekly PO

75 mg weekly PO

25 mg weekly PO

Leucovorin ameliorates

cytopenias due to pyrimethamine.

Pentamidine 300 mg monthly via

Respirgard II nebulizer

Aerosol may cause

bronchospasm. Pentamidine is

probably less effective than

TMP-SMX or dapsone regimens.

Atovaquone 1500 mg qd PO Requires fatty meal for optimal

absorption

Abbreviations: G6PD, glucose-6-phosphate dehydrogenase; TMP-SMX,

trimethoprim-sulfamethoxazole.

1696 PART 5 Infectious Diseases

For patients who cannot tolerate TMP-SMX (usually because

of hypersensitivity or bone marrow suppression), alternative drugs

include daily dapsone, weekly dapsone-pyrimethamine, atovaquone,

and monthly aerosol pentamidine. Patients who develop hypersensitivity to TMP-SMX can sometimes tolerate the drug if a gradual doseescalation protocol is used. Dapsone cross-reacts with sulfonamides

in a substantial fraction of patients and is rarely useful in patients

with a history of life-threatening reactions to TMP-SMX. Aerosolized

pentamidine is highly effective, but it is not as effective as TMP-SMX

and may not provide protection in areas of the lung that are not well

ventilated. Atovaquone is also effective and well tolerated; however,

this drug is available only as an oral preparation, and gastrointestinal

absorption is unpredictable in patients with abnormal gastrointestinal

motility or function.

■ FURTHER READING

Akgun KM, Miller RF: Critical care in human immunodeficiency

virus–infected patients. Semin Respir Crit Care Med 37:303, 2016.

Buchacz K et al: Incidence of AIDS-defining opportunistic infections

in a multicohort analysis of HIV-infected persons in the United States

and Canada, 2000–2010. J Infect Dis 214:862, 2016.

Chen P et al: Anidulafungin as an alternative treatment for Pneumocystis jirovecii pneumonia in patients who cannot tolerate trimethoprim/sulfamethoxazole. Int J Antimicrob Agents 55:105820, 2020.

Le Gal S et al: Pneumocystis infection outbreaks in organ transplantation units in France: A nation-wide survey. Clin Infect Dis 70:2216,

2020.

Ma L et al: Genome analysis of three Pneumocystis species reveals

adaptation mechanisms to life exclusively in mammalian hosts.

Nat Commun 7:10740, 2016.

Panel on Opportunistic Infections in HIV-Infected Adults

and Adolescents: Guidelines for the prevention and treatment

of opportunistic infections in HIV-infected adults and adolescents:

Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. Available at

http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed

June 22, 2021.

Zolopa A et al: Early antiretroviral therapy reduces AIDS progression/

death in individuals with acute opportunistic infections: A multicenter randomized strategy trial. PLoS One 4:e5575, 2009.

Section 17 Protozoal and Helminthic

Infections: General Considerations

221

The word parasite comes originally from the Greek parasitos (para,

alongside of; and sitos, food), meaning someone who eats at another’s

table or lives at another’s expense. Although the same is true of many

bacteria and viruses, the designation parasite is reserved, by convention, for helminths and protozoa. These organisms are larger and more

complex than bacteria, with a eukaryotic cell structure similar to that

of human host cells. Historically, this similarity has made it difficult

to find effective antiparasitic agents that do not cause unacceptable

toxicity to human cells. Fortunately, intensive research and modern

techniques have now provided suitable agents for safe and effective

treatment of most parasitic infections. See Chap. S12 for details on

diagnostic procedures and Chap. 222 for details on treatment.

Introduction to

Parasitic Infections

Sharon L. Reed

Internal parasites of human beings are divided into two types: helminths (worms) and protozoa. Helminths are multicellular organisms

that can often be seen with the naked eye (Chap. 230). There are two

phyla: Platyhelminthes (flat worms) and Nemathelminthes (roundworms). Both phyla include some genera that mature in the gastrointestinal tract and others that migrate through the tissue after ingestion

or skin penetration. Tables S12-1 and S12-2 present the helminthic

genera, their definitive and intermediate hosts, geographic distributions, and the parasitic stages in the human body.

The key to understanding which helminths use humans as definitive hosts is to remember that helminth ova develop into larvae, and

larval stages develop into adults. Humans serve as the definitive host

when they ingest helminth larvae, which develop into adults in the

intestine and usually cause mild disease, often without any symptoms.

(The exception is ingestion of the late-stage larvae of the somatic or

tissue flukes, as shown in Table S12-2.) In contrast, if humans ingest

helminth ova and serve as the intermediate host, the ova develop into

larvae, which penetrate the intestine, migrate through the tissue, and

invade organs where they mature into adults. Intermediate hosts with

parasitic invasion of organs may experience severe disease.

Protozoa are microscopic single-celled organisms. Among the many

differences between helminths and protozoans, the most important

is the ability of protozoa (like bacteria) to multiply within the human

body and cause overwhelming infections. A major mechanism promoting unrestrained growth is evasion of the host immune response

either by antigenic variation (Trypanosoma brucei) or by survival inside

host cells (e.g., Plasmodium, Babesia, Cryptosporidium, Leishmania,

and Toxoplasma). In contrast, almost all helminths require stages

in other hosts to complete their life cycles and multiply. As a result,

except for Strongyloides and Capillaria, which can complete their life

cycle in humans, increases in the burden of infection with helminths

require repeated exogenous reinfections. Thus, permanent residents of

endemic countries, who are exposed repeatedly, may have heavy severe

infections, while most travelers with one or two exposures are unlikely

to experience the full spectrum of chronic helminthic infections.

In contrast to helminthic infections, naïve patients with their first

protozoal infection usually are the most severely affected because

partial immunity often limits the number of parasites during recurrent infections. Protozoan replication to large numbers in the host

also promotes the development of drug-resistant forms, especially

in malaria (Chap. 222). Because protozoa belong to many different

phyla, it is easier to understand the pathogenesis and management of

protozoal infections when they are classified by the site of infection

(intestinal protozoans, free-living amebae, and blood and tissue protozoans) (Table S12-3). Immunocompromised hosts are at risk of disseminated infection with a number of protozoa, including Leishmania,

Toxoplasma, Cryptosporidium, and Trypanosoma cruzi, which are

AIDS-defining illnesses. In contrast, Strongyloides is the only helminth

to disseminate.

HELMINTHIC INFECTIONS

The Platyhelminthes (flatworms) are categorized as tapeworms

(cestodes) and flukes (trematodes). Tapeworms are composed of a head

or scolex bearing the holdfast organs and segments, which become

gravid as they mature. Some tapeworms can reach lengths of many

yards; the longest tapeworms develop in the intestine, where they rarely

cause serious disease. In contrast, flukes are small leaf-shaped organisms whose size is not a measure of disease severity.

■ FLATWORMS

Cestodes Tapeworms cause either intestinal or somatic infection,

depending on the species. Intestinal infections occur when the human

host ingests larvae in the tissue of the intermediate host, whereas

somatic infections occur when humans accidentally ingest ova excreted

from the wild or domesticated definitive animal host.

INTESTINAL TAPEWORMS As shown in Table S12-1, humans acquire

most intestinal tapeworms by eating the insufficiently cooked flesh of

the intermediate host. Thus, Taenia saginata is commonly called the