Respiratory syndromes attributed to parasitic infections generally occur in either immunocompromised patients or as uncommon manifestations of common parasitic infestations. There are two clinical settings in which a parasitic etiology for respiratory symptoms should strongly be considered. The first is in immunocompromtsed patients, either primarily (congenital) or acquired (human immu' nodeficiency virus [HI V] -infected, patients on immunosuppressive therapies), who present with respiratory problems. Specific criologie agents to be considered are Pneumocystis connu, Strongyloides stercorolis and Toxoplasma gondii. Conversely, identifying any of these etiologic agents as the cause of respiratory symptoms would strongly suggest a T-cell immunodeficiency. Tne second clinical setting in which to consider a parasitic etiology is in patients with respiratory symptoms associated with elevated peripheral eosinophii counts. In these patients specific parasitic etiologies could be ascariasis, hookworm, S stercoroiis, or visceral larva migrans. Further discussion is presented below by specific etiologic agent.
Pneumocystis connu is the parasitic organism most commonly associated with respiratory illness in im* munocompromised patients.1 The initial descriptions of P cflrinii-related pulmonary disease were in debilitated and premature infants in Europe following World War II. Most researchers classify this organism as a protozoan although its phylogenic taxonomy remains controversial. Tne organism is a ubiquitous pulmonary saprophyte whose only known ecological niche is the respiratory tract of mammals. Transmission of P carinii probably occurs by respiratory acquisition, but clear epidemiological data are lacking.2 Our knowledge regarding P carinii has expanded rapidly in the past few years driven by the frequency with which these infections are seen in acquired immunodeficiency syndrome (AIDS) patients. However, our basic understanding of the biology and biochemistry of this organism remains quite rudimentary.
Infections with P carinii in children present almost exclusively with tachypnea, fever, and a nonproductive cough.3 The clinical course is most often indolent with a slow progression of symptoms particularly in HlV-infected individuals; however, children may present with an acute respiratory decompensation. The diagnosis of P carinu pneumonia (PCP) would be a primary consideration in patients with a known immunodeficiency and the clinical presentation of a lower respiratory illness. The diagnosis also should be considered in the setting of unresolved or slowly progressive lower respiratory symptoms in the young patient without a previously suspected immunodeficiency.
Laboratory findings are generally more reflective of the patient's underlying immunosuppression or clinical condition rather than specifically suggestive of P carinu infection. The classic chest radiograph study in these patients reveals a bilateral, diffuse alveolarinfiltrative pattern emanating from the perihilar region. The radiographie appearance, however, can be quite variable. Assessments of pulmonary function, including blood gas analysis, frequently are abnormal.
Diagnosis of P corinti is made most often by histopathologic identification of the organism. Pneumocystis carinii cysts are visualized with methenamine silver stain or one of its variants. Pneumocystis carinu trophozoites and other morphologic forms can be visualized by Giemsa or similar types of stains. Bronchoalveolar lavage via fiberoptic bronchoscopy has become the most common procedure used to obtain specimens for detection of P carinu. The majority of patients with P carinii can be identified using this procedure. In some cases, more commonly in nonAIDS patients, open lung biopsy is needed to make the diagnosis. There are other reagents in various stages of development, including monoclonal antibodies and polymerase chain reaction techniques, which may be more widely available in the future.
Initial therapy for PCP is generally with either trimetlKjprim-sullamemoxazoleorpentamidine isethionate. A significant incidence of intolerance to therapy, particularly to trimethoprim-sulfamethoxazole, has complicated the management and prophylaxis of PCP in HIV-infected patients. Alternative treatment and prophylactic regimens have been used but are beyond the scope of this article.
Strongylaides stercoraiis is a nematode worm that is endemic to many areas of the southeastern United States.4 In some regions, up to 3% of school-aged children have been found to have S stercaredis in single-stool specimen sampling.5 In addition, there is a high prevalence of S stercoraiis in many immigrant populations in the United States. Strongyloides stercoraiis can exist in a free-living cycle in warm moist soil, which provides the natural reservoir for this parasite. A unique feature of S stercoraiis among nematodes that infect humans is that all stages of the life cycle can develop in either the soil or a human host; this allows for the development of an autoinfective cycle, which accounts for the longevity of infections seen with S stercoraiis and the overwhelming infections that can occur in immunocompromised hosts. Respiratory symptoms are initiated by the filariform larvae that reach the lungs via the venous circulation and invade alveolar spaces. Respiratory symptoms are related to the number of worms invading the alveolar microvasculature and the host immune response to this tissue invasion.
Respiratory symptoms attributed to S stercoraiis depend on the immune status of the host. In immunocompetent individuals, S stercoraiis infestation often is asymptomatic and when symptomatic, intestinal or cutaneous manifestations are most common. When respiratory system signs and symptoms occur with S stercoro/is, they usually are shortness of breath or wheezing, peripheral and sputum eosinophilia, and possibly opacities on chest radiograph, similar to Löffler's syndrome. In immunocompetent individuals, although worm burden is a factor, the host immune response may be more important in producing the symptoms.
In immunocompromised individuals, disseminated strongyloidiasis often presents with severe abdominal pain and pulmonary manifestations and can be rapidly fetal.6 Pulmonary manifestations usually are cough, dyspnea, or wheezing with or without hemoptysis. The degree of immunosuppression in patients who have presented with disseminated strongyloidiasis has been quite variable; fatal disease has occurred in patients on cytotoxic therapy for malignancies or autoimmune disease but also has occurred in patients on short courses of oral steroids for dermatitis or asthma.4 Disseminated disease also has been seen in patients with protein-calorie malnutrition, bums, and chronic infections.
Suspicion of strongyloidiasis usually is heightened with the finding of eosinophilia. However, cosinophilia often is absent in patients on cytotoxic or immunosuppressive therapy. The diagnosis of S stercorcdis is made by finding the rhabditiform larvae in fecal specimens, although this may require numerous samples because of the low number of eggs excreted daily by the adult worms and the repenetration of the larvae through the intestinal mucosa. Duodenal aspirates or duodenal samples obtained using the encapsulated string technique also may be used to identify larvae. In immunocompromised patients with pulmonary symptoms, it may be possible to identify the larvae in sputum or bronchoalveolar lavage specimens. Serological testing for S stercorahs has been useful in some settings, but has a restricted use in the setting of compromised humoral immunity (AIDS patients).
Thiabendazole remains the standard therapy for S stercoroiis infections.7 The recommended course varies from 2 days in normal individuals to a minimum of 7 days or until parasitologic and symptomatic cures have been attained in cases of disseminated disease. A reduction in the patient's immunotoxic therapy should be strongly considered if possible. Gramnegative bacteremia has been associated with disseminated stongyloidiasis and should be suspected and treated presumptively.4,6 Ivermectin, a widely used therapy for filarial infections worldwide, should be used for patients with life-threatening disseminated strongyloidiasis and is available through the Centers for Disease Control and Prevention. Patients with clinical resolution of symptoms should have stools reexamined intermittently for a few months as followup.
Ascaris lumbricoides is the largest of the human intestinal nematode parasites and infects up to a quarter of the world's population.8 The prevalence in the United States is highest in the southeastern regions. The infective form of the parasite is an egg-encased embryo that is released in the small intestine after ingestion. The embryo penetrates the intestinal wall and is carried to the lungs in the venous circulation. The embryo penetrates through the capillary bed, enters the alveolar space, and is passed up the tracheobronchial tree and then swalllowed to reach the intestinal lumen once again.
Transient respiratory symptoms associated with ascariasis are related to the larval migration through the lungs. THKe symptoms include dyspnea, cough, or substemal burning. Wheezing and rales frequently are heard on examination. These symptoms usually are associated with eosinophilia, although this may take time to develop, and a chest radiograph with transient diffuse densities is similar to what is seen with S stercoroiis and hookworm. Worm burden is one factor that contributes to symptoms, but given that proteins of A lumbricoides are potent allergens, the host immune response also is a factor.
The diagnosis is generally easy because of the high daily egg output of the gravid ascaride and is accomplished by direct examination of stool samples. Stool examination, however, usually is negative at the time of pulmonary symptoms unless the patient has had a previously patent infection. Stool exam usually will become positive a few weeks after pulmonary symptoms begin. Mebendazole is the drug of choice for treatment of ascariasis.7
Infections with Necator americamts, the hookworm species that dominates in North America, were reduced dramatically in the United States in the early part of this century.9 The area of highest prevalence in the United States remains the southeast region. The infective stage of the N americanus life cycle is the infective third-stage larvae (L3), which develops in soil of certain humidity and temperature. TKe L3 larvae penetrate the skin, enter the circulation, and are carried to the lungs via the venous system. The larvae then penetrate the capillary bed into the alveolar space, migrate up the tracheobronchial tree, and are swallowed, similar to S stercoroiis and A lumbricoides.
A Loffler-like syndrome (respiratory symptoms with eosinophilia) similar to that described for ascariasis may occur during the lung migratory phase of the parasite's life cycle. This is much less common with hookworm disease than with ascariasis. Diagnosis is made by examination of fecal material, although in light infections, concentration techniques may be necessary. Stool examination may be negative early in the clinical presentation. The treatment of choice is mebendazole.7
VISCERAL LARVA MIGRANS
Visceral larva migrans is a syndrome caused by the aberrant migration of nematode parasites of lower animals, most commonly Toxocara cams. These nematodes are similar to Ascaris in their life cycles and the egg-encased embryo that is the infective form of the parasites. These parasites have a tissue migratory phase similar to ascariasis but aberrant migration is more common and the establishment of intestinal infection is uncommon. The symptoms in visceral larva migrans are due to the host immune response to worm migration and destruction.
Visceral larva migrans is more prevalent in children under the age of 6 and in those with a history of pica and exposure to a puppy.10 They frequently are brought to medical attention because of cough, wheezing, fever, or malaise.11 Clinical signs frequently include hepatomegaly and transient infiltrates on chest radiograph. Laboratory findings include eosinophilia with leukocytosis, elevated anti-A or anti-B isohemagglutimn titers, and hypergammaglobulinemia.12 The eosinophilia in these patients can be quite dramatic.
Diagnosis is suggested by clinical presentation and laboratory findings but may be confirmed serologicaily. Occasionally, the diagnosis is made by finding typical granuloma with worm fragments in tissue sections. Although many antihelminthic therapies have been used to treat visceral larva migrans, they are of no proven value given that it generally is a self-limited illness.
OTHER PARASITIC INFECTIONS
There are other parasitic infections, which either very rarely cause pulmonary problems or are seen infrequently in the United States. Toxoplosma gondii, a protozoan parasite familiar to most pediatrie caretakers for the other syndromes it causes in children, may cause pulmonary disease as part of a disseminated clinical picture in immunocompromised patients.13 A review of the literature did not reveal any cases in the pediatrie age group. Entamoeba histolyaca can rarely cause pleuropulmonary disease from contiguous extension of hepatic disease, or lymphatic or embolie spread usually of hepatic disease.14 In areas where hydatid disease caused by Ec/u'nococcus gronulosus is prevalent (ie, the western United States including Alaska), lung cysts may lead to respiratory complaints.15 Asymptomatic, singular "coin" lesions on chest radiograph may be caused by Diroftlaria immitis, dog heartworm, and is more commonly seen in the southeastern region of the United States.
There are multiple potential causes of respiratory illnesses caused by parasitic infections that could only be acquired with travel outside of the United States. A patient's risk of having one of these infections could be evaluated with a careful epidemiologie and travel history. Parctgorumus westermani, a hermaphroditic nuke, is a relatively common cause of pulmonary disease in Southeast Asia and in restricted regions of South America and Africa. Exposure occurs with the ingestion of raw fresh water crabs or crayfish. One of the protean manifestations of malaria due to Plasmodiumfakiparum may be a febrile pulmonary decompensation. History of travel to a malaria endemic area should raise this possibility. Schistosomiasis may present as an acute febrile illness with pulmonary symptoms and eosinophilia (Katayama syndrome) and again can be ruled out with a careful travel history. Tropical pulmonary eosinophilia, a clinical diagnosis with nighttime wheezing and dramatic eosinophilia, could be caused by an infection with Brugia malayi, Wuchereria bancrofti, or other filaria species. An appropriate travel and exposure history would support or rule out these potential etiologies.
Parasitic etiologies of pulmonary symptoms generally represent some degree of immunocompromise or occur as uncommon presentations of common parasitic infections. In regions where HIV infection is more prominent, PCP probably will be the most common parasitic respiratory disease seen. In geographic regions where helminthic infections are more common, patients with respiratory symptoms and eosinophilia probably will be seen more often and require a search for a specific etiology. In more rare circumstances, travel to an endemic area may suggest a more exotic parasitic etiology for respiratory symptoms.
1. Waker PD, Kirn OC, Cushion MT. Prteumocysas carina. In: Waker PD, Genia RM, eds. Pannine Infrctons m Ae Compromised Host. New York, NY: Marce! Detker Ine; 1989:83-178.
2. Hughes WT. Natural mode of injection of acquisition for de now infection with Pneumocysas corma. J infect Dis. 1982; 145:842-848.
3. Hughes WT, Anderson DC. Pnaimxysta carina pneumonia. In: Feigin RD; Cherry JD, eds. Ttabook of Kdiatnc Infectious Diseases. Philadelphia, Pa: WB Saunders Co: 1992:289-297.
4- Gerita RM, Walzer PD. Strongyloidiasis. In: Waller PD, Genia RM, eds. Parasitic Infectons in Ae Compromised Host. New ibrk, NY: Marcel Dekket Ine; 1989:463-525.
5. Walzer PD. Milder JE, Banwell JC, et al. Epidemiologie features of Strong-flotle? stercoralis infection in an endemic area of the United Stales. Am J Trop Mea Hyg. 198231:313-319.
6. Sccwden EB, Schaffner F, Stone WJ. Overwhelming strongyloidiasis; an unappreciated opportunistic infection. Medicine (Balmore). 1978;57:527-544,
7. Drugsfbr parasitic infections. Mtd Lm Drugs Tbcr. 1993:35:111.
8. Pawiowski ZS. Ascariasis In: Warren KS, Mahmoud AAF, eds. Tropical und Geographic Mtdicine. 2nd ed New York. NY: McGraw-Hill Ine; 1990:369-378.
9. Schad GA, Banwell JG. Hookwotms, In: Warren KS, Mahmoud AAF, eds. Tropical and Geographic Metterne. 2nd ed. New York, NY: McGraw-Hill Ine; 1990379-392.
10. Glickman LT, Schantz PM. Cypress RH. Epidemidopcal characteristics and clinica] findings in patients with serologkaily prawn toiocariasis. Trans R Soc Trop MaJ Hyg. 1979;73t254-258.
11. Mot CH. Visceral Ura migrata - a discussion based on a ICVKW oí the literature. CSn ftdiatr (PWIa). 1 968;7: 505-573.
12. Glickman LT, Scharm PM- Epidemiology and pathogenesis of sxmotk loxocariasis. Epidemiol Rev 1981 i3:230-250.
13. Catterall JR, Hcfflin JM, Remington JS. Pulmmaiy tDiopbsmosis. ?p Rev Rapo Dis 1986:133:704-705.
14. Webster BH. Pulmonary complications of amebiasis. Diseases of the chest. 1956;30-315325.
15. Ayiac A, Yurdakul Y, ttiiler C, et aL Pulmonary hfdarid diease: repon of 100 patients- Arn 7VmK Snrg. 1977:23:145-151.