Pulmonary Manifestations of Parasitic Diseases

Respiratory diseases are important causes of morbidity and mortality among children throughout the world. Although diseases attributed to parasitic infection are uncommon for many physicians in temperate climates, these infections remain important conditions that must be addressed. Because of the influx of immigrants from developing countries and the volume of global travel, including children, physicians should have a basic understanding of respiratory illnesses attributed to parasitic infections.

The spectrum of syndromes related to parasitic respiratory infection is quite large. Diagnosis of a parasitic infection should be classified through the recognition of identifiable host characteristics, underlying medical conditions, and specific clinical manifestations. The etiology of acute respiratory infections caused by parasitic agents can be suggested, however, through knowledge of the specific geographic locale of the ill child or the location from which the child has arrived ( Table 13-1 ). Clinical presentations, findings on imaging studies, or individual laboratory results can differentiate infection among particular parasitic organisms. Underlying immunodeficiency should suggest infection with certain organisms, such as Strongyloides stercoralis or Toxoplasma gondii. In patients from appropriate geographic locations with respiratory symptoms and elevated peripheral eosinophil counts, infection with Ascaris lumbricoides, hookworm, S. stercoralis, or Toxocara species should be considered. This chapter reviews parasitic diseases that have pulmonary manifestations.

Table 13-1

Etiologies of Pulmonary Infiltrates Based on Geographic Distribution of Infecting Parasite

	GEOGRAPHIC DISTRIBUTION
ORGANISM	AF	AM	AS	E	OC	WS
Helminthic
Ascariasis						X
Capillariasis hepatica	X	X	X	X
Dirofilariasis						X
Echinococcosis	X	X	X	X	X
Filariasis	X	X	X
Gnathostomiasis			X *
Hookworm						X
Paragonimiasis	X	X	X	X	X
Schistosomiasis ^†	X	X	X
Strongyloidiasis						X
Toxocariasis						X
Trichinellosis ( Trichinella spiralis )						X
Protozoan
Amebiasis						X
Cryptosporidiosis						X
Malaria ( Plasmodium falciparum )	X	X	X	X	X
Toxoplasmosis						X

AF, Africa; AM, Americas; AS, Asia; E, Europe; OC, Oceania; WS, widespread.Modified from Martin G: Approach to the patient in the tropics with pulmonary disease. In Guerrant RL, ed: Tropical Infectious Diseases, vol 2, 2nd ed. Philadelphia, WB Saunders, 2006, pp 1544–1553.

* Rare in other geographic locales.

† Infiltrate early in disease, Katayama disease.

Protozoa

Malaria

Epidemiology

Malaria is endemic throughout the tropical areas of the world; one half of the world’s population lives in areas where malaria occurs. From a global perspective, there are approximately 300 to 500 million infections per year, resulting in approximately 1 million deaths ( Fig. 13-1 ). Most of these deaths occur in children.

Etiology

The Anopheles mosquito transmits the parasite ( Fig. 13-2 ). Various Plasmodium species— Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae —are responsible for human malaria. Of these four, only P. falciparum causes pulmonary disease. The disease onset is almost always within 1 year of exposure.

Clinical Manifestations

Shortness of breath and cough are the main respiratory symptoms in conscious patients; some also report chest tightness. Dyspnea often starts abruptly and progresses rapidly over a few hours, causing life-threatening hypoxia in patients with falciparum malaria.

Pathogenesis

The pathogenesis of malarial lung disease is attributed to a diffuse alveolar injury resulting in a capillary leak syndrome and acute pulmonary edema. This noncardiogenic pulmonary edema is associated with normal or low capillary wedge pressures without evidence of left ventricular dysfunction. Hypoalbuminemia and high-level parasitemia are risk factors associated with the development of pulmonary disease. Pathologic findings may include features of acute respiratory distress syndrome in some individuals; this is thought to be secondary to sequestered malaria parasites in the lung, inducing an inflammatory cascade. This mechanism mainly involves cytokines, neutrophils, and endothelial adhesion molecules. Substantial evidence implicates the neutrophil as central to the pathogenesis of microvascular lung injury, which results in increased capillary permeability and subsequent pulmonary edema.

Diagnosis

Radiographic and computed tomography (CT) findings may suggest noncardiogenic pulmonary edema. Pleural effusion, diffuse interstitial edema, and lobar consolidation may be seen. Laboratory assessments may show anemia and leukocytosis. A peripheral thick blood smear has high sensitivity for detecting parasitemia. A peripheral thin blood smear is better for species differentiation and staging of parasite development in P. falciparum .

Treatment

Effective treatment strategies for falciparum malaria depend on the pattern of parasite drug resistance in the geographic area where the infection is acquired and the severity of disease ( Table 13-2 ). The website for the Centers for Disease Control and Prevention should be reviewed to identify areas of chloroquine resistance. Severe malaria, such as that complicated by pulmonary disease, warrants therapy with parenteral medications. In addition to patient management in a critical care unit, the mortality rate is high. For physicians in nonmalarial areas, malaria always should be considered in the differential diagnosis of a sick patient who has traveled to a malaria-endemic area.

Table 13-2

Drugs to Treat Parasitic Lung Infections

INFECTION	DRUG	PEDIATRIC DOSE	ADULT DOSE
Malaria ( Plasmodium falciparum —in areas of chloroquine resistance)
Oral ( only in uncomplicated or mild disease)
Drugs of choice	Atovaquone/proguanil	<5 kg: not indicated	2 adult tabs bid or
		5–8 kg: 2 pediatric tabs once daily × 3 days	4 adult tabs once daily × 3 days
		9–10 kg: 3 pediatric tabs once daily × 3 days
		11–20 kg: 1 adult tab once daily × 3 days
		21–30 kg: 2 adult tabs once daily × 3 days
		31–40 kg: 3 adult tabs once daily × 3 days
		40 kg: 4 adult tabs once daily × 3 days
	or
	Quinine sulfate	30 mg/kg/day in 3 doses × 3–7 days	650 mg q8h × 3–7 days
	plus
	Doxycycline	4 mg/kg/day in 2 doses × 7 days	100 mg bid × 7 days
	or plus
	Tetracycline	6.25 mg/kg qid × 7 days	250 mg qid × 7 days
	or plus
	Clindamycin	20 mg/kg/day in 3 doses × 7 days	20 mg/kg/day in 3 doses × 7 days
Alternatives	Mefloquine	15 mg/kg followed 12 hr later by 10 mg/kg	750 mg followed 12 hr later by 500 mg
	Artesunate	4 mg/kg/day × 3 days	4 mg/kg/day × 3 days
	plus
	Mefloquine	15 mg/kg followed 12 hr later by 10 mg/kg	750 mg followed 12 hr later by 500 mg
Malaria ( P. falciparum— chloroquine-susceptible)
Oral
Drug of choice	Chloroquine phosphate	10 mg base/kg (maximum 600 mg base), then 5 mg base/kg at 24 hr and 48 hr	1 g (600 mg base), then 500 mg (300 mg base) 6 hr later, then 500 mg (300 mg base) at 24 hr and 48 hr
Parenteral (all Plasmodium )
Drugs of choice	Quinidine gluconate	10 mg/kg loading dose (maximum 600 mg) in normal saline over 1–2 hr, followed by continuous infusion of 0.02 mg/kg/min until PO therapy can be started	10 mg/kg loading dose (maximum 600 mg) in normal saline over 1–2 hr, followed by continuous infusion of 0.02 mg/kg/min until PO therapy can be started
	or
	Quinine dihydrochloride	20 mg/kg loading dose in 5% dextrose over 4 hr, followed by 10 mg/kg over 2–4 hr q8h (maximum 1800 mg/day) until PO therapy can be started	20 mg/kg loading dose in 5% dextrose over 4 hr, followed by 10 mg/kg over 2–4 hr q8h (maximum 1800 mg/day) until PO therapy can be started
Alternative	Artemether	3.2 mg/kg IM, then 1.6 mg/kg daily × 5–7 days	3.2 mg/kg IM, then 1.6 mg/kg daily × 5–7 days
Ascariasis ( Ascaris lumbricoides —roundworm)
Drug of choice	Albendazole	400 mg once	400 mg once
	or
	Mebendazole	100 mg bid × 3 days or 500 mg once	100 mg bid × 3 days or 500 mg once
	or
	Ivermectin	150–200 μg/kg once	150–200 μg/kg once
Hookworm ( Ancylostoma duodenale, Necator americanus )
Drug of choice	Albendazole	400 mg once	400 mg once
	or
	Mebendazole	100 mg bid × 3 days or 500 mg once	100 mg bid × 3 days or 500 mg once
	or
	Pyrantel pamoate	11 mg/kg/day(maximum 1 g) × 3 days	11 mg/kg/day (maximum 1 g) × 3 days
Strongyloidiasis ( Strongyloides stercoralis )
Drug of choice	Ivermectin	200 μg/kg/day × 2 days	200 μg/kg/day × 2 days
Alternatives	Albendazole	400 mg bid × 7 days	400 mg bid × 7 days
	or
	Thiabendazole	50 mg/kg/day in 2 doses × 2 days (maximum 3 g/day)	50 mg/kg/day in 2 doses × 2 days (maximum 3 g/day)
Amebiasis ( Entamoeba histolytica )
Severe intestinal or extraintestinal disease	Metronidazole	30–50 mg/kg/day in 3 doses × 7–10 days	750 mg tid × 7–10 days
	or
	Tinidazole	50 mg/kg/day (maximum 2 g) × 5 days	2 g once daily × 5 days
In treating extraintestinal disease follow with	Iodoquinol	30–40 mg/kg/day (maximum 2 g) in 3 doses × 20 days	650 mg tid × 20 days
	or
	Paromomycin	25–35 mg/kg/day in 3 doses × 7 days	25–35 mg/kg/day in 3 doses × 7 days
Alternative	Diloxanide furoate	20 mg/kg/day in 3 doses × 10 days	500 mg tid × 10 days
Toxocariasis (visceral larva migrans)
Drug of choice	Albendazole	400 mg bid × 5 days	400 mg bid × 5 days
	or
	Mebendazole	100–200 mg bid × 5 days	100–200 mg bid × 5 days
Echinococcosis ( Echinococcus granulosus —hydatid cyst)
Drug of choice	Albendazole	15 mg/kg/day (maximum 800 mg) × 1–6 mo	400 mg bid × 1–6 mo
	Patients may benefit from surgical resection or percutaneous drainage of cysts	15 mg/kg/day (maximum 800 mg) × 1–6 mo
Echinococcosis ( Echinococcus multilocularis )	Surgical excision is only available means of cure for this infection. In nonresectable cases, treatment with albendazole or mebendazole is recommended
Paragonomiasis ( Paragonimus westermani —lung fluke)
Drug of choice	Praziquantel	75 mg/kg/day in 3 doses × 2 days	75 mg/kg/day in 3 doses × 2 days
Alternative	Bithionol	30–50 mg/kg on alternate days × 10–15 doses	30–50 mg/kg on alternate days × 10–15 doses

Modified from Drugs for parasitic infections. Med Lett Drugs Ther 1–12, August 2004.

Amebiasis

Etiology and Epidemiology

Approximately 1% of the world’s population is infected with Entamoeba histolytica. After malaria and schistosomiasis, amebiasis is the third most common cause of mortality from parasitic diseases. Although pleuropulmonary disease in E. histolytica infection is uncommon, it can occur in 15% of individuals with an amebic liver abscess.

Pathogenesis

After a host ingests cysts in contaminated food or drink, pathogenic amebic trophozoites invade the colonic wall and disseminate hematogenously to the liver ( Fig. 13-3 ). Less commonly, infection may occur after aspiration. Disease onset may be either acute or chronic. Diarrhea is frequently absent. As an amebic liver abscess enlarges, adhesions may develop between the liver surface and the diaphragm. A sterile sympathetic pleural effusion may develop above the abscess. Alternatively, infection may spread through lymphatics or via the bloodstream and extend through the diaphragm after abscess rupture with empyema formation. The rupture frequently evokes severe pain in the right chest, back, or shoulder. Fever, hypoxemia, and circulatory collapse may follow. Classic “anchovy paste” can be obtained from an amebic hepatic abscess or from expectorate that has traveled through a hepatobronchial fistula.