Toxoplasma pneumonia and other parasitic pulmonary infections in patients with HIV

INTRODUCTION — Prior to the era of potent antiretroviral therapy, parasitic pulmonary infections were more commonly seen than they are today. However, the clinician still needs to be aware of presenting symptoms and signs of these uncommon infections, which may occur in the immunosuppressed patient with untreated or drug-resistant HIV infection.

This topic will address pulmonary infections related to Toxoplasma gondii, Strongyloides stercoralis, Cryptosporidium, and Microsporidium [1]. A more general overview of pulmonary disease in the patient with HIV is found elsewhere. (See "Evaluation of pulmonary symptoms in persons with HIV".)

TOXOPLASMOSIS — T. gondii is a ubiquitous intracellular protozoan. Although T. gondii can infect a wide range of vertebrates, feral and domestic cats are the definitive hosts. The organism undergoes its complete life cycle in the cat, resulting in the production of oocytes, which are passed with the feces into soil. Oocytes may remain infective for over one year. If ingested, Toxoplasma can invade tissue and reproduce.

The two routes of transmission to humans are:

●Ingestion of food or beverages contaminated with sporulated oocytes

●Transmission from mother to fetus.

There is no evidence of any other type of human-to-human transmission. Additional information on the transmission of toxoplasmosis is found elsewhere. (See "Toxoplasmosis in patients with HIV", section on 'Transmission'.)

Epidemiology — T. gondii is generally believed to cause subclinical infection in most immunocompetent hosts, but one review found that one-third of the reported cases of active pneumonia were in patients with no underlying immunosuppressive illness [2]. Of the remaining two-thirds, 61 percent had AIDS and 39 percent had other forms of immunosuppression. (See "Epidemiology of pulmonary infections in immunocompromised patients", section on 'Toxoplasmosis'.)

Most active cases of T. gondii disease in people with AIDS are due to reactivation of latent infection. The age-adjusted Toxoplasma IgG seroprevalence in the United States is about 10 percent, with a higher prevalence in older people [3]. In people with HIV who are seropositive for T. gondii, it is estimated that approximately 30 percent will develop Toxoplasma encephalitis within two years of the initial diagnosis of AIDS without antiretroviral therapy (ART); another 1 percent who are seronegative will develop primary toxoplasmosis [4,5].

Although encephalitis is overwhelmingly the most common manifestation of T. gondii infection in patients with AIDS, pneumonitis has become its second most common presentation. The incidence of pneumonitis is unknown, but one report estimated the prevalence of T. gondii pneumonia in France to be 5 percent, based upon a prospective study of bronchoalveolar lavage (BAL) specimens in 169 patients with AIDS [6]. Rates in the United States seem to be much lower, which may be due to lower rates of latent infection.

Clinical presentation — Active pulmonary toxoplasmosis does not usually occur in patients with HIV until the CD4 count falls below 100 cells/microL [7]. Toxoplasma pneumonitis typically presents with fever, nonproductive cough, and dyspnea.

The chest radiographs generally show diffuse bilateral interstitial and alveolar infiltrates. Other abnormalities include single or bilateral pulmonary nodules, cavitary infiltrates, lobar pneumonia, and pleural effusions. Reports of gallium scans in patients with T. gondii pneumonitis are rare, but diffuse intense uptake is reported. Serum lactate dehydrogenase (LDH) levels may be markedly elevated [8].

Diagnosis — Serologic tests for IgG, IgM, IgA, and IgE to T. gondii are available, but the results are usually not helpful in the profoundly immunosuppressed patient. However, the absence of IgG antibody to T. gondii does make the diagnosis much less likely, since most active disease is due to reactivation of latent infection.

If Toxoplasma pneumonitis is being considered, bronchoscopy with bronchoalveolar lavage (with or without transbronchial biopsy) is the preferred method of diagnosis, but its sensitivity and specificity are unknown [9,10]. The diagnosis is confirmed by observing the tachyzoite form of the organism in the BAL fluid or transbronchial biopsy. The most reliable methods of detection are Giemsa staining or eosin/methylene blue staining. The tachyzoite is 5 to 7 microns in length and is crescent-shaped. Polymerase chain reaction (PCR) testing has been used in patients with suspected pulmonary toxoplasmosis, but its performance characteristics are not known [11,12]. Immunofluorescence staining with a monoclonal antibody, or inoculation of mice followed by traditional culture may increase the yield of BAL, but these methods are not readily available [13,14].

If bronchoscopy is not diagnostic, then an open lung biopsy can be performed, either by video-assisted thoracoscopic surgery or traditional thoracotomy. Pathologically, a fibrinous exudate can be seen in the bronchi and alveoli, with an inflammatory cell interstitial infiltrate and areas of parenchymal necrosis. The organism may be seen within alveolar macrophages or freely floating within the alveoli. Unfortunately, the diagnosis of Toxoplasma pneumonitis is usually made by postmortem examination of the lungs, because it is often not considered premortem, and the special stains that are needed to make the diagnosis are not requested.

Differential diagnosis — Pulmonary toxoplasmosis may be clinically indistinguishable from other infections seen in patients with AIDS, such as Pneumocystis jirovecii (previously named Pneumocystis carinii) pneumonia, tuberculosis, cryptococcosis, or histoplasmosis. The differential diagnosis of pulmonary infiltrates in patients with AIDS is presented elsewhere. (See "Epidemiology, clinical presentation, and diagnosis of Pneumocystis pulmonary infection in patients with HIV", section on 'Differential diagnosis'.)

Treatment — The treatment of toxoplasmosis in patients with HIV includes antimicrobial therapy directed against T. gondii, as well as ART for immune recovery. (See 'When to initiate antiretroviral therapy' below.)

The combination of pyrimethamine and sulfadiazine is the regimen of choice for treatment of toxoplasmosis. However, when access to pyrimethamine is limited, an alternative regimen (eg, trimethoprim-sulfamethoxazole) is required. The regimens used for pulmonary disease are the same as those used for Toxoplasma encephalitis since there are no controlled studies specifically designed for lung involvement. The preferred and alternative regimens are described in detail elsewhere. (See "Toxoplasmosis in patients with HIV" and "Toxoplasmosis in patients with HIV", section on 'Treatment'.)

The exact duration of therapy for Toxoplasma pneumonitis is unknown. We generally administer three to six weeks of induction therapy, depending upon the severity of the disease and the response to treatment. Some studies suggest successful treatment outcomes in 50 to 77 percent of patients, although the number of cases of pulmonary toxoplasmosis is small [2].

Maintenance therapy (also called secondary prophylaxis) is prudent after initial treatment because relapses of toxoplasmosis may occur despite successful therapy [15]. The choice of regimen and the duration of maintenance therapy are discussed elsewhere. (See "Toxoplasmosis in patients with HIV", section on 'Discontinuing maintenance therapy'.)

Prevention — For patients with HIV, the risk of developing toxoplasmosis can be reduced by avoiding exposure to the pathogen or by using prophylactic antibiotics to decrease the risk of reactivation. (See "Toxoplasmosis in patients with HIV", section on 'Prevention'.)

OTHER PARASITIC PULMONARY INFECTIONS

Strongyloidiasis — S. stercoralis is an intestinal parasite that has a worldwide distribution but is predominantly found in tropical and subtropical areas, as well as the southeastern United States. The primary mode of transmission occurs when larvae from contaminated feces penetrate the skin, although infection can also occur via the fecal-oral route and from sexual transmission.

Most infected persons remain either asymptomatic or have low-grade abdominal symptoms. However, some patients, particularly those who are immunocompromised, can develop disseminated strongyloidiasis or the hyperinfection syndrome, both of which are considered "systemic strongyloidiasis" [16,17].

●Disseminated strongyloidiasis occurs when the organism, in the larval form, is found outside the usual migration pattern.

●Hyperinfection is an augmentation of the life cycle, resulting in a heavy infestation of worms in the lungs.

There have only been scattered cases of systemic strongyloidiasis in patients with HIV [16,18,19]; indeed, HIV does not appear to be a risk factor for disseminated strongyloidiasis [20]. However, strongyloides should be considered in the differential diagnosis of patients with HIV and pulmonary disease if they have previously lived or currently reside in endemic areas. Other risk factors for developing hyperinfection secondary to strongyloidiasis include high-dose glucocorticoids, organ transplantation, and HTLV-1 infection. (See "Epidemiology of pulmonary infections in immunocompromised patients", section on 'Strongyloides'.)

The diagnosis and treatment of patients with HIV and pulmonary involvement due to strongyloides are the same as for other immunocompromised hosts. This is reviewed in detail elsewhere. (See "Strongyloidiasis", section on 'Severe disease'.)

Cryptosporidium and microsporidium — Cryptosporidium and Microsporidium are causative agents of gastrointestinal disease in patients with HIV/AIDS. There are a few case reports of pulmonary disease due to these organisms in patients with AIDS before the introduction of effective antiretroviral therapy [21-23]. Fever and cough were the dominant symptoms. There are no specific treatment recommendations for pulmonary disease due to Cryptosporidium and Microsporidium; information about antiparasitic drugs that may be active against these organisms is presented elsewhere. (See "Microsporidiosis", section on 'Patients with HIV' and "Cryptosporidiosis: Treatment and prevention", section on 'Patients with advanced HIV'.)

Preventing exposure is the preferred method of prophylaxis, particularly in the patient with advanced immunosuppression. (See "Cryptosporidiosis: Treatment and prevention".)

WHEN TO INITIATE ANTIRETROVIRAL THERAPY — All patients with HIV should receive antiretroviral therapy, regardless of the CD4 count and viral load. In treatment-naïve patients who present with one of the parasitic lung diseases described above, treatment should be initiated within two weeks of diagnosis. For those failing therapy, a new regimen should be constructed. Detailed discussions of how to select an antiretroviral regimen are presented elsewhere. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Opportunistic infections in adults with HIV".)

SUMMARY AND RECOMMENDATIONS

●Prior to the era of potent antiretroviral therapy (ART), parasitic pulmonary infections were more commonly seen than they are today. However, the clinician needs to be aware of the presenting symptoms and signs of these uncommon infections, which may still occur in the immunosuppressed patient with untreated or drug-resistant HIV infection. (See 'Introduction' above.)

●Toxoplasma pneumonitis generally presents with fever, nonproductive cough, and dyspnea. The chest radiographs generally show diffuse bilateral interstitial and alveolar infiltrates. Pulmonary toxoplasmosis does not usually occur in patients with HIV until the CD4 count falls below 100 cells/microL. (See 'Clinical presentation' above.)

●If Toxoplasma pneumonitis is being considered, bronchoscopy with bronchoalveolar lavage for examination of tachyzoites is the preferred method of diagnosis. If the diagnosis is confirmed, the treatment of choice is typically a regimen that contains pyrimethamine and sulfadiazine, which is generally administered for three to six weeks. After that, maintenance therapy should be administered until immune reconstitution is achieved with ART. (See 'Diagnosis' above and 'Treatment' above and 'When to initiate antiretroviral therapy' above.)

●Strongyloides stercoralis is an intestinal parasite that has a worldwide distribution. Disseminated strongyloidiasis can cause pulmonary infection in patients with HIV; however this is rare, since HIV does not appear to be a risk factor for disseminated infection. (See 'Strongyloidiasis' above.)

●Cryptosporidium and Microsporidium typically cause gastrointestinal disease in patients with HIV/AIDS. However, there are a few case reports of pulmonary disease due to these organisms in patients with AIDS. (See 'Cryptosporidium and microsporidium' above.)

●All patients with HIV and Toxoplasma pneumonia or other parasitic pulmonary infections should receive ART, regardless of the CD4 count and viral load. In treatment-naïve patients, ART should be initiated within two weeks of diagnosis. (See 'When to initiate antiretroviral therapy' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Patricia A Tietjen, MD, who contributed to an earlier version of this topic review.

UpToDate also gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.