Pneumocystis jiroveci Case File

Pneumocystis jiroveci Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 43

A 29-year-old woman comes into the clinic for evaluation of a cough. Her symptoms started a few weeks ago and have progressively worsened. The cough is not productive. She has had intermittent, low-grade fevers and feels short of breath. She has tried some over-the-counter cough medications, which don’t seem to help. She smokes approximately a half-pack of cigarettes a day. She denies any history of pulmonary diseases. On examination, her temperature is 37.5°C (99.5°F), pulse is 100 beats per minute, respiratory rate is 26 breaths per minute, and oxygen saturation is 89 percent on room air. Her blood pressure is normal, but when applying the blood pressure cuff, you notice numerous scars in her antecubital region consistent with “needle tracks.” In general, she is a thin woman who appears to be in moderate respiratory distress and is coughing frequently. Her head and neck examination is normal. Her lung examination is notable for decreased breath sounds and rhonchi in all fields. Her cardiovascular and abdominal examinations are normal. A chest x-ray shows a bilateral interstitial infiltrate with a “ground-glass” appearance. She confides that she is HIV positive.

◆ What organism is the likely cause of her symptoms?

◆ Describe the sexual phase of reproduction of this organism.

ANSWERS TO CASE 43: Pneumocystis jiroveci

Summary: A 29-year-old woman intravenous drug user who is HIV positive has an interstitial pneumonia.

◆ Most likely etiologic agent: Pneumocystis jiroveci.

◆ Sexual phase reproduction of P. jiroveci: Haploid trophic forms conjugate to form diploid zygotes that become sporocysts; sporocysts undergo meiosis and mitosis to form the spore case that contains eight haploid spores. The spores are released by rupture of the spore case wall.

CLINICAL CORRELATION

Pneumocystis is an opportunistic organism found primarily in the lungs of humans and other animals. The reservoir of the organism in the environment is at this point unknown. Transmission of the organism is from person to person by respiratory droplet inhalation into the lungs. It is unclear whether disease results from the reactivation of a latent infection or acquisition of a new infection. The cellular immune system is primarily responsible for host defenses, with alveolar macrophages and CD4 cells playing a particularly important role. In HIV patients, the risk of developing symptomatic disease from Pneumocystis is highly correlated to the number of circulating CD4 cells, with the highest risk in those persons with CD4 counts below 200/mm3. The use of corticosteroids or other immunosuppressive drugs, treatment for malignancies, or severe malnutrition are risk factors for disease in non–HIV infected people. Classic Pneumocystis pulmonary infection is an interstitial pneumonia with plasma cell infiltrates. Typical symptoms are nonproductive cough, fever, dyspnea, and hypoxia. Chest x-rays commonly show a bilateral interstitial infiltrate extending from the hilum with a “ground-glass” appearance. In severely immunosuppressed patients Pneumocystis can disseminate most commonly to the thyroid, liver, bone marrow, lymph nodes, or spleen.

APPROACH TO THE SUSPECTED Pneumocystis PATIENT

Objectives

1. Know the life cycle, morphology, and reproduction of Pneumocystis.

2. Know the epidemiology, modes of transmission, and clinical syndromes

associated with Pneumocystis infection.

Definitions

Hypoxia: Reduction of oxygen supply to the tissues despite adequate blood perfusion.

Dyspnea: Shortness of breath leading to labored breathing.

DISCUSSION

Characteristics of Pneumocystis

Pneumocystis was originally characterized as a trypanosome; however, advanced molecular biological techniques have shown it to be closely related to fungi. It is unusual among fungi because it lacks ergosterol in its cell membranes and is insensitive to many antifungal drugs. Its life cycle has both sexual and asexual components. The trophic form of Pneumocystis is small and often seen in clusters. It multiplies asexually by binary fission and sexually by conjugation of haploid trophic forms to diploid cells that become sporocysts. These uninuclear cells undergo miosis then mitosis to form a spore case, which contains eight haploid spores. The spores are released by rupture of the cell wall, although the cyst wall remains and can be identified as empty structures.

Pneumocystis is thought to be ubiquitous in the environment, and most adults have been exposed to the organism during childhood and develop an asymptomatic infection. Pneumocystis is found in many mammalian species and is not thought to cross species lines. Pneumocystis that infects humans was recently renamed P. jirovecii.

Diagnosis

The diagnosis is confirmed by the presence of the organisms in sputum or bronchial samples obtained by bronchoalveolar lavage or other techniques, such as sputum induced by respiratory therapy. Pneumocystis can be identified microscopically by using numerous stains, such as methenamine silver, Giemsa, chemofluorescent agents such as calcofluor white, or specific immunofluorescent monoclonal antibodies. The monoclonal antibody fluorescent stain increases the sensitivity and specificity of the test. The diagnostic stage seen is usually the cyst form. The organism cannot be grown in culture.

Treatment and Prevention

Treatment for Pneumocystis is usually with sulfamethoxazole and trimethoprim (SMX-TMP); however, in allergic patients there are other options such as dapsone or pentamidine. Prophylaxis with SMX-TMP is recommended for severely immunosuppressed patients including HIV patients with a CD4 count of less than 200 cells/mm3.

COMPREHENSION QUESTIONS

[43.1] Pneumocystis jiroveci is now considered a fungus. Which of the following statements accurately describes this organism?

A. In immunocompromised patients the organism invades blood vessels causing thrombosis and infarction.

B. It grows best in a culture medium containing tissue fluid.

C. It is now classified as a fungus because it grows into septate hyphae in Sabouraud agar.

D. It is sensitive to antifungal agents such as amphotericin B.

E. Methenamine silver stain is used to visualize the organism in the clinical specimen.

[43.2] Which of the following statements best describes the laboratory diagnosis of Pneumocystis jiroveci?

A. India ink stain of bronchoalveolar lavage material

B. KOH stain of lung biopsy tissue

C. Growth of the organism on Sabouraud agar

D. Methenamine silver stain of induced sputum

[43.3] Pneumocystis jiroveci produces disease under what conditions listed below?

A. In individuals with CD4 lymphocyte counts above 400/μL

B. In the presence of immunosuppression

C. Infection in early childhood

D. Prophylaxis with SMX-TMP

Answers

[43.1] E. Pneumocystis jiroveci is often reported as the organism responsible for the described case. Pneumocystis carinii is found in rats, whereas P. jirovecii is found in humans. These species are not grown in the laboratory and do not respond to traditional antifungal chemotherapy. Being found primarily in the lungs, respiratory infections occur in immunocompromised individuals, and dissemination is rare. Specimens of bronchoalveolar lavage, lung biopsy, or induced sputum are stained (e.g., Giemsa or methenamine silver) and examined for cysts or trophozoites.

[43.2] D. Because Pneumocystis species are not able to be grown in the laboratory, staining procedures constitute the primary diagnostics techniques used. See the answer to Question 43.1 for further discussion.

[43.3] B. Pneumocystis jiroveci and P. carinii are present in the lungs of many animals, including humans. This organism rarely causes disease except in immunocompromised hosts. No other natural reservoir has ever been demonstrated, and the mode of infection is unclear. Transmission by aerosols may be possible.

MICROBIOLOGY PEARLS ❖ Pneumocystis that infects humans was recently renamed from P. carinii to P. jirovecii. ❖ Pneumocystis has a predilection for the lungs of humans and animals. ❖ Diagnosis of Pneumocystis is made by induced sputum or bronchoscopy with microscopic visualization of the cyst forms with either Papanicolaou, Giemsa, silver stain, or monoclonal antibodies.

REFERENCES

Murray PR, Rosenthal KS, Pfaller MA. Opportunistic mycoses. In: Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:664–72. 

Thomas CF, Limper AH. Pneumocystis pneumonia. NEJM 2004;350:2487–98. Walter PD. Pneumocystis carinii. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 5th ed. Philadelphia, PA: Churchill Livingstone, 2000:2781–95.

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